10 , 110 110

Respiratory Medicine (2014

Available online
www.sciencedirect.co
at
ScienceDirect

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / r m e

Obesity and symptoms of depression

contribute independently to the poor asthma
control of obesity
S.G. Kapadia a, C. Wei b, S.J. Bartlett c, J. Lang d, R.A. Wise b,
A.E. Dixon a,*, for the American Lung Association Asthma
Clinical Research Centers1
a
University of Vermont College of Medicine, Burlington, VT, USA
b Johns Hopkins University, Baltimore, MD,
USA
c
McGill University, Montreal, Canada
d Nemours Childrens Hospital, Orlando, FL,
USA

Received 4 December 2013; accepted 26 May 2014

Available online 9 June 2014

Summary
KEYWORDS Obesity is a major risk factor for poorly controlled asthma, but the reasons for poor asthma
Obesity; control in this patient population are unclear. Symptoms of depression have been associated
Asthma; with poor asthma control, and increase with higher body mass index (BMI). The purpose of
Depression this study was to assess whether depressive symptoms underlie poor asthma control in
obesity.
Methods: We determined the relationship between BMI, psychological morbidity and asthma
control at baseline in a well-characterized patient population participating in a clinical trial
conducted by the American Lung Association-Asthma Clinical Research Centers.
Results: Obese asthmatic participants had increased symptoms of depression (Center for
Epidemiologic Studies Depression Scale score in lean 10.1 8.1, overweight 10.0 8.1, obese
12.4 9.9; p Z 0.03), worse asthma control (Juniper Asthma Control Questionnaire score in
lean 1.43 0.68, overweight 1.52 0.71, obese 1.76 0.75; p < 0.0001), and worse asthma
quality of life (scores in lean 5.21 1.08, overweight 5.08 1.05, obese 4.64 1.09; p <
0.0001). Asthmatics with obesity and those with symptoms of depression both had a higher
risk of having poorly controlled asthma (adjusted odds ratio of 1.83 CI 1.23e3.52 for obesity, and 2.08 CI
1.23e3.52 for depression), but there was no interaction between the two.
Obesity and symptoms of depression 1101
* Corresponding author. Department of Medicine, University of Vermont and Fletcher Allen Health Care, Given D209, 89
Beaumont Avenue, Burlington, VT 05405, USA. Tel.: 1 (802) 656 8812; fax: 1 (802) 656 3526.
E-mail addresses: anne.dixon@vtmednet.org, anne.dixon@uvm.edu (A.E. Dixon).

1
Credit roster: American Lung Association Asthma Clinical Research Centers. The participating persons were mentioned in
the section Author contributions.

http://dx.doi.org/10.1016/j.rmed.2014.05.012 0954-
6111/ 2014 Elsevier
Ltd. All rights reserved.
Conclusion: Obesity and symptoms of depression are independently associated with
poor asthma control. As depression is increased in obese asthmatics it may be an
important comorbidity contributing to poor asthma control in this population, but
factors other than depression also contribute to poor asthma control in obesity.
2014 Elsevier Ltd. All rights reserved.

Introduction depression and measures of asthma control with

Obesity is a significant risk factor for developing
asthma and is associated with poor asthma control
[1,2]. Depression and anxiety are likewise
associated with poor asthma control, and the
prevalence of depression and anxiety are
dramatically increased in obesity. The underlying
interaction between obesity, depression, and
asthma is not well understood, yet may have critical
implications for asthma control in the setting of
obesity.
Obesity is associated with decreased
responsiveness to controller medication and poor
asthma control [3]. One study found that obese
asthmatics are hospitalized at nearly five times the
rate of lean asthmatics [4]. Given the ever
increasing prevalence of obesity [5], obesity is
contributing to an epidemic of poorly controlled
asthma.
A number of studies suggest that anxiety and
depression adversely affect asthma symptom
severity and there is a significant correlation
between severity of depressive symptoms and poor
asthma control [6,7]. Depressed asthmatics also
have an increased risk of asthma-related emergency
department visits and poor adherence to asthma
medication regimens [8].
Depression is a very common comorbidity
associated with obesity [9]. The strong association
between high BMI and depressive symptoms is more
pronounced in women, the demographic group with
the highest rate of asthma related to obesity [3].
This relationship is reversible as weight reduction
surgery significantly reduces symptoms of anxiety
and depression among obese asthmatics [10], this
surgery also improves asthma control [11].
Considering that depression is increased in obesity,
such psychological comorbidity may contribute
significantly to the poor asthma control
characteristic of obese asthmatics.
The purpose of this study was first to determine if
depression and obesity were associated with poor
asthma control, and then to determine if depression
could explain poor asthma control in obesity. We
evaluated the relationship of both markers of
obesity, hypothesizing that a significant interaction
between obesity and depression would contribute to
worse asthma control among obese asthmatics. This
study was completed in a well characterized, patient
population participating in a clinical trial of the
placebo response in asthma.
Methods
Data on obesity and symptoms of depression were
derived from participants in a multicenter clinical
trial designed to assess the placebo effect in asthma
performed by the American Lung Association
Asthma Clinical Research Centers. Details of the
main study and eligibility criteria have been
published elsewhere, and are summarized below
[12]. The study was approved by the Institutional
Review Boards at all participating centers, and all
participants signed informed consent.
Males and females at least 15 years of age who
had been diagnosed with asthma by a physician,
regularly used any prescribed asthma medication in
the last 12 months, and had a post-bronchodilator
forced expiratory volume (FEV 1) 75% predicted were
included in the trial. Participants had inadequate
control of asthma symptoms indicated by one of the
following: short-acting b2 agonist use two or more
times per week for relief of asthma symptoms,
nocturnal awakenings once or more per week due to
asthma symptoms, or a Juniper Asthma Control
Questionnaire (ACQ) score of 1.5 at their enrollment
visit.
Participants were excluded if they had a
significant smoking history (10 pack years or active
smoking in the past 6 months), or had used
montelukast or other leukotriene antagonists within
the past 14 days. Participants were also excluded if
they reported a history of hospitalization,
emergency department visits, or prednisone use for
asthma within the past 3 months, past respiratory
failure secondary to asthma, or prior adverse
reaction to montelukast. At baseline, participants
were extensively evaluated for their asthma
characteristics with the Juniper Asthma Control
Obesity and symptoms of depression 1102
Questionnaire [13], and the Juniper Asthma Quality Participant characteristics
of Life Questionnaire [14]. Spirometry was
performed according to ATS guidelines [15].
Symptoms of depression were measured by the
Center for Epidemiological Studies Depression Score
(CES-D) [16,17]. Participants asthma knowledge
and sense of asthma self-efficacy were measured by
the Knowledge, Attitude, and Self-efficacy Asthma
Questionnaire (KASE-AQ) [18].

Statistical approach
Descriptive statistics were used to summarize
baseline characteristics of the study subjects,
divided into three categories according to body
mass index (BMI): lean (BMI 18.5e24.9 kg/m 2),
overweight (BMI 25e29.9 kg/m2), and obese (BMI 30
kg/m2). Continuous variables were compared using
analysis of variance, with log transformations for
non-parametric variables, and proportions were
compared using c2 analysis. Post-hoc comparison of
groups was performed using the Bonferroni
procedure.
We determined the risk of poor asthma control
associated with obesity (defined as a BMI 30)
compared to nonobese (defined as those with a BMI
< 30) and depression (defined as a CES-D score 16
compared to those with a score < 16). We
performed multiple logistic regression including sex,
age, race, education, income and employment
status in the final model. We evaluated the
relationship between asthma control and symptoms
of depression, using an interaction term for obesity
(BMI > 30 kg/m2) and significant symptoms of
depression (defined as a CES-D score 16). Analyses
were performed with STATA 10$0 (College Station,
Texas).

Role of funding source

The study sponsors had no role in study design, data
collection, data analysis, data interpretation or
decision to submit manuscript. The corresponding
author had full access to all the data, and the final
responsibility for the decision to submit for
publication. Results
1103 S.G. Kapadia et al.
A total of 601 unique participants were enrolled in
Table 1 Baseline characteristics of participants.
Lean Overweight Obese p Value
n (%) 205 (34%) 164 (27%) 232 (39%)
Demographic characteristics
Age (years) 32.4 13.3 40.5 14.9* 41.1 12.6* <0.0001

BMI (kg/m )2
22.3 (20.9e23.7) 27.2 (26.0e28.3) 35.0 (32.6e41.1) <0.001
Women 140 (68) 106 (63) 191 (82)
Race or ethnic group (%)
White 144 (69) 104 (64) 114 (49) <0.001
Black 45 (22) 54 (32) 102 (44)
Hispanic 6 (3) 1 (1) 1 (0)
Other 10 (6) 5 (3) 15 (7)
Highest level of education (%)
<High school 19 (9) 11 (7) 19 (8) <0.001
High school 20 (10) 22 (13) 45 (20)
Some college 81 (39) 62 (37) 117 (50)
Bachelors degree 48 (23) 38 (23) 27 (12)
Some post-graduate 15 (7) 10 (6) 11 (5)
Post-graduate degree 22 (11) 21 (13) 13 (6)
Employment status (%)
Student 64 (30) 19 (12) 16 (7) <0.001
Not working 16 (8) 15 (9) 30 (13)
Full time 86 (42) 94 (57) 114 (49)
Part time 25 (12) 16 (9) 29 (13)
Retired 6 (3) 12 (7) 12 (5)
Disabled 3 (1) 3 (2) 19 (8)
Other 5 (2) 5 (3) 12 (5)
Household income (%)
<$20,000 48 (23) 21 (13) 59 (25) 0.22
$20,000e$50,000 57 (28) 52 (31) 74 (32)
$50,000e$75,000 24 (12) 21 (13) 23 (10)
>$75,000 23 (11) 23 (14) 20 (9)
Declined to answer 37 (18) 36 (22) 42 (18)
Dont know 16 (8) 11 (7) 14 (6)
Values shown are mean SD or median (IQR) for continuous variables, and n (%) for
proportions. P values shown are for analysis of variance for continuous variables, and c 2
test for proportions.
*P < 0.05 compared with lean group.

the primary study. Participant demographic

characteristics
are summarized in Table 1. The mean age of
participants was 32 years in the lean group,
overweight and obese asthmatic participants were
significantly older. Most participants were female,
constituting nearly 82% of the obese group. There
was a higher proportion of African American
participants in the obese category. Obese
asthmatics reported completing less education than
leaner participants, though there was no overall
difference in reported income. Employment status
differed among the BMI categories, with a higher
proportion of students in the lean category.

Asthma characteristics

Data on asthma characteristics in the distinct BMI

groups are reported in Table 2. Obese and
overweight asthmatics reported significantly later-
Obesity and symptoms of depression 1104
onset asthma than lean asthmatics. Obese
asthmatics tended to report more frequent use of
oral prednisone for asthma. Obese participants had
worse asthma control as assessed by the Juniper
Asthma Control Questionnaire (ACQ) and worse
asthma-related quality of life as assessed by the
Asthma Quality of Life
 1105 S.G. Kapadia et al.
Questionnaire (AQLQ) compared with both lean and depression symptoms were assessed at the second
overweight asthmatics. study visit) (Table 4).
Data on pulmonary function are also provided in When both obesity and depression were
Table 2, and differed among participants. Obese considered in the same model, there was little
asthmatics had significantly lower FEV 1 and FVC than change in the odds of having poorly controlled
lean asthmatics, and obese and overweight asthma, and the interaction
asthmatics had greater change in FVC in response to between obesity and asthma was not significant (p
bronchodilator than lean asthmatics. Z 0.58), suggesting that obesity and depression
contribute independently to poor asthma control.
Psychological morbidity Depressed patients had worse asthma control in all
BMI groups, suggesting that the
Obese asthmatics had higher depression scores as
assessed by the Center for Epidemiologic Studies Table 3 Measures of psychological morbidity.
Depression Scale (CES-D) and more frequently
Lean Overweight Obese p
surpassed the reported thresholds for mild
Value
depressive symptoms (a score of 16 and above) as
well as probable depression (a score of 23 and CES-D (aY score range, 0-60) median (IQR)
above) (Table 3) [17]. Obese asthmatics also 8 (4e24) 8 (4e24.5) 10 (5e16) 0.03
reported significantly lower self-efficacy related to
asthma compared with lean and obese asthmatics, CES-D level of depressionb n (%)
and both obese and overweight asthmatics had CES-D no 163 (80) 129 (79)
lower asthma knowledge, as assessed by the 169 (73) 0.01 depression
Knowledge, Attitude, and Self-Efficacy Asthma CES-D mild 26 (13) 25 (15) 26 (11)
Questionnaire (KASE-AQ). symptoms
CES-D 16 (7) 10 (6) 37 (16)
probable depression
Combined effect of depression and obesity
KASE-AQ (a[ score range, 5e100) mean SD
Both obesity and having symptoms of depression Self-efficacy 82.4 8.4 82.8 9.2 79.8 9.3c,d 0.001
increased the risk of having poorly controlled
asthma, as defined by a score of 1.5 or greater on Attitude 85.4 7.2 85.5 7.6 85.3 6.4 0.96
the Juniper Asthma Control Score (311 out of 605
Knowledge 12.0 2.8 11.1 2.9c 11.0 3.0c 0.0005
participants had a score of 1.5 or greater when
KASE-AQ, knowledge, attitude, and
self-efficacy asthma questionnaire.
Table 2 Asthma characteristics & pulmonary function. a
Y, Lower score is better; [, Higher score is better.
b
CES-D, center for epidemiologic studies depression
scale, threshold for mild depressive symptoms 16,
Lean probable depression Obese
Overweight 23. p Value
c
p < 0.05 ccompared to lean group.
Age asthma onset (years) 14.9 16.7 21.7 22.7 22.1 20.8c 0.0001
d p < 0.05 compared to overweight
Pack years 3.6 2.8 4.1 group.
3.0 4.0 3.1 0.8
Number of courses of prednisone use in last 12 months (n{%})
1 177 (78) 146 (77) 183 (69) 0.09
2 32 (14) 28 (15) 45 (17) 2 17 (8) 15 (8) 36 (14)
Asthma questionnaires , mean SD
ACQ (Y score range, 0e6)a 1.43 0.68 1.52 0.71 1.76 0.75c,d <0.0001

AQLQ ([ score range, 1e7)a 5.21 1.08 5.08 1.05 4.64 1.09c,d <0.0001

Pulmonary function measures, mean SD

PEF (L/min) 404.2 96.1 398.6 95.1 385.9 93.4 0.12 FEV1 (% predicted pre BD)b 88.4 13.5

85.6 13.2 84.6 13.4 c

0.01

FVC (% predicted pre BD)b 97.7 13.0 94.4 12.8c 91.8 13.0c <0.0001

FEV1/FVC (pre BD) 75.6 9.2 74.3 9.1 75.7 7.6 0.16
FEV1 % change after BD 8.9 10.2 9.9 10.9 8.8 13.0 0.63

FVC % change after BD 2.5 6.1 4.5 9.1c 4.5 11.1c <0.001
Values shown are mean and SD, and are compared by analysis of variance and n (%) for proportions.
ACQ, asthma control questionnaire; AQLQ, asthma quality of life questionnaire; PEF, morning peak expiratory flow; FEV 1,
forced expiratory volume in 1 s; FVC, forced vital capacity; BD, bronchodilator.
a
Y, Lower score is better; [ Higher score is better.
b
Predicted values for FEV1 and FVC are taken from Hankinson et al. [32].
c p < 0.05 compared with lean
group.
d p < 0.01 compared with overweight
group.
Obesity and symptoms of depression 1106
Table 4 Risk of poor asthma control in those with Values shown are mean SD from ACQ, asthma control
obesity and/or depression. questionnaire.
Odds ratio CI
Mild depression was defined using a threshold of CES-D
Obesitya 2.06 1.48e2.88 16, probable depression as CES-D 23.
Depressiona 2.44 1.65e3.63
a p < 0.05 compared with lean
Obesityb 1.83 1.23e3.52 group.
Depressionb 2.08 1.23e3.52 well as worse asthma-related quality of life. Obesity
is not only a risk factor for incident asthma, but is
Poor asthma control was defined as a score of 1.5 on also associated with worse control characterized by
the juniper asthma control questionnaire. a Uni-variate increased symptoms, more frequent use of rescue
analysis for depression (using threshold of CESD C16)
bronchodilator medications, increased risk of
and obesity separately. b Multivariate analysis
combining depression and obesity in the same model,
hospitalizations for asthma, and missed work days
which also includes age, sex, race, education, [2,7,19]. Obesity is a significant cause of poorly
employment, income, and an interaction value for controlled asthma due to many factors such as
presence of obesity and depression (p Z 0.58). altered lung mechanics, altered responses to
medications, elevated airway oxidative stress,
effects of adipokines and cytokines, and other co-
morbidities which occur in obesity such depression
contribution of depression to poor asthma control and obstructive sleep apnea [3]. We have previously
was not unique to obesity (Table 5). reported that symptoms of obstructive sleep apnea
are associated with worse asthma control [20], but
few studies have investigated the role of
Discussion psychological morbidity in the poor asthma control
of obesity.
This study demonstrates that obese asthmatics have
poor asthma control, worse asthma-specific quality Asthmatics are more likely to suffer from anxiety
of life, and suffer a greater burden of symptoms of and depression than the general population,
depression than leaner asthmatics. Obesity and irrespective of BMI [21]. Data from the 2002 World
symptoms of depression are both independently Health Survey collected by the World Health
related to poor asthma control, without a significant Organization across 54 countries suggested that
interaction between the two comorbidities. This depression was significantly associated with asthma
suggests that depression should be considered in in 65% of countries [22]. There may be a causal link
managing obese patients with poor asthma control between depression and asthma; in a longitudinal
as the prevalence of depression increases with BMI, 20 year follow up CARDIA study by Brunner et al.,
but that poor asthma control in obesity is also elevated depressive symptoms were associated with
related to factors other than depression. This study a 1.26 increased risk of developing incident asthma
has important clinical implications with regard to (independent of BMI) [23]. Depression in asthmatics
understanding the physical and mental has been associated with poor asthma control
underpinnings of poor asthma control among obese [21,24], with one study reporting that comorbid
asthmatics. depression was associated with greater health care
The present study provides further evidence of utilization and 51% higher health care costs [25].
the relationship between obesity and poor asthma Depression may contribute to poor asthma control
control as through a number of pathways. Asthmatics with
psychological comorbidity may perceive a greater
intensity of breathlessness [21]. Asthmatics with
depressive symptoms may also develop cholinergic-
Table 5 Asthma control in relation to symptoms of mediated airway constriction in the event of
depression in participants of differing BMI groups. psychological stress [26,27]. Depression may also
No Mild Probable p depression depression affect medication adherence: high levels of
depression depressive symptoms are associated with an 11-fold
increase in odds of poor adherence (measured
Lean
electronically) to inhaled corticosteroid therapy after
Asthma 1.36 0.67 1.58 0.56 1.89 0.72a hospitalization for an asthma exacerbation [27]. It is
<0.01 control also possible that poor asthma control contributes to
the development of depression. In the current study
Overweight we found that over 20% of the study population
Asthma 1.46 0.66 1.62 0.66 1.97 1.21 reached the threshold for mild depression on the
0.07 control validated CES-D questionnaire, which is in line with
previous reports on the prevalence of depression in
Obese
asthma [8,6]. Asthmatic participants with symptoms
Asthma 1.67 0.74 2.05 0.65a 1.96 0.77 0.01 of depression were approximately twice as likely to
control have poor asthma control as those without
1107
symptoms of depression. Our data provide further
evidence that symptoms of depression are
associated with poor asthma control and worse
asthma quality of life.
Many studies suggest there is a significant
relationship between depression and obesity. Meta-
analyses of cohort studies suggest a significant
association between obesity and depression [9,28];
one meta-analysis of 17 community based studies
encompassing 204,507 participants reported a
significant association between depression and
obesity, particularly among females (OR, 1.26; 95%
CI, 1.17e1.36) [9]. Our current study demonstrates
that obese asthmatics had significantly higher
scores on the CES-D questionnaire and a higher
prevalence of depression. Many factors may
contribute to the increased risk of depression with
obesity. Obesity and depression share common risk
factors such as low socioeconomic status and
insufficient physical activity [29]. Psychological
distress may be worsened by obesity because of
social stigmatization which produces low selfworth
and self-esteem, a negative body image, guilt, and
peer isolation [9,28,29]. Hypothalamic-pituitary-
adrenal axis dysfunction from psychological distress
elevates circulating cortisol levels which may
contribute to abdominal obesity. Depression and
obesity likely share common risk factors and may in
part share a common pathophysiology, whether
these factors interact with each other to produce the
worse asthma control characteristic of obesity is not
known.
A few studies have addressed the potential for a
concurrent interaction between obesity and
depression in mediating poor asthma outcomes.
Data collected from the 2006 European National
Health and Wellness Survey of 37,476 adults
demonstrated that less educated, obese, and
depressed asthmatics experience significantly
poorer asthma control [30]. Acosta-Perez et al.
examined the effects of obesity and
depressive/anxiety disorders cooccurring in a
community sample of Puerto Rican youth 10e19
years of age diagnosed with asthma: depression/
anxiety was three times more common in the obese,
but asthma exacerbations were associated with an
increased prevalence of psychological comorbidity
among the nonobese youth only [31]. A recent
single center Canadian study reported that
depression appeared to explain poor asthma control
in obese asthmatics, this differs from our own
findings; these differing results are likely related to
differences in the two study patient populations (our
own being a multi-center study with a younger more
diverse U.S. patient population) [32]. Our current
study demonstrates a clinically meaningful effect of
obesity and depression independently contributing
to significantly poorer asthma control. The presence
of depression contributed to poor asthma control in
all BMI groups. Contrary to our hypothesis, there
was no significant interaction between obesity and
depression, suggesting that the mechanisms linking
S.G. Kapadia et al.
depression and asthma are the same in lean
patients as they are in obese patients, though obese
patients have a higher prevalence of depression.
Awareness of the finding that depression contributes
to poor asthma control is likely critical in the
management of both lean and obese patients with
asthma.
This study does have some limitations. The
patient population was recruited for a clinical trial
and so may not reflect the general asthma
population, although ethnic and economic diversity
in the population was strong. This was a cross-
sectional study, and so we cannot draw any
conclusions about the direction of the association
between asthma and depression.
This study shows that depression likely
contributes to poor asthma control in obese
patients, as obese patients have a higher prevalence
of depression than lean asthmatics, and depression
is associated with poor asthma control. However,
obesity also contributes to poor asthma control
independent of depression; understanding poor
asthma control in obesity requires research into the
pathophysiology of airway disease in obesity. This
study suggests that interventions to address
psychological comorbidity should be studied in
obese asthmatics, and that improving asthma
control in obese asthmatics will require a holistic
approach to improve asthma outcomes.
Funding
Supported by the American Lung Association, and
NIH grants R01HL073494 and P30 RR031158-01.
Conflicts of interest
Sonam Kapadia: has no conflicts of interest
pertaining to this manuscript.
Christine Wei: has no conflicts of interest
pertaining to this manuscript.
Susan Bartlett: has no conflicts of interest
pertaining to this manuscript.
Jason Lang: has no conflicts of interest pertaining
to this manuscript.
Robert Wise: has no conflicts of interest pertaining
to this manuscript.
Anne Dixon: has no conflicts of interest pertaining
to this manuscript.
Author contributions
The following persons participated in the TAPE study.
Obesity and symptoms of depression
Baylor College of Medicine, Houston: N. A.
Hanania (principal investigator), M. Sockrider (co-
principal investigator), L. Giraldo (principal clinic
coordinator), R. Valdez, (coordinator).
Maria Fareri Childrens Hospital at Westchester
Medical Center and New York Medical College,
Valhalla, N.Y.: A. Dozor (principal investigator), N.
Amin and Y. C. Kim (coprincipal investigator), I.
Gherson (principal clinic coordinator), M.
Heydendael and M. Key (coordinators).
Columbia UniversityeNew York University
Consortium, New York: J. Reibman (principal
investigator), E. DiMango (co-principal investigator),
W. Hoerning (clinic coordinator at New York
University), J. Sormillon (clinic coordinator at
Columbia University).
Duke University Medical Center, Durham, N.C.: L.
Williams (principal investigator), J. Sundy (co-
principal investigator), G. Dudek (principal clinic
coordinator), R. Newton, (coordinator).
Emory University School of Medicine, Atlanta:
W.G. Teague (principal investigator), S. Khatri (co-
principal investigator), J. Costolnick, (principal clinic
coordinator), J. Peabody, R. Patel, E Hunter
(coordinators).
Illinois Consortium, Chicago: L. Smith (principal
investigator), J. Moy, E Naureckas, C.S. Olopade (co-
principal investigators), J. Hixon (principal clinic
coordinator), A. Brees, G. Rivera, S. Sietsema, V.
Zagaja (coordinators). Indiana University, Asthma
Clinical Research Center, Indianapolis: M. Busk
(principal investigator), F. Leickly, C. Williams (co-
principal investigators), S. Lynch (principal clinic
coordinator); P. Puntenney (coordinator).
Jefferson Medical College, Philadelphia: F. Leone
(principal investigator), M. HayeseHampton
(principal clinic coordinator).
Louisiana State University Health Sciences Center,
Ernest N. Morial Asthma, Allergy, and Respiratory
Disease Center, New Orleans: W.R. Summer
(principal investigator), C. Glynn (principal clinic
coordinator).
National Jewish Medical and Research Center,
Denver: S. Wenzel (principal investigator), P Silkoff
(co-principal investigator), R. Gibbs (principal clinic
coordinator), L. Lopez, C. Ruis, B. Schoen
(coordinators).
Nemours Childrens CliniceUniversity of Florida
Consortium, Jacksonville: J. Lima (principal
investigator), K. Blake (co-principal investigator), A.
Santos (principal clinic coordinator), L. Duckworth,
D. Schaeffer (coordinators). North ShoreeLong Island
Jewish Health System, New Hyde Park, 485 N.Y.: J. [1]
Karpel (principal investigator), R. Cohen (co-principal
investigator), R. Ramdeo (principal clinic
coordinator). [2]
Northern New England Consortium formerly
Vermont Lung Center at the University of Vermont),
[3]
Colchester, Vt.: C.G. Irvin (principal investigator),
A.E. Dixon, D.A. Kaminsky, E. Kent, T. Lahiri, P.
Shapiro (co-principal investigators), S. Lang[4]
1108
(principal clinic coordinator), J. Allen, A. Coote, L.M.
Doucette, K. Girard, J. Lynn, L. Moon, T.
Viola (coordinators).
The Ohio State University Medical
Center/Columbus Childrens Hospital, Columbus: J.
Mastronarde (principal investigator), K. McCoy (co-
principal investigator), J. Drake (principal clinic
coordinator), R. Compton, L. Raterman
(coordinators).
University of Alabama at Birmingham,
Birmingham: L.B. Gerald (principal investigator),
W.C. Bailey (co-principal investigator), S. Erwin
(principal clinic coordinator), H. Young, A. Kelley, D.
Laken, B. Martin (coordinators).
University of Miami, MiamieUniversity of South
Florida, Tampa: A. Wanner (principal investigator), R.
Lockey (principal investigator), E. Mendes (principal
clinic coordinator for University of Miami), M.
Grandstaff (principal clinic coordinator for University
of South Florida).
B Fimbel (coordinator).
University of Minnesota, Minneapolis: M.N.
Blumenthal (508 principal investigator), G.
Brottman, J. Hagen (coprincipal investigators), A.
Decker, D. Lascewski, S. Kelleher (principal clinic
coordinators), K. Bachman, M. Sneen (coordinators).
University of Missouri, Kansas City School of
Medicine, Kansas City: G. Salzman (principal
investigator), D. Pyszczynski (co-principal
investigator), P. Haney (principal clinic coordinator).
St. Louis Asthma Clinical Research Center:
Washington University, St. Louis University, and
Clinical Research Center, St. Louis: M. Castro
(principal investigator), L. Bacharier, K. Sumino (co-
investigators), M.E. Scheipeter (principal clinic
coordinator), J. Tarsi (coordinator).
University of California San Diego: S Wasserman
(principal investigator), J Ramsdell (co-principal
investigator). Chairmans Office, Respiratory
Hospital, Winnipeg, Man., Canada: N. Anthonisen
(research group chair). Data Coordinating Center,
Johns Hopkins University Center for Clinical Trials.
Baltimore: R. Wise (center director), J. Holbrook
(deputy director), E. Brown (principal coordinator),
M. Dale, M. Daniel, G. Leatherman, C. Levine, J.
Jones, R. Masih, S Modak, D. Nowakowski, N.
Prusakowski, D. Shade, E. Sugar.
Data and Safety Monitoring Board: L. Hudson
(chair), V. Chinchilli, P. Lanken, B. McWilliams, C.
Rinaldo, D. Tashkin. References
Ronmark E, Andersson C, Nystrom L, Forsberg B, Jarvholm
B, Lundback B. Obesity increases the risk of incident
asthma among adults. Eur Respir J 2005;25(2):282e8.
Lugogo NL, Kraft M, Dixon AE. Does obesity produce a
distinct asthma phenotype? J Appl Physiol
2010;108(3):729e34.
Dixon AE, Holguin F, Sood A, et al. An official American
Thoracic Society workshop report: obesity and asthma.
Proc Am Thorac Soc 2010;7(5):325e35.
Mosen DM, Schatz M, Magid DJ, Camargo Jr CA. The
relationship between obesity and asthma severity and
 1109 S.G. Kapadia et al.
control in adults. J Allergy Clin Immunol[19] Grammer LC, Weiss KB, Pedicano JB, et al. Obesity and
2008;122(3):507e11. e6. asthma morbidity in a community-based adult cohort in a
[5] Finucane MM, Stevens GA, Cowan MJ, et al. National, large urban area: the Chicago initiative to raise asthma
regional, and global trends in body-mass index since 1980: health equity (CHIRAH). J Asthma Off J Assoc Care Asthma
systematic analysis of health examination surveys and 2010; 47(5):491e5.
epidemiological studies with 960 country-years and 9.1[20] Dixon AE, Clerisme-Beaty EM, Sugar EA, et al. Effects of
million participants. Lancet 2011;377(9765):557e67. obstructive sleep apnea and gastroesophageal reflux
[6] Wilson DH, Appleton SL, Taylor AW, et al. Depression and disease on asthma control in obesity. J Asthma Off J Assoc
obesity in adults with asthma: multiple comorbidities and Care Asthma 2011;48(7):707e13.
management issues. Med J Aust 2010;192(7):381e3. [21] Thomas M, Bruton A, Moffat M, Cleland J. Asthma and
[7] Lavoie KL, Bacon SL, Labrecque M, Cartier A, Ditto B. psychological dysfunction. Prim Care Respir J J General
Higher BMI is associated with worse asthma control and Pract Airw Group 2011;20(3):250e6.
quality of life but not asthma severity. Respir Med[22] Wong KO, Hunter Rowe B, Douwes J, Senthilselvan A.
2006;100(4):648e57. Asthma and wheezing are associated with depression and
[8] Cazzola M, Segreti A, Calzetta L, Rogliani P. Comorbidities anxiety in adults: an analysis from 54 countries. Pulm Med
of asthma: current knowledge and future research needs. 2013;2013: 929028.
Curr Opin Pulm Med 2013;19(1):36e41. [23] Brunner WM, Schreiner PJ, Sood A, Jacobs Jr DR. Depression
[9] De Wit L, Luppino F, van Straten A, Penninx B, Zitman F, and risk of incident asthma in adults. The CARDIA study.
Cuijpers P. Depression and obesity: a meta-analysis of Am J Respir Crit Care Med 2014;189(9):1044e51.
community-based studies. Psychiatry Res[24] Lavoie KL, Cartier A, Labrecque M, et al. Are psychiatric
2010;178(2):230e5. disorders associated with worse asthma control and quality
[10] Andersen JR, Aasprang A, Bergsholm P, Sletteskog N, Vage of life in asthma patients? Respir Med 2005;99(10):
V, Natvig GK. Anxiety and depression in association with 1249e57.
morbid obesity: changes with improved physical health[25] Richardson LP, Russo JE, Lozano P, McCauley E, Katon W.
after duodenal switch. Health Qual Life Outcomes The effect of comorbid anxiety and depressive disorders on
2010;8:52. health care utilization and costs among adolescents with
[11] Dixon AE, Pratley RE, Forgione PM, et al. Effects of obesity asthma. General Hosp Psychiatry 2008;30(5):398e406.
and bariatric surgery on airway hyperresponsiveness,[26] Miller BD, Wood BL. Influence of specific emotional states
asthma control, and inflammation. J Allergy Clin Immunol on autonomic reactivity and pulmonary function in
2011; 128(3):508e15. e1e2. asthmatic children. J Am Acad Child Adolesc Psychiatry
[12] Wise RA, Bartlett SJ, Brown ED, et al. Randomized trial of 1997;36(5): 669e77.
the effect of drug presentation on asthma outcomes: the[27] Nadel JA, Barnes PJ. Autonomic regulation of the airways.
American Lung Association Asthma Clinical Research Annu Rev Med 1984;35:451e67.
Centers. J Allergy Clin Immunol 2009;124(3):436 e44. 44e1-[28] Dockray S, Susman EJ, Dorn LD. Depression, cortisol
8. reactivity, and obesity in childhood and adolescence. J
[13] Juniper EF, OByrne PM, Guyatt GH, Ferrie PJ, King DR. Adolesc Health Off Publ Soc Adolesc Med
Development and validation of a questionnaire to measure 2009;45(4):344e50.
asthma control. Eur Respir J 1999;14(4):902 e7. [29] Faith MS, Butryn M, Wadden TA, Fabricatore A, Nguyen AM,
[14] Juniper EF, Guyatt GH, Ferrie PJ, Griffith LE. Measuring Heymsfield SB. Evidence for prospective associations
quality of life in asthma. Am Rev Respir Dis 1993;147(4): among depression and obesity in population-based studies.
832e8. Obes Rev Off J Int Assoc Study Obes 2011;12(5):e438e53.
[15] Standardization of Spirometry. 1994 update. American[30] Demoly P, Paggiaro P, Plaza V, et al. Prevalence of asthma
Thoracic Society. Am J Respir Crit Care Med 1995;152(3): control among adults in France, Germany, Italy, Spain and
1107e36. the UK. Eur Respir Rev Off J Eur Respir Soc
[16] Weissman MM, Sholomskas D, Pottenger M, Prusoff BA, 2009;18(112):105e12.
Locke BZ. Assessing depressive symptoms in five [31] Acosta-Perez E, Canino G, Ramirez R, Prelip M, Martin M,
psychiatric populations: a validation study. Am J Epidemiol Ortega AN. Do Puerto Rican youth with asthma and obesity
1977;106(3): 203e14. have higher odds for mental health disorders?
[17] Radloff LS. The CES-D scale: a self-report depression scale Psychosomatics 2012;53(2):162e71.
for research in the general population. Appl Psychol Meas[32] Boudreau M, Bacon SL, Ouellet K, Jacob A, Lavoie KL.
1977;1: 6. Mediator effect of depressive symptoms on the association
[18] Wigal JK, Stout C, Brandon M, et al. The knowledge, between body mass index and asthma control in adult
attitude, and self-efficacy asthma questionnaire. Chest asthmatics. Chest 2014 [in press].
1993;104(4): 1144e8.