Respiratory Physiology & Neurobiology 238 (2017) 41–46

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Respiratory Physiology & Neurobiology

journal homepage: www.elsevier.com/locate/resphysiol

Positive airway pressure therapy in heart failure patients: Long-term

effects on lung function
Henrik Fox ∗ , Susanne Witzel, Thomas Bitter, Dieter Horstkotte, Olaf Oldenburg
Clinic for Cardiology, Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum, Bad Oeynhausen, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: The prevalence of sleep-disordered breathing (SDB) in patients with heart failure (HF) is high.
Received 9 September 2016 Positive airway pressure (PAP) is first-choice therapy, but recent data indicates that PAP therapy may
Received in revised form 17 January 2017 increase mortality in HF patients with reduced ejection fraction (HF-REF) and predominant central sleep
Accepted 21 January 2017
apnea (CSA). This study investigated long-term effects of PAP therapy on pulmonary function, including
Available online 23 January 2017
respiratory muscle strength. All patients underwent multichannel cardiorespiratory polysomnography
(PSG) and comprehensive lung function testing at baseline and follow-up (mean 588 ± 43 days).
Keywords:
Results: 350 patients (mean age 68 ± 10.7 years, 88% male) were included, inspiratory vital capacity,
Heart failure
Positive airway pressure
3.3 ± 0.9 vs 3.2 ± 0.8 L; forced expiratory volume in 1 s, 2.5 ± 0.7 vs 2.4 ± 0.7 L; lung diffusion capacity,
Obstructive sleep apnoea 6.2 ± 1.9 vs 5.9 ± 1.8 mmol/min/kPa; correction for hemoglobin, 1.1 ± 0.02 vs 1.1 ± 0.3 mmol/min/kPa/L;
Central sleep apnoea and mouth occlusion pressure, 0.42 ± 0.11 vs 0.4 ± 0.12 kPa.
Lung function Conclusions: PAP therapy had no negative nor positive impact on lung function, including respiratory
muscle strength, in stable HF-REF patients with SDB, and is therefore safe from a respiratory perspective.
© 2017 Elsevier B.V. All rights reserved.

1. Introduction
Interest in sleep-disordered breathing (SDB) in patients with
heart failure (HF) is growing, as strong epidemiological data link
SDB and HF (Bitter et al., 2009; Linz et al., 2015; Oldenburg et al.,
2007b; Woehrle et al., 2014). In addition, SDB is associated with
increased morbidity and mortality in patients with HF (Javaheri,
2005; Javaheri et al., 2007; Jilek et al., 2011; Khayat et al., 2015;
Oldenburg et al., 2016; Wang et al., 2007), and with impairment
of cardiac function and HF severity. SDB is therefore an important,
but still frequently under-recognized, risk factor for poor prognosis
in chronic HF patients (Linz et al., 2015; Oldenburg et al., 2007a;
Woehrle et al., 2014). There are two major types of SDB, and the
occurrence and distribution of sleep apnea type may be dependent
on factors such as HF severity and heart rhythm (Fox et al., 2016).
SDB can be treated using positive airway pressure (PAP) ther-
apies (Becker et al., 2003; Linz et al., 2015; Teschler et al., 2001)
or implantable devices (Abraham et al., 2015; Fox et al., 2014a,b),
which have been shown to provide good suppression of respira-
tory events (Becker et al., 2003; Linz et al., 2015; Teschler et al.,
2001). PAP therapy is considered the standard of care in SDB treat-
ment. In obstructive SDB, continuous PAP therapy is used to keep
the upper airways open. In central SDB, adaptive servo-ventilation
(ASV) was developed to overcome cessation in breathing occur-
ring as a result of a loss of central respiratory drive. Recently the
Treatment of Sleep-Disordered Breathing with Predominant Cen-
tral Sleep Apnea by Adaptive Servo-Ventilation in Patients with
Heart Failure (SERVE-HF) study showed increased mortality in
patients treated with ASV therapy, despite effective suppression
of respiratory events (Cowie et al., 2015). The reason behind this
increased mortality is not yet known. As a result, the influence of
PAP therapy on lung function is a topic of lively debate, particu-
larly because literature on this subject is scarce, and conclusive or
mechanistic studies are missing, and many unanswered questions
remain (Cowie et al., 2015). The hypothesis that PAP therapy might
have a negative influence on lung function and diffusion has not
yet been thoroughly investigated.
This study determined lung function parameters in HF-REF
patients before any treatment of SDB and after long-term PAP ther-
apy and compared the findings with values obtained in a matched
control group who did not receive PAP therapy.

∗ Corresponding author at: Clinic for Cardiology, Herz- und Diabeteszen-

trum NRW, Ruhr-Universität Bochum, Georgstrasse 11, D-32545 Bad Oeynhausen,
Germany.
E-mail address: akleemeyer@hdz-nrw.de (H. Fox).

http://dx.doi.org/10.1016/j.resp.2017.01.010
1569-9048/© 2017 Elsevier B.V. All rights reserved.
42 H. Fox et al. / Respiratory Physiology & Neurobiology 238 (2017) 41–46
Fig. 1. Flow of patients through the study (CONSORT diagram).
2. Patients and methods
2.1. Study design
This retrospective analysis of prospectively collected data
between July 2009 and March 2016, as well as the study protocol,
were approved by the institutional ethics committee. The study
was conducted in accordance with the Declaration of Helsinki and
Good Clinical Practice. All patients provided informed consent prior
to inclusion in the study.
2.2. Participants
All eligible HF-REF patients presenting with HF to our Aca-
demic Medical Center were eligible for inclusion. All study patients
underwent SDB screening with polygraphy, and those with an
apnea-hypopnea index (AHI) of ≥15/h then underwent full mul-
tichannel cardiorespiratory polysomnography (PSG). Inclusion
criteria were stable HF-REF with left ventricular ejection fraction
(LVEF) ≤45% and medically stable treatment, including indicated
device therapy, according to current European Society of Cardiology
guidelines (Ponikowski et al., 2016).
Exclusion criteria were acute cardiac decompensation, oxy-
gen therapy, ongoing infections, acute coronary syndrome within
3 months prior to enrollment, active myocarditis, complex con-
genital heart disease, constrictive pericarditis, chronic hypoxemia
(sustained oxygen saturation ≤85%) to exclude severely under-
lying lung disease or oxygenation dysfunction, including chronic
obstructive pulmonary disease [COPD] GOLD stage >II), transient
ischemic attack (TIA) or stroke within 3 months prior to enrollment,
status post-heart transplant or left ventricular assist device (LVAD)
implantation, prescribed inotrope therapy, primary hemodynami-
cally significant uncorrected valvular heart disease, pregnancy, and
participation in a pharmaceutical or treatment-related clinical trial
within 6 months of study enrollment (Fig. 1).
2.3. Assessments
During PSG, nasal airflow (measured by nasal pressure, chest
and abdominal effort), pulse oximetry, snoring and body position
were continuously recorded. PSG recordings were analyzed by a
physician specially trained in SDB and standard definitions were
used to describe and score SDB as follows: an apnea was scored
if the breathing signal had a reduction in flow of ≥90% for ≥10 s
(without any abdominal or thoracic breathing efforts for central
sleep apnea [CSA], and with visible ribcage and abdominal respi-
ratory impedance signals for obstructive sleep apnea [OSA]) (Berry
et al., 2012). Hypopnea was defined as a ≥30% reduction in flow,
lasting ≥10 s and accompanied by a ≥3% drop in oxygen satura-
tion. Patients were classified as having either predominately CSA or
OSA. Obstructive hypopnea events were scored if there was snoring
during the event, “flattening” of nasal pressure during inspiration
and/or paradoxical thoracoabdominal excursions during the event.
Hypopneas were scored as central if none of the above criteria were
met. The AHI is an established maker of SDB severity and describes
the number of episodes of apneas and hypopneas per hour of sleep.
SDB severity was graded according to guideline recommendations
(Berry et al., 2012) and our clinical routine as mild (AHI ≥5 to
<15/h), moderate (≥15 to <30/h) or severe (AHI ≥30/h). Patients
with an AHI <5/h were considered to have no relevant SDB and
were excluded. The decision on what PAP therapy to use was based
on established society recommendations.
All recordings were performed using SomnoMedics PSG equip-
ment (SomnoMedics, Randersacker, Germany). The American
Academy of Sleep Medicine (AASM) definition was used in this
study; oxygen desaturation index (ODI) referred to the number of
≥3% arterial oxygen desaturations per hour (Berry et al., 2012).
2.4. Lung function testing
All enrolled patients underwent full lung function testing using
body plethysmography at baseline and follow-up. This included
assessment of static and dynamic lung function (including forced
vital capacity [FVC], inspiratory vital capacity [IVC], forced expi-
ratory volume in one second [FEV1 ], ratio of FEV1 to FVC, peak
expiratory flow [PEF], mid expiratory flow at 25, 50 and 75% of FVC
[MEF25, 50, 75], total airway resistance [RAW] and total lung capac-
ity [TLC], as well lung diffusion capacity [TLCO; transfer factor of the
lung for carbon monoxide] and KCO [correction for hemoglobin,
based on the method of Cotes (Cotes, 1963) as recommended by
the American Thoracic Society, facilitated corrections for altitude,
hemoglobin, and carboxyhemoglobin], and mouth occlusion pres-
sure determined 0.1 s [P0.1] after the start of inspiration).
Baseline testing was performed before initiation of SDB therapy
in the PAP therapy group. All lung function tests were con-
®
ducted with the use of KoKo Px (nSpire Health, Inc., Longmont,
CO, USA). Calibration was checked daily and all lung function
testing data were reviewed and graded for quality. Acceptabil-
ity and reproducibility were assessed according to the American
Thoracic Society (ATS)/European Respiratory Soceity (ERS) crite-
ria (American Thoracic Society/European Respiratory, 2002; Miller
et al., 2005) and only tests that had high quality scores were
included in the final analysis. Respiratory muscle strength was
assessed by using the manufacturers flanged mouthpiece attached
to the tube and system valve including a little leakage to pre-
vent glottis closure and recruitment of buccal muscles. Patients
needed to hold inspiratory and expiratory pressure ideally for 1.5 s
to enable recording of a maximum pressure level sustained for one
second. Mouth occlusion pressure determined 0.1 s (P0.1) after the
start of inspiration was measured 8–15 times during spontaneous
breathing. For these measurements, several recordings were per-
formed to ensure that at least 3 tracings with reproducible values
were obtained. Results are expressed as percentage of the pre-
dicted values for gender and age. Measurements were obtained
in all patients on the same day as PSG recording. All assessments
were performed according to ATS/ERS guidelines and recommen-
 H. Fox et al. / Respiratory Physiology & Neurobiology 238 (2017) 41–46 43

Table 1
Patient demographic and clinical characteristics at baseline.

PAP group (n = 231) Control group (n = 119) p-value

Age, years 67.9 ± 10.3 68.2 ± 11.5 n.s.

Male gender, n (%) 207 (89.7) 100 (83.9) n.s.
Coronary artery disease, n (%) 140 (60.8) 70 (58.5) n.s.
NYHA class 2.5 ± 0.5 2.5 ± 0.6 n.s.
BMI, kg/m2 29.6 ± 5 28.4 ± 5.1 <0.05
Heart rate, beats/min 68.3 ± 10.1 67.5 ± 9.8 n.s.
LVEF, % 34.2 ± 7.5 34.5 ± 7.9 n.s.
Baseline NT-proBNP, pg/nL 2741 ± 7943 3718 ± 17278 n.s.
Hypertension, n (%) 226 (97.8) 116 (97.4) n.s.
Diabetes, n (%) 93 (40.1) 44 (37.3) n.s.
Nocturia (times per night) 2.3 ± 1.4 2.0 ± 1.1 n.s.
COPD GOLD I, n (%) 92 (39.8) 45 (37.8) n.s.
COPD GOLD II, n (%) 42 (18.2) 21 (17.6) n.s.
Chronic bronchitis 30 (12.9) 15 (12.6) n.s.
Asthma 18 (7.8) 10 (8.4) n.s.
Lung emphysema 42 (18.2) 21 (17.6) n.s.
Pulmonary hypertension 46 (19.9) 23 (19.3) n.s.
Mean follow-up, days 578 ± 44 592 ± 48 n.s.

Values are mean ± standard deviation, or number of patients (%).

BMI: body mass index; COPD: Chronic obstructive pulmonary disease; Global Initiative for Chronic Obstructive Lung Disease; LVEF: left ventricular ejection fraction; NT-
proBNP: amino-terminal B-type natriuretic peptide; NYHA: New York Heart Association; n.s.: not significant; PAP: positive airway pressure.

dations (American Thoracic Society/European Respiratory, 2002; Table 2

Lung function parameters in the PAP therapy and control groups at baseline and
Miller et al., 2005).
at follow-up. p-values for all comparisons within-group vs baseline, and between
In addition, data on the type of PAP therapy, PAP therapy groups at baseline and follow-up were >0.05 (not statistically significant).
pressures, therapy adherence and nightly use were collected and
PAP group (n = 231) Control group (n = 119)
analyzed. The expiratory positive airway pressure was increased
manually to control OSA and, in ASV treatment, maximum pressure Baseline Follow-up Baseline Follow-up
support was increased to control CSA, when necessary. A full-face TLCO, mmol/min/kPa 6.4 ± 1.9 6.2 ± 1.9 5.9 ± 1.8 5.9 ± 1.8
mask was recommended for the initiation of PAP therapy. Patients KCO, mmol/min/kPa/L 1.2 ± 0.02 1.1 ± 0.02 1.1 ± 0.3 1.1 ± 0.3
were advised to use PAP therapy for at least 4 h per night and 7 days P0.1, kPa 0.37 ± 0.14 0.42 ± 0.11 0.38 ± 0.13 0.4 ± 0.12
per week. Adherence to therapy was defined as the use of PAP ther- IVC, L 3.3 ± 0.9 3.3 ± 0.9 3.2 ± 0.9 3.2 ± 0.8
FEV1 , L 2.5 ± 0.7 2.5 ± 0.7 2.4 ± 0.7 2.4 ± 0.7
apy for an average of at least 3 h per night. The target was to reduce ERV, L 0.7 ± 0.4 0.6 ± 0.4 0.8 ± 0.4 0.7 ± 0.4
the AHI to less than 10/h. IC, L 2.6 ± 0.8 2.6 ± 0.8 2.5 ± 0.7 2.5 ± 0.7

Values are mean ± standard deviation.

2.5. Statistical analysis
Statistical analysis was performed using IBM SPSS 22, IBM Cor-
poration, Armonk, NY, USA, for Mac, Apple Inc., Cupertino, CA,
USA. A p-value of <0.05 was defined as statistically significant.
Data are expressed as percentages for discrete variables and as
means ± standard deviation for continuous variables. Continuous
variables were compared by ANOVA. Categorical comparisons were
compared using Chi-square analysis and non-parametric inferen-
tial statistical analyses were performed using Mann–Whitney U,
Wilcoxon rank sum test and Spearman’s rank correlation coeffi-
cient.
3. Results
A total of 350 patients were included; clinical and demographic
data by study group are summarized in Table 1. Mean AHI at base-
line was 29.7 ± 17/h; 192 patients (54.9%) had moderate SDB (AHI
≥15/h and <30/h) and 158 (45.1%) had severe SDB (AHI ≥30/h). A
total of 58% of patients had predominant CSA and 40% had pre-
dominant OSA. One-third of patients (n = 119, 34%) did not receive
any PAP therapy and served as the control group. Multiple reasons
led to non-application of PAP therapy, such as patient’s sensation of
high pressure, cold air, running nose and nose congestions, pressure
marks of the mask or its holding, mouth and mask leakage, dryness
of the mouth and individual aversion to mask based therapy, as well
as concomitant individual health conditions. There was no differ-
ence in medication between the two groups. In the group receiving
PAP therapy, 143 patients (40.9%) were treated with ASV, 3 (1%)
with bilevel PAP and 85 (24.3%) with CPAP. Therapy adherence
ERV: expiratory reserve volume; IC: Inspiratory capacity; FEV1 : forced expiratory
volume in 1 s; IVC: inspiratory vital capacity; KCO: correction for hemoglobin based
on the method of Cotes for transfer factor of the lung for carbon monoxide; P0.1:
mouth occlusion pressure at 0.1 s; TLCO: transfer factor of the lung for carbon
monoxide.
was good and comparable to adherence in SERVE HF (Cowie et al.,
2015). Therapy pressures needed were low and were comparable to
other large studies, including pressures used in the SERVE-HF study
(Cowie et al., 2015). Mean expiratory positive airway pressure was
6.7 ± 1.6 cmH2 O, minimum pressure support was 3.1 ± 0.9 cmH2 O,
and maximum pressure was 12.7 ± 4.1 cmH2 O.
Mean follow-up was 588 ± 43 days. There were no significant
changes in lung function parameters in PAP therapy users com-
pared with baseline and control (Table 2). There were also no
significant changes in lung function compared with baseline in sub-
groups of patients with predominant OSA or CSA in both the control
and PAP therapy groups, or between the two types of SDB at any
time (Table 3).
4. Discussion
The results of this study conducted in a large population of 350
patients fulfilling the cardiovascular inclusion criteria of the SERVE-
HF study (LVEF ≤45%, NYHA functional class ≥II (Cowie et al., 2015))
found that PAP therapy had no significant effects on lung function
parameters during long-term follow-up in patients with OSA or
CSA, compared with baseline and a control group not using PAP
therapy. However, previously described positive effects on inspira-
tory muscle strength were not seen.
44 H. Fox et al. / Respiratory Physiology & Neurobiology 238 (2017) 41–46
Table 3
Lung function parameters by type of SDB in the PAP therapy group. p-values for all comparisons between OSA and CSA at baseline and follow-up in both the PAP therapy and
control groups were >0.05 (not statistically significant).
PAP group (n = 231)
Baseline Follow-up
OSA CSA OSA
TLCO, mmol/min/kPa 6.2 ± 1.9 6.2 ± 1.6 6.1 ± 1.9
KCO, mmol/min/kPa/L 1.2 ± 0.3 1.1 ± 0.3 1.2 ± 0.2
P0.1, kPa 0.35 ± 0.14 0.38 ± 0.14 0.38 ± 0.13
IVC, L 3.2 ± 0.8 3.3 ± 0.9 3.1 ± 0.9
FEV1 , L 2.4 ± 0.8 2.4 ± 0.7 2.4 ± 0.7
ERV, L 0.6 ± 0.4 0.7 ± 0.4 0.6 ± 0.4
IC, L 2.6 ± 0.8 2.6 ± 0.8 2.6 ± 0.8
Values are mean ± standard deviation.
ERV: expiratory reserve volume; IC: Inspiratory capacity; FEV1 : forced expiratory volume in 1 s; IVC: inspiratory vital capacity; KCO: correction for hemoglobin based on the
method of Cotes for transfer factor of the lung for carbon monoxide; P0.1: mouth occlusion pressure at 0.1 s; TLCO: transfer factor of the lung for carbon monoxide.
This important topic was investigated because the recent ran-
domized, multicenter, controlled SERVE-HF study (Cowie et al.,
2015) reported an increase in mortality in HF-REF patients random-
ized to ASV versus control. Since the publication of these findings,
there has been much speculation as to the mechanisms underlying
the unexpected results (Mehra and Gottlieb, 2015; Oldenburg and
Horstkotte, 2015), but the specific effects of PAP therapy on lung
function parameters has not yet been thoroughly investigated. It
not yet known whether or not SDB has a negative impact on lung
function, thus negatively influencing cardiac function in this con-
text (Linz et al., 2016). Our study is the first study to systematically
analyze the influence of PAP therapy on lung function parameters
in a defined chronic HF population, treated according to current
European Society of Cardiology guidelines (McMurray et al., 2012)
and compared with a control group. This topic is relevant given the
growing interest in SDB and its association with morbidities and
prognosis in HF patients (Javaheri et al., 2007; Jilek et al., 2011;
Khayat et al., 2015). PAP therapy is the mainstay of SDB treatment,
but recent investigations have questioned the value of PAP therapy
for lack of benefit (Arzt et al., 2013) or the occurrence of unwanted
effects (Cowie et al., 2015), including hemodynamic alterations
(Oldenburg et al., 2012).
One small study randomized 17 patients to nasal continuous
positive airway pressure (CPAP) or a control group and documented
improved inspiratory muscle strength, increased LVEF and reso-
lution of dyspnea and fatigue (Granton et al., 1996), while other
studies have highlighted the negative influence of ventilation ther-
apy on diaphragm atrophy and reduced respiratory muscle strength
(Grosu et al., 2012; Jaber et al., 2011). Inspiratory muscle strength is
known to be reduced in patients with chronic HF (Anker et al., 1997;
Coats, 1996; Lindsay et al., 1996; Meyer et al., 2001) and it has been
suggested that wasting may be an independent predictor of poor
prognosis in chronic HF (Meyer et al., 2001). We found that TLCO
was already reduced at baseline in our study population (at 64.7%
of expected values). It was previously reported that lung diffusion
capacities were impaired in patients with HF (Szollosi et al., 2008)
and, as mentioned above, it has been suggested that PAP therapy
might improve muscle strength in patients with chronic HF and
CSA (Granton et al., 1996).
One potential explanation for these findings may be changes
in lung physiology. Underlying mechanisms such as augmented
chemosensitivity to hypercapnia may be an important factor in
the pathogenesis of CSA (Narkiewicz et al., 1999; Wilcox et al.,
1998) because there are reports on changes in chemosensitivity
with CPAP treatment of CSA in congestive HF (Yasuma et al., 2007).
This was indicated by a flattening of the slope of the regression line
for minute ventilation versus carbon dioxide pressure (PCO2 ) after 3
months of CPAP treatment, without changes in the apneic threshold
(Yasuma et al., 2007). Such documented changes in chemosensi-
Control group (n = 119)
Baseline Follow-up
CSA OSA CSA OSA CSA
5.9 ± 1.7 6.0 ± 1.4 5.7 ± 1.7 6.1 ± 1.6 5.6 ± 1.8
1.1 ± 0.3 1.1 ± 0.2 1.0 ± 0.3 1.2 ± 0.2 1.0 ± 0.3
0.43 ± 0.08 0.35 ± 0.15 0.38 ± 0.14 0.39 ± 0.12 0.4 ± 0.14
3.1 ± 0.9 3.2 ± 1.0 3.2 ± 0.8 3.2 ± 0.9 3.2 ± 0.7
2.4 ± 0.7 2.3 ± 0.8 2.4 ± 0.6 2.3 ± 0.8 2.3 ± 0.6
0.7 ± 0.4 0.7 ± 0.3 0.8 ± 0.4 0.7 ± 0.3 0.7 ± 0.4
2.6 ± 0.8 2.5 ± 0.8 2.5 ± 0.6 2.5 ± 0.8 2.5 ± 0.7
tivity, without alteration of the apneic threshold could play a role
in improving CSR during CPAP treatment, although CPAP alone is
not able to actively ventilate central apneas with open airways.
One possible theory is that PAP therapy may diminish chemosen-
sitivity (controller gain) to stabilize the respiratory control system,
because augmented chemosensitivity to hypercapnia is believed
to be a major factor in the pathogenesis of CSA in patients with HF
(Narkiewicz et al., 1999; Wilcox et al., 1998; Yasuma et al., 2007).
These influences of respiration in HF are directly linked to vari-
ous lung function parameters because HF patients often experience
reductions in lung function (Agarwal et al., 2012) that by them-
selves deteriorate and contribute to HF symptoms and reductions
in quality of life. Moreover, it is known that severe impairment
of lung function is associated with impaired left ventricular filling
(Funk et al., 2008). In addition, published data suggest left ventric-
ular diastolic and systolic dysfunction are often found in mild, and
even subclinical, lung function impairments (Barr et al., 2010), but
the direct influence of PAP therapy for SDB on lung function has not
been studied yet and our investigation is the first to report on this
important topic, showing PAP therapy to be safe in HF-REF patients,
although HF-REF itself seems to be associated with impaired lung
function. It is known that chronic HF patients often have respiratory
muscle weakness (McParland et al., 1992), which not only interferes
with lung function and capacity, but is also believed to be associ-
ated with aggravation of HF symptoms (Granton et al., 1996). A
small study of 17 patients showed that PAP therapy may improve
respiratory muscle strength in chronic HF (Granton et al., 1996), a
finding confirmed by our study with respect to the safety of PAP
therapy, but with no significant changes in our large study popu-
lation. Our findings also suggest that respiratory muscle strength
might be slightly different in patients with different types of SDB
(mouth occlusion pressure CSA 0.38 ± 0.14 kPa in patients with CSA
vs 0.35 ± 0.14 kPa in those with OSA; NS). Whether PAP therapy
could be considered as a type of exercise for respiratory muscles
or whether other mechanisms are involved remains unknown and
needs to be investigated further.
Regarding the search for an explanation of the findings of the
SERVE-HF trial, our study contributes additional information that
PAP therapy does not appear to have any (negative) impact on lung
function, including respiratory muscle strength.
A major limitation of our study is its retrospective nature,
patients were not randomized to the therapy and control groups.
In addition, follow-up time points were not mandated by a study
protocol, but instead were based on routine clinical care.
In conclusion, long-term PAP therapy does not influence lung
function in HF-REF patients. However, these HF-REF patients with
SDB had impaired lung function at baseline and had a variety
of SDB phenotypes. Nevertheless, pulmonary parameters are of
 H. Fox et al. / Respiratory Physiology & Neurobiology 238 (2017) 41–46
importance in the field of PAP therapy and should be taken into
consideration whenever PAP therapy is used.
Disclosures
All authors state that they have no conflicts of interest to declare.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors
Acknowledgement
English language editorial assistance was provided by Nicola
Ryan, independent medical writer.
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