SS v4n2.indb - Sleep Science

Transcrição

iSSN 1984-0659
Sleep
Science
Oficial publication of Associação Brasileira de Sono e Federação
LatinoAmericana de Sociedades de Sono
Quarterly
Sleep Science 2011 v. 4, n. 2, p. 39-80, Abr/Jun 2011
Editor in Chief
Monica Levy Andersen
Associated Editors
Claudia Moreno
Geraldo Lorenzi-Filho
Lia Rita Azeredo Bittencourt
Editorial Board
Ana Amelia Benedito-Silva (São Paulo, Brazil)
Arne Lowden (Stockholm, Sweden)
Dalva Poyares (São Paulo, Brazil)
Darwin Vizcarra (Lima, Peru)
David Gozal (Louisville, USA)
Deborah Sucheki (São Paulo, Brazil)
Denis Martinez (Porto Alegre, Brazil)
Diego Golombek (Buenos Aires, Argentina)
Ennio Vivaldi (Santiago, Chile)
Fernanda Louise Martinho (São Paulo, Brazil)
Fernanda Ribeiro Almeida (Vancouver, Canada)
Fernando Louzada (Curitiba, Brazil)
Francisco Hora (Salvador, Brazil)
James Krueger (Washington, USA)
John Araújo (Natal, Brazil)
Katsumasa Hoshino (Botucatu, Brazil)
Ligia Lucchesi (São Paulo, Brazil)
Lucia Rotenberg (Rio de Janeiro, Brazil)
SPONSORED BY
Executive Editors
Silvério Garbuio
Technical Editors
Edna Terezinha Rother
Maria Elisa Rangel Braga
Gabriel Natan Pires
Luciano Ribeiro Pinto Jr (São Paulo, Brazil)
Luis Vicente Franco de Oliveira (São Paulo, Brazil)
Luiz Carlos Gregorio (São Paulo, Brazil)
Luiz Menna-Barreto (São Paulo, Brazil)
Marco Túlio de Mello (São Paulo, Brazil)
Michel Cahali (São Paulo, Brazil)
Nicola Montano (Milan, Italy)
Patrício D. Peirano (Santiago, Chile)
Paulo Tavares (Distrito Federal, Brazil)
Pedro de Bruin (Fortaleza, Brazil)
Roberto Frussa Filho (São Paulo, Brazil)
Rogério Santos Silva (São Paulo, Brazil)
Rosana Alves (São Paulo, Brazil)
Sergio Tufik (São Paulo, Brazil)
Shahrokh Javaheri (Cincinnati, USA)
Thomas Kilduff (California, USA)
Veralice Meireles Sales de Bruin (Fortaleza, Brazil)
SUPPORTED BY
Associação Brasileira do Sono (ABS)
Rua Dr. Diogo Faria, 508 – Vila Clementino – CEP 04037-001 – São Paulo – SP – Brasil
www.sbsono.com.br
E-mail: [email protected]
Tel.: +55 11 5908-7111
Expedient
Sleep Science - ISSN 1984-0659 is published quarterly by the Associação Brasileira do Sono (ABS) and Federação Latinoamericana de Sociedades do Sono (FLASS), Brazil.
The authors are fully responsible for the concepts expressed in the articles published in the journal. Total or partial reproduction
of articles is authorized since the source is mentioned.
Associação Brasileira de Sono (ABS)
Website: www.sbsono.com.br
President: Francisco Hora de Oliveira Fontes
Vice-president: Andrea Bacelar
Secretary: Maurício Bagnato
Treasurer: Michel Cahali
Federation of Latin American Sleep Societies (FLASS)
Website: www.laflass.com
Council Members:
President: Darwin Vizcarra (Peru)
Vice-President: Darwin Vizcarra Escobar MD (Peru)
Secretary: Rosana D’Alves MD (Brasil)
Treasurer: Patricio Peirano MD (Chile)
Immediate Past-President: Julia Santín MD (Chile)
Past-president: Ricardo Velluti MD (Uruguay)
FLASS representative at the WFSRSMS council: Daniel P. Cardinali (Buenos Aires, Argentina) 2007-2011
MEMBER SOCIETIES
SBS (Brasil)
SAMS (Argentina)
SUIS (Uruguay)
ACMES (Colombia)
SOCHIMES (Chile)
APEMES (Peru)
Writing and management: the manuscripts should be submitted to Sleep Science Journal in the e-mail:
[email protected]
Executive secretary: Aline Silva
All mail should be sent to the address below:
Associação Brasileira do Sono – Rua Dr. Diogo Faria, 508 – Vila Clementino – CEP 04037-001 – São Paulo – SP – Brasil
Phone: +55 11 5908-7111
Free distribution
Circulation: 2,000 copies by issue
Production/Page design/Graphic project:
Zeppelini Editorial Ltda.
Rua Bela Cintra, 178 – Cerqueira César – São Paulo – SP
CEP 01415-000 – São Paulo – SP
Phone/Fax: +55 11 2978-6686
Cover and copyediting/proofreading: Zeppelini Editorial Ltda.
Translation: American Journal Experts (AJE)
©2010 – Sleep Science
Contents
Quarterly
Sleep Science 2011 v. 4, n. 2, p. 39-80, Abr/Jun 2011
iV
EDITORIAL
ORIGINAL ARTICLES
39
Gender differences in the relationship of sleep pattern and body composition in
healthy adults
Diferenças do gênero na relação entre o padrão de sono e a composição corporal em adultos saudáveis
Ioná Zalcman Zimberg, Cibele Aparecida Crispim, Rafael Marques Diniz, Murilo Dattilo, Bruno Gomes dos Reis, Daniel
Alves Cavagnolli, Alexandre Paulino de Faria, Sérgio Tufik, Marco Túlio de Mello
45
Impact of aerobic physical exercise on Restless Legs Syndrome
Impacto do exercício físico na Síndrome das Pernas Inquietas
Andrea Maculano Esteves, Marco Túlio de Mello, Ana Amélia Benedito-Silva, Sérgio Tufik
SHORT COMMUNICATION
49
Job satisfaction and sleep quality in nursing professionals
Satisfação no trabalho e qualidade de sono entre trabalhadores de enfermagem
Edla Maria Silveira Luz, Elaine Marqueze, Claudia Moreno
REVIEW ARTICLES
52
Updates on the sleep-wake cycle
Atualizações sobre o ciclo vigília-sono
Rosa Hasan, Flávio Alóe
61
Are there benefits of exercise in sleep apnea?
Existem benefícios do exercício físico na apneia do sono?
Roberto Pacheco da Silva, Karlyse Claudino Belli, Alicia Carissimi, Cintia Zappe FioriChristiane Carvalho Faria, Denis
Martinez
68
Swallowing in obstructive sleep apnea syndrome
A deglutição na síndrome da apneia obstrutiva do sono
Luciana Almeida Moreira, Michel Burihan Cahali
72
Upper airway resistance syndrome:still not recognized and not treated
Síndrome da resistência da via aérea superior: ainda não-reconhecida e não-tratada
Luciana Palombini, Maria-Cecilia Lopes, Sergio Tufik, Guilleminault Christian, Lia Rita A. Bittencourt
79
Authors instructions
EDITORIAL
Flavio Aloe and Carlos H. Schenck at one of the annual Sunday “Brazil night” dinners during the Associated Professional Sleep Society meetings in the
United States. (Photo taken by our close friend and colleague, Geraldo Rizzo).
Flavio Aloe, MD: A tribute for a deceased
sleep medicine leader in Brazil
The recent, untimely death of Flavio Aloe, MD, a shining light and vital force in Brazilian Sleep Medicine, is an occasion for experiencing gratitude and appreciation besides
shock and sadness. I first met Flavio on June 11, 1997 in San Francisco, California. I had
just finished giving a lecture on “Epic Dream Disorder” (relentless nocturnal dreaming
with non-restorative sleep) during the annual meeting of the Associated Professional
Sleep Societies (APSS). After my talk, Flavio came up to me and extended an invitation
on behalf of the Brazilian Neurological Society. I was asked to lecture on RBD, the Differential Diagnosis of Sleep-related Injury, and Recent Discoveries in the Parasomnias
of Interest to Neurologists, at the XVIII Congress of the Brazilian Neurological Society
in São Paulo during August 1998. I gladly accepted Flavio’s offer, and soon befriended
a unique person who was passionate about sleep medicine and who was fully committed
to further developing this new field in Brazil.
Over the course of nearly 14 years, Flavio and I had frequent communications about
new findings in sleep medicine and how they could be disseminated in Brazilian educational forums. Flavio and I served as Co-Chairs for the symposium “Update on RBD,”
presented at the 3rd International Congress on Sleep Medicine, WASM (World Associa-
Carlos H. Schenck, MD
Professor of Psychiatry at University of Minnesota Medical School, Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center – Minneapolis (MN), USA.
Correspondence address: Hennepin County Medical Center, 701 – Park Avenue – Minneapolis (MN), USA. E-mail: [email protected].
1
1
Sleep Sci. 2011;4(2):iv–vi
v
tion of Sleep Medicine), and 12th Brazilian Congress on Sleep Medicine, in São Paulo,
on November 10, 2009. Flavio was also one of the speakers at that symposium, and
delivered one of his characteristically thorough well-researched talks. (Flavio was always well-prepared for any sleep medicine-related activity as anyone who knew him
was fully aware of). Flavio, his close friend and colleague, Geraldo Rizzo, MD, and I
attended the cutting-edge conference, 6th International Symposium on Narcolepsy, in
Monte Verita, Ascona, Ticino, Switzerland, at the end of September 2009. This conference was organized by Claudio Bassetti, MD, from Lugano, Switzerland, who last year
was a distinguished invited speaker in Rio, with Flavio playing an instrumental role in
that process.
Flavio and I coauthored two book chapters on violent sleep disorders, and on nocturnal eating disorders linked to the sleep-wake cycle1,2. Also, in our sleep center’s review
on sleep and sex3, we mentioned the important and fascinating case report by Flavio
Aloe and colleagues on sexsomnia being linked with multiple parasomnias4. This was
one of the earliest reported links on how sexsomnia is frequently embedded in a rich
history of multiple parasomnias (or else with obstructive sleep apnea as the second most
common scenario), rather than as an isolated parasomnia. This early observation, reinforced by subsequent publications, carries important medical-legal consequences.
After I gave Flavio an inscribed copy of my first book, “Paradox lost: Midnight in the
battleground of sleep and dreams” 5, he asked me if I could provide him with an additional
copy of my book — to give to his 90-year-old father, who was still a very intellectually engaged and curious man. Clearly, for Flavio and his father, “the apple does not fall far from
the tree”. Moreover, Flavio was very active in promoting my book with a literary agent in
Rio, for the purpose of finding a Portuguese language publisher. Over several years, we
nearly found a publisher, and to date the process continues, thanks to Flavio’s persistence.
This example shows how selfless Flavio was — always giving of himself to people interested in sleep medicine, and not asking for much or anything in return.
Here is another recent example: Flavio connected me with the noted Brazilian neurologist and movement disorders specialist, Alan Eckeli, MD, about collaborating in
writing a paper on two cases of Sleep Related Eating Disorder associated with Parkinson’s Disease — an association not previously reported. Flavio did not request being a
coauthor; he just brought interested parties together for the good of the field of sleep
medicine and of neurology. That paper was recently accepted for peer-reviewed journal
publication.6
For almost 15 years, Flavio and I organized the annual Sunday evening “Brazil dinner” during the June APSS meetings. (Although Flavio trained in sleep medicine in
New York with Michael Thorpy, MD, our center was fortunate to have trained Brazilians Marcia Assis, MD, and Rosana Alves, MD, as former excellent sleep medicine fellows). The Figure shows a photo of us from one of those dinners.
Flavio left an impressive legacy, as the Brazilian sleep and neurology communities
know so well. He and Stella Tavares, MD, ran an excellent sleep medicine fellowship
program at the University of São Paulo, and Flavio was proud to say that he reviewed
each page of each polysomnogram with his fellows, leaving no “sleep stone unturned”
for careful scrutiny. Flavio was a solid gold person, devoted father to Piero and a special
colleague and friend to many people. I feel blessed for many reasons to have been friend
and colleague of Flavio Aloe, and so my wife Andrea, and I wish to honor his memory
and legacy in the field of sleep medicine in Brazil by establishing this year the Flavio
Aloe Award for the best abstract and poster at the annual meeting of the Brazilian Sleep
Society in Belo Horizonte in November 2011. We will always miss you, Flavio, and
your banner will be carried high and with your dedicated spirit by the Brazilian sleep
medicine community for generations into the future.
vi
REFERENCES
1. Aloe F, Schenck C, Teixeira V. Transtornos do sono e violência. In: Taborda JGV, Chalub M,
Abdalla-Filho E (Eds). Psiquiatria Forense (Forensic Psychiatry). Porto Alegre: Artes Médicas Sul,
Ltda Editora; 2004. p. 327-43.
2. Aloe F, Azevedo AP, Tavares S, Schenck C. Transtornos alimentares relacionados com o ciclo sonovigília. In: Mancini MC, Geloneze B, Salles JEN, Lima JG, Carra MK (eds). Tratado de Obesidade
(Monograph on Obesity). Itapevi: AC Farmacêutica (em coedição Guanabara Koogan Ltda); 2010.
p. 383-8.
3. Schenck CH, Arnulf I, Mahowald MW. Sleep and sex: what can go wrong? A review of the literature
on sleep related disorders and abnormal sexual behaviors and experiences. Sleep. 2007;30(6):683702.
4. Alves R, Aloe F, Tavares S. Sexual behavior in sleep, sleepwalking, and possible REM behavior
disorder: a case report. Sleep Res Online 1999;2:71-2.
5. Schenck CH. Paradox Lost: Midnight in the Battleground of Sleep and Dreams. Minneapolis, MN:
Extreme-Nights, LLC, 2005. Disponível em: <www.sleeprunners.com>.
6. Sobreira Neto MA, Penna MA, Sobreira ES, Chagas MH, Rodrigues GR, Fernandes RM, et al.
Sleep-related eating disorder in two patients with early-onset Parkinson’s disease. Eur Neurology
2011;66:106-9.
ORIGINAL ARTICLE
Gender differences in the relationship of sleep
pattern and body composition in healthy adults
Diferenças do gênero na relação entre o padrão de sono e a
composição corporal em adultos saudáveis
Ioná Zalcman Zimberg1, Cibele Aparecida Crispim1,2, Rafael Marques Diniz1, Murilo Dattilo1, Bruno Gomes dos Reis1,
Daniel Alves Cavagnolli1, Alexandre Paulino de Faria1, Sérgio Tufik1, Marco Túlio de Mello1
ABSTRACT
Objective: To investigate the gender differences in relationship between body composition and sleep pattern in healthy subjects. Methods: Fifty-two healthy volunteers (27 women) participated in this
study. Subjects underwent overnight polysomnography and measurements of body composition were taken in the following morning after a 12-hour fast. Validated protocols were used to evaluate sleep
(polysomnography) and anthropometry (body mass, height, skinfolds
and body circumferences). Results: A positive correlation between
percentage of slow-wave sleep and percentage of lean body mass
(r=0.46, p=0.016) was found in women. In men, awakenings during
sleep were correlated positively with indices such as body mass index (r=0.62, p<0.01), fat mass (kg) (r=0.61, p<0.01), fat percentage
(r=0.56, p<0.01), waist circumference (r=0.58, p<0.01), hip circumference (r=0.45, p<0.01), and waist-to-hip ratio (r=0.50, p=0.01).
Body mass index, body fat percentage, waist circumference, and waistto-hip ratio were correlated with apnea-hypopnea index (r=0.40,
p=0.03; r=0.46, p<0.01; r=0.49, p<0.01; and r=0.56, p<0.01) in
both genders. Conclusion: This study showed important statistical
associations between different sleep variables and anthropometric
characteristics in healthy subjects, suggesting a possible relationship
between greater body fat deposition and impairment of sleep quality.
In addition, it was noticed that these associations differ between genders and deserve further exploration.
keywords: sleep/physiology; sleep disorders/diagnosis; body mass
index; body composition; body fat distribution; polysomnography;
human; female.
RESUMO
Objetivo: Investigar as diferenças de gênero na relação entre composição corporal e padrão de sono em indivíduos saudáveis. Métodos:
Cinquenta e dois voluntários saudáveis (27 mulheres) participaram do
estudo. Os sujeitos foram submetidos à polissonografia e mensurações
de composição corporal foram feitas na manhã seguinte, após 12 horas
de jejum. Protocolos validados foram usados para avaliar o sono (polissonografia) e antropometria (massa corporal, altura, dobras cutâneas
e circunferências corporais). Resultados: Correlação positiva entre
porcentagem de sono de ondas lentas e massa corporal magra (r=0,46;
p=0,016) foram encontradas em mulheres. Em homens, despertares durante o sono foram positivamente correlacionados com índices
como índice de massa corporal (r=0,62, p<0,01), massa gorda (kg)
(r=0,61, p<0,01), percentual de gordura (r=0,56, p<0.01), circunferência de cintura (r=0,58, p<0.01), circunferência de quadril (r=0,45,
p<0.01) e relação cintura-quadril (r=0,50, p=0,01). Índice de massa
corporal, percentual de gordura, circunferência de cintura e relação
cintura quadril foram correlacionadas com o índice de apneia e hipopneia (r=0,40, p=0,03; r=0,46, p<0,01; r=0,49, p<0,01; e r=0,56,
p<0,01) em ambos os gêneros. Conclusões: Este estudo demonstrou
importantes associações estatísticas entre diferentes variáveis de sono
e características antropométricas em indivíduos saudáveis, sugerindo
uma possível relação entre maior deposição de gordura e diminuição
na qualidade de sono. Ademais, atesta-se que essas associações diferem
entre gêneros e incitam investigações mais aprofundadas.
Palavras-chave: sono/fisiologia; transtornos do sono/diagnostico;
índice de massa corporal; composição corporal; distribuição da gordura corporal; polissonografia; humanos; feminino.
INTRODUCTION
Sleep has been increasingly recognized for its contribution
to physical and psychological health1. Moreover, sleep loss
due to voluntary curtailment of time in bed has become a
hallmark of modern society2. Studies show that most people
need between 7 and 8 hours of daily sleep, however, over less
than 50 years, a reduction of sleep duration by 1.5 to 2 hours
seems to have occurred2-4.
Study carried out at Centro de Estudos em Psicobiologia e Exercício (CEPE), São Paulo (SP), Brazil.
1
Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil.
2
Universidade Federal de Uberlândia (UFU), Uberlândia (MG), Brazil.
Financial support: AFIP, Sleep Institute, CEDIP/FAPESP (#998/14303-3), CEPE, UNIFESP, FADA, CAPES and CEMSA.
Conflict of interests: nothing to declare.
Corresponding author: Marco Túlio de Mello – Rua Professor Francisco de Castro, 93 – CEP 04020-050 – São Paulo (SP), Brazil –
Received: February 2, 2011 – Accepted: July 2, 2011
Sleep Sci. 2011;4(2):39–44
40
Relationship between sleep pattern and body composition
Several studies have observed an association between
short sleep duration and increased body mass index (BMI)
or increased risk for being overweight5-13. Compared with
sleeping 7 to 8 hours per night, Patel et al.14 found that
sleeping less than 5 hours was associated with a BMI that
was, on average, more than 2.5 kg/m2 in men and 1.8 kg/m2
in women, after adjustments were made for multiple potentially confounding variables. Moreover, measures of adiposity also have been associated with time of sleep, showing
that short sleep duration is associated with higher body fat
percentage and waist circumference15-17.
However few studies that examined the association between sleep quality and body composition in health individuals are available in the literature17 as well as gender
differences in these variables18. In front of this, the aim of
this study was to investigate whether sleep architecture is
associated with body composition in healthy adults and if
this association is influenced by gender.
METHODS
Participants and study design
Fifty-two non-obese, healthy volunteers (27 women), between
19 and 45 years old (men: 27.3±6.0; women: 28.8±6.7),
were recruited from the community and from the medical
and technical staff and students of Universidade Federal de
São Paulo (UNIFESP) and Associação Fundo de Incentivo a
Pesquisa (AFIP). All individuals were sedentary (according
to International Physical Activity Questionnaire – IPAQ),
did not work in shift work, featured no abnormalities in a
clinical electrocardiogram at rest and under physical strain,
and did not have any health problems according to medical
evaluation. After clinical evaluation, all subjects underwent
overnight polysomnography (PSG). Subjects who presented
values of apnea-hypoapnea index (AHI) >1519, and those
who presented periodic leg movements (PLM) >520, assessed
by means of PSG were excluded. Enrollment was voluntary
after being informed about the procedures and objectives of
the study.
The research was performed in Sleep Institute and Centro de Estudos em Psicobiologia e Exercício/Associação Fundo de
Incentivo à Pesquisa (CEPE/AFIP) in 2007, situated in São
Paulo city (SP), Brazil. It was approved by the Committee
of Ethics of Universidade Federal de São Paulo (#0018/08)
and the volunteers were informed about all the stages of
the study and signed a written and informed consent before participation.
Sleep evaluation
Volunteers arrived at the sleep laboratory at 21h30 for
electrode attachment and went to bed at 23h. Sleep paramSleep Sci. 2011;4(2):39–44
eters were recorded in one night of PSG in the laboratory.
The PSG consisted of the simultaneous and continuous
registration of the electroencephalogram (C4-A1, C3-A2,
O2-A1, and O1-A2), left and right electrooculogram, submentonian and tibialis anterior muscles electromyography,
electrocardiogram, nasal and oral airflow, thoracic cage and
abdominal respiratory motion, oxyhemoglobin saturation
(SaO2), snoring and body positioning. All data were collected and stored using an EMBLA S7000® and recordings
were taken in 30-second epochs. PSGs were scored by a
blinded, experienced sleep technician and staged according
to standard criteria21. Analyses included measures of total
sleep time (TST), sleep efficiency, stages 1, 2, 3 (slow wave
sleep – SWS), rapid eye movement (REM) sleep, REM
sleep latency, wake time after sleep onset (WASO), AHI,
oxygen saturation and PLM.
Arousals were defined according to guidelines of the
Sleep Disorders Atlas Task Force of the American Sleep Disorders Association22, and respiratory events classified using
criteria of the American Academy of Sleep Medicine19. Episodes of apnea were defined as complete cessation of airflow
for 10 seconds or more, and hypopnea was scored if there
was at least a 50% reduction in airflow for 10 seconds or a
discernable decrement in airflow for 10 seconds in association with either an oxyhemoglobin desaturation of at least
3% or an arousal. Apnea/hypopnea events were classified as
obstructive, central or mixed according to the presence or
the absence of breathing efforts and the AHI was calculated
considering number of episodes of apnea and hypopnea per
hour of sleep.
Body composition evaluation
Measurements of body mass, height, skinfolds, and body
circumferences were taken in the following morning of the
PSG exam after a 12-hour fast. Height was measured with a
Sanny estadiometer (American Medical do Brasil Ltda., Brazil) with a 0.1 cm precision. Body weight was measured to
the nearest 0.1 kg using a Filizola scale (Star model, Filizola,
Brazil). Body mass (kg) divided by the square height (m²)
was used to calculate BMI.
Three measurements of triceps, subscapular, midaxillary,
chest, suprailiac, abdominal, and thigh skinfolds were taken
using a Lange skinfold caliper (Beta Technology Incorporated, USA) with a 0.1 mm precision. The mean value was
used to estimate the body fat percentage according to Jackson & Pollock23 and Jackson et al.24, equations for men and
women, respectively.
A Sanny measuring tape (American Medical do Brasil Ltda., São Paulo) with a 10 mm precision was used to
measure the waist (WC) and hip (HP) circumferences. WC
divided by HP was used to calculate the waist-to-hip ratio
Zimberg IZ, Crispim CA, Diniz RM, Dattilo M, Reis BG, Cavagnolli DA, Faria AP, Tufik S, Mello MT
(WHR). The WC and WHR were considered central obesity indices.
All measurements were taken by trained professional and
all protocols were previously validated.
Statistical analyses
Student’s t-test for independent samples was used for gender comparisons between individuals’ characteristics of sleep
and body composition. Pearson’s correlation was used to assess the association between sleep parameters and variables
of body composition. Data were analyzed using Statistica
6.0 (StatSoft, Inc., Tulsa, OK, USA). All values were expressed as mean±standard deviation (SD). Statistical tests
were accepted as significant when p≤0.05.
RESULTS
The characteristics of the volunteers are described in Table 1
and, in general, they were young adults, non-obese, with
normal body fat percentage, and waist circumference. When
compared by gender, men presented significantly higher values of body mass, height, BMI, lean mass, WC and WHR
than women, as expected.
Regarding the sleep variables, women had reduced total
sleep time (≤6 hours) in comparison with normative data21.
Men had a significantly higher percentage of stage 1 sleep
and AHI than did women. AHI in men were higher when
compared to normative data. Although there were no statistically significant differences between genders, the percentage of waking after sleep onset was higher, and REM sleep
was lower when compared to normative data21.
The correlations of sleep pattern with BMI and body
composition are described in Table 2. Stage 1 of sleep was
positively correlated to lean mass and WHR (r=0.29). Stage
2 of sleep was also correlated to WHR (r=0.28 and r=-0.36,
respectively). WASO showed a significant correlation with
weight and adiposity measures as BMI, fat mass, WC, and
HC (r=0.35; r=0.42; r=0.40; r=0.29; r=0.31, respectively).
Furthermore, AHI positively correlated with BMI, lean
mass, fat mass, WC, and WHR (r=0.43; r=0.46; r=0.29;
r=0.50; r=0.55).
When genders were separately analyzed, a positive significant correlation between SWS percentage and lean mass
percentage was found in women (Figure 1), but not in men
(r=0.08, p=0.33). Only women presented a negative correlation between fat mass percentage (r=-0.46, p=0.016) and
SWS percentage.
Table 1. Body composition and sleep characteristics of volunteers.
Men (n=25) Women (n=27) p value
Body composition variables
Age (yr)
0.45
27.3±6.0
28.7±6.8
Body Mass (kg)
0.00
76.9±14.9
58.2±8.5
Height (m)
0.00
1.75±0,1
1.61±0.1
BMI (kg/m²)
0.01
25.0±4.3
22.4±2.6
Lean mass (kg)
0.00
61.1±7.8
44.9±4.9
Fat mass (kg)
0.21
15.9±8.9
13.4±4.5
Body fat (%)
0.11
19.5±7.8
22.5±4.9
0.00
WC (cm)
85.1±12.1
72.2±6.7
HC (cm)
0.20
99.0±10.5
95.9±6.1
WHR
0.00
0.9±0.1
0.7±0.1
Sleep variables
TST (min)
0.38
369.3±40.3
353.6±78.7
Sleep latency (min)
0.16
16.6±15.5
11.3±11.3
Sleep efficiency (%)
0.83
87.3±6.9
87.8±7.9
Stage 1 (%)
0.03
3.8±2.2
2.6±1.8
Stage 2 (%)
0.34
55.1±6.6
53.1±7.9
SWS (%)
0.41
23.1±6.5
24.6±6.3
REM (%)
0.20
17.9±4.6
19.7±5.1
WASO (min)
0.92
37.3±25.7
38.0±28.7
AHI (events/hr)
0.00
8.4±7.5
2.6±2.5
PLM (events/hr)
0.27
0.6±1.5
1.8±5.2
Epworth Sleepiness Scale
0.91
8.3±2.5
8.4±3.6
In bold p≤0.05; Student’s t test.
BMI: body mass index; WC: waist circumference; HC: hip
circumference; WHR: waist-to-hip ratio; TST: total sleep time; SWS:
slow-wave sleep (stage 3 of sleep); REM: rapid eye movement; WASO:
wake after sleep onset; AHI: apnea-hypoapnea index; PLM: periodic leg
movements.
Table 2. Correlations between body composition measurements and sleep variables.
Sleep effic
Stage
Stage
TST (min)
SWS (%)
REM (%)
WASO (min)
AHI
(%)
1 (%)
2 (%)
BMI (kg/m²)
-0.01
-0.24
0.18
0.10
-0.06
-0.15
0.35
0.43
Lean mass (kg)
-0.02
-0.16
0.30
0.09
-0.07
-0.19
0.11
0.46
Fat mass (kg)
-0.02
-0.23
0.13
0.10
-0.08
-0.09
0.42
0.29
Body fat (%)
-0.01
-0.16
-0.02
0.08
-0.10
0.02
0.40
0.06
WC (cm)
0.03
-0.20
0.25
0.19
0.06
-0.15
0.29
0.50
HC (cm)
0.01
-0.09
0.13
0.02
-0.18
-0.07
0.31
0.17
WHR
0.09
-0.15
0.29
0.28
-0.22
-0.11
0.14
0.55
In bold characters: p<0.05; Pearson’s correlation.
TST: total sleep time; Sleep effic: sleep efficiency; SWS: slow-wave sleep (stage 3 of sleep); REM: rapid eye movement; WASO: wake after sleep onset;
AHI: apnea-hypoapnea index; BMI: body mass index; WC: waist circumference; HC: hip circumference; WHR: waist-to-hip ratio.
Sleep Sci. 2011;4(2):39–44
41
Slow Wave Sleep (%)
Only in men, WASO was positively correlated with
BMI (r=0.62, p<0.01), fat mass (r=0.61, p<0.01), lean
mass (r=0.41¸ p=0.04), fat percentage (r=0.56, p<0.01),
WC (r=0.58, p<0.01), HC (r=0.45, p=0.02), and WHR
40
35
30
25
20
15
10
5
0
60
r=0.46, p=0.02
65
70
75
80
85
90
Lean body mass (%)
Figure 1. Correlation between slow-wave sleep percentage and lean body
mass percentage in women. A corresponding best-fit line along with the
Person’s correlation coefficient (r) and its p value was shown.
0,70
0,50
0,40
0,30
0,20
WHR
HC (cm)
WC (cm)
Body fat (%)
Lean mass (kg)
0,00
Fat mass (kg)
0,10
BM (kg/m2)
WASO correlation
0,60
WASO: wake after sleep onset; BMI: body mass index; WC: waist circumference; HC: hip circumference; WHR: Waist-to-hip ratio.
Figure 2. Significant correlations between body composition measurements and wake after sleep onset in men.
35
r=0.51, p=0.01
30
25
AHI
42
20
15
10
5
0
0,7
0,75
0,8
0,85
0,9
0,95
1
WHR
Figure 3. Correlation between apnea-hypoapnea index and waist-to-hip
ratio in men. A corresponding best-fit line along with the Person’s correlation coefficient (r) and its p value was shown.
Sleep Sci. 2011;4(2):39–44
(r=0.50, p=0.01), as shown in Figure 2. Furthermore, a
positive correlation between WHR and AHI (r=0.51,
p=0.01) was also found (Figure 3). All these correlations
were not found in women.
DISCUSSION
In the present study, several significant correlations between anthropometric variables and sleep were found, indicating that these aspects can be associated. It is important to highlight that a bidirectional influence can occur
between sleep and anthropometric variables, that is, sleep
may influence body composition and body composition can
influence sleep pattern. The first is well demonstrated in
the literature, but little is known about how parameters
like body fat percentage, waist and hip circumferences can
affect sleep pattern.
Although our results indicated expected differences in
anthropometric variables between the genders, the same occurred with sleep pattern which evidenced a higher stage 1
and AHI in men, a finding previously reported by our group.
Previously, Silva et al.18, demonstrated in a large group of
Brazilian patients that men had higher stage 1, stage 2, and
AHI than women, whereas women had significantly more
SWS than men.
Given the speculative nature of these results and the
lack of evidence in this area, it is difficult to compare these
results with other researches. One of the few studies that
analyzed the relationship between body composition and
sleep was done by Rontoyanni et al.16. Their results demonstrated a negative correlation between sleep duration
and fat percentage in healthy women, supporting the idea
that sleep duration is significantly associated with body
fat. On the other hand, in a study conducted by Stranges
et al.15, negative correlations between sleep duration and
body mass and central adiposity were observed. In our
study no association between sleep duration and greater
body mass and/or adiposity was found. Nevertheless, we
verified an association between body composition and sleep
quality variables.
Rao et al.17 published the first large scale study to examine the relationship of sleep architecture, specifically SWS,
with measures of body composition such as BMI, waist circumference and percentage body fat. This study showed
that older men in the lowest quartile of SWS had an average
BMI of 27.4kg/m2, compared to 26.8 for those in the highest quartile of SWS. Furthermore, participants in the lowest
quartile of SWS had a 1.4-fold increased odds for obesity
(p=0.03, 95%CI: 1.0-1.8) compared to those in the highest
quartile. Authors concluded that independent of sleep duration, percentage time in SWS is inversely associated with
BMI and other measures of body composition. The authors
Zimberg IZ, Crispim CA, Diniz RM, Dattilo M, Reis BG, Cavagnolli DA, Faria AP, Tufik S, Mello MT
did not found a relationship between adiposity variables and
SWS. In our study we observed in women a negative correlation between percentage of SWS sleep and percentage of fat
mass. It also was observed that the WHR correlates negatively with the percentage of stage 4 sleep and positively
with stage 1 sleep in both genders. According to Rao et al.17,
it is possible that increased BMI may alter sleep architecture
and decrease SWS.
The alteration of the ideal sleep architecture can bring
about harmful effects. As an example, Tasali et al.25, in a
recent study demonstrated that the reduction of the SWS
was related to a greater insulin resistance, indicating its role
in glucose homeostasis. These data suggest that a smaller
amount of SWS (which occurs in obese individuals) can contribute to an increased risk of type 2 diabetes.
Although in our study it was not possible to demonstrate
a cause-effect relationship between body composition and
apnea, some positive correlations between AHI and anthropometric variables were found especially in men, demonstrating that body fat distribution can be associated with
a higher risk for apnea. Some studies show that obesity is a
pathogenic factor in apnea26-29 and that approximately 70%
of the patients with sleep apnea are obese30. This association
occurs because excessive weight can lead to a pharyngeal
narrowing due to the fat deposition on the pharynx walls or
on parapharyngeal structures, such as tongue, soft palate and
uvula30,31. Still, the risk of apnea development is more associated with the accumulation of fat in the central region32, a
fact also observed in the present study.
The role of sleep fragmentation in the relationship between sleep duration and obesity it is not clear yet. In the
Rotterdam Study, whereas actigraphy was used to assess
sleep, the degree of sleep fragmentation was a stronger predictor of adiposity than reduced sleep duration33. Persons
with more fragmented sleep had a higher BMI and more
obesity, and the association of short sleep with obesity was
substantially attenuated after adjustment for sleep fragmentation. This indicates that sleep fragmentation may be
part of the mechanism by which short sleep is related to
a higher prevalence of obesity. The results of this study
are in agreement with the data described by van den Berg
et al.33. However, Rao et al.17, did not found significant
relationship between arousal index (as a measure of sleep
fragmentation) and measures of body composition.
Some significant associations between anthropometric variables and sleep differed between genders (SWS and
lean and fat mass in women, and WASO and BMI, fat mass,
lean mass, fat percentage, WC, HC, and WHR in men).
The potential gender difference in the relationship between
sleep and adiposity deserves further exploration, especially
since discordant have also been observed in different age
groups6,14,15,33-36. Future metabolic studies should be done in
different genders to determine if they have a different hormonal response to short sleep duration.
A limitation of the present study was the single night
of PSG. An adaptation to the laboratory could potentially
influence the response to sleep. Another limitation is that
we did not control menstrual cycle phase of women involved
in the study.
This study demonstrated an important association between different sleep variables and adiposity measurements
in healthy individuals, suggesting that a greater deposition
of body fat can be associated with an impairment of sleep
quality and not only the inverse, as shown in several studies.
However, more studies are necessary to elucidate the real
influence of sleep and its disturbances on several factors responsible for the control of body mass.
Acknowledgments
This study was supported by AFIP, CEPE, Centro de Estudo
Multidisciplinar em Sonolência e Acidentes (CEMSA), Centro de
Pesquisa, Inovação e Difusão-Fundação de Amparo à Pesquisa do
Estado de São Paulo (CEPID/SONO-FAPESP) (#98/14303-3),
National Counsel of Technological and Scientific Development (CNPq), Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior (CAPES), FAPESP, UNIFESP, Fonte de Auxílio
aos Docentes e Alunos of UNIFESP. We thank all volunteers
and researchers involved in this study.
References
1. Taheri S. The link between short sleep duration and obesity: we
should recommend more sleep to prevent obesity. Arch Dis Child.
2006;91(11):881-4.
2. National Sleep Foundation. Sleep in America 2011 Poll [Internet].
Washington: National Sleep Foundation; 2002. [cited 2010 Nov. 12].
Available from<http://www.sleepfoundation.org/site/c.huIXKjM0IxF/
b.2417141/k.2E30/The_National_Sleep_Foundation.htm>.
3. Ursin R, Bjorvatn B, Holsten F. Sleep duration, subjective sleep
need, and sleep habits of 40- to 45-year-olds in the Hordaland
Health Study. Sleep. 2005;28(12):1260-9.
4. Kripke DF, Simons RN, Garfinkel L, Hammond EC. Short and
long sleep and sleeping pills. Is increased mortality associated?
Arch Gen Psychiatry. 1979;36(1):103-16.
5. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004;1(3):E62.
6. Hasler G, Buysse DJ, Klaghofer R, Gamma A, Ajdacic V, Eich
D, et al. The association between short sleep duration and
obesity in young adults: a 13-year prospective study. Sleep.
2004;27(4):661-6.
7. Heslop P, Smith GD, Metcalfe C, Macleod J, Hart C. Sleep duration and mortality: The effect of short or long sleep duration on
cardiovascular and all-cause mortality in working men and women. Sleep Med. 2002;3(4):305-14.
Sleep Sci. 2011;4(2):39–44
43
44
8. Bjorvatn B, Sagen IM, Oyane N, Waage S, Fetveit A, Pallesen S,
et al. The association between sleep duration, body mass index
and metabolic measures in the Hordaland Health Study. J Sleep
Res. 2007;16(1):66-76.
9. Kohatsu ND, Tsai R, Young T, Vangilder R, Burmeister LF,
Stromquist AM, et al. Sleep duration and body mass index in a
rural population. Arch Intern Med. 2006;166(16):1701-5.
10.Vorona RD, Winn MP, Babineau TW, Eng BP, Feldman HR,
Ware JC. Overweight and obese patients in a primary care population report less sleep than patients with a normal body mass
index. Arch Inter Med. 2005;165(1):25-30.
11.Patel SR, Malhotra A, White DP, Gottlieb DJ, Hu FB. Association between reduced sleep and weight gain in women. Am J
Epidemiol. 2006;164(10):947-54.
12.Gangwisch JE, Malaspina D, Boden-Albala B, Heymsfield SB. Inadequate sleep as a risk factor for obesity: analyses of the NHANES
I. Sleep. 2005;28(10):1289-96.
13.Vioque J, Torres A, Quiles J. Time spent watching television,
sleep duration and obesity in adults living in Valencia, Spain. Int
J Obes Relat Metab Disord. 2000;24(12):1683-8.
14.Patel SR, Blackwell T, Redline S, Ancoli-Israel S, Cauley JA,
Hillier TA, Lewis CE, Orwoll ES, Stefanick ML, Taylor BC, Yaffe
K, Stone KL; Osteoporotic Fractures in Men Research Group;
Study of Osteoporotic Fractures Research Group. The association
between sleep duration and obesity in older adults. Int J Obes
(Lond). 2008;32(12):1825-34.
15.Stranges S, Cappuccio FP, Kandala NB, Miller MA, Taggart
FM, Kumari M, et al. Cross-sectional versus prospective associations of sleep duration with changes in relative weight and
body fat distribution: the Whitehall II Study. Am J Epidemiol.
2008;167(3):321-9.
16.Rontoyanni VG, Baic S, Cooper AR. Association between nocturnal sleep duration, body fatness, and dietary intake in Greek
women. Nutrition. 2007; 23(11-12):773-7.
17.Rao MN, Blackwell T, Redline S, Stefanick ML, Ancoli-Israel S,
Stone KL; Osteoporotic Fractures in Men (MrOS) Study Group.
Association between sleep architecture and measures of body composition. Sleep. 2009;32(4):483-90.
18.Silva A, Andersen ML, De Mello MT, Bittencourt LR, Peruzzo
D, Tufik S. Gender and age differences in polysomnography findings and sleep complaints of patients referred to a sleep laboratory.
Braz J Med Biol Res. 2008;41(12):1067-75.
19. Sleep-related breathing disorders in adults: recommendations for
syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine
Task Force. Sleep. 1999;22(5):667-89.
20. Recording and scoring leg movements. The atlas task force. Sleep.
1993;16(8):748-59.
21. Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Bethesda, Md: U.S. Department of Health, Education and
Welfare; 1968.
22. EEG arousals: scoring rules and examples: a preliminary report
from Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep. 1992;15(2):173-84.
23.Jackson AS, Pollock ML. Generalized equations for predicting
body density of men. Br J Nutr. 1978;40(3):497-504.
Sleep Sci. 2011;4(2):39–44
24.Jackson AS, Pollock ML, Ward A. Generalized equations for
predicting body density of women. Med Sci Sports Exerc.
1980;12(3):175-81.
25.Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow-wave
sleep and the risk of type 2 diabetes in humans. Proc Natl Acad
Sci USA. 2008;105(3):1044-9.
26.Fleetham JA. A wake up call for sleep disordered breathing. BMJ.
1997;14(7084):839-40.
27. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The
occurrence of sleep disordered breathing among middle-aged
adults. N Engl J Med. 1993;328(17):1230-5.
28.Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R,
Resnick HE; Sleep Heart Health Study Investigators. Sleepdisordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol.
2004;160(6):521-30.
29.Shimura R, Tasumi K, Nakamura A, Kasahara Y, Tanabe N, Takiguchi Y, et al. Fat accumulation, leptin and hypercapnia on obstructive sleep apnea-hypopnea syndrome. Chest. 2005;127(2):543-9.
30.Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED,
Longmore DB, et al. Sites and sizes of fat deposition around the
pharynx in obese patients with obstructive sleep apnea and weight
matched controls. Eur Respir J. 1989:2(7);613-22.
31.Shelton KE, Woodson H, Gay S, Suratt PM. Pharyngeal fat in
obstructive sleep apnea. Am Rev Respir Dis. 1993;148(2):462-6.
32.Schafer H, Pauleit D, Sudhop T, Gouni-Berthold L, Ewing S,
Berthold HK. Body fat distribuition, serum leptin and cardiovascular risk factors in men with obstructive sleep apnea. Chest.
2002;122(3):829-39.
33.Van den Berg JF, Knvistingh Neven A, Tulen JH, Hofman A,
Witteman JC, Miedema HM, et al. Actigraphic sleep duration
and fragmentation are related to obesity in the elderly: the Rotterdam Study. Int J Obes (Lond). 2008;32(7):1083-90.
34.Chaput JP, Brunet M, Tremblay A. Relationship between
short sleeping hours and childhood overweight/obesity: results from the ‘Québec en Forme’ Project. Int J Obes (Lond).
2006;30(7):1080-5.
35.Knutson KL. Sex differences in the association between sleep and
body mass index in adolescents. J Pediatr. 2005;147(6): 830-4.
36.Yu Y, Lu BS, Wang B, Wang H, Yang J, Li Z, et al. Short
sleep duration and adiposity in Chinese adolescents. Sleep.
2007;30(12):1688-97.
ORIGINAL ARTICLE
Impact of aerobic physical exercise
on Restless Legs Syndrome
Impacto do exercício físico na Síndrome das Pernas Inquietas
Andrea Maculano Esteves1,2, Marco Túlio de Mello1,2, Ana Amélia Benedito-Silva3, Sérgio Tufik1
ABSTRACT
Objective: Therapeutic approaches to the Restless Legs Syndrome
and Periodic Limb Movement sleep disorders are often implemented
concomitantly. The objective of this study was to assess the effect of
aerobic physical exercise on the symptoms of Restless Legs Syndrome.
Methods: The study included 11 patients who were diagnosed with
RLS and with on the severity scale established by the International
Restless Legs Syndrome Scale (IRLSS), which was translated and validated into Brazilian Portuguese. The patients completed 72 sessions
of aerobic exercises prescribed at Anaerobic Ventilatory Threshold Intensity on an ergometric cycle. Patients performed 3 50-minute sessions per week for approximately 6 months. Each patient completed
a severity scale questionnaire of Restless Legs Syndrome prior to the
first training session and after sessions 1, 36 and 72. Results: In response to aerobic physical exercise, the patients demonstrated a significant reduction in symptoms of Restless Legs Syndrome after 36
sessions (score: 24 to 15). This reduction was maintained even after 72
sessions (score: 7) of aerobic exercises (p<0.001). Conclusions: The
aerobic exercise proved to be efficient in diminishing Restless Legs
Syndrome symptoms.
keywords: restless leg syndrome/therapy; exercice; sleep disorders;
exercise therapy.
RESUMO
Objetivo: As abordagens terapêuticas para os distúrbios do sono, Síndrome das Pernas Inquietas e Movimentos Periódicos das Pernas, são
frequentemente implementadas concomitantemente. Assim, o objetivo deste estudo foi avaliar o efeito do exercício físico aeróbio sobre os
sintomas da Síndrome das Pernas Inquietas. Métodos: Foram estudados 11 pacientes diagnosticados com Síndrome das Pernas Inquietas
e com a escala de gravidade estabelecida pela International Restless Legs
Syndrome Study Group, que foi traduzida e validada para o português.
Os pacientes realizaram 3 sessões de 50 minutos por semana completando 72 sessões de exercício físico aeróbio prescrito na Intensidade do
Limiar Anaeróbio Ventilatório em um ciclo ergométrico. Foi preenchido um questionário de escala de gravidade de Síndrome das Pernas
Inquietas antes do início da primeira sessão de treino e depois das sessões 1, 36 e 72. Resultados: Em resposta ao exercício físico aeróbio,
os pacientes demonstraram uma redução significativa nos sintomas
da síndrome após 36 sessões (pontuação: 24 a 15). Essa redução foi
mantida mesmo após 72 sessões (pontuação: 7) de exercícios aeróbios
(p<0,001). Conclusão: Nossos resultados sugerem que o exercício
físico aeróbio é eficaz na diminuição dos sintomas da Síndrome das
Pernas Inquietas.
Palavras-chave: síndrome das pernas inquietas/terapia; exercício;
transtornos do sono; terapia por exercício.
INTRODUCTION
Therapeutic approaches to the Restless Legs Syndrome (RLS)
and Periodic Limb Movement (PLM) sleep disorders are often implemented concomitantly1,2.
The variability in the epidemiological data on RLS is
likely due to the non-standardized diagnosis of the disorder.
In 1995, the International Restless Legs Syndrome Study
Group (IRLSSG) published a standard for RLS diagnosis3.
The report defined RLS as a movement-relieved disorder,
citing the presence of discomfort in the legs that worsens
at night or when at rest as one of the diagnosis criteria. In
addition to differing diagnostic criteria, varying data collection strategies have been employed. These differences
may have also affected findings and lead to different types of
treatment. Depending on the severity of the sleep disorder
and its impact on patient health, several types of RLS/PLM
treatment have been described in the literature4.
Aukerman et al. investigated a program of combined exercises (aerobic and muscular strength). The 11 volunteers who
participated in aerobic and strength exercises 3 times per week
for 12 weeks showed a statistically significant reduction in RLS
symptoms, compared with those in the control group (12 volunteers), by week 6. The International Restless Legs Syndrome
Scale (IRLSS) was used to analyze RLS-related variables at the
start of the program and after 3, 6, 9 and 12 weeks5.
Study carried out at Centro de Estudos em Psicobiologia e Exercício da Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil.
1
Departamento de Psicobiologia da Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil.
2
Centro de Estudos em Psicobiologia e Exercício da Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil.
3
Escola de Artes, Ciências e Humanidades da Universidade de São Paulo (USP), São Paulo (SP), Brazil.
Corresponding author: Andrea Maculano Esteves – Departamento de Psicobiologia da Universidade Federal de São Paulo – Rua Professor Francisco de Castro, 93 – Vila
Clementino – CEP 04020-050 – São Paulo (SP), Brazil – E-mail: [email protected]
Received: February 16, 2011 – Accepted: June 27, 2011
Sleep Sci. 2011;4(2):45–48
46
Exercise and RLS
De Mello et al. recorded polysomnography (PSG) data
from athletes with spinal cord injuries while performing
acute exercise (maximum effort test level) and chronic exercise (training for 44 days at ventilatory threshold 1). They
found that PLM during sleep diminished significantly. The
effect of aerobic physical exercise did not significantly differ
from L-dopa treatment (the standard pharmacological treatment for RLS/PLM)6-9.
In a recent study conducted by our group, both acute (1
session) and chronic aerobic physical exercise (72 sessions)
were effective in reducing the levels of PLM and inducing
beta-endorphin release10.
The analyses presented here are an extension of the results obtained by Esteves et al.10. The results were not published together
because the IRLSS questionnaire had not yet been validated.
Therefore, the objective of the current study was to assess the reduction of RLS symptoms in response to aerobic physical exercise.
Materials and methods
The study was approved by the Ethics Research Committee of
Universidade Federal de São Paulo (UNIFESP), CEP n.º 481/01.
Candidate patients were initially contacted based on diagnoses provided by the Sleep Institute. The 11 (6 women)
participants selected were those who presented complaints
of leg discomfort and whose diagnosis was performed by a
physician. They displayed no other signs of sleep disorder
or clinical disease and had never received pharmacological treatment for RLS/PLM. All of the subjects underwent
ECGs at rest and during stress and were tested for any pathology that would contraindicate physical exercise. Based
on the results, experimental sample was standardized.
A full-night PSG was performed to analyze the baseline
parameters of each participant’s sleep11.
Experimental procedure
The volunteers performed 50 minutes of aerobic training on
an ergometric cycle 3 times per week. Over the course of 6
months, each patient completed 72 sessions.
The morning after the 36th and 72nd sessions of aerobic physical
exercise, each volunteer filled out the IRLSS questionnaire12,13.
Questionnaire adapted from IRLSS
The IRLSS questionnaire used in the current study contained
ten questions evaluating RLS symptoms based on severity,
frequency and impact on quality of life12. This questionnaire, translated into Brazilian Portuguese, demonstrated
good reliability and validity13.
Physical training regimen
Aerobic physical exercise was determined based on the Maximum Effort Test (MET) and Anaerobic Ventilatory ThreshSleep Sci. 2011;4(2):45–48
old (the point at which respiratory response to work deviates
from linearity). Stretching was performed for 10 minutes
before and after sessions14.
Maximum Effort Test
The MET was used to measure aerobic capacity and to determine the volume and intensity of aerobic physical exercise for each individual. Tests were conducted at a controlled
temperature (24oC±2) on an ergometric cycle (Life Cycle
9.500 HR, USA). The respiratory and metabolic variables
were generated by measuring gaseous respiratory exchanges
with a metabolic system (COSMED PFT4, ITALY). After
an initial warm-up for 3 minutes at 33 watts, a progressive
load of 25-watts was added every 2 minutes. The test was
terminated when the volunteer reached exhaustion or the
maximal heart rate (HRmax=220 - age)14.
Statistical analysis
Repeated measures of ANOVA were used for statistical analysis followed by the Tukey test. Data are expressed as the
means and standard errors (SE). The significance level was
set at 5% (p≤0.05), and calculations were performed with
the aid of the software Statistica, version 7.
Results
Table 1 shows the physical characteristics and baseline parameters of the participants’ sleep.
Statistical analysis of the RLS data showed a significant decrease in questionnaire scores after sessions 36
Table 1. Physical characteristics and parameters of participants’ sleep (n=11)
Physical characteristics
Age (years)
50.2±3.78
Gender
6F/5M
Height (cm)
164±0.02
Body mass (kg)
66.45±3.33
BMI (kg/m2)
24.50±0.94
Sleep parameters - PSG
Total sleep time (hour)
5.08±0.60
Sleep efficiency (%)
65.03±7.77
Sleep latency (min)
39.4±9.50
REM sleep latency (min)
143.22±25.19
Wake time during TST (min)
109.22±25.23
Wake index per hour
10.45±2.06
Stage 1 (%)
5.21±1.78
Stage 2 (%)
72.21±3.42
Stage 3 (%)
1.90±0.63
Stage 4 (%)
5.17±2.07
REM (%)
15.50±2.82
Apnea index per hour
3.68±1.93
PLM index per hour
27.21±4.73
Values are expressed as mean and standard deviation.
BMI: body mass index; PSG: polysomnography; PLM: periodic limb
movement; REM: rapid eye movement; TST: total sleep time.
Esteves AM, Mello MT, Benedito-Silva AA, Tufik S
and 72, compared with baseline values (F(2, 20)=48.438;
p<0.001) (Figure 1).
Discussion
The results demonstrate that aerobic physical exercise, performed at Anaerobic Ventilatory Threshold intensity, was
efficacious in diminishing symptoms of RLS.
Symptoms of RLS were significantly reduced after 36
sessions (12 weeks) of training. Aerobic physical exercise
improved RLS symptoms in a time frame similar to that of
pharmacological treatment for RLS/PLM15,16.
The current findings corroborate the results presented in
Aukerman et al., in which a 12-week program of combined
aerobic and resistance exercise improved RLS scores5.
Data presented in Garcia-Borreguero et al. demonstrated
a correlation between IRLS scores and the objective parameters of PLM motor dysfunction, thus demonstrating a common pathophysiological mechanism17.
The present study found that aerobic exercise at Anaerobic Ventilatory Threshold intensity was efficient in diminishing RLS symptoms after 36 sessions (as scored by the
IRLSS). A previous study found a similar result for PLM
indexes after 72 sessions (evaluated by PSG)10.
The perceived improvement in symptoms of RLS before the reduction of PLM with the practice of physical
exercise may be associated with the different forms of
evaluation. Unlike the results obtained from the IRLSS
questionnaire, PSG data reflect a particular night and do
not exclude the possibility of the volunteer being exposed
to external factors that affect their night’s sleep. The reduction in perceived symptoms of RLS may directly or
indirectly suggest that aerobic physical exercise improved
the participants’ quality of life. However, the improvement of RLS symptoms likely preceded the diminished
PLM symptoms because the subjective evaluation is more
readily perceived by the patients.
Thus, the results of this study demonstrate that aerobic
physical exercise reduces symptoms of RLS. However, future studies are needed to determine the relationship and
pathophysiology of these disorders and why physical exercise is effective in the improvement of their symptoms.
Acknowledgments
This work was supported by grants from Fundação
de Amparo à Pesquisa do Estado de São Paulo (FAPESP),
number 03/06297-3, and Centros de Pesquisa, Inovação e
Difusão (CEPID), number 98/143033; the Psychopharmacological Research Support Foundation (AFIP); the
Psychobiology and Exercise Research Center (CEPE); and
research agencies National Counsel of Technological and
Scientific Development (CNPq) and Fundo de Auxílio aos
Docentes e Alunos (FADA).
30
25
IRLSS
20
*
15
10
*
5
0
Baseline
36ª
72ª
Physical Exercise Session
* Differs from baseline (ANOVA - Tukey).
Figure 1. International Restless Legs Syndrome Scale (IRLSS) questionnaire scores for the baseline period and after training sessions 36 and 72. Data
expressed as mean±standard errors.
Sleep Sci. 2011;4(2):45–48
47
48
Exercise and RLS
References
1. Hilker R, Burghaus L, Razai N, Jacobs AH, Szelies B, Heiss WD.
Functional brain imaging in combined motor and sleep disorders.
J Neurol Sci. 2006;25(1-2):223-6.
2. Hornyak M, Feige B, Dieter R, Ulrich V. Periodic leg movements in sleep and periodic limb movement disorder: Prevalence, clinical significance and treatment. Sleep Med Rev.
2006;10:169-77.
3. Walters AS. Towards a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group
Mov Disord. 1995;10(5):634-42.
4. Pigeon WR, Yurcheshen M. Behavioral sleep medicine interventions for restless legs syndrome and periodic limb movement disorder. Sleep Med Clin. 2009;4(4):487-94.
5. Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L,
Bailey B. Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med. 2006;19(5):487-93.
6. De Mello MT, Lauro FA, Silva AC, Tufik S. Incidence of periodic
leg movements and of the restless legs syndrome during sleep following acute physical activity in spinal cord injury subjects. Spinal Cord. 1996;34(5):294-6.
7. De Mello MT, Poyares Dl, Tufik S. Treatment of periodic leg
movements with a dopaminergic agonist in subjects with total
spinal cord lesion. Spinal Cord. 1999;37(9):634-7.
8. De Mello MT, Silva AC, Esteves AM, Tufik S. Reduction of periodic leg movement in individuals with paraplegia following aerobic physical exercise. Spinal Cord. 2002;40(12):646-9.
9. De Mello MT, Esteves AM, Tufik S. Comparison between dopaminergic agents and physical exercise as treatment for periodic
limb movements in patients with spinal cord injury. Spinal Cord.
2004;42(4):218-21.
Sleep Sci. 2011;4(2):45–48
10.Esteves AM, de Mello MT, Pradella-Hallinan M, Tufik S. Effect of
acute and chronic physical exercise on patients with periodic leg
movements. Med Sci Sports Exerc. 2009;41(1):237-42.
11.Rechtschaffen A, Kales A. Manual of standardized terminology,
techniques, and scoring system for sleep stages of human subjects.
Brain Information Service/Brain Research Institute, UCLA, Los
Angeles, 1968.
12.Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP,
et al. Validation of the International Restless Legs Syndrome
Study Group rating scale for restless legs syndrome. Sleep Med.
2003;4(2):121-32.
13.Masuko AH, Carvalho LB, Machado MA, Morais JF, Prado LB,
Prado GF. Translation and validation into the Brazilian Portuguese of the restless legs syndrome rating scale of the International Restless Legs Syndrome Study Group. Arq Neuropsiquiatr.
2008;66(4):832-6.
14.American College of Sports Medicine: Diretrizes do ACSM para
os testes de esforço e sua prescrição. 6th ed. Rio de Janeiro: Guanabara Koogan: 2002.
15.Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome
with gabapentin: a doubleblind, crossover study. Neurology.
2002;59(10):1573-9.
16.Trenkwalder C, Hundemer HP, Lledo A, Swieca J, Polo O,
Wetter TC, Ferini-Strambi L, de Groen H, Quail D, Brandenburg U; PEARLS Study Group. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology.
2004;62(8):1391-7.
17.Garcia-Borreguero D, Larrosa O, de la Llave Y, Granizo JJ, Allen
R. Correlation between rating scales and sleep laboratory measurements in restless legs syndrome. Sleep Med. 2004;5(6):561-5.
SHORT COMMUNICATION
Job satisfaction and sleep quality in nursing professionals
Satisfação no trabalho e qualidade de sono entre trabalhadores de enfermagem
Edla Maria Silveira Luz1, Elaine Marqueze2, Claudia Moreno2
magem no hospital; admissão e escalonamento de pessoal; enfermagem do trabalho; saúde do trabalhador; trabalho em turnos; doenças
profissionais; carga de trabalho.
These findings are particularly applicable to nursing services,
in which work schedules are organized for the continuous
care of patients and include night work and irregular hours4.
Much scientific evidence exists about the negative physiological and psychological effects of work organization5.
Nursing is a profession that is part of a political, economic, and social context; thus, it is directly influenced by all of
these factors, both through legal questions and through the
economic policies adopted in Brazil at the beginning of the
1990s. In addition, transformations in the labor world have
impacted nursing. These factors can be observed in workers experiencing fear of unemployment and in workers subjected to long shifts and low wages, among other issues6. Job
dissatisfaction is considered by Dejours7 to be one of the fundamental burdens of health care workers because it is related
to significant aspects of the occupation. It may be caused
by feelings of indignation at being required to perform an
uninteresting task or by feeling dissatisfied with both salary
and work recognition.
Some studies have suggested that sleep disturbances,
which are common among shift workers, are associated
with psychosocial problems, such as job satisfaction8-10.
Assuming that sleep quality can influence job satisfaction, our aim was to assess the correlation between sleep
quality and job satisfaction among nursing professionals who work 12-hour shifts in a charity hospital in the
Southern Region of Brazil.
INTRODUCTION
In the modern world, labor-related issues should no longer
be simply thought of as the immediate connection between
workers and their objectives. Changes in work environments
are more intense due to organizational, technological, and
social changes1.
Studies have reported that shift work can lead to alterations in sleep, digestive and nervous disturbances, cardiovascular diseases, and a disruption of family and social life2,3.
METHODS
This was a cross-sectional, quantitative epidemiological
study. The study was conducted in a regional charity hospital in the Southern state of Santa Catarina in Brazil. After
obtaining formal authorization from the hospital to perform
the study, the project was approved by the Ethics Committee of the Universidade do Sul de Santa Catarina.
The study population consisted of nursing assistants and
technicians who worked 12-hour night shifts. Of the 140
ABSTRACT
This study aimed to verify the correlation between job satisfaction and
sleep quality among nursing technicians and assistants who worked
12-hour night shifts at a philanthropic hospital in Tubarão (SC), Brazil. The participants of this study were 81 professionals, average age
31.9 years old (SD=8.18). Spearman correlation test showed a correlation between sleep quality and job satisfaction (r=-0.41; p<0.00).
Some aspects were reported as very satisfactory by these workers such
as work content and motivation towards the work as well as the extension in which they identify themselves with the hospital image.
keywords: job satisfaction; nursing staff, hospital; personnel staffing and scheduling; occupational health nursing; occupational health;
shift work; occupational diseases; workload.
RESUMO
O objetivo deste estudo foi verificar a correlação entre satisfação no
trabalho e qualidade de sono em profissionais de enfermagem que trabalhavam em turnos noturnos de 12 horas em hospital filantrópico de
Tubarão (SC). Fizeram parte deste estudo 81 profissionais, com idade
média de 31,9 anos (DP=8,18). O teste de correlação de Spearman
mostrou que melhor qualidade de sono leva à satisfação no trabalho
(r=-0,41; p<0,00). Alguns aspectos mostraram-se bastante satisfatórios para esses trabalhadores, como conteúdo e motivação pelo trabalho, relacionamento com colegas e sua identificação com a imagem do
hospital.
Palavras-chave: satisfação no emprego; recursos humanos de enfer-
Curso de Medicina da Universidade do Sul de Santa Catarina (UNISUL), Tubarão (SC), Brazil.
Departamento de Saúde Ambiental da Faculdade de Saúde Pública da Universidade de São Paulo (USP), São Paulo (SP), Brazil.
Corresponding author: Edla Maria Silveira Luz – Universidade do Sul de Santa Catarina – Avenida José Acácio Moreira, 787 – Dehon – Caixa Postal: 370 – CEP 88704900 – Tubarão (SC), Brasil – E-mail: [email protected]
Received: October 26, 2010 – Accepted: July 29, 2011
1
2
Sleep Sci. 2011;4(2):49–51
50
Job satisfaction and sleep quality
nursing professionals in the hospital, 81 worked the night
shift. The night shift workers were distributed among the 17
nursing units in the hospital that participated in the study.
These professionals worked one night (a 12-hour shift, from
7 pm until 7 am) and were off duty the following night, a
system that is termed “12 per 36 hours”.
The professionals in each work area were individually invited to participate in the research. The individual meetings
were held in the work place. The timing and duration of the
meetings depended on the availability of each professional
and the needs of the study.
The data collection was performed between April and
May of 2005. We used three questionnaires: 1) the Personal Data Questionnaire; 2) the Occupational Stress Indicator (OSI)11,12; and 3) the Pittsburgh Sleep Quality Index
(PSQI)13. It is important to point out that the Pittsburgh
Sleep Quality Index is negative scored, with the minimum
score meaning better sleep (score 0) and the maximum (score
21) meaning worse sleep.
We performed a descriptive analysis of the data and tested the Spearman rank-order correlation between job satisfaction and sleep quality.
RESULTS
The study participants worked in different sections of the
hospital. Most participants were from the Intensive Care
Unit (22.2%), followed by the surgery center (9.9%) and
the obstetrical center (9.9%). The remaining participants
(58%) were from different departments, such as pediatrics,
maternity, and emergency medicine.
The median age of the participants was 31.9 years, with
a maximum of 51 years and a standard deviation 8.18 years.
The majority were women (90.1%). Of the 81 workers who
participated in this study, 50.6% had children less than 12
years of age, and 49.4% do not have children in this age
group. The majority of the workers did not have secondary
employment (80.2%).
7.4%
7.4%
29.6%
Very good
Good
Poor
Very poor
55.6%
Figure 1. Subjective sleep quality.
Sleep Sci. 2011;4(2):49–51
The Pittsburgh Sleep Quality Index had a mean of 11.4
points and a standard deviation of 3.1 points. The greatest
concentration of scores was between 5 points and 20 points,
and the median was 11 points.
Although the majority of those interviewed (42%) reported sleep of short duration (<5 hours/day), few considered their
sleep quality poor or very poor (37%) (Figure 1). Only 14.8%
of the subjects reported sleeping more than 7 hours.
Almost half of the workers (48.1%) reported disturbances in their sleep one to two times per week, and 4.9% reported problems in their sleep three times per week or more.
The percentage of workers who reported using medication
to sleep one or two times per week was 14.8%.
The job satisfaction and quality of sleep variables were
significantly correlated (r=-0.41 and p=<0.0), with a higher
job satisfaction corresponding to better sleep quality.
The job satisfaction variable had a mean of 65.7 points and
a standard deviation of 17.3 points. The minimum value possible on the scale is 22, and the maximum is 132 points.
The psychosocial job aspects that were most unsatisfactory for the study participants were communication and
flow of information (66.5%), use of individuals’ potential
(65.5%), the way that conflicts are resolved (60.5%), participation in important decisions (59.3%), evaluation procedures (59%), volume of work to be performed (58%), how
changes and innovations are implemented (55.8%), job security (51.9%), opportunities for reaching their career aspirations (51.8%), the type of assignments received (50.6%),
style of supervision by superiors (48.2%), flexibility and free
time (48.1%), salary in relation to experience (43.2%), psychological climate in the company (43.2%), and career opportunities (43.2%).
The aspects that gave the most satisfaction were relationships with other people in the company (67.9%), job content (60.5%), work motivation (58%), identification with
the image and achievements of the company (55.5%), the
possibility of growth and development at work (53%), and
the organizational structure of the company (46.9%).
DISCUSSION
The results of this study provided evidence for the correlation between job satisfaction and sleep quality, supporting
the idea that sleep quality indicates the degree of adaptation
to job demands in this population. According to Karagozoglu and Bingöl and the results presented here, poor sleep
quality is correlated with lower job satisfaction14. The association between sleep problems and work concerns has also
recently been demonstrated by Kristiansen et al.15.
For decades, studies have demonstrated that shift workers and night shift workers experience reduced sleep dura-
Luz EMS, Marqueze E, Moreno C
tion that is not compensated for during their free time16-19.
The accumulation of long-term sleep debt directly affects
job satisfaction, leading to lower job satisfaction due to the
shorter sleep duration20. As observed by Takahashi et al.21,
moreover, reduced sleep duration increases somnolence,
which can also be associated with low job satisfaction.
Regarding the actual work performed, the workers in
this study demonstrated satisfaction with the way they perceived their work, a finding that has also been previously
reported22-24. Silva studied the administrative professionals
of a large company in the Portuguese financial sector and
reported similar results. Satisfaction with the actual work
performed was identified as one of the major correlations
with job satisfaction24.
Although the prevalence of sleep medication use among
the workers was not high, the use frequency (up to two
times per week) deserves attention. Gordon et al. have
stressed that night shift workers show a quality of life-related increase in the use of alcohol, stimulants, and nervous
system depressants25.
Employee health is essential for good performance in any
institution. In nursing, low wages, demanding activities,
and tiring and repetitive night shifts aggravate the situation. This study demonstrated the significant relationship
between the psychosocial aspects of job satisfaction and
sleep quality.
The study population suffered from the influence of shift
work and night shift work. Shift work directly affects sleep
quality and consequently affects job satisfaction. Potential
changes should consider meeting the needs, expectations,
and wishes of employees to the extent that they are compatible with the demands of the tasks. Such changes will require
long-term, gradual implementation that may be constrained
by the economic, administrative, and human-resource limits
of organizations.
REFERENCES
1. Leopardi MT. Processo de trabalho em saúde: organização e subjetividade. Florianópolis: UFSC: Papa-Livros; 1999.
2. Mosendane T, Raal FJ. Shift work and its effects on the cardiovascular system. Cardiovasc J Afr. 2008;19(4):210-5.
3. Noel S. [Morbidity of irregular work schedules]. Rev Med Brux.
2009;30(4):309-17. Article in French.
4. Chung MH, Kuo TB, Hsu N, Chu H, Chou KR, Yang CC. Sleep
and autonomic nervous system changes - enhanced cardiac sympathetic modulations during sleep in permanent night shift nurses.
Scand J Work Environ Health. 2009;35(3):180-7.
5. Admi H, Tzischinsky O, Epstein R, Herer P, Lavie P. Shift work
in nursing: is it really a risk factor for nurses’ health and patients’
safety? Nurs Econ. 2008;26(4):250-7.
6. Gelbcke FL. Interfaces dos aspectos estruturais, organizacionais
e relacionais do trabalho de enfermagem e o desgaste do tra-
balhador [tese]. Florianópolis:. Universidade Federal de Santa
Catarina; 2002.
7. Dejours C. A leitura do trabalho: estudo de psicopatologia do trabalho. São Paulo: Cortez/Oboré; 1987.
8. Munir F, Nielsen K. Does self-efficacy mediate the relationship
between transformational leadership behaviours and healthcare workers’ sleep quality? A longitudinal study. J Adv Nurs.
2009;65(9):1833-43.
9. Yeh YC, Lin BY, Lin WH, Wan TT. Job stress: its relationship to
hospital pharmacists’ insomnia and work outcomes. Int J Behav
Med. 2010;17(2):143-53.
10.Braeckman L, Verpraet R, Van Risseghem M, Pevernagie D, De
Bacquer D. Prevalence and correlates of poor sleep quality and
daytime sleepiness in Belgian truck drivers. Chronobiol Int.
2011;28(2):126-34.
11.Swan JA, Moraes LF, Cooper CL. Developing the occupational stress
indicator (OSI) for use in Brazil: a report on the reliability and validity of the translated OSI. Stress Med. 1993;9(4):247-53.
12.Robertson IT. Cooper CL, Willians J. The validity of the occupational stress indicator. Work Stress. 1990;4(1):29-39.
13.Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ.
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatr Res. 1989;28(2):193-213.
14.Karagozoglu S, Bingol N. Sleep quality and job satisfaction of
Turkish nurses. Nurs Outlook. 2008;56(6):298-307 e3.
15.Kristiansen J, Persson R, Bjork J, Albin M, Jakobsson K, Ostergren PO, et al. Work stress, worries, and pain interact synergistically with modelled traffic noise on cross-sectional associations with self-reported sleep problems. Int Arch Occup Environ
Health. 2011;84(2):211-24.
16.Fischer FM. Trabalho em turnos: alguns aspectos econômicos,
médicos e sociais. Rev Bras Saúde Ocup. 1981;9(36):3-40.
17.Ferreira LL. Trabalho em turnos: temas para discussão. Rev Bras
Saúde Ocup. 1987;15(58):27-32.
18.Rutenfranz J, Knauth P, Fischer FM. Trabalho em turnos e noturnos. São Paulo: Hucitec; 1989.
19.Harrington JM. Working long hours and health. BMJ.
1994;308(6944):1581-2.
20.Tokuda Y, Hayano K, Ozaki M, Bito S, Yanai H, Koizumi S. The
interrelationships between working conditions, job satisfaction,
burnout and mental health among hospital physicians in Japan: a
path analysis. Ind Health. 2009;47(2):166-72.
21.Takahashi M, Nakata A, Haratani T, Otsuka Y, Kaida K, Fukasawa
K. Psychosocial work characteristics predicting daytime sleepiness
in day and shift workers. Chronobiol Int. 2006;23(6):1409-22.
22.Martinez MC, Paraguay AI, Latorre M do R. [Relationship between psychosocial job satisfaction and health in white collar
workers]. Rev Saude Publica. 2004;38(1):55-61. Article in Portuguese.
23.Marqueze EC, Moreno CR. Satisfação no trabalho e capacidade
para o trabalho entre docentes universitários. Psicol Estud.
2009;14(1):75-82.
24.Silva GB da. Para uma análise da satisfação no trabalho. Sociol
Probl Pratic. 1998;6:149-78.
25.Gordon NP, Cleary PD, Parker CE, Czeisler CA. Sleeping pill use,
heavy drinking and other unhealthful practices and consequences
associated with shift work: a national probability sample study. J
Sleep Res. 1985;14(1):94.
Sleep Sci. 2011;4(2):49–51
51
REVIEW ARTICLE
Updates on the sleep-wake cycle
Atualizações sobre o ciclo vigília-sono
Rosa Hasan2, Flávio Alóe1†
ABSTRACT
In this review, the authors highlight the main findings on the neural
mechanisms of the sleep-wake cycle, emphasizing the importance of
hypothalamic control of the sleep and wake cycle. The anterior, posterior, and lateral hypothalamic regions are the three divisions involved
in this anatomical-functional control. The galaninergic and inhibitory
GABAergic systems of the ventrolateral preoptic nucleus of the anterior hypothalamus and the neurons producing melanin concentrating
hormone of the lateral hypothalamus are responsible for the inhibition
of the waking system and they are, therefore, responsible for the initiation and maintenance of non-rapid-eye-movement and rapid-eyemovement sleep. The neurons of the suprachiasmatic nucleus of the
anterior hypothalamus are responsible for the circadian rhythm of the
sleep-wake cycle. The histaminergic nuclei of the posterior hypothalamus and hypocretinergic ones of the lateral hypothalamus are active
during wakefulness, stimulating the aminergic system of the brainstem and inhibiting both the ventrolateral preoptic nucleus and also
the melanin concentrating hormone systems and, thus, establishing a
stable waking state. The inhibition-stimulation interaction between
the posterior and lateral hypothalamic system of wakefulness and the
GABAergic sleep system of the anterior hypothalamus is the base
model of the reciprocal interaction, which results in the stability of
the wake or sleep states. Changes in these nuclei or pathways result in
the instability of the sleep-wake cycle and in sleep disorders.
keywords: sleep-wake transition disorders; ventromedial hypothalamic nucleus; gamma-aminobutyric acid; melatonin/metabolism;
GABA modulators; hypothalamic hormones; sleep/physiology; sleep,
REM/physiology; histamine.
RESUMO
Nesta revisão, os autores ressaltam os principais achados sobre os mecanismos neurais do ciclo sono-vigília, ressaltando a importância do
controle hipotalâmico do ciclo sono e vigília. As regiões hipotalâmicas
anterior, posterior e lateral constituem as três divisões envolvidas no
controle anatomofuncional. Os sistemas GABAérgico inibitório e galaninérgico do núcleo pré-óptico ventrolateral do hipotálamo anterior
e os neurônios produtores do hormônio concentrador de melanina do
hipotálamo lateral são responsáveis pela inibição do sistema de vigília
e, portanto, são responsáveis pelo início e pela manutenção do sono
não REM e do sono REM. Os neurônios dos núcleos supraquiasmáticos do hipotálamo anterior são responsáveis pelo ritmo circadiano do
ciclo sono e vigília. Os núcleos histaminérgicos do hipotálamo posterior e os hipocretinérgicos do hipotálamo lateral apresentam-se ativos
durante a vigília, estimulando o sistema aminérgico do tronco cerebral ao mesmo tempo que inibe o núcleo pré-óptico ventrolateral e o
sistema hormônio concentrador de melanina, promovendo assim um
estado de vigília estável. A interação de inibição-estimulação, entre o
sistema hipotalâmico posterior e o lateral de vigíla e o sistema de sono
GABAérgico do hipotálamo anterior, é a base do modelo da interação
recíproca, que resulta na establidade dos estados de vigília ou sono.
Alterações desses núcleos ou vias resultam em instablidade do ciclo
sono-vigília e em distúrbios do sono
Palavras-chave: transtornos da transição sono-vigília; núcleo hipotalâmico ventromedial; ácido gama-aminobutírico; melatonina/metabolismo; moduladores GABAérgicos; hormônios hipotalâmicos;
sono/fisiologia; sono REM/fisiologia; histamina.
INTRODUCTION
Sleep is a complex behavioral state and it is one of the great
mysteries of modern neuroscience1. Currently, the control
of the sleep-wake cycle is attributed to the hypothalamic
system and its functional interactions2. The main elements
of the neurobiology of normal sleep in humans, based on
experimental models, are going to be described in the following sections.
NORMAL SLEEP
Sleep is a behavioral state represented by only a temporary
change in the level of mobility, movement and, especially,
awareness, and sleep differs from a coma and deep anesthesia
due to its prompt and complete reversibility3. Sleep is not
a passive, homogeneous event with reduced central nervous
system (CNS) activity, but an odd amalgam of physiologi-
Study carried out at Instituto de Psiquiatria of Hospital das Clínicas of Faculdade de Medicina at Universidade de São Paulo (FMUSP), São Paulo (SP), Brazil.
1
Instituto de Psiquiatria, Hospital de Clínicas, Universidade de São Paulo (USP), São Paulo (SP), Brazil.
2
Faculdade de Medicina do ABC (FMABC), Santo André (SP), Brazil.
†
In Memorian
Financial support: none.
Conflict of interests: Dra. Rosa Hasan receives grants from Aché and is speaker for Libbs and Dr. Flávio Alóe, when this manuscript was writted, received grants from
Aché, Apsen and Cristália and was speaker for Libbs.
Corresponding author: Rosa Hasan – Instituto de Psiquiatria – Hospital das Clínicas de São Paulo – Rua Ovídio Pires de Campos, 785 – Caixa Postal 3671 – CEP
01060-970 – São Paulo (SP), Brazil – E-mail: [email protected]
Sleep Sci. 2011;4(2):52–60
Hasan R, Alóe F
cal events with different levels of activity in the central and
peripheral nervous system over time3.
STAGES OF SLEEP
There are two distinct states of sleep, based on the electrophysiological characteristics of the electroencephalogram
(EEG), electrooculogram, and electromyogram4: synchronized, or non-rapid-eye-movement (NREM), sleep; desynchronized, or rapid-eye-movement (REM), sleep
Normal sleep consists of an alternation between REM
and NREM.
NREM sleep
Synchronized, or NREM, sleep, is characterized by synchronous brain electrical activity on the EEG, with distinctive
graphic elements4, and it is divided into three stages: N1,
N2 and N34. The stages, N1-N3, progressively represent
the depth of sleep, with a higher arousal threshold.
Normal sleep begins with NREM sleep at the N1 stage,
which is a short and transitional stage that moves to the
N2 stage of sleep when the EEG begins to exhibit waves of
higher amplitude and lower frequency that contain K-complexes and sleep spindles (Figure 1). The N2 stage occupies
about 50% of the night of a healthy young adult5. The N3
stage is characterized by the presence of large amplitude and
slow waves (delta waves) in the EEG (Figure 2), and it is also
known as deep sleep, or slow-wave sleep (SWS).
During NREM sleep, there is a significant reduction
in the energy consumption, a reduction of the somatic and
CNS metabolism, and a reduction of the autonomic nervous
system (ANS) activity. A reduction in neuromuscular tone
can also be observed when mental activity reaches its minimum, and there are no dreams. A definition of NREM sleep
would be: “a state of relative brain inactivity in a partially
inactive neuromuscular system”3.
REM sleep
REM sleep is not divided into stages, but it is characterized
by EEG desynchronization (Figure 3). The presence of REM
episodes and muscle relaxation, with a significant reduction
of neuromuscular tone, characterizes this sleep stage4. There
is an activation of the autonomic nervous system, which
results in changes in the heart and respiratory rates, blood
pressure, cardiac output, cerebral blood flow, and penile
erections in men. Dream reports indicate mental activity. A
definition of this state would be: “an active brain in a paralyzed body”3.
REM sleep occupies about 25% of total sleep time in
a healthy young adult5. During REM sleep, there is an increase in the regional cerebral metabolism in brain regions
that control behavior, such as in those involved in visual
K - complex
Channel 1 - Right eye
Channel 2 - left eye
Channel 3 - central EEG
Channel 4 - occipital EEG
Sleep spindle
Sleep spindle Theta wave
Channel 5 - EMG
K - complex
Sleep spindle
K - complex
Figure 1. NREM sleep stage N2. K-complexes and spindles are present
in the EEG.
Channel 1 - Right eye
Channel 2 - left eye
Channel 3 - central EEG
EEG: high voltage and low frequency
Channel 4 - occipital EEG
Channel 5 - EMG
Figure 2. Slow-wave sleep or REM sleep stage N3. Low frequency and
high voltage EEG.
EEG dessynchronization
Muscle atonia
Rapid eyes-movement
Figure 3. REM sleep, with EEG desynchronization, rapid eye movements, and muscle atonia.
control (visual dreams), and there is a marked metabolic deactivation of the cortical regions related to executive cognitive functions3,6.
Sleep cycle
The stages of sleep alternate throughout the night, forming the NREM-REM cycles. The distribution of these
Sleep Sci. 2011;4(2):52–60
53
54
Sleep physiology
stages in a normal night of eight hours of sleep shows a
greater amount of SWS in the first half of the night, with a
predominance of REM sleep in the second one (Figure 4)5.
The normal sleep onset latency is less than 30 minutes, and
normal REM sleep onset latency is from 70 to 120 minutes
after sleep onset5. Sleep efficiency is calculated as the total
sleep time divided by the total recording time in the polysomnography (PSG)5.
FUNCTIONS OF SLEEP
What is the real function of sleep in humans and mammals?
There is evidence that sleep plays a role in saving energy and
in the reversal of metabolic changes in the CNS and somatic
hormone secretion7. Animal studies have shown that sleep
deprivation causes death in mice more quickly than the caloric deprivation does7.
There are several hypotheses regarding the function of
REM sleep, with the most accepted theories being associated with procedural learning tasks, memory consolidation,
synthesis of new information, and organization of information in networks of associations6,7. Despite the existence of
evidence for those theories, there is not a unique hypothesis
unifying the several mentioned theories7.
Sleep has had an important role in neuronal plasticity
and in the consolidation of episodic memory and learning6-8.
Therefore, sleep would have a role in the preservation of the
individual and species evolution (Chart 1).
MECHANISMS OF SLEEP-WAkE CYCLE
Anatomical regions associated with wakefulness
Wakefulness is the result of a joint action of the ascending
reticular formation (RF) (glutamatergic neurons) in combination with the aminergic nuclei (serotonin, noradrenaline,
dopamine, and histamine), having cholinergic receptors located in the pons, bulbs, and basal forebrain, and in the posterior and lateral hypothalamic nuclei (histamine and hypocretin, respectively)2,3,6-10, as can be seen in Figures 5 and 6.
RF
The RF is a neuroanatomical structure that extends from
the brainstem (medulla oblongata) throughout the midbrain
and hypothalamus, and it reaches the thalamus10 (Figure 5).
The RF segment at the height of the brainstem receives an
extensive network of general somatic afferents (touch, temperature pain, and body position), and special somatic and
visceral excitatory projections significantly contribute to
wakefulness. The RF has the autonomy to maintain wakefulness and consciousness10. It is also capable of maintaining
alertness with a minimum of external stimuli, showing that
the existence of a traffic reduction of excitatory impulses for
the onset of sleep or for the reduction of wakefulness is not
Sleep Sci. 2011;4(2):52–60
V
REM
N1
NREM-REM
cicle
NREM-REM cicle
N2
N1stage: 3 to 5%
N2 stage: 45 to 55%
N3 stage: 25%
REM sleep: 25%
Sleep eficiency > 85%
N3
Figure 4. Hypnogram of healthy and young adult. The percentages of
each sleep stage are presented.
Chart 1. Functions of sleep7.
Energy conservation;
Regulation of brain and body temperature;
Immune system regulation;
Neuroendocrine system regulation;
Neural plasticity (learning and declarative memory);
Cognitive development;
Affective regulation.
Figure 5. Reticular formation and ascending reticular system (ARAS).
Thalamus
VLPO
Magnocellular
basal forebrain
(acetylcholine)
Perifornical area
(hypocretin)
Tuberomammillary nucleus
(histamine)
Ventral tegmental area
and Substantia nigra (dopamine)
Pedunculopontine and Laterodorsal
tegmental nuclei
(acetylcholine)
Raphe nuclei
(seretonin)
Locus coeruleus
(norepinephrine)
Figure 6. Hypocretinergic, aminergic, and cholinergic systems of the ARAS3.
Hasan R, Alóe F
enough, but it is necessary that there is an active inhibition
of the RF by other neural systems (GABAergic and MCH
systems)2.
The RF activity is maximal during wakefulness, whereas
its activity is substantially reduced by the GABAergic inhibitory system of the nucleus of the anterior hypothalamus
during NREM and REM. The RF is an active region during
wakefulness (“wake-on”) and inactive during sleep3,9.
Ascending reticular activating system
The ascending reticular activating system (ARAS) is a functional concept, not an anatomical structure, which clusters neural systems with different neurotransmitters2,3,6-10.
These systems are located in the brainstem reticular formation, with its glutamatergic interneurons, thalamocortical
system, nuclei noradrenergic, serotonergic, dopaminergic,
pontine and basal forebrain cholinergic and histaminergic
hypothalamic systems (Figures 5 and 6)2,3,8-10.
The ARAS is responsible for wakefulness and desynchronization of the cortical and cognitive alerts10. Redundancy and inter-relationships among these ARAS component systems represent an evolutionary adaptation for the
maintenance, optimization, and specificity of wakefulness
for the adaptation and survival of the individual and some
species8-10.
Monoaminergic systems
The ascending reticular activating monoaminergic system
consists primarily of the dorsal raphe nucleus (DRN – serotonergic) and locus coeruleus (LC – noradrenergic) of the
brainstem, medial forebrain, and meso cortical-limbic dopaminergic system, which connect the ventral periaqueductal
gray dopaminergic matter, called vPAG area, to the lateral
hypothalamus and the tuberomammillary nucleus (histaminergic TMN) of the posterior hypothalamus (Figure 6). These
systems belong to the ARAS project diffusely to the cortex
and thalamic reticular nuclei (Figure 5)8,10. The aminergic
activity during wakefulness stimulates the thalamocortical
circuits, but it is reduced during NREM sleep and absent
during REM sleep. Aminergic neurons are called “REMoff”3,6,8,9. The aminergic system projects to the anterior hypothalamus to inhibit GABAergic cells of the ventrolateral
pre-optic (VLPO) nuclei of the anterior hypothalamus3,8,9.
Cholinergic pontine-mesencephalic system
There are two cholinergic pontine-mesencephalic nuclei,
the laterodorsal nucleus (LDN) and the pedunculopontine
nucleus (PPN), and a cholinergic nuclei located in the basal
forebrain (Figure 6). This cholinergic system makes excitatory connections with the RF, the limbic system (amygdala), and the direct cortical projections8,9. These cholinergic
projections are fundamental to the various manifestations of
REM sleep. For example, there is an EEG desynchronization
and a significant reduction of neuromuscular tone during
REM sleep, with the latter being a typical manifestation of
REM8.
The neuromuscular tone control during REM sleep involves the area anatomically adjacent to the PPN and LDN,
which is called the sublocus coeruleus nucleus. These cholinergic neurons project to the anterior bulbar region through
the reticulospinal tract, which causes the glycinergic and
GABAergic inhibitory synapses in the brainstem motoneurons and spinal anterior horn to induce post-synaptic inhibition of motor neurons and, thus, a significant reduction of
the characteristic neuromuscular tone of REM sleep. Lesions
in the region of sublocus coeruleus nucleus cause REM sleep
without atonia8,11.
In contrast to aminergic activity, which is absent during REM sleep, cholinergic activity is maximal during REM
sleep and wakefulness, but it is absent during NREM8,9. The
cholinergic cells are called “REM-on”8,9.
Posterior hypothalamus and sleep-wake cycle
Type - 1 and type - 2 hypocretinergic system
The diminished hypocretinergic system, containing about
50,000 neurons, is located in the posterior and lateral regions of the hypothalamus12,13 (Figure 6). Both hypocretin-1
and -2 are excitatory neurotransmitter peptides that are
synthesized exclusively by these hypothalamic cells from a
common substrate, pre-pro-hypocretin12,13. There are two
sub-populations of hypocretinergic receptors in the CNS,
receptors 1 and 2, which are both excitatory G protein-coupled transmembrane receptors that are encoded by chromosomes 1 and 6 in humans13,14. Hypocretinergic-1 receptors
activate phospholipase-A and allow the influx of calcium,
whereas the hypocretinergic-2 receptors inhibit adenylate
cyclase12-14.
Hypocretin-1 binds, with high affinity, to the hypocretinergic-1 receptor but also to the hypocretinergic-2
receptors, with an affinity rate from 100 to 1000 times
smaller. Hypocretin-2 binds to hypocretin-1 and -2 receptors. Therefore, the hypocretinergic-1 receptor has a higher
selectivity for hypocretin-112-14.
Hypocretins are exclusively excitatory and regulate the
sleep-wake cycle, energy balance, ANS activity, and neuroendocrine activity14. The hypocretins have excitatory projections to the ARAS and the reticular thalamic nuclei (thalamocortical circuits), and direct projections to the cerebral
cortex and limbic system (amygdala complex) (Figure 6)15,16.
The densest projections of hypocretinergic neurons project
to the LC, mammillary nucleus tuber, and DRN15,16. The
hypocretins are also excitatory and project to the cholinergic
Sleep Sci. 2011;4(2):52–60
55
56
Sleep physiology
nuclei in the pons (pedunculopontine tegmental and laterodorsal nucleus) and the basal forebrain cholinergic nucleus
(Figure 6). However, there are no synaptic projections of
hypocretins to the anterior hypothalamus GABAergic region, the VLPO. In contrast, the VLPO and the melanin
concentrating hormone (MCH) neurotransmitters inhibit
hypocretinergic cells2,3,9.
The hypocretinergic system receives excitatory afferents
from the limbic behavioral system, basal forebrain (cholinergic-adenosine nucleus) and suprachiasmatic nucleus (SCN)
of the anterior hypothalamus9,17. The excitatory efferent from
the limbic system to the hypocretinergic system plays a key
role in the stability of wakefulness during the main period
of activity in important behaviors, such as seeking food or
survival (fight or flight)18. The hypocretinergic system is the
end effector responsible for the occurrence and stability of
the wake state during sleep deprivation. During sleep deprivation, the limbic system is responsible for the stimulation
and increased neurotransmission of hypocretin, which supports the state of wakefulness during sleep deprivation3,6.
The hypocretinergic system shows maximum activity
during wakefulness by stimulating all of the excitatory circuits responsible for wakefulness, which are absent during
NREM and REM sleep. The hypocretins increase monoaminergic tone, which indirectly inhibits the VLPO through
the aminergic system, preventing the onset of sleep19,20.
Hypocretinergic activity is minimal or absent during sleep,
and during sleep loss, there are extensive GABAergic inhibitory projections from the VLPO to the hypocretinergic
system, making the hypocretinergic system activity minimal or absent during sleep (Figure 7)19.
Anterior hypothalamus
The anterior hypothalamus VLPO galaninergic and GABAergic inhibitory neurons are only activated during NREM and
REM sleep9,19. The VLPO is related to SWS and REM sleep,
and the VLPO cells directly project to the DRN, LC, penduculopontine tegmental and dorsolateral pontine cholinergic nuclei, and to the hypocretinergic system, it inhibits
these wakefulness-promoting excitatory nuclei (Figure 7)19.
Inhibitory activity derived from the VLPO to the aminergic and the hypocretinergic systems allows the appearance
of NREM and REM sleep due to the inhibition of the hypocretinergic and aminergic cells8,9. The VLPO receives inhibitory synapses from the DRN and the LC, but it does not
receive inhibitory synapses from the hypocretinergic system.
In addition, the VLPO receives inhibitory synapses from the
limbic system nuclei (infralimbic cortex and amygdala central nucleus), which explains the persistence of wakefulness
during stressful situations, and the suprachiasmatic nuclei
explains the VLPO circadian rhythm8,9.
Sleep Sci. 2011;4(2):52–60
Hypocretin
VLPO
TMN
LDT/PPT
Raphe
LC
VLPO: ventrolateral preoptic nucleus; LDT: laterodorsal tegmental
cholinergic nuclei; PPT: pedunculopontine tegmental nucleus; TMN:
tuberomammillary nucleus of the posterior hypothalamus; DRN: dorsal
raphe nucleus; LC: locus coeruleus3.
Figure 7. VLPO inhibitory projections. VLPO axons (GABAergic and
galaninergic) project to the wake-promoting monoaminergic neurons.
Therefore, the VLPO and hypocretinergic-aminergic
system show a reciprocal functional relationship of mutual
inhibition between both systems20. When the VLPO is activated during sleep, it inhibits the hypocretinergic-aminergic
system cells. Similarly, when hypocretin-aminergic neurons
are activated during wakefulness, they inhibit the VLPO.
This model assumes that reciprocity of sleep or wakefulness
would remain stable, while a component of the balance remained sufficiently activated9,20.
The suspension of the basal forebrain excitatory stimuli
(adenosine accumulation) combined with the inhibition
that was originated from the VLPO in the aminergic and
hypocretinergic system are responsible for the initiation and
maintenance of NREM sleep19,21.
MCH
The MCH was originally described in the salmon pituitary,
and it is found in all studied mammals and vertebrates22.
The MCH molecule is similar to somatomedin. Neurons responsible for MCH neurotransmission (about 6,000 MCH
cells in mice against 3,000 hypocretin cells) are morphologically similar to hypocretinergic cells, with a fusiform or
multipolar shape, containing two to five dendrites22. The
MCH neurons and hypocretinergic cells are co-localized in
the lateral hypothalamus region. The MCH neuronal projections in the brains of primates are also similar to the projections of hypocretinergic cells.
MCH neurotransmission exerts inhibitory effects on hypocretinergic neurons, and the MCH and hypocretinergic systems have different functions and biochemical substrates and
a reciprocal neurofunctional relationship. The MCH system is
Hasan R, Alóe F
inactive during the daytime and it occasionally can be rapidly
activated during NRE, reaching a maximum during REM
sleep, especially during periods of significant reductions in
neuromuscular tone. The rebound of REM sleep induces c-Fos
expression in the MCH cells, and an intraventricular injection
of MCH increases the amount of REM and, to a lesser extent,
NREM sleep in rats. The MCH system reduces motor activity, temperature and metabolism and activates the parasympathetic system22. The MCH peptide has hypnotic and anorectic
effects in rats, and the MCH-KO rats are usually hyperactive,
with low weight and hypermetabolism22.
Circadian pacemaker
The SCN is an anatomical structure located in the anterior hypothalamus. It is the main central timer structure (biological
clock) capable of generating its own endogenous rhythm23.
The main stimulus synchronizer of the SCN is sunlight,
which acts as an excitatory stimulus for the SCN activity.
Studies in animals have shown that the initial stage of photosynchronization of the SCN is in the retinal ganglion cells,
which are responsible for photo-reception, and the excitatory
transduction of light stimulation from the retinohypothalamic tract to the SCN23,24. The SCN cells transmit rhythmic
information photo-synchronized with adjacent hypothalamic
nuclei responsible for the periodicity of the ANS activity, the
secretion of hormones, the melatonin secretion, the changes of
body temperature, appetite, sleep propensity and the duration
of the sleep-wake cycle23. The SCN signal can also be synchronized by other neural pathways representing nonphotic
stimuli, such as time of meals and physical activity24,25.
The main SCN efferents that are relevant for the sleepwake cycle are located in the VLPO and in the hypocretinergic system9. The SCN afferents that project to the VLPO
are inhibitory. Thus, the SCN inhibits the VLPO during
the photo-period and relieves inhibition at the end of the
main photo-period19,23. When the sunlight is gone, the SCN
signal decreases, allowing the onset of NREM sleep8,9. The
functional relationship between the SCN and the hypocretinergic system is excitatory. The reduced SCN activity
at the end of the main photo-period (solar day) is reflected
in the reduction of hypocretin-aminergic activity, which is
critical to the waking state; the reduction of hypocretinaminergic activity allows the onset of sleep3,8,9.
The photo-synchronized signal of the SCN cells is sent
to the pineal gland, which is responsible for the secretion
of melatonin24,25. Photo-stimulation inhibits the secretion
of melatonin, which occurs during the night sleep or dark
period, and melatonin exerts a self-inhibitory effect in the
activity of the SCN at the end of the main photo-period, being one more mechanism in the cascade of events to reduce
hypocretin-aminergic activity to sleep onset9,23.
Homeostatic control of sleep
Adenosine is a product of neuronal cellular energetic metabolism, which accumulates in the extracellular space in the
synaptic cleft during wakefulness21. Adenosine shows a local
inhibitory effect in the basal forebrain cholinergic nuclei21,
and it accumulates where there is local neuronal metabolic
and electrical activity, such as during the main wakefulness period or during sleep fragmentation or deprivation.
Microdialysis studies in monkeys confirmed that the basal
forebrain regions in the CNS region are where the largest local extracellular accumulation of adenosine during wakefulness occurs. Therefore, the basal forebrain is considered the
site of the homeostatic control of the sleep-wake cycle, and
adenosine is the neuromodulator that plays a key role in the
homeostatic control of sleep21.
The local inhibitory action of adenosine occurs in the
basal forebrain cholinergic cells. The basal forebrain sends
excitatory projections to the hypocretinergic system, and
inhibitory ones to the VLPO9,20,21. The activity decrease of
these cholinergic cells disinhibits the VLPO GABAergic
cells and no longer stimulates the hypocretinergic system,
initiating NREM sleep at the end of the wakefulness period,
when the level of adenosine rises8,9,21. The reduction of basal
forebrain cholinergic activity by adenosine accumulation
disinhibits the VLPO, which, combined with the reduction
of the excitatory activity of the SCN, triggers NREM sleep.
This is the double trigger for the sleep onset8,9. The antagonistic effects of adenosine-1 receptors by caffeine are responsible for stimulating the inhibiting effects on sleep23.
Sleep-wake switch
The inhibitory bi-directional functional relationship between the hypocretinergic-aminergic systems and the
VLPO constitutes a mechanism of stability control between wakefulness and sleep behavioral states (Figure
8)2,3,9. This type of anatomical-functional relationship is
called sleep switch8,20,26.
8
Sleep-wake switch
Norepinephrine
Serotonin
Hypocretin
Locus ceruleus
(norepinephrin)
Dorsal raphe
nucleus
(serotonin)
Hypocretins
GABA
VLPO
GABA
MCH
Inhibition
Stimulation
Figure 8. Sleep-wake switch.
Sleep Sci. 2011;4(2):52–60
57
58
Sleep physiology
The visceral, special, and somatic sensory afferents activate the ARAS and, therefore, they activate the hypocretinergic and aminergic systems during wakefulness (Figures 5 and 9)10. The hypocretinergic system activity during
wakefulness is responsible for the aminergic tonus stability
and activity14. Glutamatergic interneurons, which are located between hypocretinergic system neurons, reinforce the
hypocretin neuronal activity in a progressive manner, which
secondarily reinforces the aminergic system and promotes a
long, stable, and consolidated wakefulness period without
the oscillations or transitions moving the equilibrium of the
balance towards the waking state (Figure 10)10,26. Consolidated periods of wakefulness are adaptively important for
seeking food and preserving the species and individuals7.
Changes of state from wakefulness to sleep require a strong
adjustment of activity in the hypocretinergic-aminergic system or VLPO inhibitory system9,20.
The aminergic-hypocretinergic activity is minimal during
NREM sleep, hence, there are extensive GABAergic inhibitory projections from the VLPO to the aminergic-hypocretinergic system, making the aminergic-hypocretinergic activity
minimal or absent during sleep (Figure 7)19. The absence of
sunlight at the end of the photo-period disables the SCN and
adenosine accumulation, which occurs during the main period
of wakefulness and inhibits the cholinergic cells in the basal
forebrain17,21. These two factors, combined with a reduction of
the sensory afferent related to resting posture, the reduction of
ARAS activity and cognitive relaxation (limbic system), meet
the conditions necessary to suspend the inhibitory influence of
the SCN, basal forebrain and limbic system over the VLPO,
thus releasing its inhibitory activity. The VLPO inhibits the
aminergic-hypocretinergic system by shifting the equilibrium
of the balance of sleep towards NREM sleep (Figure 11)19,26.
With the progression of NREM sleep, the electric silence of
the aminergic-hypocretinergic system, REM-off, disinhibits
the cholinergic system nuclei, and REM-on generates a second switch that controls REM sleep2,9,26.
RECIPROCAL INTERACTION MODEL OF REM
AND NREM SLEEP
Once the onset of sleep has been reached, another neuronal
interaction mechanism is activated, which explains the alternation of NREM and REM sleep8,20. This is achieved by
the interaction between the cholinergic and hypocretinergicmonoaminergic nuclei8,9. This working model establishes that
NREM sleep is predominantly GABAergic-aminergic, and
that REM sleep is predominantly GABAergic-glutamatergiccholinergic8,20. This model proposes two types of cell groups:
REM-sleep-activated cholinergic and glutamatergic cells
(“REM-on”)3,6,8,9 and aminergic-hypocretin cells, which are
inactivated during REM sleep (“REM-off”) (Figure 12)8,9,20.
Sleep Sci. 2011;4(2):52–60
Wakefulness
Acetylcholine
(BF)
Histamine
(TMN)
Dopamina
(VTA)
Acetylcholine
(PPT; LDT)
Norepinephrine
(LC)
Reticular
Motor neurons formation
LDN: laterodorsal cholinergic nuclei; PPN: pedunculopontine nucleus;
VTA: ventral tegmental area; RF: reticular formation.
Serotonin
(raphe)
Figure 9. Nuclei, pathways, and projections responsible for wakefulness.
Wakefulness
Reciprocal Interation
O
VLPBA
A
G H
MC
nes
Ami retin
oc
Hyp
Inhibition
Stimulation
MCH: melanin-concentrating hormone.
Figure 10. Predominance of hypocretinergic-aminergic activity during
wakefulness.
NREM SLEEP
Reciprocal Interation
A
Hyp mines
ocre
tin
Inhibition
VLP
GAB O
MCHA
Stimulation
Figure 11. Predominance of GABAergic activity during NREM sleep.
During wakefulness and NREM sleep, the hypocretinergic-aminergic system, REM-off, is tonically activated,
whereas the cholinergic tone is higher during wakefulness
than during NREM sleep. The hypocretinergic-aminergic
system inhibits the cholinergic-glutamatergic system,
REM-on, which inhibits REM sleep8. During the latter, the
VLPO neurons fire more intensely and progressively, deepening sleep. The GABAergic inhibitory activity of the VLPO
Hasan R, Alóe F
REFERENCES
Reciprocal interaction in REM sleep
REM-off
Locus ceruleus
(norepinephrin)
Dorsal raphe
nucleus
(serotonin)
Hypocretins
norepinephrin
serotonin
-
REM-on
+ acetylcholine
LDT and PPT
(Acetylcholine)
VLPO
GABA
MCH
Figure 12. Reciprocal interaction model of REM sleep.
Reciprocal interaction in REM sleep
REM-off
REM-on
Am
Hyp ines
ocre
tins
-
VLPO
GABA
MCH
LDT
(Ace and PP
T
tylch
oline
)
Figure 13. Reciprocal interaction model of REM sleep, with a predominance
of cholinergic activity provided by REM-off system GABAergic inhibition.
over the hypocretinergic-aminergic system (REM-off cells),
which inhibits the REM-on cells system, the glutamatergic
and the cholinergic mesopontine (LDN and PPN) is gradually reduced during NREM sleep to monitor the equilibrium of the balance towards REM sleep8,20 (Figure 13). The
inhibition of the hypocretinergic-aminergic system (REMoff cells) releases the mesopontine cholinergic system from
the inhibitory influences that initiate its activity to generate
the various correlates of REM sleep (EEG desynchronization, significant reduction of characteristic neuromuscular
tone and REM)3,11. Therefore, REM sleep occurs only when
the VLPO inhibits the aminergic-hypocretinergic system,
which suspends its inhibitory activity on cholinergic and
glutamatergic activity (Figure 12)7,26.
CONCLUSIONS
Specific neuronal populations that act as switches of the reciprocal interaction are compatible with the occurrence of rapid
transitions between wakefulness, NREM and REM sleep, behavioral states of wakefulness, and consolidated sleep.
1. Hobson JA. Sleep. New York: Scientific American Library; 1989.
2. Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus:
emerging therapeutic targets for sleep disorders. Nat Neurosci.
2002;5 (Suppl):1071-5.
3. Alóe F, Azevedo AP, Hasan R. Mecanismos do ciclo sono-vigília.
Rev Bras Psiquiatr. 2005;27(Suppl I):33-9.
4. Iber C, Ancoli-Israel S, Cheeson A, Quan SF; the American Academy of Sleep Medicine. The AASM manual for scoring of sleep
associated events: rules, terminology and technical specifications.
Wetchester, IL: American Academy of Sleep Medicine; 2007.
5. Alóe F, Kriger A, Assis M. Estudos do sono. In: Mutarelli EG, editor. Exames complementares em Neurologia. São Paulo: Sarvier;
2006. p.455-99.
6. Pace-Schott EF, Hobson J.A. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Neurosci.
2002;3(8):591-605.
7. Siegel J. Clues to the function of mammalian sleep. Nature.
2005;437(7063):1264-71.
8. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep
state switching. Neuron. 2010;68(6):1023-42.
9. Adamantidis A, De Leccea L. Physiological arousal: a role for hypothalamic systems. Cell Mol Life Sci. 2008;65(10):1475-88.
10. Steriade M. Arousal: revisiting the reticular activating system.
Science. 1996;272(5259):225-36.
11. Curtis DR, Hosli L, Johnston GA, Johnston IH. The hyperpolarization of spinal motorneurons by glycine and related amino
acids. Exp Brain Res. 1968;5(3):235-58.
12. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate
feeding behavior. Cell. 1998;92(5):1 page following 696.
13. De Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE,
et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA. 1998;95(1):322-7.
14. Kilduff TS, Peyron C. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci.
2000;23(8):359-65.
15. Espanha RA, Baldo BA, Kelley AE, Berridge CW. Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal
forebrain sites of action. Neuroscience. 2001;106(4):699-715.
16. Peyron C, Tighe DK, van den Pol AN, de Leceal L, Heller HC,
Sutcliffe JG, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 2002;18(23):999610015.
17. Van Gelder RN. Recent insights into mammalian circadian
rhythms. Sleep. 2004;27(1):166-71.
18. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein- coupled receptors that regulate
feeding behavior. Cell. 1998;92(4):573-85.
19. Sherin JE, Shiromani PJ, McCarley RW, Saper C. Activation of ventrolateral preoptic neurons during sleep. Science.
1996;271(5246):216-9.
20. Lu J, Sherman D, Devor M, Clifford B. Saper CB. A putative flip–flop switch for control of REM sleep. Nature.
2006;441(7093):589-94.
21. Porkka-Heiskanen T, Kalinchuk AV. Adenosine, energy metabolism and sleep homeostasis. Sleep Med Rev. 2011;15(2):123-35.
Sleep Sci. 2011;4(2):52–60
59
60
Sleep physiology
22.Hassani OK, Lee MG, Jones BE. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci USA.
2009;106(7):2418-22.
23.Czeiler CA, Buxton OM, Khalsa SBS. The human circadian timing and sleep-wake regulation. In: Fryger MH, Roth T, Dement
WC, editors. Principles and practice of sleep medicine. 4th ed.
Philadelphia: WB Saunders; 2005. p.375-94.
Sleep Sci. 2011;4(2):52–60
24.Krout KE, Kawano J, Mettenleiter TC, Loewy AD. CNS inputs to the
suprachiasmatic nucleus of the rat. Neuroscience. 2002;110(1):73-92.
25.Mrozovsky N. Beyond the suprachiasmatic nucleus. Chronobiol
Int. 2003; 20(1):1-8.
26.Chamberlin NL, Arrigoni E, Chou TC, Scammell TE, Greene
RW, Saper CB. Effects of adenosine on gabaergic synaptic inputs to identified ventrolateral preoptic neurons. Neuroscience.
2003;119(4):913-8.
REVIEW ARTICLE
Are there benefits of exercise in sleep apnea?
Existem benefícios do exercício físico na apneia do sono?
Roberto Pacheco da Silva1,4, karlyse Claudino Belli1,2,3,4, Alicia Carissimi1,5, Cintia Zappe Fiori1,4,
Christiane Carvalho Faria2,4, Denis Martinez1,4,5
ABSTRACT
Out of the many sleep disorders, obstructive sleep apnea-hypopnea
syndrome is one of the most harmful. This syndrome is an important
risk factor for the development of cardiovascular disease and patient
mortality. Exercise is a way to reduce cardiovascular mortality, which
also results in improved sleep quality and may act on the pathogenesis
of obstructive sleep apnea-hypopnea syndrome. However, evidence
about the actual role of exercise in this syndrome is still scarce. We
reviewed the existing literature about the possible benefits of exercise in patients with obstructive sleep apnea-hypopnea syndrome. We
performed a search in the PubMed database using MESH Terms related to physical exercise and sleep apnea. Out of the 149 references
identified, we selected randomized controlled trials or case studies
in English or Portuguese that included patients with OSAHS. After
searching titles, abstracts and full texts, we located only three studies
that investigated the effects of exercise on the diagnostic and severity
indices of obstructive sleep apnea-hypopnea syndrome. In these three
papers, groups that exercised showed a reduction in the severity of the
syndrome. Despite the insufficient level of evidence in the literature,
the agreeing positive results of the studies suggest a potential benefit
of exercise on obstructive sleep apnea-hypopnea syndrome.
keywords: exercise; sleep apnea syndromes; cardiovascular diseases;
sleep apnea, obstructive.
RESUMO
Dentre os distúrbios do sono, a síndrome da apneia-hipopneia obstrutiva do sono é um dos mais deletérios à saúde. Essa síndrome é um
importante fator de risco para o aparecimento de doenças cardiovasculares, aumentando a taxa de mortalidade dos pacientes. Sabe-se que o
exercício físico é uma das formas de reduzir a mortalidade cardiovascular, o que também resulta em melhora do sono e pode atuar sobre
fatores fisiopatológicos da síndrome da apneia-hipopneia obstrutiva
do sono. Contudo, evidências sobre o real papel do exercício físico na
síndrome ainda são escassas. O objetivo dessa revisão foi investigar os
possíveis benefícios do exercício físico na síndrome da apneia-hipop-
neia obstrutiva do sono. Foi realizada uma busca na base de dados do
PubMed, utilizando termos MESH e outros relacionados ao exercício
físico e à apneia do sono. Das 149 referências encontradas, foram selecionados os ensaios clínicos randomizados ou os estudos de casos, em
inglês ou português, com amostra de indivíduos adultos portadores de
síndrome da apneia-hipopneia obstrutiva do sono. Após seleção dos
títulos, resumos e textos completos, foram localizados somente três
estudos que investigaram os efeitos do exercício físico sobre os marcadores de presença e gravidade dessa síndrome. Nos três artigos, os
grupos submetidos ao exercício evidenciaram redução na gravidade
da síndrome. Apesar do nível de evidência insuficiente dos artigos, a
concordância de resultados positivos dos estudos sugere potencial de
benefício do exercício sobre a SAHOS.
Palavras-chave: exercício; síndromes da apneia do sono; doenças
cardiovasculares; apneia do sono tipo obstrutiva.
INTRODUCTION
Exercise is a culturally and scientifically accepted non-drug
intervention that is beneficial to health. There is evidence
that it facilitates general wellness1 and sleep, in particular2.
During sleep, breathing disorders can occur – in particular, obstructive sleep apnea-hypopnea syndrome (OSAHS),
which is assuming epidemic proportions. Over two decades,
reports of the prevalence of OSAHS increased from 4% in
men and 2% in women3 to 32% of the total population4.
The prevalence of OSAHS is 95% in the elderly, and more
than 50 million Brazilians suffer from this syndrome4.
Additionally, OSAHS is an important risk factor for
cardiovascular diseases5, including systemic hypertension6,7
resistant hypertension8,9, stroke10, obesity11 and metabolic
syndrome12. American cardiology associations published a
comprehensive document highlighting the need to inves-
Study carried out at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre (RS), Brazil.
1
Interdisciplinary Sleep Research Laboratory, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre (RS), Brazil.
2
Exercise Pathophysiology Research Laboratory, Cardiology Division, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre (RS), Brazil.
3
Research on Research Group – Duke University, Durham, USA; Department of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil.
4
Graduate Program in Cardiology and Cardiovascular Sciences, Cardiology Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre (RS), Brazil; Universidade
Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil.
5
Graduate Program in Medical Sciences, Cardiology Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre (RS), Brazil; Universidade Federal do Rio Grande
do Sul (UFRGS), Porto Alegre (RS), Brazil.
Financial support: none.
Corresponding author: Roberto Pacheco da Silva – Cardiology Unit, Hospital de Clínicas Porto Alegre – Rua Ramiro Barcelos, 2.350 – CEP 90035-002 - Porto Alegre (RS),
Brazil – E-mail: [email protected]
Sleep Sci. 2011;4(2):61–67
62
Exercise and sleep apnea
tigate sleep apnea in cardiopathies13,14. Patient mortality
is increased with OSAHS and its comorbidities15,16, while
treatment for OSAHS reverses the consequences17 and reduces mortality18,19.
Exercise reduces cardiovascular mortality20-22 and may
modify the deleterious effects of OSAHS on the circulatory
system23-26. However, evidence about the role of exercise in
OSAHS is still scarce. Thus, this review reports the direct
and indirect benefits of exercise in OSAHS.
ed by consensus of the authors. The following information
was extracted from articles: (1) authors; (2) years of publication; (3) type of study; (4) sample size; (5) age of the sample;
(6) weight; (7) body mass index (BMI); (8) intervention; (9)
apnea-hypopnea index (AHI) pre- and post-treatment and
(10) statistical significance of change with treatment. These
data are shown in Table 1.
The references obtained for the other topics described below in this paper, were based non-systematic reviews.
METHODOLOGY OF THE REVIEW ON EXERCISE
AS TREATMENT OF OSAHS
Studies of exercise and OSAHS included in this review
were randomized clinical trials or case studies written in
English or Portuguese and examined adult human patients
with OSAHS.
The search strategy is described in Appendix A and was
conducted on December 16, 2010. For the search, we used
the Medical Subject Headings (MeSH) terms “sleep apnea
syndromes”, “sleep apnea, central”, “sleep apnea, obstructive”
and “exercise” with their respective entry terms and Boolean
operators in PubMed. Using these terms resulted in 149 results. One of the investigators (RPS) reviewed the results of
this search, first by title, then by the abstract and full text.
Finally, we selected 45 potentially relevant articles for review
and discussed these with the other authors. After reading the
full texts, three articles were chosen, as described in Table 1.
Obstructive sleep apnea-hypopnea
syndrome
There are two types of sleep apnea: central, which is caused
by the central nervous system, and obstructive, which involves physical changes in the pharynx27. In central apnea,
which is caused by failure of the ventilatory drive, there is
no movement of the thorax and abdomen. Regardless of the
cause, episodes of airflow reduction to 10% or less of basal
value for 10 seconds or more are called apneas. Reductions of
50% or more of ventilatory flow, associated with a decrease
of at least 3% in oxygen saturation or an arousal, are called
hypopneas. This situation normalizes rapidly after an arousal
interrupts the apnea, resulting in the recovery of ventilation
and normalization of arterial blood oxygen28.
The severity of OSAHS is determined by the apnea-hypopnea index (AHI). The total number of apneas and hypopneas of the individual is divided by the number of hours of
sleep. Normal values are below 5/hour; OSAHS is diagnosed
as mild if AHI is between 5 and 14, moderate if AHI is
between 15 and 29 and severe if AHI ≥30. Patients with
OSAHS (AHI >5) present additional symptoms, including
Data collection process
Data extraction was conducted by the first author and reviewed by the second author. Any discrepancies were correct-
Table 1. Studies describing exercise effects on apnea-hypopnea index (AHI).
First
Year of
Sample
Age
BMI
Design
Weight (kg)
Author
publication
analyzed (n)
(years)
(kg/m2)
Intervention
AHI
Pre
AHI
Post
P
6 months, 3 times/
week; Aerobic exercise,
Norman
2000
Case study
9
48±9
111±11
35±4 30-45 minutes, 50-80% 22±9 12±7 < 0.01
VO2max; and resistance
exercise
6-months, 2 times/
Giebelhaus
2000
Case study
11
52±6
80*
27±3 120 minutes; and power 33±22 24* < 0.05
exercise (repetitive light
weight-lifting)
3-months, 3 times/
Randomized
Sengul
2009
10
54±7
86±8
30±3 45-60 minutes, 60-70% 15±5 11±5
0.02
controled trial
VO2max; and breathing
exercise, 15-30min
10
Control group
18±6 17±11 0.58
Data presented as mean±standard deviation. AHI: apnea-hypopnea index; BMI: body mass index; VO2max: peak oxygen uptake.
* This study did not report standard deviation for this variable.
Sleep Sci. 2011;4(2):61–67
Silva RP, Belli KC, Carissimi A, Fiori CZ, Faria CC, Martinez D
excessive daytime sleepiness and snoring. Although not all
snorers have OSAHS, untreated snoring can have cardiovascular consequences29.
In obstructive sleep apnea, there are several mechanisms
of airway occlusion. These include fat accumulation in the
neck, anatomic abnormalities, disorders of the upper airway
muscles and unbalances in respiratory control, all of which
contribute to airway obstruction during sleep30.
OSAHS AND CARDIOVASCULAR INJURY
The main cardiovascular consequences arising from OSAHS
are generated by cyclic intermittent hypoxia and arousals31.
Intermittent hypoxia and arousals result in chronic hyperactivity of the sympathetic nervous system, increased heart rate,
blood pressure, sensitivity of central and peripheral chemoreceptors and decreased baroreceptor activation31,32. They can
also result in oxidative stress, inflammation, endocrine disorders and endothelial dysfunction23,33,34. These changes are
mechanisms that underlie the onset of cardiovascular and
metabolic diseases35. Concomitantly, patients present a reduction in exercise capacity associated with reduced peak oxygen
consumption (peak VO2), chronotropic incompetence and altered blood pressure response and heart rate24.
The potential mechanism for the reduction of peak VO2
in patients with OSAHS is related to the patient’s base pathology. During exercise, peak VO2 increases in response to
metabolic demand by muscle activation. For this, the cardiovascular system is responsible for optimizing the delivery of blood and oxygen to working muscles and increasing
cardiac output (CO). Any factor that limits CO (filling pressure, ventricular compliance, heart rate, contractility, blood
pressure and/or afterload) can interfere with the exercise capacity of the individual25.
OSAHS affects left ventricular function26. The increased
ventricular afterload results from the increase in negative intrathoracic pressure during airway obstruction. As a result
of the larger intrathoracic pressure swings, there are fluctuations in the ejection fraction, heart rate, and CO. The
rapid increase in CO and the increase in coronary vascular
tone during the apnea cycle can cause episodes of myocardial
ischemia. Other factors that can affect left ventricular function include a reduction in vagal activity, increased platelet
aggregation, and insulin resistance36.
The intermittent hypoxia associated with OSAHS reduces
the production of nitric oxide (NO)37 and impairs endothelial
function25,38. Nitric oxide-dependent mechanisms may reduce
the exercise capacity of patients with the disease39.
OSAHS AND OBESITY
The main risk factor for development of OSAHS is obesity40,
and about 70% of patients with breathing-related sleep dis-
orders are obese41. This risk factor also contributes to the
onset of cardiovascular and metabolic disease in this population35. The risk of developing moderate to severe sleep disorders is increased by six times with a 10% increment in body
mass. Each 1% increase in body mass is associated with a 3%
increase in AHI42.
Patients with higher BMI show a higher prevalence of
most types of severe OSAHS40. The increase in body fat and
intra-abdominal pressure reduces functional residual capacity. Combined with the increased consumption of oxygen in
tissues, it results in faster depletion of oxygen stocks during
apnea43. Due to more intense oxygen desaturation in obese
individuals as compared with non-obese individuals, strategies for weight loss, including exercise, have been suggested
as an alternative to reduce the severity of OSAHS35.
Weight loss via increased physical activity and changes
in diet and lifestyle has been studied as a treatment for
sleep disorders44. Therefore, increasing physical activity
could reduce the body mass of these patients, improve their
sleep disturbance and be considered an important goal for
treatment45.
BENEFITS OF EXERCISE ON SLEEP
Although sleep and exercise act in diametrically opposed
ways from the physiological point of view, the benefits of
these two states are related. Advances in knowledge have
revealed new associations between the mechanisms that act
on exercise and sleep2,46. Therefore, promoting or improving sleep through exercise is believed to be healthy, safe and
simple and might even be an alternative in the treatment
of insomnia2. Both aerobic and resistance exercises improve
sleep quality47. Gary and Lee48 reported that a 12-week
walking program increased the total sleep time for patients
by 20%, improving their quality of life.
The elderly population seems to benefit the most from
physical activity. Besides improved quality of sleep, older
adults also show improvements in their chronic pain and
functional capacity. Compared to the elderly, young adults
and children need longer and more intense exercise to obtain
similar benefits47.
The facilitation of sleep induction after exercise supports
the role of sleep in the conservation of energy, in muscle
recovery and body temperature regulation2. Exercise causes
energy depletion, muscle micro-damage, body temperature
elevation and changes in melatonin levels46, all of which are
restored during sleep2.
The reduction of body temperature is part of the process
of inducing sleep. Melatonin, produced by the pineal gland
in darkness, shortens sleep latency and reduces body temperature. The hypothesis that exercise downregulates temperature explains the increase in deep sleep after exercise.
Sleep Sci. 2011;4(2):61–67
63
64
Physical activities may upregulate the body’s ability to lose
heat, facilitating the sleep-related temperature drop46.
The optimum benefit of exercise is obtained when it is
practiced 4-8 hours before bedtime. However, exercise at
any time of day enhances sleep. In addition to aerobic and
resistance exercises, Tai Chi Chuan also improves the sleep
of practitioners47.
POTENTIAL CARDIOVASCULAR BENEFITS OF
PHYSICAL ACTIVITY IN OSAHS
Cardiovascular function is also affected by OSAHS. During
cardiopulmonary exercise testing (CPET), 35% of OSAHS
patients have a hypertensive response and 45% show abnormal VO2 peaks (84% below expected values)49.
During CPET, chronotropic incompetence and a delay in
HR recovery may predict cardiovascular events and mortality in OSAHS patients24,50. Resistance training affects HR in
the long run, through adjustments in the autonomic nervous
system. These adjustments are represented by a reduction in
sympathetic activation and increased parasympathetic activity, resulting in a decrease in resting HR50.
Nitric oxide is the most potent vasodilator produced in
the body. During exercise, the shear stress (the tangential
force that blood flow exerts on the vessel wall) stimulates
the endothelium, increasing NO production and the vasodilatory response. This causes increased blood flow, triggering acute, subacute and chronic adaptive responses to
exercise throughout the entire cardiovascular and muscular
systems51,52. Exercise may have a hypotensive effect of variable magnitude according to the type, intensity and duration
of exercise52,53. Activities with an intensity between 40 and
70% of peak VO2, longer than 30 minutes in duration and
repeated 5 to 7 times per week lowers blood pressure54,55.
Meta-analysis of more than a dozen studies on the effect
of resistance exercises, such as weight training, revealed that
increases in peak VO2 and the metabolic equivalent of task
(MET) caused a 2% (-3±3 mmHg) and 4% (-3±2 mmHg)
reduction in systolic and diastolic pressure at rest, respectively, in hypertensive subjects56. For each MET increase in
peak VO2 of the individual, there is a reduction between 8
and 17% in cardiovascular mortality20,22.
EXERCISE AS TREATMENT OF OSAHS
The three studies that investigated the effect of exercise on
AHI are summarized in Table 1. Norman et al.57 studied 8
men and 1 woman with a mean age of 49 years who underwent exercise 3 times a week for 6 months. Their exercise
sessions consisted of 30-45 minutes of walking on a treadmill and riding a stationary bicycle with an intensity equivalent to 50-80% of the subject’s peak VO2. Bodybuilding
exercises were used to complement each training session.
Sleep Sci. 2011;4(2):61–67
The authors observed a 46% reduction in AHI, with a 5%
reduction in BMI from 31 to 30 kg/m2 and of cervical circumference from 43 to 41 cm. Five patients treated with a
continuous positive airway pressure (CPAP) device showed a
reduction in AHI from 21 to 11/h, much like the group without the equipment, whose AHI was reduced from 22 to 12/h.
In both cases, there was a change in the OSAHS classification,
from moderate to light, irrespective of the use of CPAP57.
Due to the 5% reduction in BMI, it is difficult to attribute the reduction in AHI exclusively to the direct effect of
exercise. However, one can infer that the reduction in AHI
was greater than expected by simple weight loss, using as
a basis the data of Young et al., which showed a 3% reduction in AHI for each 1% reduction in weight58. In that case,
the expected drop in AHI for that magnitude of weight loss
would be approximately 15%, which is quite different from
the 46% reported.
Giebelhaus et al.59 showed that exercising just 2 days a
week also improves AHI. The physical training program, lasting 6 months, consisted of 120 minutes of aerobic exercise
and 120 minutes of weight training on separate days. Ten men
and one woman with a mean age of 52 years were evaluated.
All study subjects were treated with a CPAP machine for a
period of 3-12 months (6±1.4 months). The authors observed
a 27% reduction in AHI from 33 to 24/h, i.e., from severe to
moderate OSAHS. In that sample, the change in body weight
of the patients from 79.7 to 80.4 kg was not significant, leaving no doubt about the isolated effect of exercise.
Sengul et al.60 performed a randomized controlled study
that evaluated aerobic performance and AHI after 3 months
of physical exercise in patients with mild OSAHS who were
not using CPAP. Twenty subjects were studied, 10 participating in the intervention group and 10 in the control group.
Only the mean age was significantly different among groups:
54 years in the intervention group and 48 years in the control group. Both groups predominantly included individuals
not practicing regular physical activity. The training applied
to the intervention group consisted of aerobic exercises, performed three times per week on a treadmill and ergometric
bike for 45-60 minutes with an intensity of 60-70% of peak
VO2. Breathing exercises were also performed for 15 to 30
minutes. The controls remained without intervention.
In the same study60, after 3 months, the authors observed
that the controls maintained constant anthropometric and
AHI variables. The intervention group showed a decrease in
AHI from 15 to 11 events per hour of sleep, or a reduction
of 27%, with no reduction in anthropometric variables such
as BMI and neck circumference. In this study, the effects of
exercise and weight loss on AHI were also confounded. There
was a 2% drop in BMI from 29.8 to 29.2 kg/m2, which would
explain a 6% reduction in AHI but not the 27% observed.
FINAL Considerations
Despite being a less controllable form of therapy, changes
in lifestyle are part of the medical prescription. Exercise has
been shown in the three reviewed trials to be an effective
intervention for reduction of OSAHS severity. Furthermore,
exercise can play an important role in treating the main
OSAHS factors, through reduction of both the cardiovascular risk factors and the body mass of patients. Preventing
weight gain through exercise can prevent the emergence or
worsening of OSAHS. Physical training reduces cardiovascular events and OSAHS severity, regardless of the use of
other therapies such as CPAP or decreasing BMI. The limited number of studies requires additional investigation of
the effectiveness of the role of exercise in OSAHS before this
treatment modality can be universally recommended. Nevertheless, the agreement among the reviewed articles suggests a potential benefit of exercise on OSAHS.
FINANCIAL SUPPORT
Students received grants from the Brazilian government through
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
and National Council of Technological and Scientific Development (CNPq). The main support was offered by the Research
Incentive Fund (FIPE) of the Hospital de Clínicas de Porto Alegre.
REFERENCES
1. Murphy MH, McNeilly AM, Murtagh EM. Session 1: Public
health nutrition: Physical activity prescription for public health.
Proc Nutr Soc. 2010;69(1):178-84.
2. Youngstedt SD. Effects of exercise on sleep. Clin Sports Med.
2005;24(2):355-65, xi.
3. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults.
N Engl J Med. 1993;328(17):1230-5. Comment in: N Engl J
Med. 1993;328(17):1271-3. N Engl J Med. 1993;329(19):1429;
author reply 1429-30. N Engl J Med. 1993;329(19):1429. N
Engl J Med. 1993;329(19):1429; author reply 1429-30.
4. Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive
sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study.
Sleep Med. 2010;11(5):441-6.
5. Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90(1):47-112. Erratum
in: Physiol Rev. 2010;90(2):797-8.
6. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of
the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378-84. Comment in: N Engl
J Med. 2000;343(13):966-7. N Engl J Med. 2000;343(13):966;
author reply 967. N Engl J Med. 2000;343(13):967.
7. Nieto FJ, Young TB, Lind BK, Shahar E, Samet JM, Redline S, et
al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health
Study. JAMA. 2000;283(14):1829-36.
8. Gonçalves SC, Martinez D, Gus M, de Abreu-Silva EO, Bertoluci
C, Dutra I, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest. 2007;132(6):1858-62.
9. Gus M, Gonçalves SC, Martinez D, de Abreu Silva EO, Moreira LB, Fuchs SC, et al. Risk for obstructive sleep apnea by
Berlin Questionnaire, but not daytime sleepiness, is associated with resistant hypertension: a case-control study. Am J
Hypertens. 2008;21(7):832-5. Comment in: Am J Hypertens.
2008;21(7):728.
10.Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM,
Mohsenin V. Obstructive sleep apnea as a risk factor for stroke
and death. N Engl J Med. 2005;353(19):2034-41. Comment in: N Engl J Med. 2005;353(19):2070-3. N Engl J Med.
2006;354(10):1086-9; author reply 1086-9. N Engl J Med.
2006;354(10):1086-9; author reply 1086-9.
11.Shah N, Roux F. The relationship of obesity and obstructive sleep
apnea. Clin Chest Med. 2009;30(3):455-65, vii.
12.Mugnai G. Pathophysiological links between obstructive sleep
apnea syndrome and metabolic syndrome. G Ital Cardiol (Rome).
2010;11(6):453-9. Article in Italian.
13.Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras
A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T; American Heart Association Council for
High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology; American Heart Association
Stroke Council; American Heart Association Council on Cardiovascular Nursing; American College of Cardiology Foundation. Sleep
apnea and cardiovascular disease: an American Heart Association/
American College Of Cardiology Foundation Scientific Statement
from the American Heart Association Council for High Blood
Pressure Research Professional Education Committee, Council on
Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung,
and Blood Institute National Center on Sleep Disorders Research
(National Institutes of Health). Circulation. 2008;118(10):1080111. Erratum in: Circulation. 2009;119(12):e380.
14.Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009;373(9657):82-93.
15.Lavie P, Herer P, Lavie L. Mortality risk factors in sleep apnoea: a
matched case-control study. J Sleep Res. 2007;16(1):128-34.
16.Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB,
OĆonnor GT, et al. Sleep-disordered breathing and mortality: a
prospective cohort study. PLoS Med. 2009;6(8):e1000132. Comment in: Portgrad Med. 2009;121(6):197-9.
17.Jean-Louis G, Brown CD, Zizi F, Ogedegbe G, Boutin-Foster C,
Gorga J, et al. Cardiovascular disease risk reduction with sleep apnea treatment. Expert Rev Cardiovasc Ther. 2010;8(7):995-1005.
18.Martínez-García MA, Soler-Cataluña JJ, Ejarque-Martínez L, Soriano Y, Román-Sánchez P, Illa FB, et al. Continuous positive
airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study.
Am J Respir Crit Care Med. 2009;180(1):36-41.
19.Buchner NJ, Sanner BM, Borgel J, Rump LC. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit
Care Med. 2007;176(12):1274-80. Comment in: J Fam Pract.
2008;57(3):155.
20.Bairey Merz CN, Alberts MJ, Balady GJ, Ballantyne CM, Berra
K, Black HR, Blumenthal RS, Davidson MH, Fazio SB, Ferdinand KC, Fine LJ, Fonseca V, Franklin BA, McBride PE, Mensah
GA, Merli GJ, O’Gara PT, Thompson PD, Underberg JA; American Academy of Neurology; American Association of CardiovasSleep Sci. 2011;4(2):61–67
65
66
cular and Pulmonary Rehabilitation; American College of Preventive Medicine; American College of Sports Medicine; American
Diabetes Association; American Society of Hypertension; Association of Black Cardiologists; Centers for Disease Control and
Prevention; National Heart, Lung, and Blood Institute; National
Lipid Association; Preventive Cardiovascular Nurses Association.
ACCF/AHA/ACP 2009 competence and training statement: a
curriculum on prevention of cardiovascular disease: a report of
the American College of Cardiology Foundation/American Heart
Association/American College of Physicians Task Force on Competence and Training (Writing Committee to Develop a Competence and Training Statement on Prevention of Cardiovascular
Disease): developed in collaboration with the American Academy
of Neurology; American Association of Cardiovascular and Pulmonary Rehabilitation; American College of Preventive Medicine; American College of Sports Medicine; American Diabetes
Association; American Society of Hypertension; Association of
Black Cardiologists; Centers for Disease Control and Prevention;
National Heart, Lung, and Blood Institute; National Lipid Association; and Preventive Cardiovascular Nurses Association. Circulation. 2009;120(13):e100-26.21. Clark AM, Haykowsky M,
Kryworuchko J, MacClure T, Scott J, DesMeules M, et al. A meta-analysis of randomized control trials of home-based secondary
prevention programs for coronary artery disease. Eur J Cardiovasc
Prev Rehabil. 2010;17(3):261-70.
22.Petrović-Oggiano G, Damjanov V, Gurinović M, Glibetić M.
Physical activity in prevention and reduction of cardiovascular
risk. Med Pregl. 2010;63(3-4):200-7. Article in Serbian.
23.Garvey JF, Taylor CT, McNicholas WT. Cardiovascular disease in
obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J. 2009;33(5):1195-205.
24.Aron A, Zedalis D, Gregg JM, Gwazdauskas FC, Herbert
WG. Potential clinical use of cardiopulmonary exercise testing
in obstructive sleep apnea hypopnea syndrome. Int J Cardiol.
2009;132(2):176-86.
25.Kraiczi H, Caidahl K, Samuelsson A, Peker Y, Hedner J. Impairment of vascular endothelial function and left ventricular filling:
association with the severity of apnea-induced hypoxemia during
sleep. Chest. 2001;119(4):1085-91.
26.Otto ME, Belohlavek M, Romero-Corral A, Gami AS, Gilman G,
Svatikova A, et al. Comparison of cardiac structural and functional changes in obese otherwise healthy adults with versus without
obstructive sleep apnea. Am J Cardiol. 2007;99(9):1298-302.
27.Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein
MD; Adult Obstructive Sleep Apnea Task Force of the American
Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea
in adults. J Clin Sleep Med. 2009;5(3):263-76.
28.Lee AJ, Wei-Hsiu L. The effects of physical activity on sleep quality. Med Sci Sports Exerc. 2002;34(5):S70.
29.da Silveira FJ, Duarte RL. Consequences of untreated snoring. J
Bras Pneumol. 2010;36 Suppl 2:28-31.
30.Owens RL, Eckert DJ, Yeh SY, Malhotra A. Upper airway function in the pathogenesis of obstructive sleep apnea: a review of the
current literature. Curr Opin Pulm Med. 2008;14(6):519-24.
31.Torre-Bouscoulet L, Castorena-Maldonado A, Sada-Ovalle I, MezaVargas MS. Mechanisms of cardiovascular damage in obstructive
sleep apnea. Rev Invest Clin. 2008;60(6):502-16. Article in Spanish.
Sleep Sci. 2011;4(2):61–67
32.Caples SM, Garcia-Touchard A, Somers VK. Sleep-disordered
breathing and cardiovascular risk. Sleep. 2007;30(3):291-303.
33.Atkeson A, Yeh SY, Malhotra A, Jelic S. Endothelial function in
obstructive sleep apnea. Prog Cardiovasc Dis. 2009;51(5):351-62.
34.Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003;290(14):190614. Comment in: JAMA. 2004;291(5):557; author reply 557-8.
35.Leinum CJ, Dopp JM, Morgan BJ. Sleep-disordered breathing
and obesity: pathophysiology, complications, and treatment. Nutr
Clin Pract. 2009;24(6):675-87.
36.Parati G, Lombardi C, Narkiewicz K. Sleep apnea: epidemiology,
pathophysiology, and relation to cardiovascular risk. Am J Physiol
Regul Integr Comp Physiol. 2007;293(4):R1671-83.
37.Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, et al.
Amelioration of vascular endothelial dysfunction in obstructive
sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG,
NG-dimethylarginine. Circ J. 2005;69(2):221-6.
38.Carlson JT, Rångemark C, Hedner JA. Attenuated endotheliumdependent vascular relaxation in patients with sleep apnoea. J Hypertens. 1996;14(5):577-84.
39.Maxwell AJ, Schauble E, Bernstein D, Cooke JP. Limb blood
flow during exercise is dependent on nitric oxide. Circulation.
1998;98(4):369-74.
40.Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol. 2005;99(4):1592-9.
41.Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales
A. Sleep apnea and sleep disruption in obese patients. Arch Intern
Med. 1994;154(15):1705-11.
42.Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered
breathing. JAMA. 2000;284(23):3015-21.
43.Findley LJ, Ries AL, Tisi GM, Wagner PD. Hypoxemia during
apnea in normal subjects: mechanisms and impact of lung volume. J Appl Physiol. 1983;55(6):1777-83.
44.Tuomilehto HP, Seppä JM, Partinen MM, Peltonen M, Gylling
H, Tuomilehto JO, Vanninen EJ, Kokkarinen J, Sahlman JK,
Martikainen T, Soini EJ, Randell J, Tukiainen H, Uusitupa M;
Kuopio Sleep Apnea Group. Lifestyle intervention with weight
reduction: first-line treatment in mild obstructive sleep apnea.
Am J Respir Crit Care Med. 2009;179(4):320-7. Comment in:
Am J Respir Crit Care Med. 2009;180(1):101; author reply
101-2. Am J Respir Crit Care Med. 2009;180(2):190-1; author
reply 191. Evid Based Nurs. 2009;12(4):111.
45.Hastings PC, Vazir A, O’Driscoll DM, Morrell MJ, Simonds AK.
Symptom burden of sleep-disordered breathing in mild-to-moderate
congestive heart failure patients. Eur Respir J. 2006;27(4):748-55.
Comment in: Eur Respir J. 2006;28(2):459; author reply 459-60.
46.Atkinson G, Davenne D. Relationships between sleep, physical
activity and human health. Physiol Behav. 2007;90(2-3):229-35.
47.Buman MP, King AC. Exercise as a treatment to enhance sleep.
Am J Lifestyle Med. 2010;4(6):500-14.
48.Gary R, Lee SY. Physical function and quality of life in older women
with diastolic heart failure: effects of a progressive walking program
on sleep patterns. Prog Cardiovasc Nurs. 2007;22(2):72-80.
49.Przybyłowski T, Bielicki P, Kumor M, Hildebrand K, MaskeyWarzechowska M, Korczynski P, et al. Exercise capacity in patients with obstructive sleep apnea syndrome. J Physiol Pharmacol. 2007;58 Suppl 5(Pt 2):563-74.
50.Myers J, Tan SY, Abella J, Aleti V, Froelicher VF. Comparison of
the chronotropic response to exercise and heart rate recovery in
predicting cardiovascular mortality. Eur J Cardiovasc Prev Rehabil. 2007;14(2):215-21.
51.Green DJ. Exercise training as vascular medicine: direct impacts
on the vasculature in humans. Exerc Sport Sci Rev. 2009;37(4):
196-202.
52.Moreira WD, Fuchs FD, Ribeiro JP, Appel LJ. The effects of two
aerobic training intensities on ambulatory blood pressure in hypertensive patients: results of a randomized trial. J Clin Epidemiol. 1999;52(7):637-42.
53.Thijssen DH, Maiorana AJ, O’Driscoll G, Cable NT, Hopman MT, Green DJ. Impact of inactivity and exercise on the
vasculature in humans. Eur J Appl Physiol. 2010;108(5):
845-75.
54.Wallace JP. Exercise in hypertension. A clinical review. Sports
Med. 2003;33(8):585-98.
55.Pescatello LS. Exercise and hypertension: recent advances in exercise prescription. Curr Hypertens Rep. 2005;7(4):281-6.
56.Kelley GA, Kelley KS. Progressive resistance exercise and resting
blood pressure: A meta-analysis of randomized controlled trials.
Hypertension. 2000;35(3):838-43.
57.Norman JF, Von Essen SG, Fuchs RH, McElligott M. Exercise
training effect on obstructive sleep apnea syndrome. Sleep Res
Online. 2000;3(3):121-9.
58.Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive
sleep apnea: a population health perspective. Am J Respir Crit
Care Med. 2002;165(9):1217-39.
59.Giebelhaus V, Strohl KP, Lormes W, Lehmann M, Netzer N.
Physical exercise as an adjunct therapy in sleep apnea-an open
trial. Sleep Breath. 2000;4(4):173-6.
60.Sengul YS, Ozalevli S, Oztura I, Itil O, Baklan B. The effect of
exercise on obstructive sleep apnea: a randomized and controlled
trial. Sleep Breath. 2009;15(1):49-56.
APPENDIX A
Strategy of literature search performed on December 16, 2010.
Legend
Most recent queries
#10
Search (#8) AND #9
#9
Search (exercise[MeSH Terms]) OR (Exercises[Text Word]) OR Exercise, Physical[Text
INTERVENTION
Word]) OR (Exercises, Physical[Text Word]) OR (Physical Exercise[Text Word]) OR (Physical
Exercises[Text Word]) OR Exercise, Isometric[Text Word]) OR (Exercises, Isometric[Text
Word]) OR (Isometric Exercises[Text Word]) OR (Isometric Exercise[Text Word]) OR
(Warm-Up Exercise[Text Word]) OR (Exercise, Warm-Up[Text Word]) OR (Exercises,
Warm-Up[Text Word]) OR (Warm Up Exercise[Text Word]) OR Warm-Up Exercises[Text
Word]) OR (Exercise, Aerobic[Text Word]) OR (Aerobic Exercises[Text Word]) OR (Exercises,
Aerobic[Text Word]) OR (Aerobic Exercise[Text Word]) OR (Exercise Therapy[MeSH
Terms]) OR (Therapy, Exercise[Text Word]) OR (Exercise Therapies[Text Word]) OR
(Therapies, Exercise[Text Word]) OR (Resistance Training[Text Word]) OR (Training,
Resistance[Text Word]) OR (Strength Training[Text Word]) OR (Training, Strength[Text
Word]) OR (Weight-Lifting Strengthening Program[Text Word]) OR (Strengthening
Program, Weight-Lifting[Text Word]) OR (Strengthening Programs, Weight-Lifting[Text
Word]) OR (Weight Lifting Strengthening Program[Text Word]) OR (Weight-Lifting
Strengthening Programs[Text Word]) OR (Weight-Lifting Exercise Program[Text Word])
OR (Exercise Program, Weight-Lifting[Text Word]) OR Exercise Programs, WeightLifting[Text Word]) OR (Weight Lifting Exercise Program[Text Word]) OR (Weight-Lifting
Exercise Programs[Text Word]) OR (Weight-Bearing Strengthening Program[Text Word])
OR (Strengthening Program, Weight-Bearing[Text Word]) OR (Strengthening Programs,
Weight-Bearing[Text Word]) OR (Weight Bearing Strengthening Program[Text Word])
OR (Weight-Bearing Strengthening Programs[Text Word]) OR (Weight-Bearing Exercise
Program[Text Word]) OR (Exercise Program, Weight-Bearing[Text Word]) OR (Exercise
Programs, Weight-Bearing[Text Word]) OR (Weight Bearing Exercise Program[Text Word])
OR (Weight-Bearing Exercise Programs[Text Word])
#8
Search (Sleep Apnea, Obstructive OR Apnea, Obstructive Sleep OR Apneas, Obstructive Sleep
PATIENTS
OR Obstructive Sleep Apneas OR Sleep Apneas, Obstructive OR Obstructive Sleep Apnea
Syndrome OR Syndrome, Sleep Apnea, Obstructive OR Syndrome, Obstructive Sleep Apnea
OR Obstructive Sleep Apnea OR Sleep Apnea Syndrome, Obstructive OR Upper Airway
Resistance Sleep Apnea Syndrome OR Syndrome, Upper Airway Resistance, Sleep Apnea OR
Sleep Apnea Syndromes OR Apnea Syndrome, Sleep OR Apnea Syndromes, Sleep OR Sleep
Apnea Syndrome OR Apnea, Sleep OR Apneas, Sleep OR Sleep Apnea OR Sleep Apneas OR
Sleep Hypopnea OR Hypopnea, Sleep OR Hypopneas, Sleep OR Sleep Hypopneas OR SleepDisordered Breathing OR Breathing, Sleep-Disordered OR Sleep Disordered Breathing OR
Sleep Apnea, Mixed Central and Obstructive OR Mixed Central and Obstructive Sleep Apnea
OR Sleep Apnea, Mixed OR Mixed Sleep Apnea OR Mixed Sleep Apneas OR Sleep Apneas,
Mixed OR Hypersomnia with Periodic Respiration)
Time
12:16:00
12:13:49
Result
149
94.477
12:12:59
22.975
Sleep Sci. 2011;4(2):61–67
67
REVIEW ARTICLE
A deglutição na síndrome da apneia obstrutiva do sono
Luciana Almeida Moreira1, Michel Burihan Cahali1,2
ABSTRACT
Obstructive sleep apnea syndrome and primary snoring are associated with the presence of neurogenic lesions and impaired sensory
function in the upper airway, which are presumably caused by lowfrequency vibrations produced by snoring or intermittent hypoxia.
The clinical impact of this peripheral neuropathy on the pharynx has
not been thoroughly investigated with respect to the management
of patients with obstructive sleep apnea syndrome. Several authors
have shown changes in swallowing associated with this syndrome,
such as early bolus escape, the presence of pharyngeal residue, laryngeal penetration, and increased latency before triggering of the
swallowing reflex. In this article, we review the main features of
swallowing that may be altered in obstructive sleep apnea syndrome
and the mechanisms involved in its pathophysiology as well as the
results of studies that have evaluated swallowing in patients after
treatment for this syndrome.
keywords: deglutition; deglutition disorders; sleep apnea, obstructive; snoring.
RESUMO
A síndrome da apneia obstrutiva do sono e também o ronco primário estão associados à presença de lesões neurogênicas e comprometimento da função sensorial na via aérea superior, supostamente causados pelas vibrações de baixa frequência produzidas pelo
ronco ou pela hipóxia intermitente. O impacto clínico dessa neuropatia periférica na faringe tem sido, habitualmente, pouco explorado no manejo dos pacientes com síndrome da apneia obstrutiva
do sono. Vários autores têm demonstrado alterações na deglutição
associadas a essa síndrome, tais como escape precoce do bolo alimentar, resíduo faríngeo, penetração laríngea e aumento da latência para disparo do reflexo da deglutição. Neste artigo, revemos as
principais características da deglutição que podem estar alteradas
na síndrome da apneia obstrutiva do sono e os mecanismos envolvidos em sua fisiopatologia, bem como os resultados de estudos da
deglutição após o tratamento dessa síndrome.
Palavras-chave: deglutição; transtornos de deglutição; apneia do
sono tipo obstrutiva; ronco.
INTRODUCTION
Obstructive sleep apnea syndrome (OSAS) is characterized
by repeated episodes of partial or complete obstruction of
the airway during sleep, resulting from narrowing of the
pharynx and a decrease in the tone of the pharyngeal dilator
muscles1. OSAS may be preceded by an early stage of primary snoring2. Neurogenic lesions in the oropharynx and the
soft palate are associated with OSAS and primary snoring,
but their cause is unknown. Some authors believe that the
lesions are triggered by low-frequency vibrations produced
by snoring or intermittent hypoxia3-5.
Because the pharynx is the site of the lesions, many authors have suggested that there may be a swallowing dysfunction associated with OSAS. The onset of the swallowing
reflex and the propagation of the food bolus are dependent
on adequate pharyngeal sensitivity and function. Moreover,
continuous OSAS may affect efferent neuromuscular activity
and the upper airway function control centers6-11.
The aim of this paper is to review the evidence in the literature regarding swallowing dysfunction in primary snoring and in OSAS.
NEUROGENIC LESIONS IN OSAS
Neurogenic lesions are found in the oropharynx of individuals who snore, and these lesions are thought to be caused
by low-frequency vibrations produced by stertor. This assertion is supported by several histological studies, such as that
of Friberg et al., in which mucosal biopsies of the soft palate showed an increased number of abnormal nerve endings
in people who snore3. The same author performed biopsies
of the palatopharyngeal muscle and found morphological
changes typical of neurogenic involvement, such as grouping of tissues by fiber type, clusters of atrophied areas, and
fascicular atrophy, both in primary snorers and in patients
with OSAS4. Moreover, changes in the neural regulation of
Study carried out at Departamento de Otorrinolaringologia do Hospital do Servidor Público Estadual “Francisco Morato de Oliveira” (HSPE-FMO), São Paulo (SP), Brasil.
1
Departamento de Otorrinolaringologia do Hospital do Servidor Público Estadual “Francisco Morato de Oliveira” (HSPE-FMO), São Paulo (SP), Brasil.
2
Departamento de Otorrinolaringologia do Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo (SP), Brasil.
Corresponding author: Luciana Almeida Moreira – Rua Borges Lagoa, 1427 – CEP 04039-508 – São Paulo (SP), Brazil – E-mail: [email protected]
Sleep Sci. 2011;4(2):68–71
Moreira LA, Cahali MB
microcirculation were detected in the soft palate mucosa of
snorers and some patients with mild OSAS12. Other authors
have also reported findings consistent with peripheral nerve
injury in muscle biopsies from apnea patients13,14.
Intense snoring causes stretching and low-frequency vibration of pharyngeal tissues15. Takeuchi et al. demonstrated
that long-term exposure to low-frequency vibration due to
the occupational use of vibrating tools (chain saw, pneumatic
drill) causes peripheral nerve injury and lesions in the microcirculation of the fingers in humans16. It has also been demonstrated in dogs that oscillatory pressure waves (30 Hz and
+/- 3 cmH2O) applied to the upper airway at the same frequency as snoring, affected pharyngeal receptors, increased
local dilator muscle activity, and disrupted sleep17.
Kimoff et al. have demonstrated a selective impairment
of sensory function of the upper airway mucosa in OSAS
patients. They found both decreased vibration sensitivity
and reduced tactile discrimination between two points in
the oropharynx of patients with primary snoring and OSAS
compared to a non-snoring group without OSAS. Furthermore, these effects did not occur in control areas, such as the
lips and hands5. Nguyen et al. also noted a decrease in the
sensitivity of the larynx and velopharynx, which positively
correlated with the severity of the OSAS18.
These data suggest changes in afferent and/or efferent
neural pathways involved in the upper airway reflexogenic
mechanism in OSAS patients4. There is speculation about
the role of this neuropathy in the progression of pharyngeal
collapsibility, which is observed in OSAS4; it is known that
the permeability of the upper airway depends on the balance
between the negative inspiratory pressure and the action of
pharyngeal dilator muscles, which, in turn, requires a fully
functioning neural afferent pathway to be stimulated1.
A possible causal relationship between snoring and the
neurogenic lesions can be argued for. Although peripheral
neuropathy can theoretically precede the onset of snoring,
this is not universally found among snoring individuals and
seems to arise during the course of the disease4.
Swallowing dysfunction in OSAS
Swallowing is a process divided into four distinct phases.
In the oral preparatory phase, voluntary chewing and bolus
formation take place. The oral phase itself consists on the
elevation and posterior impulsion of food to the back of the
oral cavity, featuring the final voluntary activity of swallowing. The pharyngeal phase is represented by the pharyngeal
reflex, in which the most complex part of swallowing takes
place in a rapid and coordinated fashion. The soft palate rises
to seal off the nasopharynx, the larynx closes to protect the
lower airway, and the caudal propulsion of the food bolus
and relaxation of the cricopharyngeal muscle take place. In
the esophageal phase, after the food passes through the upper esophageal sphincter, it is pushed through the esophageal muscles by primary and secondary peristalsis. The process is finalized with the relaxation of the lower esophageal
sphincter and the arrival of food in the stomach19.
Normal evocation of the swallowing reflex and the propagation of the food bolus through the pharynx are dependent
on adequate pharyngeal sensitivity and function. The presence of sensory lesions in the pharyngeal mucosa of snorers
may compromise the mechanism of swallowing10,11.
Teramoto et al. performed a swallowing provocation test
and showed a delayed triggering of the swallowing reflex
(the food in the pharynx took longer to evoke the pharyngeal reflex) and the need for a greater volume of food bolus
to initiate it in OSAS patients compared to a control group.
This finding implies an increased risk of tracheal aspiration
among OSAS patients6.
On the other hand, Jobin et al. reported a significant
reduction in the latency of the swallowing reflex in OSAS
patients who were younger and obese, patients of a caucasian
ethnicity (while Teramoto et al. studied Japanese patients),
and patients with more severe OSAS. This study suggests an
impairment of the reflex inhibitory modulation and central
control of swallowing7.
In studies using barium videofluoroscopy, Jaghagen et
al. detected subclinical abnormalities in swallowing in more
than half of patients with untreated primary snoring and
OSAS compared to only 7% in the controls. The patients
were significantly older than the controls, but the risk of
swallowing dysfunction was not positively correlated with
the severity of OSAS. The most frequent alteration was premature spillage of the food bolus (48%) to different levels
of the pharynx before onset of the swallowing reflex. This
finding corroborates the hypothesis that the neurogenic lesions of the oropharynx in snorers impair the sensory function of the mucosa and the triggering of the swallowing reflex. When early spillage occurs, chewing and breathing are
not inhibited, and this may result in laryngeal penetration,
when food reaches the laryngeal vestibule but does not pass
through the glottis, or tracheal aspiration, when food passes
through the glottis8,9.
Another observed abnormality is the presence of residual
food in the pharynx after complete swallowing and recovery
of breathing, which occurs in 11% of patients. This also implies a risk of penetration/aspiration because the patient is
not aware of the presence of the residual food, and the lower
airway is unprotected. Laryngeal penetration was observed
in 5% of the OSAS cases, but there was no tracheal aspiration, which may explain why many patients do not report
dysphagia. Meanwhile, in the control group, there were no
cases of pharyngeal residue, laryngeal penetration, or tracheSleep Sci. 2011;4(2):68–71
69
70
al aspiration. The only change observed was early escape of
the bolus in one control individual (7%)8,9.
Jaghagen et al. evaluated swallowing in primary snoring and OSAS patients who were selected for surgical
treatment (uvulopalatopharyngoplasty and uvulopalatoplasty). During the preoperative evaluation, 17% of the
patients had symptoms of dysphagia (i.e. clinical dysphagia). Among the asymptomatic patients (83%), more
than half (51%) showed swallowing disorders during
videofluoroscopic testing (i.e. subclinical dysphagia). In
the postoperative period, considering the asymptomatic
group, no significant difference was observed between
patients with or without pharyngeal swallowing dysfunction with regards to the risk of developing clinical
dysphagia. For those who were asymptomatic before the
surgery, 29% reported dysphagia symptoms afterwards,
but only half had the diagnosis confirmed by videofluoroscopy20.
Okada et al. reported two cases of patients with severe
OSAS and swallowing dysfunction who improved after
treatment with nasal continuous positive airway pressure
CPAP and weight loss. They performed the swallowing
provocation test before the treatment and one year after, and
observed decreased latency of the onset of the swallowing
reflex and also disappearance of tracheal aspiration in one
patient. However, it was not possible to determine whether
the patient’s improvement was due to weight loss or the use
of CPAP21.
Recently, Valbuza et al. used nasal fiberoptic examination and observed subclinical swallowing abnormalities in
patients with moderate to severe OSAS compared to a control group. Early escape of the food bolus occurred in 64% of
patients, and food residue in the pharynx was found in 55%
of patients. No cases of laryngeal penetration or tracheal aspiration were reported22.
Pharyngeal swallowing dysfunction is often a slowly progressive disorder in which the individual develops compensatory mechanisms, such as changes in the diet or chewing
rate. Thus, symptoms may appear only when the compensatory strategies are overcome by the severity of the disorder.
Before this point is reached, active medical intervention can
detect swallowing impairment23.
We observe that in most cases, the complaint of dysphagia is not mentioned spontaneously by OSAS patients,
but its perception reveals the potential impacts of OSAS
on the patients’ quality of life, which is an additional motivator for seeking and adhering to treatment. This aspect
is often ignored in the management of OSAS, and specific
treatments (maneuver orientation, postural adjustments, facilitating therapies, and changes in the diet) may also have a
positive impact on the quality of life of these patients.
Sleep Sci. 2011;4(2):68–71
References
1. Remmers JE, de Groot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol.
1978;44(6):931-8.
2. Strohl KP, Redline S. Recognition of obstructive sleep apnea. Am
J Respir Crit Care Med. 1996;154(2 Pt 1):279-89.
3. Friberg D, Gazelius B, Hökfelt T, Nordlander B. Abnormal afferent nerve endings in the soft palatal mucosa of the sleep apnoics
and habitual snorers. Regul Pept. 1997;71(1):29-36.
4. Friberg D, Ansved T, Borg K, Carlsson-Nordlander B, Larsson
H, Svanborg E. Histological indications of progressive snorers
disease in an upper airway muscle. Am J Respir Crit Care Med.
1998;157(2):586-93.
5. Kimoff RJ, Sforza E, Champagne V, Ofiara L, Gendron D. Upper
airway sensation in snoring and obstructive sleep apnea. Am J
Respir Crit Care Med. 2001;164(2):250-5.
6. Teramoto S, Sudo E, Matsuse T, Ohga E, Ishii T, Ouchi Y et al.
Impaired swallowing reflex in patients with obstructive sleep apnea syndrome. Chest. 1999;116(1):17-21.
7. Jobin V, Champagne V, Beauregard J, Charbonneau I, McFarland DH, Kimoff RJ. Swallowing function and upper
airway sensation in obstructive sleep apnea. J Appl Physiol.
2007;102(4):1587-94.
8. Jäghagen EL, Berggren D, Isberg A. Swallowing dysfunction related to snoring: A videoradiographic study. Acta Otolaryngol.
2000;120(3):438-43.
9. Jäghagen EL, Franklin KA, Isberg A. Snoring, sleep apnoea and
swallowing dysfunction: a videoradiographic study. Dentomaxillofacial Radiol. 2003;32(5):311-6.
10.Broussard DL, Altschuler SM. Central integration of swallow and
airway-protective reflexes. Am J Med. 2000;108Suppl 4a:62S-67S.
11.Ertekin C, Aydogdu I. Neurophysiology of swallowing. Clin
Neurophysiol. 2003;114(12):2226-44.
12.Friberg D, Gazelius B, Lindblad LE, Nordlander B. Habitual
snorers and sleep apnoics have abnormal vascular reactions of the
soft palatal mucosa on afferent nerve stimulation. Laryngoscope.
1998;108(3):431-6.
13.Woodson BT, Garancis JC, Toohill RJ. Histopathologic changes
in snoring and obstructive sleep apnea syndrome. Laryngoscope.
1991;101(12 Pt 1):1318-22.
14.Edström L, Larsson H, Larsson L. Neurogenic effects on the
palatopharyngeal muscle in patients with obstructive sleep apnoea: a muscle biopsy study. J Neurol Neurosurg Psychiatry.
1992;55(10):916-20.
15.Schäfer J. [How can one recognize a velum snorer?]. Laryngorhinootologie 1989;68(5):290-4. German.
16.Takeuchi T, Futatsuka M, Imanishi H, Yamada S. Pathological
changes observed in the finger biopsy of patients with vibrationinduced white finger. Scand J Work, Environ Health. 1986;12(4
Spec No):280-3.
17.Plowman L, Lauff DC, Berthon-Jones M, Sullivan CE. Waking
and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs. J Appl Physiol. 1990;68(6):2564-73.
18.Nguyen AT, Jobin V, Payne RJ, Naor N, Beauregard J, Kimoff
RJ. Laryngeal and velopharyngeal sensory impairment in obstructive sleep apnea. Sleep. 2005;28(5):585-93.
19.Jotz GP, Dornelles S. Fisiologia da deglutição. In: Costa SS, Cruz
OLM, Oliveira JAA. Otorrinolaringologia: princípios e prática.
Porto Alegre: Artmed; 2006. p. 753-6.
Moreira LA, Cahali MB
20.Jäghagen EL, Berggren D, Dahlqvist A, Isberg A. Prediction and
risk of dysphagia after uvulopalatopharyngoplasty and uvulopalatoplasty. Acta Otolaryngol. 2004;124(10):1197-203.
21.Okada S, Ouchi Y, Teramoto S. Nasal continuous positive airway pressure and weight loss improve swallowing reflex in patients with obstructive sleep apnea syndrome. Respiration.
2000;67(4):464-6.
22.Valbuza JS, Oliveira MM, Zancanella E, Conti CF, Prado LBF,
Carvalho LBC et al. Swallowing dysfunction related to obstructive sleep apnea: a nasal fibroscopy pilot study. Sleep Breath.
2011;15(2):209-13.
23.Buchholz DW, Bosma JF, Donner MW. Adaptation, compensation and decompensation of the pharyngeal swallow. Gastrointest
Radiol. 1985;10(3):235-9.
Sleep Sci. 2011;4(2):68–71
71
REVIEW ARTICLE
Upper airway resistance syndrome:
still not recognized and not treated
Síndrome da resistência da via aérea superior: ainda não-reconhecida e não-tratada
Luciana Palombini1, Maria-Cecilia Lopes1, Sérgio Tufik1, Guilleminault Christian2, Lia Rita A. Bittencourt1
ABSTRACT
The upper airway resistance syndrome (UARS) is a sleep breathing disorder described by Guilleminault et al., in 1993, to identify patients that present increased respiratory effort and airflow
limitation during sleep associated with an increase in the upper
airway resistance. Patients usually complain of daytime sleepiness,
fatigue, snoring, and difficulty to maintain sleep. Complains related to cognitive impairment, headache, anxiety, and irritability
are also frequent. The physical examination shows nasal obstruction, increase in soft tissue and craniofacial abnormalities associated with decrease in the upper airway space. Nocturnal polysomnography does not show apneas or hyponeas for diagnostic
criteria of obstructive sleep apnea syndrome (OSAS), and respiratory abnormalities consist on periods of increase in respiratory
effort, sleep fragmentation, presence of respiratory event related
arousal (RERAs) and presence of flattening of respiratory curve,
which indicates airflow limitation. Controversies exist regarding
the characterization of upper airway resistance syndrome as part of
a continuum with other sleep breathing disorders, or as a separate
entity that may not progress to obstructive sleep apnea syndrome.
Treatment of upper airway resistance syndrome is more challenging than obstructive sleep apnea syndrome, since patients have
lower tolerance for continuous positive airway pressure (CPAP)
use. Other treatment modalities have been investigated, but they
are still not established for clinical practice. Recognition of upper airway resistance syndrome is important, since it may prevent
long-term consequences or progression to more severe forms of
sleep-related breathing disorders.
keywords: airway resistance; polysomnography; electroencephalography; sleep apnea, obstructive; sleepiness; arousal; respiration.
RESUMO
A síndrome da resistência da via aérea superior (SRVAS) é um distúrbio respiratório do sono, descrito por Guilleminault et al., em
1993, para identificar pacientes que apresentam aumento do esforço respiratório e limitação ao fluxo aéreo durante o sono, associado
com aumento na resistência da via aérea superior durante o sono.
Estes pacientes geralmente queixam-se de sonolência diurna, fadiga, ronco e dificuldade para manter o sono. Queixas relacionadas a
prejuízo cognitivo, cefaleia, ansiedade e irritabilidade também são
frequentes. O exame físico demonstra obstrução nasal, aumento dos
tecidos moles e anormalidades craniofaciais associadas à diminuição
no espaço aéreo superior. A polissonografia noturna não apresenta
apneias e hipopneias suficientes para o diagnóstico da síndrome da
apneia obstrutiva do sono (SAOS), e as anormalidades respiratórias
consistem de períodos de aumento do esforço respiratório, fragmentação do sono, presença de eventos respiratórios relacionados
ao despertar e presença de achatamento da curva respiratória, o que
indica limitação ao fluxo aéreo. Controvérsias existem em relação
à caracterização da síndrome da resistência da via aérea superior,
como sendo parte de um contínuo com outros distúrbios de sono
ou como uma entidade clínica distinta que não necessariamente
progride à síndrome da apneia obstrutiva do sono. O tratamento
da síndrome da resistência da via aérea superior é mais desafiante
do que o da síndrome da apneia obstrutiva do sono, uma vez que os
pacientes têm menor tolerância ao uso do CPAP (continuous positive
air pressure). Outras modalidades de tratamento tem sido investigadas, contudo, a resposta a estas modalidades não esta totalmente
estabelecida para a prática clínica. O reconhecimento da síndrome
da resistência da via aérea superior é importante, uma vez que pode
prevenir consequências a longo prazo para formas mais graves de
distúrbios respiratórios do sono.
Palavras-chave: resistência das vias respiratórias; polissonografia; eletroencefalografia; apnéia do sono tipo obstrutiva; respiração
com pressão positiva; nível de alerta; respiração.
INTRODUCTION
The upper airway resistance syndrome (UARS) is a sleeprelated breathing disorder characterized by clinical signs
and symptoms, including daytime sleepiness and/or fatigue, and increased upper airway resistance associated
with frequent arousals and sleep fragmentation. In 1993,
the term ‘upper airway resistance syndrome’ was first
Study carried out at the Departamento de Psicobiologia of Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brasil.
1
Disciplina de Medicina e Biologia do Sono no Departamento de Psicobiologia da Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brasil.
2
Stanford Sleep Disorders Center, Redwood City, CA, US.
Financial support: This work was supported by grants from the Associação Fundo de Incentivo à Psicofarmacologia (AFIP), Fundação de Amparo à Pesquisa do Estado
de São Paulo (FAPESP), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Corresponding author: Luciana Palombini – Rua Napoleão de Barros, 925 – CEP 04024-002 – São Paulo (SP), Brazil – E-mail: [email protected]
Received: April 11, 2011 – Accepted: May 16, 2011
Sleep Sci. 2011;4(2):72–78
Palombini L, Lopes M, Tufik S, Guilleminault C, Bittencourt LR
used, by Guilleminault et al.1, to describe a subgroup of
patients with conditions that were formerly diagnosed as
idiopathic hypersomnia or central nervous system (CNS)
hypersomnia. These terms were used to describe excessive
daytime sleepiness (EDS), without a clear cause defined
by the nocturnal polysomnography (PSG) or the multiple
sleep latency test (MSLT). Patients with the UARS demonstrated repetitive increased upper airway resistance episodes defined by increasingly negative inspiratory esophageal pressure (Pes), which occurred concomitantly with
decreased oronasal airflow in the absence of frank apneas
or oxygen desaturation. These episodes were brief, typically lasting one or three breaths, and resulted in brief
electroencephalograms (EEG) arousals (from two to four
seconds), followed immediately by decreased upper airway resistance. Since this initial description, several studies have been published demonstrating the importance of
recognizing UARS.
Some consider UARS as part of a spectrum that includes benign snoring, obstructive hypopnea, obstructive
sleep apnea, and hypoventilation. Others consider the
UARS as a distinct entity, since it presents some differences in the clinical presentation and different aspects of
the pathophysiology. Furthermore, the progression from
UARS to obstructive sleep apnea syndrome (OSAS) is
questionable, and there is no data on follow-up to demonstrate the evolution of this condition.
The UARS was described as part of the efforts to describe a generally unrecognized patient population that is
nonobese and whose clinical features do not match those
reported with OSAS. Unfortunately, many sleep breathing abnormalities are still ignored due to the belief that
sleep-disordered breathing is synonymous with OSAS
and patients must be overweight or clearly obese with a
large neck.
Today, more than a decade later after the former initial
description, patients with UARS are often not recognized
and not treated. These patients come to the sleep clinic
complaining of daytime sleepiness or fatigue and have a
PSG, which do not demonstrate the presence of OSAS.
Symptoms such as fatigue, lack of energy, irritability
and decreased memory and concentration presented by
these patients may be labeled as depression or as related
to stress. PSG patterns indicating increased upper airway
resistance are frequently missed. These patients are misinterpreted as not having a sleep-related breathing disorder, treatment is not indicated, and they are told to come
back on the future for a follow-up.
UARS need to be suspected by every sleep specialist,
so patients can get early treatment and prevent long-term
consequences.
PATHOPHYSIOLOGY
The UARS pathophysiology is considered similar to OSAS
in some aspects. However, some aspects indicating UARS
as a different entity with different pathophysiology have
been suggested by some studies. One aspect is regarding
different upper airway responses. It has been demonstrated that OSAS and UARS present differences regarding
presence or absence of neurogenic lesions, caused by frequent trauma related to abnormal breathing. Data from
Friberg2 provided evidence of local neurogenic lesions of
the upper airway in OSAS, and these lesions are associated with slowing of impulse conduction3. Afifi et al.4
demonstrated that OSAS present an abnormal response to
respiratory-related evoked potentials, indicating a specific dampening of cortical processing of inspiratory effort
related information. They concluded that OSAS patients
present neurogenic lesions in the pharynx and upper larynx that interfere with normal control of the upper airway
patency, which leads to apneas and hypopneas caused by
an abnormal balance between intrathoracic effort and upper airway muscle contractions, created by local sensory
impairment. Some studies have demonstrated that UARS
patients do not present these local destructions5.
The authors suggested that OSAS and UARS may
have different pathophysiology with the following conception: the blunting or elimination of sensory input
from the upper airway predispose muscle tone to many
challenges and this lead to a narrow upper airway at the
onset of the inspiration, leading to airway collapse. In
UARS, however, the absence of neurogenic lesions in the
upper airways and the persistence of sensory input lead
to a faster arousal and changes, despite the presence of a
narrow airway related to anatomical changes at the point
with a variable location, from the external valve of the
nose to the base of the tongue6.
Differences on the impact and changes observed on the
autonomic nervous system (ANS) have also been demonstrated between OSAS and UARS patients. In the OSAS,
there is a hyperactivity of the sympathetic tone related
to oxygen saturation drops and arousals. UARS subjects
present an inhibition of sympathetic tone7 related to abnormal inspiratory effort associated with increased airway
resistance. The release of the vagal tone is responsible for
the observation of mild orthostatism and vagal dominance, during sleep.
In summary, the UARS have upper airway reflexes
intact during wake and sleep, while they are impaired
in OSAS. Furthermore, in OSAS, the presence of repetitive SaO2 drops excite the sympathetic tone during sleep,
leading to progressive sympathetic tone resetting and hyperactivity, a response that is not present in UARS.
Sleep Sci. 2011;4(2):72–78
73
74
Upper airway resistance syndrome
CLINICAL PRESENTATION
By definition, UARS patients have daytime sleepiness or
fatigue. Initial studies in adults8 included only men; it
was later recognized that the syndrome was also present in
women, with a roughly equal gender distribution1. Contrary to what is seen in OSAS patients, UARS patients
are typically nonobese, with body mass index (BMI) ≤25
kg/m21,8. They are also frequently younger than OSAS patients.
Patients with UARS have symptoms that overlap with
OSAS patients, but recent studies showed some clinical
differences9. Chronic insomnia tends to be more common
in patients with UARS, and many of them report nocturnal awakenings and difficulty in falling back to sleep.
They often complain of sleep onset and maintenance insomnia, which is thought to be due to “conditioning”,
as a consequence of frequent sleep disruptions10. Other
presentation includes parasomnias, such as sleepwalking
and sleep terrors, myialgia, depression, and anxiety. Gold
et al. emphasized that UARS patients have complaints
more related to functional somatic complains, such as
headaches, sleep-onset insomnia, and irritable bowel syndrome. Their patients had polysomnographic findings of
UARS11. It is frequent that UARS is misinterpreted as
chronic fatigue syndrome, fibromyalgia, or as psychiatric disorders, such as attention deficit disorder/attention
deficit hyperactivity disorder (ADD/ADHD)12. Patients
refer cold hands and feet. Some of them refer lightheadness or tendency to faint upon standing abruptly. This
last complaint may be explained by the finding that lowblood pressure (BP) (SBP<100 mmHg) is more commonly associated with UARS13, whereas hypertension is more
commonly associated with OSAS (Table 1).
PHYSICAL EXAMINATION
Clinical examination shows low-BP in about one-fourth
of subjects, often associated with worsening during orthostatic maneuvers13,14. The physical examination needs
to include evaluation of the nose, maxilla, mandible, and
soft tissues.
Upper airway examination frequently shows craniofacial abnormalities including low soft palate, long uvula,
increased overbites, and high, narrow and hard palate.
Despite the differential clinical features, it is sometimes difficult to dissociate patients with UARS from
those with mild OSAS, based on symptoms and clinical
signs alone. Diagnosis can only be confirmed by PSG.
PSG
Patients with UARS have symptoms related to daytime
alertness impairment associated with PSG parameters,
Sleep Sci. 2011;4(2):72–78
Table 1. Most important clinical aspects of UARS compared to OSAS.
Aspects
UARS
OSAS
Age
Young
Children, middle age men
Menopausal woman
Gender
1:1
2:1
Sleep onset
Insomnia
Fast
Snoring
Common
Almost always
Apneas
Absence
Frequent
Daytime
Tiredness
Daytime
symptoms
Fatigue
sleepiness
BMI
Normal
Increased
Somatic
Fibromialgia,
Rare
complaints
headache
ANS
Cold extremities
Rare
symptoms
fainting
BP
Low or normal
High
BMI: body mass index; ANS: autonomic nervous system; BP: blood
pressure.
indicating increase in upper airway resistance. They also
must have an indication of increased upper airway resistance and respiratory effort during sleep, in the absence of
apneas/hypopneas criteria that fulfill OSAS criteria.
Increased respiratory effort during sleep in UARS patients was initially described using an esophageal pressure
monitoring, and it still is considered the gold-standard of
diagnosis1. The use of a pediatric feeding catheter instead
of a balloon has made the procedure better tolerable in
adults15. Three abnormal patterns indicative of increased
respiratory effort during sleep have been described; Pes
crescendo, sustained continuous respiratory effort, and Pes
reversal16.
Airflow limitation is defined by an increase in respiratory effort without the increase in airflow, it is also an
indication of upper airway initial decrease in area. The
development of a plateau on the inspiratory flow signal
from a nasal cannula can also be used as a marker of increased upper airway resistance and flow limitation and,
hence, may be used to indicate presence of periods of increased resistance17. Flow limitation will appear as a ‘flattening’ of the normal bell-shape curve of normal breath,
with a drop in the amplitude of the curve by 2 to 29%
compared to the normal breaths immediately preceding.
The nasal cannula/pressure transducer is more sensitive
than thermistor in picking up respiratory changes and
detecting flow limitation, which is demonstrated in respiratory event related arousal (RERAs) (term defined by
AASM to describe flow limitation leading to arousal).
However, sensitivity comparable with Pes measurement
has not been demonstrated.
UARS patients have nocturnal PSG with normal apnea hypopnea index (AHI), no significant oxygen desaturation and presence of flow limitation during sleep, as
Figure 1. RERA example with increased respiratory effort leading to
an arousal.
well as other non apnea hypopnea respiratory events. The
American Academy of Sleep Medicine (AASM) task force
for sleep-related breathing disorders defined the term
RERA to describe events involving the increased respiratory effort and arousal (Figure 1). The event must fulfill
the criterion for an abnormal breathing pattern indicated
by a progressively more negative esophageal pressure or
flattening of the respiratory curve, which last ten seconds
or longer leading to an arousal.
Other noninvasive markers of increased upper airway
resistance have been proposed, such as: brief arousals accompanying increasing snoring intensity, beat to beat BP
measurement18, forced oscillation technique19 pulse transit time (PTT)20, and respiratory inductive plethismography21. Although other respiratory measurements have
been investigated, the measurement of esophageal pressure remains the gold-standard for detecting increase in
respiratory effort.
It has also been demonstrated that, in UARS patients,
clinical complaints of fatigue and sleepiness are associated with sleep instability. UARS is a subtype of SDB,
which is strongly associated with daytime complaints
and sleep disruption22. UARS patients have an increase
in alpha EEG rhythm during sleep23, which is correlated
with low-arousal threshold16. Typically, an arousal can occur associated with flow limitation and abnormal increase
in respiratory efforts during sleep. These patients have
peaks in Pes measured around -33±7 cm H2O, in 1993.
However, it is often observe Pes reversal (normalization of
Pes) without classic ASDA arousal in the end of event (in
2000)24. Flow limitation in nasal cannula can be associated with EEG changes25. Cyclic alternant pattern (CAP)
in NREM sleep has been described as a new marker of
sleep instability and sleep disruption in adults with several sleep disorders26. This pattern was increased in severe OSAS patients and it was decreased after continuous
positive air pressure (CPAP) treatment of OSA patients26.
UARS is associated with sleep disruption and insomnia
complaints. Parrino et al. have been calling the insomnia
as an internal noise that has an increase in CAP rate in
NREM sleep. UARS patients have also an internal noise
associated with increase in respiratory effort. The analyses
of CAP have been showing that there is sleep instability
in NREM sleep in UARS patients27
The MSLT helps to objectively confirm the subjective
symptom of EDS28. But, often, the MSLT scores are not
very demonstrative. Similarly, the Epworth Sleepiness
Scale may not provide a valid impression, and fatigue and
visual analog scales have been better tools to investigate
the UARS.
CONSEQUENCES
Daytime sleepiness
The increased respiratory effort, due to increased upper
airway resistance during sleep, leads to increased arousals lasting only seconds29, heading to sleep fragmentation and daytime sleepiness. However, often subjects will
complain more of daytime fatigue, or difficulty to concentrate. The level of negative intrathoracic pressure is
the most likely stimulus for arousal, possibly mediated
by the mechanoreceptors in the upper airway and chest
wall.
Disrupted nocturnal sleep and complaint of
‘insomnia’
Subjects may perceive more the repetitive arousal and
nocturnal disruption and may develop conditioning secondary to arousal during sleep with fear of poor sleep. If
left untreated, the pattern may be one of ‘insomnia’ with
nocturnal arousal, and if secondary conditioning occurs,
long sleep latency may give a mixed presentation. The
association between insomnia and sleep disorders breathing (SDB) is another important subject. The interaction
between insomnia and SDB has been important to better understand the arousal ability process, which can be
an important differential factor to recognize subtypes of
SDB.
Effect on blood pressure
Several studies have established the association between
OSAS and hypertension30,31. A positive correlation between chronic loud snoring and stroke or hypertension
has been reported. Patients with UARS have a higher risk
for abnormal BP control32. A review by Silverberg and
Oksenberg32 showed 30 to 40% incidence of OSAS and
30 to 75% incidence of nonapneic snoring in hypertensive
individuals. In a study by Guilleminault33, 110 UARS
patients were evaluated using 48-hour continuous amSleep Sci. 2011;4(2):72–78
75
76
bulatory BP monitoring, before and after treatment with
nasal CPAP. Five out of six subjects used CPAP on a regular basis and their chronic borderline BP was completely
controlled. No changes were seen in the sixth subject who
discontinued his CPAP after three days. In another group
of seven normotensive subjects, continuous radial artery
BP recording was obtained during sleep along with PSG
recording. Increased systolic and diastolic were observed
during the breaths with the greatest inspiratory effort,
even though there was no associated oxygen desaturation.
A further increase was seen accompanying the arousals.
Three of these subjects underwent echocardiography during sleep, which demonstrated a leftward shift of the intreventricular septum with pulsus paradoxus at the time
that the peak end-expiratory pressure was more negative
than -35 cm H2O.
Similar BP changes have been observed by Lofaso et
34
al. . The authors concluded that undetectable arousals
were occurring during these events, and it was the autonomic response to arousal that led to BP rise rather than
changes in intrathoracic pressure or intraventricular septal shift. The exact mechanism is still debated. It is likely
that both arousal and homodynamic factors are involved
in BP changes.
There is also a subgroup of UARS individuals that the
BP may be in fact lower than normal. The presence of orthostatic hypotension and intolerance with cold extremities and dizziness at standing upright was documented in
these patients13. The authors hypothesized that subjects
with sleep-disordered breathing, who do not suffer recurrent hypoxemia (UARS), have repetitive episodes of
systemic hypotension that eventually lead to sympathetic
nerve dysfunction. In contrast, subjects with sleep-disordered breathing, who suffer hypoxemia (OSAS), have
repetitive pressure responses that eventually lead to daytime hypertension.
TREATMENT
In the original description of UARS, by Guilleminault
et al., in 1993, patients were successfully treated with
nasal CPAP. It was used to confirm the diagnosis and to
document potential improvement. CPAP was titrated to
achieve a Pes pressure of less than -7 cm H2O. Although
most subjects initially accepted it, 98% rejected it as a
log-term treatment modality35. Rausher et al. studied the
effect of CPAP in patients with RDI <5 and with symptoms of snoring and arousal index of 20±10/hr. However,
esophageal pressure was not followed-up in this study.
Out of 11 patients, only 19% accepted the treatment,
with a mean daily use time at six months of 2.8±1.5 h. As
expected, 73% of those who used it reported a decrease in
Sleep Sci. 2011;4(2):72–78
daytime sleepiness. The criteria that could predict CPAP
compliance could not be determined36. Thus, data suggest that CPAP is an effective form of therapy, but the
compliance rate is unfortunately poor.
Recent studies have demonstrated that adding cognitive behavioral therapy (CBT) to CPAP treatment is beneficial for patient’s chronic insomnia or psychosomatic
symptoms secondary to UARS37.
Septoplasty and radiofrequency reduction of enlarged
nasal inferior turbinates can be successful in treating
UARS. But, often, anatomical abnormalities involve
soft tissue in soft palate and the maxilla and mandible
skeletal structures. Correction absence of primary cause
of the abnormal breathing, such as crowded airway and
narrow jaw, will leave patients untreated and potentially
may lead to develop local neuropathy and occurrence of
OSAS. The classical surgical procedures have been considered too aggressive to treat UARS. Uvulo-flap as well
as distraction osteogenesis have been helpful for management of UARS38.
Orthodontic approaches, such as rapid maxillary distraction, which are conveniently performed in children
and teenagers, are not directly applicable in adults. This is
due to complete ossification of the maxilla and mandible.
In adults, midline incisions of the maxilla and mandible
are necessary prior to the placement of internal jaw distractors. Distraction osteogenesis applied to sleep-related
breathing disorders showed promising clinical improvement. This combined surgical and orthodontic treatment
is much less invasive than traditional jaw advancement
surgery. However, patients are required to wear braces
for an extended time after jaw expansion for orthodontic
purposes.
Oral appliances can achieve satisfactory outcomes in
UARS39. Further well-documented studies are required,
before the exact role of surgery and oral appliances in
UARS patients can be established.
In summary, UARS treatment may be more demanding than OSAS, as patients usually tolerate nasal CPAP
less and become quickly noncompliant. Treatment of the
underlying causes of the upper airway anatomical problems is the usual approach, which may consist on aggressive treatment of nasal allergies, usage of palatal soft
tissue surgery, orthognatic surgery, or the use of dental
devices.
CONCLUSIONS
UARS has been increasingly recognized, but it is still not
part of the routine in clinical practice in sleep centers,
and several patients remained untreated. The early nonrecognition in life of the syndrome and the anatomical
abnormalities surrounding the upper airway responsible
for the symptoms will probably lead to complications and
perhaps even development of OSAS. Considering that the
prevention is much less costly to society than the syndrome’s treatment with permanent lesions, recognition
and treatment of UARS should also be a priority.
REFERENCES
1. Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A
cause of excessive daytime sleepiness. The upper airway resistance syndrome. Chest. 1993;104(3):781-7.
2. Friberg D. Heavy snorer’s disease: a progressive local neuropathy. Acta Otolaryngol. 1999;119(8):925-33.
3. Mackenzie RA, Skuse NF, Lethelean AF. A micro-electrode
study of periphereal neuropathy in man. Part 2. Response to
conditioning stimuli. J Neurosci. 1997;34(2):175-89.
4. Afifi L, Guilleminault C, Colrain IM. Sleep and respiratory
stimulus specific dampening of cortical responsiveness in
OSAS. Respir Physiol Neurobiol. 2003;136(2-3):221-34.
5. Guilleminault C, Li K, Chen NH, Poyares D. Two-point palatal discrimination in patients with upper airway resistance
syndrome, obstructive sleep apnea and normal control subjects. Chest. 2002;122(3):866-70.
6. Bao G, Guilleminault C. The upper airway resistance syndrome
– one decade later. Curr Opin Pulm Med. 2004;10(6):461-7.
7. Guilleminault C, Poyares D, Rosa A, Huang YS. Heart rate
variability, sympathetic and vagal balance, and EEG arousals in upper airway resistance syndrome and mild OSA. Sleep
Med. 2005;6(5):451-7.
8. Guilleminault C, Stoohs, Duncan S. Snoring I. Daytime sleepiness in regular heavy snorers. Chest. 1991;99(1):40-8.
9. Guilleminault C, Bassiri A. Clinical features and evaluation of
obstructive sleep apnea-hypopnea syndrome and the upper airway resistance syndrome. In: Kryger MH, Roth TH, Dement
WC, editors. Principles and practice of sleep medicine. 4th
edition. Philadelphia: WB Saunders; 2005. p. 1043-52.
10.Guilleminault C, Palombini L, Poyares D, Chowdhuri S. Chronic insomnia, premenopausal women and sleep disordered breathing: part 2. Comparison of nondrug treatment trials in normal
breathing and UARS post menopausal women complaining of
chronic insomnia. J Psychosom Res. 2002;53(1):617-23.
11.Gold AR, Dipalo F, Gold MS, O’Hearn D. The symptoms and
signs of upper airway resistance syndrome: a link to functional
somatic syndromes. Chest. 2003;123(1):87-95.
12.Lewin DS, Di Pinto M. Sleep disorders and ADHD: shared and
common phenotypes. Sleep. 2001;27(2):188-9.
13.Guilleminault C, Faul JL, Stoohs R. Sleep-disordered
breathing and hypotension. Am J Respir Crit Care Med.
2001;164(7):1242-7.
14.Guilleminault C, Khramtsov A. Upper airway resistance syndrome in children: a clinical review. Semin Pediatr Neurol.
2001;8(4):207-15.
15.Epstein MD, Chicoine SA, Hanumara RC. Detection of upper
aiwrway resistance syndrome using a nasal cannula/pressure
transducer Chest. 2000;117(4):1073-7.
16.Guilleminault C, Poyares D, Palombini L, Koester U, Pelin Z,
Balck J. Variability of respiratory effort in relationship with
sleep stages in normal controls and upper airway resistance
syndrome patients. Sleep Med. 2001;2(5):397-405.
17.Ayap I, Norman RG, Krieger AC, Rosen A, O’Malley RL,
Rapoport DM. Non-invasive detection of respiratory effort-related arousals (RERAs) by a nasal cannula/pressure transducer.
Sleep. 2000;23(6):763-71.
18.Pitsom DJ, Stradling JR. Value of beat-to-beat blood pressure
changes, detected by pulse transit time, in the management
of obstructive sleep apnea/hypopnea syndrome. Eur Respir J.
1998;12(3):685-92.
19.Farré R, Montserrat JM, Navajas D. Noninvasive monitoring o respiratory mechanics during sleep. Eur Respir J.
2004;24(6):1052-60.
20.Guilleminault C, Poyares D, Rosa A, Huang YS. Heart rate
variability, sympathetic and vagal balance and EEG arousals in
upper airway resistance, syndrome and mild obstructive sleep
apnea. Sleep Med. 2005;6(5):41-7.
21.Loube DI, Andrada T, Howard RS. Accuracy of respiratory inductive pletismography for the diagnosis of upper airway resistance syndrome. Chest. 1999;115(5):1333-7.
22.Guilleminault C, Poyares D. Arousal and upper airway resistance syndrome. Sleep Med. 2002;3 Suppl 2:S15-20.
23. Black J, Guilleminaul G, Colrain IM, Carrillo O. Upper airway resistance syndrome. Central electroencephalographic
power and changes in breathing effort. Am J Respir Crit Care
Med. 2000;162(2 Pt 1):406-11.
24.Black JE, Guilleminault C, Colrain IM, Carrillo O. Upper airway resistance syndrome. Central and eletroencephalographic
power and changes in breathing effort. Am J Respir Crit Care
Med. 2000;162(2 Pt 1):406-11.
25.Chervin RD, Burns JW, Subotic NS, Roussi C, Thelen B, Ruzicka DL. Correlates of respiratory cycle-related EEG changes in children with sleep-disordered breathing effort. Sleep.
2004;27(1):116-21.
26.Terzano MG, Parrino L. Clinical applications of cyclic alternating pattern. Physol Behav. 1993;54(4)807-13.
27.Guilleminault C, Lopes MC, Hagen CC, da Rosa A. The cyclic
alternating pattern demonstrates increased sleep instability
and correlates with fatigue and sleepiness in adults with upper
airway resistance syndrome. Sleep. 2007;30(5):641-7.
28.Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR,
Keenan S. Guidelines for the multiple sleep latency test (MSLT): a
standard measure of sleepiness. Sleep. 1986;9(4):519-24.
29.American Sleep Disorders Association. EEG arousals: scoring
rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep. 1992;15(2):173-84.
30.Budhiraja R, Sharief I, Quan SF. Sleep-disordered breathing
and hypertension. J Clin Sleep Med. 2005;1(4):401-4.
31.Caples SM, Garcia-Touchard A, Somers VK. Sleep-disordered
breathing and cardiovascular risk. Sleep. 2007;30(3):291303.
32.Silverberg D, Okensberg A. Essential hypertension and
abnormal upper airway resistance during sleep. Sleep.
1997;20(9):806-11.
33.Guilleminault C, Stoohs R, Shiomi T, Kushida C, Schnittger I. Upper airway resistance syndrome, nocturnal blood
pressure monitoring, and borderline hypertension. Chest.
1996;109(4):901-8.
Sleep Sci. 2011;4(2):72–78
77
78
34.Lofaso F, Coste A, Gilian L, Harf A, Guilleminault C, Goldenberg F. Sleep fragmentation as a risk factor for hypertension in
middle-aged nonapneic snorers. Chest. 1996;109(4):896-900.
35.Guilleminault C, Kim YD, Stoohs R. Upper airway resistance syndrome. Oral Maxillofacl Surg Clin North Am. 1995;7: 243-56.
36.Raucher H, Formaneck D, Zwick H. Nasal continuous positive
pressure for noapneic snoring? Chest. 1995;107(1):58-61.
37.Guilleminault C, Palombini L, Poyares D, Chowdhuri S.
Chronic insomnia, premenopausal women, and sleep dis-
Sleep Sci. 2011;4(2):72–78
ordered breathing. Part 2: Comparison of nondrug treatment trials in normal breathing and UARS post-menopausal
women complaining of chronic insomnia. J Psychosomat Res.
2002;53(1):617-23.
38.Guilleminault C, Li KK. Maxillomandibular expansion for the
treatment of sleep-disordered breathing: preliminary result.
Laryngoscope. 2004;114(5):893-6.
39.Yoshida K. Oral device therapy for the upper airway resistance
syndrome patients. J Prosthet Dent. 2002;87(4):427-30.
79
Authors instructions
SCOPE AND POLICY
The SLEEP SCIENCE journal (ISSN 1984-0659 print version) published
every three months, is the official organization of Associação Brasileira
de Sono (ABS) and Federação Latino-Americana de Sociedades de Sono
(FLASS) for publication of scientific papers concerning sleep, chronobiology, and related topics.
After being approved by the Editorial Board, all articles will be evaluated by two or three qualified reviewers, and confidentiality will be preserved throughout the review process. Articles that fail to present merit,
have significant errors in methodology or are not in accordance with the editorial policy of the journal will be directly rejected by the Editorial Board,
with no recourse. Original manuscripts, those that have not been published
elsewhere except in abstract form, on any aspect of sleep will be considered.
The accuracy of all concepts presented in the manuscript is the exclusive responsibility of the authors. The journal reserves the right to make stylistic,
grammatical and other alterations to the manuscript. Manuscripts must
not be concurrently submitted to any other publication, print or electronic.
Articles may be written in Portuguese, Spanish or English.
Papers should state that the protocol has been approved by the Ethics Committee of the Institution where the research was carried out. All
studies involving human subjects should inform that written consent has
been obtained from all subjects (individually).
PRESENTATION AND SUBMISSION OF MANUSCRIPTS
It is requested that the authors strictly follow the editorial guidelines of
the journal, particularly those regarding the maximum number of words,
tables and figures permitted, as well as the rules for producing the bibliography. Failure to comply with the author instructions will result in the
manuscript being returned to the authors so that the pertinent corrections
can be made before it is submitted to the reviewers. Special instructions apply to the preparation of Special Supplements and Guidelines, and authors
should consult the instructions in advance by visiting the homepage of the
journal.
Abbreviations should be used sparingly and should be limited only to
those that are widely accepted. All abbreviations should be defined at first
use.
The following rules were based on the standard proposed by the International Committe of Medical Journal Editors (ICMJE) and published in the article Uniform Requirements for Manuscripts Submitted to Biomedical Journals, updated in October 2009, and available from: http://www.icmje.org/
MANUSCRIPT FORMAT
This journal publishes contributions in the following categories:
Original Articles: each manuscript should clearly state its objective
or hypothesis; the design and methods used (including the study setting
and time period, patients or participants with inclusion and exclusion criteria, or data sources and how these were selected for the study; the essential features of any interventions; the main outcome measures; the main
results of the study, and a section placing the results in the context of published literature.The text should be divided into separate sections (Introduction, Material and Methods, Results, Discussion), without a separate
for conclusions. The text (excluding the title page, abstracts, references,
tables, figures and figure legends) should consist of 2,000 to 3,000 words;
table and figures should be limited to a total of 5 and 40 references.
Authors should state in the cover letter that the manuscript is intended to be a full-length paper.
Short Communication: a short communication is a report on a single
subject which should be concise but definitive. This scope of this section is
intended to be wide and to encompass methodology and experimental data on
subjects of interest to the readers of the journal. The text should not exceed 12
pages double-spaced, typed in 23 line each, have a maximum of two figures
or tables (or one of each) and 20 references. Authors should state in the cover
letter that the manuscript is intended to be a Short-Communication.
Review Article: a review article should provide a synthetic and critical analysis of a relevant area and should not be merely a chronological
description of the literature. The text may be divided into sections with
appropriate titles and subtitles. The text should not exceed 5,000 words,
excluding references and illustrations (figures or tables). The number of
illustrations should not exceed 8 and 60 references.
The authors should state in the cover letter that the manuscript is
intended to be a Review Article.
Case Report: a case report should have at least one of the following
characteristics to be published in the journal: of special interest to the
clinical research community; a rare case that is particularly useful to demonstrate a mechanism or a difficulty in diagnosis; new diagnostic method;
new or modified treatment; a text that demonstrates relevant findings and
is well documented and without ambiguity.
Case Reports should not exceed 1,500 words, excluding title page,
abstract, references and illustrations. The number of references should not
exceed 20.
Overview: an Overview does not contain unpublished data. It presents the point of view of the author(s) in a less rigorous form than in a
regular review or mini-review and is of interest to the general reader. The
text should not exceed 5,000 words, excluding references and illustrations
(figures or tables). The number of illustrations should not exceed 8 and
60 references.
MANUSCRIPT PREPARATION
The title page should include the title in English and in Portuguese; a
running title to be used as a page heading, which should not exceed 60
letters and spaces; the full names and institutional affiliations of all authors; complete address, including telephone number, fax number and
e-mail address, of the principal author; and a declaration of any and all
sources of funding.
Abstract: The abstract should present the information in such a way
that the reader can easily understand without referring to the main text.
Abstracts should not exceed 250 words. Abstracts should be structured
as follows: Objective, Methods, Results and Conclusion. Abstracts for review articles and case reports may be unstructured.
Abstracts for Short Communications and Case Reports should not
exceed 100 words and should not be structured.
Keywords: Three to six keywords in English defining the subject of
the study should be included.
Tables and Figures: All tables and figures should be in black and white,
on separate pages, with legends and captions appearing at the foot of each.
All tables and figures should be submitted as files in their original format.
Tables should be submitted as Microsoft Word files, whereas figures should
be submitted as Microsoft Excel, .tiff or .jpg files. Photographs depicting
surgical procedures, as well as those showing the results of exams or biopsies,
in which dying and special techniques were used will be considered for publication in color, at no additional cost to the authors. Dimensions, units and
symbols should be based on the corresponding guidelines set forth by the AsSleep Sci. 2011;4(2):79–38
80
sociação Brasileira de Normas Técnicas (ABNT, Brazilian Association for the
Establishment of Technical Norms), available from: http://www.abnt.org.br.
Legends: Legends should accompany the respective figures (graphs,
photographs and illustrations) and tables. Each legend should be numbered with an Arabic numeral corresponding to its citation in the text.
In addition, all abbreviations, acronyms, and symbols should be defined
below each table or figure in which they appear.
References: References should be listed in order of their appearance
in the text and should be numbered consecutively with Arabic numerals.
The presentation should follow the Vancouver Style, updated in October
of 2004, according to the examples below. The titles of the journals listed
should be abbreviated according to the style presented by the List of Journals
Indexed in the Index Medicus of the National Library of Medicine, available
at: http://www.ncbi.nlm.nih.gov/entrez/journals/loftext.noprov.html.
A total of six authors may be listed. For works with more than six
authors, list the first six, followed by ‘et al.’.
12];102(6):[about 3 p.]. Available from: http://www.nursingworld.org/
AJN/2002/june/Wawatch.htm
Homepages/URL
8. Cancer-Pain.org [Internet]. New York: Association of Cancer Online
Resources, Inc., c2000-01 [updated 2002 May 16; cited 2002 Jul 9].
Available from: http://www.cancer-pain.org/
Others situations
In other situations not mentioned in these author instructions, the recommendations given by the ICMJE should be followed, specifically those
in the article Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication (Updated October 200 9), available from: http://www.icmje.org/. Additional
examples for special situations involving references can be obtained at:
www.nlm.nih.gov/bsd/uniform_requirements.html
Examples:
Journal articles
1. Tufik S, Lindsey CJ, Carlini EA. Does REM sleep deprivation induce
a supersensitivity of dopaminergic receptors in the rat brain? Pharmacology. 1978;16(2):98-105.
2. Andersen ML, Poyares D, Alves RS, Skomro R, Tufik S. Sexsomnia:
abnormal sexual behavior during sleep. Brain Res Rev. 2007;56:271-82.
Abstracts
3. Moreno CRC, Carvalho FA, Matuzaki LA, Louzada FM. Effects of irregular working hours on sleep and alertness in Brazilian truck drivers
[abstract]. Sleep. 2002;25:399.
Chapter in a book
4. Andersen ML, Bittencourt LR. Fisiologia do sono. In: Tufik S, editor.
Medicina e biologia do sono. São Paulo: Manole; 2007. P. 48-58.
Official publications
5. World Health Organization. Guidelines for surveillance of drug resistance in tuberculosis. 2nd ed. Geneva: WHO; 2003. p. 1-24.
Thesis
6. Bittencourt L. Avaliação davariabilidade do Índice de apnéia e hipopnéia em pacientes portadores da síndrome da apnéia e hipopnéia do sono
obstrutiva [tese]. São Paulo: Universidade Federal de São Paulo; 1999.
Electronic publications
7. Abood S. Quality improvement initiative in nursing homes: the ANA
acts in an advisory role. Am J Nurs [Internet]. 2002 [cited 2002 Aug
Sleep Sci. 2011;4(2):79–38
SUBMISSION OF MANUSCRIPT
The manuscript must be accompanied by a letter signed by all authors,
with permission for publication and a statement that is unprecedented
and has not been submitted for publication in another journal or book.
That letter must include: a) conflicts of interest; b) certificate of approval by the ethics committee of the institution where the research was
carried out when the investigation involves experiments on humans or
animals; c) documentation of the possible sources of funding work; d) a
statement that participants provided signed consent forms, in the case
of medical research on humans; e) letter of transfer of copyright to the
Journal Sleep Science.
Important note: the journal Sleep Science in support of policies for the
registration of clinical trials of the World Health Organization (WHO)
and the ICMJE, recognizing the importance of such initiatives for recording and promoting international information on clinical studies, open access, will only accept for publication from August 2009 articles of clinical
research that have received an identification number to one of the Clinical
Trial Registry validated by the criteria established by WHO and ICMJE,
available from: http://clinicaltrials.gov or the Pubmed website.
All manuscripts submissions for the Sleep Science must be submitted
via e-mail, to [email protected]
Associação Brasileira de Sono – Sleep Science
Rua Marselhesa, 500 – 13º andar – Vl. Clementino
São Paulo, SP – Brazil
CEP 04020-060
Fax: +55 11 5908 7111

SS v4n2.indb - Sleep Science

Transcrição

Documentos relacionados

o passado aqui tão perto

News Wrap

GRUPO 4 - Tipo A

Full text... - Sleep Science

Job satisfaction and sleep quality in nursing

The beneficial effects of massage therapy for insomnia in

BISQ Questionnaire for Infant Sleep Assessment: translation into

Why modeling? Mathematical models of the human

Full text... - Sleep Science

Swallowing in obstructive sleep apnea syndrome