(Transnasal Insufflation) Apnea With an Open

Predictors for Treating Obstructive Sleep
Apnea With an Open Nasal Cannula System
(Transnasal Insufflation)
Georg Nilius, Thomas Wessendorf, Joachim Maurer, Riccardo Stoohs,
Susheel P. Patil, Norman Schubert and Hartmut Schneider
Chest 2010;137;521-528; Prepublished online December 1, 2009;
DOI 10.1378/chest.09-0357
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Original Research
SLEEP MEDICINE
Predictors for Treating Obstructive Sleep
Apnea With an Open Nasal Cannula System
(Transnasal Insufflation)
Georg Nilius, MD; Thomas Wessendorf, MD; Joachim Maurer, MD; Riccardo Stoohs, MD;
Susheel P. Patil, MD, PhD; Norman Schubert, R-PSGT; and Hartmut Schneider, MD, PhD
Background: Obstructive sleep apnea (OSA) is a disorder that is associated with increased morbidity and mortality. Although continuous positive airway pressure effectively treats OSA, compliance is variable because of the encumbrance of wearing a sealed nasal mask throughout sleep. In
a small group of patients, it was recently shown that an open nasal cannula (transnasal insufflation
[TNI]) can treat OSA. The aim of this larger study was to find predictors for treatment responses
with TNI.
Methods: Standard sleep studies with and without TNI were performed in 56 patients with a wide
spectrum of disease severity. A therapeutic response was defined as a reduction of the respiratory
disturbance index (RDI) below 10 events/h associated with a 50% reduction of the event rate
from baseline and was used to identify subgroups of patients particularly responsive or resistant
to TNI treatment.
Results: For the entire group (N 5 56), TNI decreased the RDI from 22.6 6 15.6 to 17.2 6 13.2
events/h (P , .01). A therapeutic reduction in the RDI was observed in 27% of patients. Treatment
responses were similar in patients with a low and a high RDI, but were greater in patients who
predominantly had obstructive hypopneas or respiratory effort-related arousals and in patients
who predominantly had rapid eye movement (REM) events. The presence of a high percentage
of obstructive and central apneas appears to preclude efficacious treatment responses.
Conclusion: TNI can be used to treat a subgroup of patients across a spectrum from mild-to-severe
sleep apnea, particularly if their sleep-disordered breathing events predominantly consist of
obstructive hypopneas or REM-related events but not obstructive and central apneas.
CHEST 2010; 137(3):521–528
Abbreviations: CPAP 5 continuous positive airway pressure; NREM 5 nonrapid eye movement; OSA 5 obstructive
sleep apnea; RDI 5 respiratory disturbance index; REM 5 rapid eye movement; RERA 5 respiratory effort-related
arousal; TNI 5 transnasal insufflation; TST 5 total sleep time
sleep apnea (OSA) is a common disorObstructive
der that is associated with increased morbidity
and mortality.1,2 Continuous positive airway pressure
(CPAP) is the only treatment shown to reduce both
cardiovascular and neurobehavioral morbidities.3,4
Approximately 25% to 50% of patients with OSA will
either refuse or not tolerate the use of CPAP
therapy,5,6 primarily because of the mask and head
gear required for maintaining positive pressure during sleep.7,8 Thus, improvements in nasal interfaces
and overall comfort might improve adherence to
therapy.
Manuscript received February 10, 2009; revision accepted
September 24, 2009.
Affiliations: From the HELIOS-Klinik Hagen-Ambrock Germany (Dr Nilius), University Witten-Herdecke; Ruhrlandklinik
(Dr Wessendorf), Essen, Germany; HNO-Klinik der Universität
(Dr Maurer), Mannheim, Germany; Somnolab (Dr Stoohs), Dortmund, Germany; and the Department of Pulmonary and Critical
Care Medicine (Drs Patil and Schneider, Mr Schubert), Johns
Hopkins University, Baltimore, MD.
Funding/Support: This study was sponsored by Selion Inc.
(HL 72126, P50 HL084945-01).
Correspondence to: Georg Nilius, MD, Ambrocker Weg 60,
58091 Hagen, Germany; e-mail: [email protected]
© 2010 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians (www.chestpubs.org/
site/misc/reprints.xhtml).
DOI: 10.1378/chest.09-0357
www.chestpubs.org
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521
Recently, it has been demonstrated that the transnasal insufflation (TNI) of warm and humidified air
at a flow rate of 20 L/min through an open nasal cannula system led to a therapeutic reduction of the
sleep-disordered event rate in approximately onethird of the patients studied.9 Because of the small
number of patients studied, it was not possible to
determine polysomnographic predictors for treatment
responses.
In the current study, we examined the polysomnographic responses to TNI in a larger clinical sample
of patients. The primary goal of this study was to
identify polysomnographic characteristics on a baseline sleep study that may be used to predict TNI
treatment responses. Because the major mechanism
of action of TNI appears to be through a small
increase in end-expiratory pharyngeal pressure, lower
levels of pressure should be sufficient to alleviate
hypopneas.4,10 We therefore hypothesized that TNI
would have a positive therapeutic effect in patients
with sleep-disordered breathing and that TNI would
be more effective in treating patients who predominantly have hypopneas rather than apneas.
Materials and Methods
The study was conducted under the supervision of the ethics
committees of the Universität Witten-Herdecke and according to
“Good Clinical Practices” and the Declaration of Helsinki.11 In
addition, the study was reviewed and approved by the institutional
review board of each participating center, including the reading
center at the Johns Hopkins Sleep Disorders Center, which
scored all sleep studies and performed the data analysis. Study
procedures, risks, and benefits were reviewed, and written informed
consent was obtained for each participant prior to enrollment in
the study.
Subjects
Recruitment of participants for the study was conducted
at four sleep disorder centers between November 2006 and
August 2007. Participants were eligible if they met all of the following inclusion criteria: (1) a baseline sleep study that demonstrated a total nonrapid eye movement (NREM) and rapid eye
movement (REM) sleep stage respiratory disturbance index
(RDI) of . 5 events per hour, (2) presence of excessive daytime
sleepiness by self-report, (3) clinical criteria for CPAP treatment
according to the standard practice of care of each sleep laboratory, (4) patients had not previously used CPAP in the management of their disease, and (5) a CPAP titration study that
demonstrated a nasal pressure less than the median prescribed
pressure of each laboratory (range of CPAP pressure was from
8-11 cm H2O).
Patients were excluded from participating in the study, if they
had significant comorbidities, including (1) a past surgery of the
nose or pharyngeal structure in the last 12 months or other medical and mechanical treatment of OSA; (2) other sleep-associated
disorders, such as restless leg syndrome, periodic leg movement
disorder, central sleep apnea disorders, or Cheyne-Stokes breathing; (3) lung disorders (COPD) and heart failure; and (4) bleeding
disorders or use of oral anticoagulation medication.
522
Study Materials
Polysomnography: Standard sleep studies were conducted
using the study sites’ local recording platform (Alice [Respironics
Deutschland GmbH & Co. KG; Herrsching, Germany], Rembrandt [Medcare Deutschland GmbH; Wessling, Germany],
Somnologica [Embla Systems GmbH; Munich, Germany], and
Jaeger [VIAASYS Healthcare GmbH; Höchberg, Germany]) according to standard clinical practice of each center and the guidelines
of the German Sleep Medicine Society (Deutsche Gesellschaft
fuer Schlafmedizin). All sleep studies consisted of the following
signals: EEG (montage C3/A2 and C4/A4); right and left electrooculogram; chin, left and right leg electromyogram; a single, bipolar
ECG; oxyhemoglobin saturation by finger pulse oximeter; nasal and
oral airflow monitored by a nasal pressure transducer and an oronasal
thermistor; chest and abdominal excursions by inductive plethysmography or strain gauges; snoring sounds with a neck microphone; and
body position by a mercury gauge and video monitoring.
Recordings were stored in real time (European Data Format) and
sent to a central reading center at the Johns Hopkins Sleep Disorders
Center via an independent study monitoring agency (Marshall
Assoc.; Maxismedical; Frankfurt, Germany). At the reading center,
recordings were first deidentified and formatted to provide uniform
scoring platforms for all studies. Sleep studies were scored by experienced registered polysomnographic technicians who were unaware
of the purpose and hypotheses of the current study. Finally, all scored
sleep studies were reviewed by a Diplomate of American Board of
Internal Medicine, Sleep Medicine (S. P. P.), who was also masked to
the treatment status. Polysomnographic indices were then entered
into a custom-made database after quality assurance assessments
confirmed reliability for scoring and reviewing sleep stages, respiratory events, and respiratory arousals, as previously published.9
Study Protocols
The study protocol consisted of three consecutive nights. Night
1 (baseline sleep study) was used for characterizing standard sleep
and breathing indices off TNI. Night 2 (CPAP titration study) was
used for the stepwise increase in nasal pressure and the observation
of the airflow signal from the built-in pneumotachographs of the
CPAP devices. The effective nasal pressure for CPAP was defined as
the pressure at which inspiratory flow limitation was abolished and a
normal non-flow limited airflow contour ensued during NREM and
REM sleep. On the third night (TNI treatment night), participants
were asked to initiate sleep on 10 L/min on TNI for reasons of comfort. After lights out, TNI was then increased in a ramplike fashion
(automatically) to 20 L/min over a period of 5 to 10 min.
Sleep Study Analysis
Polysomnographic indices were obtained from sleep studies
that had at least 240 min of recording time or 180 min of sleep,
and signal quality of airflow and respiratory effort belts allowed
discerning the type and duration of sleep-disordered respiratory
events. Out of a total of 65 enrolled patients, 56 patients met these
criteria. Sleep stages and arousal were defined according to published criteria.12 Respiratory events were defined as follows:
Obstructive apnea and presence of central sleep apnea was identified
if the airflow was absent or nearly absent for at least 10 s. Hypopnea was identified when there was a . 30% reduction in airflow
that was associated with a decrease in oxyhemoglobin desaturation
of more than 3%. In addition, respiratory effort-related arousals
(RERAs) were identified as a series (more than three breaths) of
flow-limited breaths that demonstrated either a discernible reduction in airflow from baseline of , 30% or an increase in respiratory
effort without concordant increases in airflow that was terminated
by an arousal. Central apnea was identified if the absence of airflow was associated without discernable excursions of either the
Original Research
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chest or abdomen. The RDI was defined as the number of apneas,
hypopneas, and RERAs per hour for NREM, REM, and total
sleep. The predominance of specific events was used to define
three subgroups with mild upper airway obstruction: (1) Patients
with increasing proportions of obstructive hypopneas were identified by the percent rate of hypopneas, which was computed by
calculating the proportions of obstructive hypopneas to all respiratory events (apneas, hypopneas, and RERAs) for each patient
during NREM sleep and creating subgroups of patients with
increasing proportions of hypopneas (. 50%, . 66%, and . 90%
hypopneas, respectively). (2) Patients with a predominance of
RERAs (upper airway resistance syndrome) were identified if
the apnea and hypopnea rate was , 10 events/h and if they had an
RERAs to apnea + hypopnea ratio of . 2:1. (3) Patients with
REM-dependent sleep-disordered breathing had a NREM event
rate of , 10 events/h and a REM-to-NREM event ratio of . 2:1,
as described previously.13,14
Statistical Analysis
The primary outcome of treatment efficacy of TNI was defined
as follows: for individuals with a baseline RDI . 10 events/h, if
the RDI fell more than 50% and below 10 events/h sleep, and for
individuals whose baseline RDI was , 10, if the RDI fell below
five events/h and by more than 50% from baseline. Based on the
findings of the previous study,9 a sample size calculation revealed
that 40 subjects were needed with 80% power and type 1 error of
5% in order to detect a change in RDI of 20 events/h. A paired
Student t test was used to compare the RDI between baseline and
treatment conditions in all sleep states.
In secondary analyses, we examined potential polysomnographic, demographic, and anthropometric factors that might predict a treatment response or nonresponse to TNI. These factors
included the effects of age, sex, BMI, prescribed CPAP pressure,
the proportion of hypopneic events, and central sleep apnea.
To determine whether the treatment responses observed differed from normal night-to-night variability of the RDI, we first
determined the proportion of patients that were effectively treated
for the entire group and for subgroups with increasing proportions of hypopneas (. 50%, . 66%, and . 90% hypopneas,
respectively). Since the treatment night was not randomized, the
observed therapeutic effects of TNI may be attributed to the
expected spontaneous night-to-night variability in sleep apnea
severity. We therefore compared TNI response rates to the reported
night-to-night variability in sleep apnea severity reported in the
study of Stepnowsky et al,15 (13%), using the one-sample test of
proportions. In the subset of patients who predominantly have
REM-related obstructive sleep apnea, the Wilcoxon matchedpairs signed-rank test was used to compare differences between
baseline and treatment condition, because of the nonnormal distribution of the data.
Table 1—Anthropometric and Polysomnographic
Indices at Baseline
Data
Numbers
Sex, male (female)
42 (12)
Age, y
50.5 6 10.4
BMI, kg/m2
28.0 6 3.5
Polysomnographic indices
Prescribed CPAP, cm H2O
7.5 6 1.9
TST, min
332.0 6 65.0
SE, % TST
82.2 6 12.2
N1, % TST
14.0 6 11.8
N2, % TST
56.3 6 12.7
N3, % TST
10.7 6 9.5
REM, % TST
19.0 6 7.0
RDI, events/h
22.6 6 15.6
NREM-RDI, events/h
21.9 6 16.4
REM-RDI, events/h
24.4 6 21.3
Sleep apnea subgroups
Predominance of RERAs (UARS), No. of patients (%)
3 (5)
REM event predominance, No. of patients (%)
11 (20)
26 (46)
Predominance of hypopneas (. 50%), No. of
patients (%)
16 (29)
Predominance of apneas (. 50%), No. of patients (%)
CPAP 5 continuous positive airway pressure; N1 5 sleep stage 1; N2 5
sleep stage 2; N3 5 sleep stage 3; NREM 5 nonrapid eye movement;
RDI 5 respiratory disturbance index; REM 5 rapid eye movement;
RERA 5 respiratory effort-related arousal; SE 5 sleep efficiency; TST 5
total sleep time; UARS 5 upper airway resistance syndrome.
Polysomnographic Responses to TNI
Figure 1 shows mean and individual responses
of the RDI to TNI compared with baseline for
the entire night, and for NREM and REM sleep stages.
On average, TNI led to a slight reduction of the RDI
in NREM, REM, and the entire night, due to heterogeneous response rates between participants.
Although TNI decreased RDI in the majority of
patients, eight participants demonstrated a marked
increase in the RDI (as defined by in increase of more
Results
Subjects
Table 1 shows the anthropometric and polysomnographic characteristics of the baseline sleep study of all
participants. The study population consisted mostly of
men (79%). The majority of patients had obstructive
hypopnea or obstructive apnea, suggesting a moderateto-severe degree of upper airway obstruction, whereas
only a minority had milder degrees of upper airway
obstruction (upper airway resistance syndrome, n 5 3;
or predominant REM events, n 5 11).
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Figure 1. Responses of RDI to TNI. 5 mean ± SD; x 5 example of a single responder (see Figure 2, case 1); * 5 example of
a nonresponder (see Figure 2, case 2); NREM 5 nonrapid eye
movement; RDI 5 respiratory disturbance index; REM 5 rapid
eye movement; TNI 5 transnasal insufflation.
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523
than 10 events/h compared with baseline) due to
positional apneas and technical limitations. (See Limitations in “Discussion” section.)
Figure 2 shows the respiratory pattern at baseline
and on TNI in one patient (see asterisk in Fig 1) who
had a complete resolution of sleep-disordered breathing (Fig 2A) and in another patient (see x in Fig 1)
in whom the RDI increased significantly with TNI
(Fig 2B). In the patient shown in Figure 1A, TNI
abolished inspiratory flow limitation and stabilized
the breathing pattern. In contrast, in the patient shown
in Figure 1B the RDI increased from 20 to 58 events/h
because of a positional effect on sleep apnea severity.
This patient spent considerably more time supine on
the treatment night compared with baseline (43% vs
23% total sleep time [TST], respectively). When
comparing the RDI for the supine position, the RDI
decreased from 72 events/h with 54% apneas to
51 events/h with no apneas. Thus, albeit there was no
clinical efficacious reduction in the RDI, TNI converted apneas to hypopneas.
For the entire group, we observed that TNI led to
a conversion of apneas to hypopneas without increasing the rate of RERAs. Specifically, the percent rate of
apneas to all events (apneas/hypopneas and RERAs)
decreased from 46.3% 6 4.4% to 18.4% 6 4.1%
(P , .05) during REM sleep and 34.4% 6 7.4% vs
27.4% 6 8.1% TST (not significant) during NREM
sleep. The rate of RERAs during NREM and REM
sleep combined was 5.8 6 0.9 events/h at baseline
and 3.9 6 0.5 events/h at treatment night on TNI.
Predictors for Efficacious Responses to TNI
Anthropometric and Clinical Characteristics; Event
Type and Rate: Anthropometric characteristics, including sex, age, BMI, prescribed CPAP pressure, and
baseline polysomnograph, indies, did not differ between
those participants who met our definition for a response
to those who had a suboptimal reduction in the RDI
(see Table 2). Figure 3 shows how polysomnographic
characteristics including sleep apnea severity (Fig 3A),
event type (Fig 3B), and the degree of upper airway
obstruction as defined by the proportion of hypopneas
to all events in percent (Fig 3C) influence the response
rate to TNI. First, we found that RDI did not predict
response rates to TNI (Fig 3A). Second, in the eight
individuals who had .10 % central apneas at baseline
(Fig 3B), none had a positive response rate to TNI. The
response rate was greatest in patients who predominantly had obstructed compared with central events.
Third, a greater hypopnea rate was associated with an
increased response rate in a dose-dependent fashion
(Fig 3C). Although patients who predominantly had
apneas (. 50% of all events) had a low response rate of
18.8% (three of 16 patients), the response rate increased
from 33% (. 50% hypopnea), 38% (. 66% hypopnea),
and to 50% (. 90% hypopnea) with increasing
degrees of hypopneas, respectively. The response rate
to TNI was significantly greater in all patients with
obstructive events (Fig 3B) and all groups independent
of the proportion of hypopneas (Fig 3C) compared with
the expected night-to-night variability in sleep apnea
severity of 13%.15
Figure 2. Respiratory pattern of a responder. (A) Case 1, marked with x in Fig 1. (B) Case 2, a
nonresponder (marked with * in Fig 1). Spo2 (%) 5 oxyhemoglobin saturation. See Figure 1 legend for
expansion of other abbreviations.
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Table 2—Comparison of Anthropometric and Clinical
Data Between Responder and Nonresponder
Variable
Sex, male (female)
Age, y
BMI, kg/m2
Prescribed CPAP,
cm H2O
TST, min
SE, % TST
N1, % TST
N2, % TST
N3, % TST
REM, % TST
RDI, events/h
NREM-RDI,
events/h
Suboptimal Response
Therapeutic Response
34 (7)
50.1 6 10.0
28.4 6 3.1
7.6 6 1.9
15 (5)
51.5 6 11.7
26.8 6 4.3
7.1 6 1.9
334.2 6 69.8
81.0 6 0.1
14.0 6 0.1
58.0 6 0.1
9.0 6 0.1
19.0 6 0.1
21.6 6 15.0
20.9 6 15.1
325.9 6 48.7
84.0 6 0.1
15.0 6 0.2
52.0 6 0.2
14.0 6 0.1
19.0 6 0.1
25.2 6 17.5
24.6 6 19.7
See Table 1 for expansion of abbreviations.
Subgroups With Mild Upper Airway Obstruction:
A predominance of RERAs (upper airway resistance
syndrome) was observed in three individuals at baseline and in six on TNI. The total RDI decreased
in two individuals below five events/h, and the third
developed central apneas on TNI at a rate of
12 events/h, offsetting the reduction in RERAs in individuals with REM-sleep-disordered breathing.
A predominance of REM-sleep-disordered breathing
was observed in 10 individuals at baseline and five
on TNI. As shown in Figure 4A, all but one individual
with REM-sleep-disordered breathing at baseline
reduced the REM RDI on TNI (mean decrease from
24.3 6 2.0 to 11.6 6 2.9 events/h). The nonresponder
slept predominantly on his side during the baseline
sleep study but mostly supine during TNI treatment
night. For this group, 55% had an efficacious decrease
in REM RDI as defined above (Fig 4B). Moreover,
four of the 10 individuals decreased the total RDI
below five events/h.
Discussion
In this study, we confirmed that TNI reduced the
overall sleep-disordered breathing event rate below a
clinically acceptable threshold in approximately onequarter of patients who required CPAP therapy. Our
findings indicate that: (1) Patients with a wide range of
RDI had similar response rates, indicating that treatment responses to TNI are independent of the sleep
apnea disease severity. (2) The response rate was
markedly increased in patients who predominantly
had hypopneas and patients with mild upper airway
obstruction as indicated by a predominance of RERAs
and REM-related events. (3) The presence of . 10%
central apneas predicted poor response. (4) Anthropometric characteristics and the level of prescribed
CPAP pressure did not predict treatment responses.
Thus, TNI treatment responses depend on the severity,
but not the frequency, of upper airway obstruction.
Predictors of Response to TNI
As in our prior TNI pilot study,9 we found that TNI
reduced apneas and hypopneas. The major reason for
decreased RDI can be attributed primarily to the
increase in pharyngeal pressure that is associated with
an increase in the inspiratory airflow.16 At a rate of
20 L/min, TNI increases nasal pressure by approximately 2 cm H2O and increases inspiratory airflow
by approximately 100 mL/s.9 In general, the peak
inspiratory airflow for hypopneas and for flow-limited
breaths averages approximately 150 to 200 mL/s.10
Figure 3. Predictors of efficacious responses to TNI. RERAS 5 respiratory effort-related arousals. See
Figure 1 legend for expansion of abbreviations.
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525
sleep.26 Our current data suggest that response rates
to TNI would also be higher in adults with a predominance of REM-sleep-disordered breathing events.
Predictors of No Response to TNI
Figure 4. TNI efficacy to REM sleep apnea. See Figure 1 legend
for expansion of abbreviations.
The additional flow from TNI, therefore, will increase
the inspiratory airflow to 250 to 300 mL/second, a
level previously associated with stabilization of breathing patterns.10,17,18 In the current study, we did not
quantify airflow; thus, it was not possible to determine whether the individuals with hypopnea who did
not respond had more severe upper airway obstruction
as reflected by reduced levels of inspiratory airflow.
Additional, nonquantifiable factors that may have
contributed to the therapeutic response include the
following: First, small increases in pharyngeal pressure
may have increased lung volume, which may improve
both oxygen stores and upper airway patency.19-21
Second, as ventilation improves during sleep, enhanced
sleep continuity (decreased arousal frequency) may
further stabilize breathing and reduce the RDI.22,23
Finally, additional benefits may have accrued from
insufflating air directly into the nose, producing concomitant reductions in dead space ventilation.
REM Sleep Apnea: TNI was more effective in
improving sleep-disordered breathing in REM sleep
compared with NREM sleep, as indicated by a shift
from apneas to hypopneas for REM events and by
the response rate in individuals with predominant
REM apneas in which all but one patient had a significant reduction in the REM event rate with TNI.
REM sleep is associated with a loss in muscular tone
and a decrease in ventilatory demand. It is possible
that small increases in pharyngeal pressure are more
effective in stabilizing upper airway musculature in
the presence of a hypotonic musculature of the pharynx and chest wall during REM sleep as compared
with a more tonic state in NREM sleep.24,25 Alternatively, TNI might have increased tidal inspiratory volumes and satisfied patient’s ventilatory demand
during REM sleep. Regardless of the mechanism,
our finding is comparable to that of a recently documented study in which a high response rate to TNI
was observed in children if they had predominant
REM events but flow limitation during NREM
526
Patients with predominate obstructive or central
apneas (. 50% apneas to all events) responded poorly
(three of 18, 16.6%) to TNI for several reasons. First,
as noted, inspiratory airflow would be expected to
increase to a maximum of 100 mL/s at a TNI flow rate
of 20 L/min.9 In patients with apnea, such an increase
in airflow would not be enough, would correspond to
hypopneas, and would not eliminate sleep-disordered
breathing altogether.27,28 Second, in patients with a
significant proportion of central sleep apnea, it is possible that the additional airflow from TNI led to an
exaggeration of ventilatory overshoot.22,29 Third, it is
possible the insufflation of air into the nose may have
washed out the anatomic dead space, which may have
reduced CO2 rebreathing and thereby contributed to
the occurrence of central apneas. Further studies are
required to explore possible mechanisms.
Limitations
There are several limitations that merit consideration. First, nine initially enrolled patients were
excluded from the analysis because the sleep studies
did not meet our criteria for study participation as
mentioned in the “Methods” section. We do not
believe that the exclusion affected our results because
insufficient sleep at baseline rather than at TNI nights
was the primary reason for exclusion. Second, our primary intention was to emulate usual clinical care,
which includes changes in body position and displacement of the nasal cannula (which occurred), and thus
the effectiveness of therapy in certain individuals was
underestimated. The major limitation of the study was
the lack of quantification of airflow that might have
helped to predict responses to TNI more accurately.
We predict that patients with RERAs or hypopneas of
at least 150 mL/s would be the most likely to respond
for the reasons noted above.
Additional logistical concerns include the following:
First, we did not determine the night-to-night variability of the RDI in our study population. Instead, we used
reported night-to-night variability in RDI. The therapeutic response rate was twice as high as the 13% one
would anticipate, making polysomnographic responses
to TNI most likely attributable to the mechanisms of
action as discussed above. Second, all patients were
first titrated on CPAP according to clinical standards in
each laboratory. Although a comparison on the efficacy
of CPAP vs TNI would be potentially of interest, it
would have required randomizing TNI and CPAP
nights, which was beyond the scope of the current
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study. Finally, we observed an increase in the RDI in
eight individuals. Increases were related to (1) positional sleep apnea (n 5 5), wherein subjects spent disproportionately more time supine with TNI compared
with the baseline, (2) an inadvertent reduction the TNI
flow rate below 17 L/min (n 5 1), and (3) an increase in
central apneas on the night with TNI (n 5 2). These
limitations have to be considered in future clinical trials.
Clinical Implication
TNI offers an alternative to the standard CPAP
therapy in patients who predominantly have obstructive hypopnea. The efficacy of TNI can be easily
assessed within a single night and can be predicted
on the basis of the presence of at least 90% hypopnea
and RERAs. It is of note that a predominance of hypopneas are seen in children,30,31 and RERAs are seen in
patients with upper airway resistance syndrome32 and
females with fibromyalgia;33 therefore, these populations may be ideal for this form of therapy. Finally,
more precise measurements of inspiratory airflow
may provide a quantitative way of predicting patients
who will respond to TNI. Thus, further trials, on subgroups of patients with sleep-disordered breathing
using TNI over a longer period of time are necessary
to determine its clinical usefulness.
Acknowledgments
Author contributions: Dr Nilius: contributed to conception and
design of the study, acquisition of data in the study center Hagen,
analysis and interpretation of data, draft of article, critical revision,
and final approval.
Dr Wessendorf: contributed to conception and design of the study,
acquisition of data in the study center Essen, critical revision of
the draft, and final approval.
Dr Maurer: contributed to conception and design of the study,
acquisition of data in the study center Mannheim, critical revision
of the draft, and final approval.
Dr Stoohs: contributed to conception and design of the study,
acquisition of data in the study center Dortmund, critical revision
of the draft, and final approval.
Dr Patil: contributed to conception and design of the study, analysis
of the data in the central reading center, statistical analysis, draft of
the article, critical revision of the draft, and final approval.
Dr Schubert: contributed to analysis of the data in the central
reading center, statistical analysis, critical revision of the draft, and
final approval.
Dr Schneider: contributed to conception and design of the study,
interpretation of data, draft of article, critical revision, and final
approval.
Financial/nonfinancial disclosures: The authors have reported
to CHEST the following conflicts of interest: Dr Nilius has
received funds from Weimann, Heinen und Löwenstein, and
Fisher & Paykel. Dr Wessendorf has received funds from ResMed.
Dr Maurer has received funds from Weinmann, Heinen &
Löwenstein, MPV Truma, and ResMed. Funding for the study on
TNI described in this presentation was in part provided by Seleon
GmbH. Under a separate licensing agreement between Seleon
GmbH and the Johns Hopkins University, Dr Schneider is entitled
to a share of royalties received by the University on sales of
products described in this manuscript. The terms of this arrangement are being managed by the Johns Hopkins University in
accordance with its conflict of interest policies. Drs Stoohs, Patil,
www.chestpubs.org
and Schubert have reported to CHEST that no potential conflicts
of interest exist with any companies/organizations whose products
or services may be discussed in this article.
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Original Research
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© 2010 American College of Chest Physicians
Predictors for Treating Obstructive Sleep Apnea With an Open Nasal
Cannula System (Transnasal Insufflation)
Georg Nilius, Thomas Wessendorf, Joachim Maurer, Riccardo Stoohs,
Susheel P. Patil, Norman Schubert and Hartmut Schneider
Chest 2010;137; 521-528; Prepublished online December 1, 2009;
DOI 10.1378/chest.09-0357
This information is current as of April 13, 2010
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References
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