Sleep Breath (2014) 18:69–75
DOI 10.1007/s11325-013-0850-3
ORIGINAL ARTICLE
Increased prevalence of obstructive lung disease in patients
with obstructive sleep apnea
Sari Greenberg-Dotan & Haim Reuveni & Asher Tal &
Arie Oksenberg & Arnon Cohen & Fadia T. Shaya &
Ariel Tarasiuk & Steven M. Scharf
Received: 21 October 2012 / Revised: 24 March 2013 / Accepted: 10 April 2013 / Published online: 4 June 2013
# Springer-Verlag Berlin Heidelberg 2013
Abstract
Study purposes This study aims to determine whether there
is an increased prevalence of obstructive lung diseases
(OLDs) in patients with obstructive sleep apnea (OSA).
We also determined whether among the OLD patients there
is a difference in the prevalences of specific chronic disease
co-morbidities between patients with and without OSA.
Methods The prevalences of COPD, asthma, and COPD
combined with asthma (ICD-9 coding) were compared be-
tween 1,497 adult OSA patients and 1,489 control patients,
who were matched for age, gender, geographic location, and
primary care physician. The prevalences of specific co-
This work was supported by a Competitive Grant from the Israeli
Institute for Health Policy and Health Services Research, award no. B/
17/2000. This was performed in the Division of Pulmonary and Critical
Care Medicine, University of Maryland Sleep Disorders Center,
Baltimore, MD, USA.
S. Greenberg-Dotan : H. Reuveni : A. Tal : A. Tarasiuk
Sleep–Wake Disorders Unit, Soroka University Medical Center,
Faculty of Health Sciences, Ben-Gurion University of the Negev,
Beer-Sheva, Israel
A. Oksenberg
Sleep Disorders Unit, Loewenstein Hospital Rehabilitation Center,
Raanana, Israel
S. Greenberg-Dotan (*) : A. Cohen
Chief Physician’s office, Headquarters of Clalit Health Services,
P.O.B 16250, Tel-Aviv, Israel
e-mail: sari@post.bgu.ac.il
F. T. Shaya
Department of Pharmaceutical Health Services Research, School
of Pharmacy, University of Maryland, Baltimore, MD, USA
S. M. Scharf
Division of Pulmonary and Critical Care Medicine, University of
Maryland Sleep Disorders Center, Baltimore, MD, USA
morbidities were measured in the OLD groups between
patients with OSA and the matched control group.
Results COPD, asthma, and COPD combined with asthma
were found to be more prevalent among OSA patients com-
pared to the matched controls. Prevalences among patients
with and without OSA, respectively, were COPD—7.6 and
3.7 % (P<0.0001), asthma—10.4 and 5.1 % (P<0.0001),
COPD plus asthma—3.3 and 0.9 % (P < 0.0001). The
Charlson Comorbidity Index was greater for OSA patients
(2.3±0.2) than for controls (1.9±1.8; P<0.0001). These
trends held for all severity ranges of OSA. Patients with
OSA and COPD were characterized by more severe hypoxia
at night compared with the OSA patients without OLD.
Conclusion OSA was associated with an increased preva-
lence of OLDs.
Keywords Asthma . COPD . Obstructive lung disease .
Sleep apnea
Introduction
Obstructive sleep apnea (OSA), a common disorder [1]
characterized by repetitive closure of the upper airway, is
associated with excess morbidity and mortality [2]. Similar-
ly, obstructive lung diseases (OLD), including chronic ob-
structive pulmonary disease (COPD) and asthma, are
common and associated with excess morbidity and mortality
[3]. COPD is overwhelmingly caused by smoking, while
asthma is often related to allergic factors. OLDs are charac-
terized by airflow limitation and share some clinical fea-
tures, although their pathogenesis is different.
The coincidence of OSA in COPD is known as overlap
syndrome. There is considerable controversy regarding the
prevalence of OSA in patients with COPD, with reported
values ranging up to approximately 15 % of COPD patients
70
[4, 5]. Patients with OSA are at a higher risk of developing
respiratory insufficiency, pulmonary hypertension,
hypoventilation, and more profound nocturnal hypoxemia
than patients with COPD alone [6, 7]. Both OSA and OLDs
are associated with systemic inflammation [8], and OSA and
COPD are independent risk factors for the development of
cardiovascular disease [9]. There is some controversy as to
whether the association between OLD and OSA is that
expected merely on the basis of the conjunction of two
relatively common clinical conditions or whether having
OSA or OLD confers increased risk for having the other [5].
In the current study, we explored the prevalence of
OLDs (COPD and asthma) in patients with OSA com-
pared to matched patients from the database of the
largest health maintenance organization (HMO) in Israel.
Our working hypothesis was that OLD is no more
prevalent in patients with OSA than in a matched co-
hort of patients without OSA and that there is no
difference in the prevalence of important co-morbidities
in OLD patients with and without OSA.
Methods
Study population
Our sample was drawn from the database of patients insured
by from the Clalit Health Services (CHS). This HMO is the
largest in Israel and insures 60 % of the general population.
We also determined the prevalence of specific chronic dis-
ease co-morbidities that influence health care burden in
patients. The Institutional Ethics Committees of the Soroka
University Medical Center, the Loewenstein Hospital Reha-
bilitation Center, and the central CHS approved the protocol
as a non-interventional chart review.
Study design
This is a case–control study. Between January 2001 and April
2003, patients aged 40 to 89 with polysomnographically
proven OSA (apnea–hypopnea index (AHI) ≥5 events
per hour of sleep) were recruited consecutively and
prospectively [10–12]. Apneas were defined as a
>90 % reduction in airflow and hypopneas as 30–
90 % reduction in airflow with 4 % drop in oxygen
saturation. Data on sleep study results from 1,497 pa-
tients were collected from two Sleep–Wake Disorders
Laboratories in Beer-Sheva, Israel, and the sleep labo-
ratory of Loewenstein Hospital Rehabilitation Center in
Raanana, Israel. Information about co-morbidity was
obtained from the records of subjects enrolled in CHS.
The study population included consecutively recruited
patients≥18 years old, with OSA (n=1,497), defined as
Sleep Breath (2014) 18:69–75
AHI ≥5. This was calculated as the number of apneas plus
the number of hypopneas per hour of sleep. Patients were
excluded from analysis if they had cancer or were hospital-
ized for more than 50 days in the 5 years preceding the data
collection.
The control group was selected from the general popula-
tion in the CHS database. For comparison, the control group
was matched to OSA patients by age (within one decade),
gender, geographic location, and, to control for clinical
practice habits, primary care physician. Because data on
body mass index (BMI) were not available in the CHS
database, we could not match for this variable. Patients in
the control cohort were excluded if they had a concomitant
diagnosis of any sleep disorder, had a polysomnogram
(PSG), or had been prescribed positive airway pressure
treatment for any reason. Altogether the control group
consisted of 1,489 subjects.
Data collection
PSG Overnight PSG monitoring was performed using
standard techniques appropriate to the collection period
[13, 14]. Briefly, this involved multichannel monitoring,
including electroencephalography, electrooculography, and
submentalis and anterior tibialis electromyography, electro-
cardiography, airflow (nasal–oral thermistors), respiratory
effort (pneumobelts), body position, and oxygen saturation
(SaO2—pulse oximetry). Severity of disordered breathing
was characterized by the AHI and the time (min) spent with
saturation less than 90 % (T90). Sleep quality was charac-
terized by total sleep time (TST— min), sleep efficiency
(TST/time in bed), and arousal index (number of arousals
per hour of sleep).
Comorbid diagnoses CHS has a cumulative database which
allows tracking medical diagnoses according to the Interna-
tional Classification of Diseases (ICD-9). Physicians enter
these diagnoses during hospital and clinic visits. We
reviewed the database for the diagnoses of COPD [ICD-9
code 491.x −492.x, 496.x] and asthma [493.x]. As a mea-
sure of co-morbidity burden, we calculated the age-adjusted
Charlson Comorbidity Index (CCI) with Deyo modification
[15, 16] from appropriate co-morbidity data on the CHS
database.
Data and statistical analysis
Analyses were done using Statistical Package for the Social
Sciences (SPSS v 17.0). Continuous variables were com-
piled and presented as mean with standard deviation. We
used one-way analysis of variance (ANOVA-1) and the chi-
square test (χ2) as appropriate to determine statistical sig-
nificance between variables. Among the OSA patients, to
Sleep Breath (2014) 18:69–75
adjust for BMI and age, we used GLM—ANCOVA (one-
way ANOVA with co-variants) procedure, adjusted by
Bonferroni correction. The null hypothesis was rejected at
the 5 % level.
Results
Among the 1,497 OSA patients, the mean age was 55.5
± 11.1, and 1,145 (76.5 %) were males. Among the
1,489 matched controls, mean age was 55.4±11.1 and
1,140 (76.6 %) were males. These differences were not
significant.
Table 1 shows the prevalence of OLD of various types
and the CCI scores among the OSA patients, stratified for
severity of OSA, and matched controls. OLD of all catego-
ries was more prevalent among OSA patients compared
with the matched controls. Ratios of prevalences in OSA
to those in controls ranged between two and ten times. This
effect was greater among women (Table 2)—over threefold
for women and less than twofold for men. In addition, the
CCI was significantly greater for all severities of OSA (mild
OSA—AHI 5–14.9, moderate OSA—AHI 15–29.9, severe
OSA—AHI >30) patients compared with their matched
controls.
Table 3 shows the prevalences of specific co-
morbidities in patients with and without OSA, associat-
ed with each type of OLD. For patients with COPD,
OSA was associated with a greater prevalence of diabe-
tes (50.9 vs. 22 %, P= 0.004) and obesity (78.9 vs.
31.7 %, P<0.0001). While the prevalence of pulmonary
hypertension was greater in COPD patients with OSA
than in those without, the difference only reached bor-
derline significance (21.1 vs. 7.3 %, P=0.062). Patients
with asthma showed no difference in prevalences be-
tween those with and those without OSA. Similarly,
there were no significant differences between preva-
lences of various co-morbidities for patients with com-
bined asthma and COPD between OSA and non-OSA
patients.
In Table 4, we show demographic characteristics and
sleep measures among OSA patients. Because group
sizes were vastly disparate between OSA patients with
and without OLD and because the ANOVA assumes
rough parity of group sizes, we chose a random sample
of 100 OSA patients without OLD with which to com-
pare the OSA patients with OLD. Regarding age, BMI,
and smoking burden, compared with patients with no
OLD, COPD patients were older, heavier, and had a
greater smoking burden. There were no differences be-
tween the asthma patients and non-OLD patients for
asthma. For the patients labeled as having both COPD
and asthma, the only significant difference was age.
71
Regarding sleep-related characteristics, among the
groups, no differences were found in AHI, TST, sleep effi-
ciency, arousal index, and severity of OSA as assessed by
AHI. Patients with COPD were characterized by a greater
value in T90 compared with the non-OLD patients. Since
age and BMI both influence the severity of OSA, we ad-
justed (ANCOVA) AHI and T90 for age and BMI. T90
remained higher for the COPD patients than the non-OLD
patients.
Discussion
We have demonstrated an increased prevalence of OLD
among OSA patients compared to well-matched con-
trols without OSA. The higher prevalence of OLD
among OSA patients is consistent throughout all de-
grees of OSA severity. In addition, for patients with
COPD, OSA was associated with a greater prevalence
of diabetes and obesity than in COPD patients without
OSA. By contrast, patients with asthma and combined
COPD/asthma showed no difference in the prevalences
of these co-morbidities between those with and without
OSA. Finally, even after adjusting for BMI and age,
T90 was greater in patients with COPD than OSA
patients without this disorder. In the ensuing discussion,
we consider these findings in the light of the existing
literature and the limitations of the study.
Our study supports the notion that there is an asso-
ciation between OLD and OSA. Our findings are con-
sistent with the findings of others [9, 17]. It should be
noted that one critique leveled at some of the previous
studies is that the findings were based on small groups
that were highly selected. Our study was a reasonably
large one, in which there was no selection based on any
clinical symptoms suggestive of OSA in the control
matched group. Recently, in a review of diagnostic
coding in a large unselected population of adults 40–
64 years old, Shaya et al. [18] reported a higher prev-
alence of OSA among COPD patients, but not among
asthmatics or patients with combined COPD/asthma. On
the other hand, based on the severity of airflow obstruc-
tion (FEV1), a large epidemiologic study (Sleep Heart
Health Study) [19] found that OLD was actually less
prevalent in patients with moderate to severe OSA than
in those without.
The reasons for the discrepant findings described
above are not clear. Studies relying only on reviews
of diagnostic codes (e.g., Shaya et al. [18]) suffer from
the possibility of reporting bias and inaccuracies in
diagnosis due to practice patterns and availability of
resources. The current study offers the advantage that
patients with laboratory-proven OSA were well
72 Sleep Breath (2014) 18:69–75

Table 1 Prevalence of OLD among OSA and control patients—total and stratified according to OSA severity and co-morbidities

All OSAa, All control, Mild OSAb, Matched Moderate Matched Severe OSAd, Matched
n=1,497 n=1,489 n=459 controls, OSAc, n=445 controls, n=593 controls,
n=457 n=443 n=589

COPD, % (n) 7.6 % (107) 3.7 %** (47) 7.4 % (31) 3.1 %** (12) 6.5 % (27) 3.4 %* (13) 8.7 % (49) 4.3 %* (22)
OR (95 % CI) 2.2 (1.5–3.1) 2.5 (1.3–4.9) 1.9 (0.99–3.8) 2.1 (1.3–3.6)
Asthma, % (n) 10.4 % (146) 5.1 %** (65) 12.5 % (52) 3.4 %** (13) 10.6 % (44) 6.6 %* (25) 8.8 % (50) 5.2 %* (27)
OR (95 % CI) 2.2 (1.6–2.9) 4.1 (2.2–7.6) 1.7 (0.99–2.8) 1.8 (1.1–2.8)
COPD + asthma, % (n) 3.3 % (50) 0.9 %** (14) 3.9 % (18) 0.4 %** (2) 3.6 % (16) 1.1 %* (5) 2.7 % (16) 1.2 % (7)
OR (95 % CI) 3.6 (2–6.6) 9.3 (2.1–40.3) 3.3 (1.2–9) 2.3 (0.9–5.6)
Charlson co-morbidity 2.3±2 1.9±1.8** 1.9±1.8 1.7±1.6* 2.4±2.2 1.9±1.7** 2.5±2.2 2.1±1.9**
score
a
All OSA—AHI >5
b
Mild OSA—AHI 5–14.9
c
Moderate OSA—AHI 15–29.9
d
Severe OSA—AHI >30
*p<0.05; **p<0.0001 (statistical significance of controls compared with corresponding OSA patients)

matched to patients on the basis of geography and
practice patterns (i.e., matched for physician) as well
as age and gender. However, we acknowledge that we
did not have objective data supporting the diagnosis of
COPD but had to rely on coding based on physician
diagnosis. Regarding the findings of the Sleep Heart
Health Study, namely, that airflow obstruction was less
severe in OSA patients, it is possible that the rigid
selection criteria for this study may have screened out
many patients with COPD. We believe that there is a
need for additional study related to the question of the
association between OSA and OLD [8, 16]. Regarding
adult asthma, others have reported an association [12,
20], findings consistent with those presented here.
Among women, the difference in COPD prevalences
between OSA and control was greater than among men
[21]. The reasons for this are not clear. It is possible
that there are gender-based differences in the extent to
which the pro-inflammatory state engendered or OLD
affects upper airway physiology more than among men.
Gender-based differences in susceptibility to OLD in
the presence of OSA should be explored in future
studies.
One interesting finding was that the mean BMI
among the patients with OSA who had COPD was
actually greater than among patients with OSA without
OLD. This finding might be thought of as unexpected,
given the fact that some patients with COPD are actu-
ally underweight, a characteristic that worsens prognosis
[22]. However, it is possible that since we selected
patients with OSA, we would have selected patients
more likely to be overweight because of the known
association between BMI and the propensity for OSA.
What mechanisms can explain the association between
OSA and COPD? Obesity is known to be a predisposing
factor for asthma [23]. While there is still controversy, there

Table 2 Prevalence of OLD among OSA and control patients—total and stratified according to OSA severity and co-morbidities: a gender
comparison

Men Women

All control, n=1,140 All OSAa, n=1,145 All control, n=349 All OSAa, n=352

COPD, % (n) 4.1** (40) 7.2 (76) 2.3** (7) 9 (31)

OR (95 % CI) 1.8 (1.2–2.7) 4.3 (1.9–9.8)
Asthma, % (n) 4.6** (44) 8.5 (90) 6.8** (21) 16.2 (56)
OR (95 % CI) 2 (1.3–2.8) 2.7 (1.6–4.5)
COPD + asthma, % (n) 6.4** (73) 11.5 (132) 7.2** (25) 20.2 (71)
OR (95 % CI) 1.9 (1.4–2.6) 3.3 (2–5.3)
a
All OSA—AHI >5
*P<0.05; **P<0.0001 (statistical significance of controls compared with corresponding OSA patients)
Sleep Breath (2014) 18:69–75 73

Table 3 Specific co-morbidities in patients with OLD among patients with OSA (AHI≥ 5) and matched controls

COPD Asthma COPD and asthma

OSA (n=57) No OSA P OSA (n=96) No OSA P Both with Both without P
(n=41) (n=82) OSA (n=50) OSA (n=27)

Hypothyroidism 1.8 % (1) 0 NS 1 % (1) 1.2 % (1) NS 2 % (1) 0 NS

Diabetes 50.9 % (29) 22 % (9) 0.004 29.2 % (28) 23.2 % (19) NS 40 % (20) 40.7 % (11) NS
Obesity 78.9 % (45) 31.7 % (13) <0.0001 43.8 % (42) 35.4 % (29) NS 58 % (29) 48.1 % (13) NS
Hyperlipidemia 80.7 % (46) 68.3 % (28) NS 61.5 % (59) 50 % (41) NS 70 % (35) 48.1 % (13) NS (0.059)
Depression 15.8 % (9) 7.3 % (3) NS 14.6 % (14) 9.8 % (8) NS 24 % (12) 3.7 % (1) 0.023
IHD 49.1 % (28) 39 % (16) NS 19.8 % (19) 17.1 % (14) NS 34 % (17) 29.6 % (8) NS
Hypertension 70.2 % (40) 65.9 % (27) NS 53.1 %(51) 41.5 % (34) NS 68 % (34) 59.3 % (16) NS
Pulmonary hypertension 21.1 % (12) 7.3 % (3) NS (0.062) 1 % (1) 3.7 % (3) NS 10 % (5) 3.7 % (1) NS

P for differences between patients with OSA and those presumed without (controls)

are data to suggest the same for COPD [24]. While the
mechanism for the association between obesity and OLDs
is not well known, the systemic inflammatory state
associated with obesity may contribute to this associa-
tion [25]. Patients with COPD are overwhelmingly
smokers or ex-smokers. Smoking can lead to inflamma-
tion of the upper airway which in turn could lead to
swelling, narrowing, and thus increasing the propensity
to airway closure. Indeed OSA was reported to be
approximately three times more prevalent in ever- smokers
than never-smokers [26, 27].
Regarding co-morbidity burden (CCI), as shown in
Tables 1 and 2, for all degrees of OSA severity, there was
a greater co-morbidity burden in OSA patients than in those
without. Table 3 demonstrates that diabetes and obesity
were the principal co-morbidities associated with OSA in
the COPD patients. The association between OSA and dia-
betes in the general population is well known [28]. We have
demonstrated that this holds as well for patients with COPD.
Depression is known to be associated with both OSA [29]
and COPD [30]. Among patients with OLD, the prevalence
of depression appeared greater in patients with OSA
(Table 3). However, because the numbers were small, this
difference did not reach statistical significance except for
patients with combined COPD/asthma diagnosis. Similarly,
pulmonary hypertension appeared more prevalent among
patients with COPD and OSA than among patients with
COPD alone; however, again the numbers were small and
did not reach statistical significance. Data in Tables 3 and 4
were in the context of multiple comparisons and should be
considered as hypothesis generating analyses that need
confirmation.

Table 4 Sleep characteristics among OSA patients using random subsample of OSA patients with COPD (AHI ≥ 5)

None, n=100 COPD, n=57 P, COPD Asthma, n=96 P, asthma COPD + P, COPD +
vs. none vs. none asthma, n=50 asthma vs. none

Age (year) 56±12 64±11 <0.0001 57±10 0.724 60±12 0.046

BMI (kg/m2) 32±7 35±6 0.016 33±7 0.456 34±6 0.166
Smoking tobacco (pack year) 29±23 53±40 0.002 21±16 0.126 40±30 0.081
TST (min) 300±102 297±77 0.872 295±100 0.814 289±104 0.667
Sleep efficiency (%) 79±19 77±14 0.692 80±14 0.812 79±13 0.874
Arousal index (events/hour) 35±22 38±24 0.778 33±23 0.776 24±16 0.065
AHI (events/hour) 34±25 41±25 0.093 29±23 0.194 29±24 0.211
T90 (%) 14±25 28±32 0.016 12±22 0.474 22±33 0.188
AHI adjusted for BMI and age, 35±2 39±3 0.411 29±2 0.148 27±4 0.080
mean ± SE
T90 adjusted for BMI and age, 15±3 26±4 0.037 12±3 0.441 21±4 0.243
mean ± SE

Values are mean ± SD. Comparing mean the values was done by one-way ANOVA
AHI apnea–hypopnea index, BMI body mass index, T90 percent sleeping time in which oxygen saturation was below 90 %
74
Regarding OSA severity, we did not find a differ-
ence in AHI between the OLD and the non-OLD pa-
tients with OSA. However, as seen in Table 4, the
degree of hypoxemia seen on PSG, as judged by the
T90, was greater in patients with COPD than in pa-
tients with OSA but with no OLD. This is consistent
with previous studies [11]. This is expected as disor-
dered breathing events would have more severe effects
on oxygen transport in damaged lungs than in others.
The airflow obstruction in COPD is relatively constant
over the 24-h period and is often associated with pa-
renchymal destruction, both factors that would reduce
oxygen transport. In the asthma patients, we did not
find a difference in T90 between this group and the
non-OLD patients with OSA. The degree of airflow
obstruction among the asthmatic patients is highly var-
iable, and there is little parenchymal destruction. In
asthma, airflows may be normal in patients not
experiencing symptoms. Patients in the throes of an
asthma attack are not likely to undergo routine PSG,
and thus it is unlikely that hypoxemia would have been
worse in these patients. Interestingly, we did not find
worse oxygenation in the group with both OLD diag-
noses compared with the non-OLD patients. It might be
expected that patients with a combined diagnosis
should at least experience the degradation of oxygen
transport seen in the COPD patients. However, we
point out that symptoms of COPD and asthma often
overlap. It is possible that older patients with asthma
and little parenchymal destruction would have received
a diagnosis of COPD but would in fact have a pathophysiology
more suited to asthma.
Limitations of the study
While the diagnosis of OSA was based on accepted
objective criteria, the diagnosis of COPD was based
on coding, and from the database, we could not confirm
the accepted clinical and physiologic criteria for airflow
obstruction. Another limitation is that we could not
obtain BMI data on patients without the diagnosis of
OSA as this information did not appear in the database.
Hence, we cannot determine whether obesity or OSA
per se constitute independent risks for OLD. Similarly,
we did not have data among the non-OSA controls
regarding smoking burden. Thus, we cannot determine
whether the increased prevalence of COPD among the
OSA patients was possibly related to differences in
smoking burden than among the controls. We acknowl-
edge that there may have been undiagnosed OSA
among the “controls.” However, to the extent that there
is undiagnosed OSA among the controls, this would
have tended to minimize the differences between the
Sleep Breath (2014) 18:69–75
OSA and the controls in terms of prevalence of OLDs.
Finally, data on smoking were not available in the
database. It is extremely likely that the prevalence of
smoking was higher in the COPD group than in the
asthma or control groups. Smoking is a possible con-
founder for this study as it is a risk for COPD and is
associated with OSA as well. The lower age limit of 40
is commonly used for studies of COPD so as to avoid
confounding the diagnosis with asthma in younger pa-
tients. Finally, we chose to study stable patients as
defined in the “Methods” section. Thus, we may have
excluded patients with unstable respiratory disease who
required hospitalization.
Conclusions
In the current study, we demonstrate an increased prev-
alence of OLD among patients with a diagnosis of
OSA compared with a matched population without
OSA. This was true for COPD, asthma, and patients
with both diagnoses. Further, increased prevalence rates
of OLD were found in all ranges of OSA severity.
While the reasons for this association are not clear,
future studies could provide additional information for
the mechanisms leading to the association of these two
serious conditions.
Disclosure The authors have no conflicts of interest to disclose.
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