Depression, asthma and bronchodilator response in a nationwide study of U.S. adults

Abstract

Background

Little is known about the relation between two common co-morbidities (depression and anxiety) and asthma or bronchodilator response (BDR).

Objective

To examine the association between depressive symptoms and asthma or BDR in U.S. adults.

Methods

Cross-sectional study of 20,272 adults 20–79 years from the 2007–2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9), and classified as: none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a PHQ-9 ≥15. Anxiety was defined as ≥5 days feeling anxious in the prior month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and ≥1 asthma attack in the previous year. BDR (as percentage of baseline FEV₁) was measured in 1,356 participants with FEV₁/FVC<0.70 and/or FEV₁<70% of predicted. Logistic or linear regression was used for the multivariable analysis.

Results

Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 higher odds of asthma than those with minimal or no depressive symptoms (95% confidence interval 2.6–4.5, P<0.01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI=−7.5% to −0.8%, P=0.02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR.

Conclusion

Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma.

INTRODUCTION

Asthma is a major public health issue around the world¹, affecting approximately 28 million adults in the United States (U.S.)². A common feature of asthma is reversible airflow obstruction, measured as positive change in forced expiratory volume in 1 second (FEV₁) after administration of an inhaled short-term β₂ agonist, such as albuterol (bronchodilator response or BDR). BDR is often used as part of the diagnostic evaluation of asthma and in the assessment of asthma control^{3, 4}.

In the U.S., 16 million adults (or 7% of the adult population) suffer from at least one major depressive episode each year⁵. Of interest, depression and anxiety are more common in adults with asthma than in those in the general population^{6, 7}. Moreover, depressive symptoms and anxiety-related disorders have been associated with reduced pulmonary function and increased airway resistance, emergency department visits and hospitalizations, and poorer quality of life in children or adults with asthma^8–13. However, whether depressive symptoms are associated with asthma independently of anxiety symptoms is currently unclear.

Recent findings suggest that depression and its common precipitating stressors cause asthma morbidity through changes in the expression of genes that regulate relevant autonomic, neuroendocrine, and immunologic responses¹⁴. Chronic psychosocial stress has been associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in white blood cells of children with asthma¹⁵. Consistent with potential down-regulation of the β2-adrenergic receptor by stressors, we recently showed that increased anxiety, and particularly chronic stress or anxiety, is associated with reduced BDR in children with asthma¹⁶. On the basis of our findings in children, as well as a plausible role for depression on asthma morbidity, we hypothesized that depression (a common co-morbidity of anxiety disorders) leads to reduced BDR in adults with asthma.

In the present study, we investigate the relationship between depressive symptoms and BDR in a nationwide study of U.S. adults. Moreover, we examine whether depressive symptoms are associated with asthma or BDR in adults, independently of anxiety symptoms.

METHODS

Subject recruitment and study procedures

The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional nationwide survey designed to assess the health and nutritional status of non-institutionalized children and adults in the U.S.¹⁷ NHANES combines interview and physical examination of study participants by highly trained personnel. Participants are selected using a stratified multistage probability design, and are thus a representative sample of the U.S. population. As part of the study design, ethnic minorities (African Americans, Asians and Mexican Americans) and persons 60 years and older are over-sampled to increase statistical power for data analysis in these groups. In this analysis, we included data for 20,272 adults aged 20 to 79 years old who participated in the 2007–2008, 2009–2010, or 2011–2012 NHANES study cycles.

Depression was measured using the Patient Health Questionnaire (PHQ-9), a nine-item self-administered screening instrument that contains questions about the frequency of depressive symptoms over the past two weeks. Response categories for the nine-item instrument were scored from 0 to 3 (0= “not at all,” 1= “several days,” 2= “more than half the days” and 3= “nearly every day”). The total PHQ-9 score is based on the sum of the points for each question, and thus ranges from 0 to 27. Depression severity was classified as minimal (PHQ-9 score <5), mild (5–9), moderate (10–14), moderately severe (15–19), and severe (≥20)¹⁸. A PHQ-9 score ≥ 15 (comprising moderately severe to severe depression) is consistent with major depression¹⁹. NHANES participants were also asked about the number of days that they had felt worried, tense or anxious in the previous 30 days. As in prior work¹⁶, anxiety symptoms were then categorized as binary (at or above the upper quartile [5 days] vs. the lowest three quartiles [4 days or fewer]) for the number of days feeling anxious in the prior month in our primary analysis, and as continuous in secondary analyses.

Participants were not eligible for spirometry if they were on supplemental oxygen or had: painful ear infections; current chest pain or a physical problem with forceful expiration; surgery (of the eye, chest or the abdomen) in the prior 3 months; heart disease; history of aneurysm, detached retina, hemoptysis, or collapsed lung; or tuberculosis exposure. Eligible participants performed spirometry following American Thoracic Society (ATS) recommendations²⁰ by NHANES Mobile Examination Center (MEC) physicians. The best FEV₁ and forced vital capacity (FVC) were selected for analysis. Based on NHANES study protocol, participants whose baseline FEV₁/FVC ratio was below the lower limit of normal (LLN)²¹ and/or whose baseline FEV₁ was below 70% of the predicted value for their demographic characteristics underwent a repeat spirometry, 15 minutes after inhalation of albuterol. Participants were excluded from bronchodilator administration if they: had recently used a short-acting inhaled β2-agonist or had a previous adverse reaction to albuterol; had a history of congenital heart disease, hypertension, or major arrhythmia; had an implanted defibrillator; were pregnant; or were breastfeeding.

Informed consent was obtained from all study participants. The NHANES was approved by the institutional review board of the National Center for Health Statistics of the Center for Disease Control and Prevention (CDC). Further details on NHANES measurements and procedures may be found in the NHANES website (http://www.cdc.gov/nchs/nhanes.htm); specific details on spirometry and bronchodilator administration can be found in the NHANES manual (http://www.cdc.gov/nchs/data/nhanes/nhanes_11_12/Respiratory_Health_Bronchodilator.pdf).

Statistical analysis

Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and participant report of at least one asthma attack in the previous year. Participants who had neither an asthma diagnosis nor an asthma attack in the previous year were selected as control subjects. Participants who reported a lifetime diagnosis of asthma but no asthma attacks in the previous year were excluded from this analysis. BDR was defined as: ([post-bronchodilator FEV₁ − pre-bronchodilator FEV₁]/pre-bronchodilator FEV₁) × 100.

Primary sampling units and strata for the complex NHANES survey design were taken into account for data analysis. Sampling weights, stratification, and clusters provided in the NHANES dataset were incorporated into the analysis to obtain proper estimates and their standard errors. Wald chi-square tests and t-tests were used for bivariate analyses of binary and continuous variables, respectively. Logistic regression was used for the multivariable analysis of depression or anxiety and asthma, and linear regression was used for the multivariable analysis of depression or anxiety and BDR. All multivariable models were adjusted for age, gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, or other), educational attainment (≤ 12^th grade, completed high school or had a graduate education diploma, completed some college or an Associate in Arts (AA) degree, and college degree or higher), body mass index (BMI), smoking status (never, former, or current), and pack-years of smoking. All multivariate models of BDR were additionally adjusted for baseline (pre-bronchodilator) FEV₁. All statistical analyses were conducted using the SAS SURVEY procedure and SAS 9.3 software (SAS Institute Inc., Cary, NC).

RESULTS

During the study period (2007 to 2012), there were 20,272 adults ages 20 to 79 years who completed both a baseline spirometry and the PHQ-9, and who could be classified as having current asthma or not. Of the 18,637 NHANES participants without asthma (control subjects), 15,063 had a spirometry of good quality; 1,194 (7.9%) of these 15,063 subjects had a BDR measurement (because they had a reduced FEV₁/FVC and/or a reduced baseline FEV₁) and are thus included in the analysis of BDR. Of the 1,635 NHANES participants with current asthma, 1,214 had a spirometry of good quality; 192 (15.8%) of these 1,214 subjects underwent a BDR measurement (because they had a reduced FEV₁/FVC and/or a reduced baseline FEV₁), and are thus included in the analysis of BDR.

The main characteristics of the 20,272 participants included in the analysis of asthma are shown in Table 1. Compared with control subjects (n=18,637), subjects with current asthma (n=1,635) were significantly more likely to be female and non-Hispanic Black, to be current or former smokers, to have lower household income and educational level, to lack private health insurance, and to have anxiety and a greater severity of depressive symptoms. Compared with control subjects, those with current asthma were also significantly more likely to have lower measures of lung function but higher BMI and pack-years of smoking. Table 2 shows the results of the multivariable analysis of depressive symptoms and asthma in all 20,272 participants. In this analysis, subjects with mild to severe depressive symptoms had significantly higher odds of asthma than those with minimal or no depressive symptoms, even after adjustment for anxiety and other covariates (Model 1). Moreover, the estimated magnitude of the observed association increased with greater severity of depressive symptoms (P for linear trend <0.01). Similar results were obtained in an analysis combining the last two categories (moderately severe and severe) into one (major depression, Model 2). We obtained similar results after excluding former or current smokers from the analysis, despite reduced sample size (Table E1).

Table 1.

Characteristics of all study participants and participants with bronchodilator response (BDR) by asthma status, 2007–2012 NHANES

	All subjects n=20,272		Subjects with BDR measures n=1,356
Characteristics	No asthma n=18,637	Current asthma n=1,635	No asthma n=1,194	Current asthma n=162
Age (years)	47.2 ± 0.2	47.4 ± 0.4	50.3 ± 0.7	45.1 ± 1.8*
Male gender	9453 (50.1)	603 (36.7)*	792 (63.3)	84 (55.6)
Race/ethnicity
Non-Hispanic White	8546 (69.0)	823 (71.2)*	717 (79.0)	91 (74.0)
Non-Hispanic Black	3692 (10.7)	411 (14.5)	192 (6.9)	34 (10.5)
Hispanic	5072 (13.9)	303 (9.2)	216 (7.8)	25 (8.0)
Other	1327 (6.4)	98 (5.1)	69 (6.3)	12 (7.5)
Education
≤ 12th grade	4997 (17.7)	484 (20.8)*	305 (16.8)	36 (10.8)*
High school/GED/AA	9559 (53.6)	866 (55.3)	629 (54.0)	79 (52.7)
College and above	4054 (28.7)	285 (23.8)	260 (29.2)	47 (36.5)
Household income < $20,000/year	3845 (14.2)	513 (20.1)*	232 (12.6)	48(18.9)
Covered by private health insurance	7628 (64.6)	557 (56.0)*	548 (70.6)	71 (69.5)
Smoking status
Never	10189 (55.4)	725 (46.0)*	406 (34.2)	71 (42.7)
Former	4559 (24.6)	426 (26.3)	364 (30.4)	45 (30.6)
Current	3882 (20.2)	483 (27.7)	423 (35.5)	46 (26.7)
Body mass index (kg/m2)	28.6 ± 0.1	30.9 ± 0.3*	27.2 ± 0.2	28.7 ± 0.6*
Pack-years of smoking	7.8 ±0.4	11.6 ± 0.9*	15.7 ±1.1	9.6 ± 1.8*
Pre-bronchodilator FEV1 (L)†	3.26 ± 0.01	2.81± 0.04*	2.92 ± 0.03	2.78 ± 0.10*
Pre-bronchodilator FVC (L)†	4.15 ± 0.02	3.78 ± 0.05*	4.42 ± 0.05	4.24 ± 0.13*
Pre-bronchodilator FEV1/FVC (%)	78.3 ± 0.2	74.0 ± 0.4*	65.8 ± 0.2	65.4 ± 0.7
Bronchodilator response as a percent of baseline FEV1			5.8 ± 0.23	9.4 ± 0.67*
Use of asthma medications		1105 (65.4)		109 (65.0)
Depression severity‡
Minimal	14281 (78.4)	917 (60.5)*	969 (83.2)	113 (69.6)
Mild	2781 (14.6)	370 (21.6)	162 (12.8)	34 (22.4)
Moderate	1006 (4.5)	176 (8.9)	48 (2.9)	8 (4.3)
Moderately severe	416 (1.8)	124 (6.5)	11 (0.6)	4 (2.3)
Severe	153 (0.7)	52 (2.4)	4 (0.5)	3 (1.4)
Major depression§	569 (2.5)	176 (8.9)*	15 (1.0)	7 (0.4)
Felt anxious more than 5 days in the past 30 days	5894 (32.7)	774 (44.1)*	316 (27.8)	60 (36.0)

GED = General Educational Development; AA = Associate of Arts; FEV₁ = Forced Expiratory Volume in the first second; FVC = forced vital capacity. Results shown as mean ± standard error for continuous variables, and as number (%) for binary variables

^*P<0.05 comparison between participants with and without asthma in each group.

^†Adjusted for age, gender, height, and height squared

^‡Depression severity is defined by Patient Health Questionnaire-9 (PHQ-9): 0–4=minimal; 5–9=mild; 10–14=moderate; 15–19=moderately severe, ≥20=severe

^§Major depression is defined by PHQ-9 ≥ 15 and comprises moderately severe to severe depressive symptoms

Table 2.

Multivariate analysis of depression severity and asthma in all study subjects and subjects with bronchodilator response (BDR)

	All subjects, n=20,272		Subjects with BDR measures, n=1,356
	Model 1	Model 2	Model 3	Model 4
	Odds ratio (95% confidence interval), two-sided P value
Depression severity†
Minimal	1.0		1.0	-
Mild	1.68 (1.31, 2.16). <0.01		2.13 (1.08, 4.22), 0.03
Moderate	2.03 (1.56, 2.61), <0.01		2.25 (0.78, 6.68), 0.14
Moderately severe	3.18 (2.37, 4.26), <0.01		6.25 (0.99, 39.33), 0.05
Severe	3.95 (2.38, 6.56),<0.01*		6.13 (1.37, 27.06), 0.02*
Anxiety‡	1.04 (0.88, 1.23), 0.68		0.90 (0.49, 1.66), 0.73
Depression severity
Minimal	-	1.0	-	1.0
Mild		1.68 (1.31, 2.16), <0.01		2.13 (1.07, 4.22), 0.03
Moderate		2.03 (1.58, 2.61), <0.01		2.25 (0.76, 6.68), 0.14
Major depression§		3.37 (2.55, 4.45), <0.01*		6.20 (1.68, 22.98), <0.01
Anxiety		1.04 (0.88, 1.23), 0.66		0.90 (0.49, 1.66), 0.73

All models adjusted for age, gender, race/ethnicity, education, body mass index, smoking status, pack-years of smoking and anxiety.

^*P for linear trend <0.01.

^†Severity of depressive symptoms severity defined by Patient Health Questionnaire-9 scores: 0–4=minimal; 5–9=mild; 10–14=moderate; 15–19=moderately severe, ≥20=severe.

^‡Feeling anxious more than 5 days in the past 30 days.

^§Major depression: PHQ-9 ≥ 15, comprising moderately severe to severe depressive symptoms.

The main characteristics of the 1,356 participating adults with BDR measures are shown in Table 1. Compared to control subjects (n=1,194), those with asthma (n=162) were significantly younger and more likely to have higher educational attainment and BMI, fewer pack-years of smoking, lower FEV₁ and FVC, and a higher BDR. There were no significant differences in gender, race/ethnicity, household income, health insurance coverage, smoking status, depression severity or anxiety between subjects with and without asthma. Table 2 shows the findings of the multivariable analysis of asthma in the 1,356 subjects with BDR. In this analysis, which was adjusted for anxiety and other covariates, the magnitude of the estimated effect of moderately severe to severe depressive symptoms on asthma was greater (odds ratio=6.13 to 6.25, Model 3) than that from the analysis in all subjects (odds ratio= 3.18 to 3.95, Model 1 in Table 2). Similar findings were obtained when moderately severe to severe depressive symptoms were collapsed into one category (major depression, Model 4). We found no significant association between anxiety and asthma, either among all subjects or among subjects with BDR measures (Table 2).

The results of the multivariable linear analysis of depressive symptoms and BDR are shown in Figure 1, separately for adults with and without asthma. Among adults with asthma, those with major depression had a BDR that was significantly lower (β= −4.6%) than those with no depressive symptoms (i.e. adults with asthma and major depression have BDR that is 4.6 percentage points lower than adults with asthma without major depression). In terms of the absolute change in FEV₁ values, adults with asthma and major depression had a mean decrement in FEV₁ of 107 ml (95% confidence interval = 5–218 ml, data not shown). In this analysis, neither mild depressive symptoms nor moderate depressive symptoms were significantly associated with BDR (left panel). Among adults without asthma, depressive symptoms were not significantly associated with BDR (right panel).

Figure 1. Multivariable analysis of depressive symptoms† and bronchodilator response in 1,356 adult participants, stratified by asthma status.

Results shown as β coefficient (95% confidence interval) of change in BDR (i.e. adults with asthma and major depression have BDR that is 4.6 percent lower than adults with asthma without major depression). All models were adjusted for age, gender, race/ethnicity, educational attainment, body mass index, smoking status, pack-years of smoking, and pre- bronchodilator FEV₁.

†Severity of depressive symptoms defined by Patient Health Questionnaire-9 scores: 0–4=none to minimal; 5–9=mild; 10–14=moderate; ≥15=major depression (comprising moderately severe to severe symptoms).

*P < 0.05 for comparison of major depression vs. minimal to no depressive symptoms.

We next estimated the independent effects of depressive symptoms and anxiety on BDR, separately in adults with and without asthma (Table 3). In a multivariable analysis, anxiety was not significantly associated with BDR in adults with or without asthma (Model 1). Among subjects with asthma, those with major depression had a BDR that was significantly lower (by ~4.2%) than that of those without major depression (e.g. a PHQ-9 score <15, comprising no depression, minimal, and moderate depression [Model 2]). Major depression was not significantly associated with BDR in subjects without asthma (Model 2). Our findings for major depression and BDR in adults with and without asthma were not changed after additional adjustment for anxiety (Model 3). Moreover, we obtained similar results after additional adjustment for use of asthma medications in the multivariable analysis among subjects with asthma (data not shown).

Table 3.

Multivariable analysis of major depression, anxiety and bronchodilator response in 1,356 adult participants, stratified by asthma status

	Model 1	Model 2	Model 3
	β (95% confidence interval), two-sided P value
No asthma (n=1194)
Anxiety*	0.15 (−0.81, 1.10), 0.76	--	0.09 (−0.91, 1.08), 0.86
Major depression†	--	1.65 (−0.55, 3.84), 0.14	1.59 (−0.88, 4.06), 0.20
Current asthma (n=162)
Anxiety	−0.33 (−3.26, 2.61), 0.82	--	0.07 (−2.87, 3.02), 0.96
Major depression	--	−4.11 (−7.86, −0.36), 0.03	−4.15 (−7.51, −0.79), 0.02

All models adjusted for age, gender, race/ethnicity, education, body mass index, smoking status, pack-years of smoking and pre-bronchodilator (baseline) FEV₁.

^*Feeling anxious more than 5 days in the past 30 days

^†Major depression: PHQ-9 score ≥ 15 (compared to those with PHQ-9 score < 15)

Secondary analyses in which anxiety was considered as a continuous variable yielded very similar results to those of our primary analysis using anxiety as a binary variable (data not shown).

DISCUSSION

To our knowledge, this is the first report of an association between major depression and reduced bronchodilator response in subjects with asthma.

Major depression may lead to dysregulation of the hypothalamic pituitary axis and autonomic nervous system, resulting in persistent secretion of cortisol and catecholamines, down-regulation of the glucocorticoid and β2-adrenergic receptors, and –ultimately- abnormal immune responses and increased airway inflammation, and reduced response to short-acting β2-agonist in subjects with asthma²². Alternatively, major depression may lead to airway inflammation through increased production of pro-inflammatory cytokines, including IL-1 and Il-6^{23, 24}.

Major depression can result from or be accompanied by chronic stress or anxiety, which was recently shown to be associated with reduced BDR in children with asthma¹⁶. However, our results in the current analysis were unchanged after adjustment for anxiety symptoms in the previous month, and such symptoms were also not associated with BDR in the subgroup of 162 adults with asthma and BDR measures. Our negative findings for anxiety and BDR may be due to limited statistical power due to small sample size, age-related effects (e.g. stronger effects of stress or anxiety in children¹⁶ than in adults with asthma), or insufficient assessment of chronic stress and anxiety-related disorders (e.g. lack of data on post-traumatic stress disorder).

A recent longitudinal study showed that depression (defined as a Center for Epidemiologic Studies Depression (CESD) scale score ≥16 and/or self-reported use of antidepressant medications) is associated with 1.26 times higher risk of incident (new-onset) asthma among U.S. white and African American adults (95% confidence interval for hazard ratio= 1.02 to 1.56)²⁵. In another longitudinal study, African American women with a CESD scale score ≥33 had twice the risk of incident asthma as those with a CESD scale score <16 (which suggests no significant depression)²⁶. Our current study differs from and expands on previous reports in that we include Hispanic and Asian subjects, show a linear association between the severity of depressive symptoms and asthma, and adjust for concurrent anxiety symptoms. Moreover, we show that the estimated effect of moderately severe to severe depressive symptoms on asthma is greater in subjects with lung function abnormalities suggestive of airflow obstruction (who may have a greater predisposition to or severity of asthma). We report stronger estimates of the effect of depression on asthma than those from prior reports, which may be explained by differences in study design (e.g. cross-sectional vs. longitudinal) and study populations, as well as in the assessment of the severity of depressive symptoms.

Our study has considerable strengths, including data on the severity of depressive symptoms in a representative sample of U.S. adults, performance of standardized procedures by uniformly trained personnel, and BDR measurements in a subset of adults (with and without asthma) with abnormal spirometry. We also acknowledge limitations of our study, beyond those discussed above. First, temporality cannot be established in this cross-sectional study, and we cannot thus exclude “reverse causation” (e.g. more severe asthma leading to both reduced BDR and depressive symptoms)³⁰. However, “reverse causation” is unlikely as a major explanation for our findings, since all analyses were adjusted for baseline FEV₁. Moreover, a recent longitudinal study of U.S. adults showed no association between asthma and incident depressive symptoms²⁴. Second, we lack detailed data on medication use or medication adherence, and thus cannot exclude non-adherence with anti-inflammatory medications (e.g. inhaled corticosteroids) as an explanation for our results for BDR in adults with asthma. However, we recently showed that non-adherence fails to explain reduced BDR among highly stressed children with asthma¹⁶. Third, BDR was only measured in adults with reduced FEV₁/FVC and/or FEV₁ in NHANES, and thus our findings cannot be extrapolated to all subjects with asthma. However, assessment of BDR is more important in subjects with asthma who exhibit signs of airway obstruction (e.g. low FEV₁ or FEV₁/FVC). Moreover, our results for depressive symptoms are similar (in both direction and magnitude) to those obtained for chronic stress or anxiety disorders (e.g. panic disorder) in a recent study of children with asthma. Fourth, misclassification of chronic obstructive pulmonary disease as asthma is possible in a study of adults. However, our results were similar after excluding former and current smokers from the analysis. Finally, the number of people reporting major depression was relatively small, and we lack data on use of antidepressant medications, which may further indicate greater severity of depressive symptoms.

In summary, our findings suggest that major depression is associated with reduced BDR in adults with asthma. Our results also suggest that the severity of depressive symptoms is strongly correlated with increased risk of asthma in adults, independently of anxiety symptoms. Future studies should address whether the treatment of depression affects the development of asthma or asthma morbidity in adults.

Highlight Box.

1. What is already known? Depression has been associated with asthma, but it is not clear whether anxiety symptoms explain this association. Whether depression influences bronchodilator response (BDR) is unknown.

2. What does this article add to our knowledge? We found that depressive symptoms are associated with asthma in adults, and that major depression is associated with reduced BDR in adults with asthma. The observed association between depressive symptoms and asthma or BDR is independent of anxiety symptoms.

3. How does this study impact current management guidelines? Physicians caring for adults with asthma should be aware of co-existing depression and asthma, and appropriately treat concurrent depression.

Abbreviations

FEV₁

forced expiratory volume in 1 second

FVC

forced vital capacity

BDR

bronchodilator response

NHANES

National Health and Nutrition Examination Survey

PHQ-9

Patient Health Questionnaire

BMI

body mass index

HPA

hypothalamic–pituitary–adrenal

ADRB2

β2-adrenergic receptor