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Original Research: Asthma |

Mediator Effect of Depressive Symptoms on the Association Between BMI and Asthma Control in AdultsDepressive Symptoms, BMI, and Asthma Control FREE TO VIEW

Maxine Boudreau, BSc; Simon L. Bacon, PhD; Karine Ouellet, BSc; Ariane Jacob, BSc; Kim L. Lavoie, PhD
Author and Funding Information

From the Montreal Behavioural Medicine Centre (Mss Boudreau, Ouellet, and Jacob and Drs Bacon and Lavoie) and Research Centre (Mss Boudreau, Ouellet, and Jacob and Drs Bacon and Lavoie), Hôpital du Sacré-Cœur de Montréal–a University of Montréal affiliated hospital; Department of Psychology (Mss Boudreau, Ouellet, and Jacob and Dr Lavoie), University of Quebec at Montreal; Department of Exercise Science (Dr Bacon), Concordia University; and Research Centre (Drs Bacon and Lavoie), Montreal Heart Institute–a University of Montréal affiliated hospital, Montreal, QC, Canada.

CORRESPONDENCE TO: Kim L. Lavoie, PhD, Montreal Behavioural Medicine Centre, Hôpital du Sacré-Cœur de Montréal–a University of Montréal affiliated hospital, 5400 Gouin W, Montreal, QC, H4J 1C5, Canada; e-mail: k-lavoie@crhsc.rtss.qc.ca


FUNDING/SUPPORT: Direct funding support for this study was provided by the Social Sciences and Humanities Research Counsel of Canada. Additional support was received from the Fonds de la recherche en santé du Québec (FRSQ) (Chercheur-boursier awards to Drs Bacon and Lavoie; scholarships to Mss Boudreau, Ouellet, and Jacob), the Canadian Institutes of Health Research (New Investigator awards to Drs Bacon and Lavoie; scholarship to Ms Boudreau), the FRSQ Respiratory Health Network (scholarship to Ms Boudreau), and the Fonds Québecois de la recherche sur la société et la culture (scholarship to Ms Jacob).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(2):348-354. doi:10.1378/chest.13-1796
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BACKGROUND:  Obesity has been associated with worse asthma control. Depression has also been shown to be disproportionally prevalent among patients with asthma and among patients with obesity. However, no studies have examined the mediating effect of depression on the obesity-asthma relationship. This study examined the extent to which depressive symptoms may mediate the obesity-asthma relationship in an adult sample.

METHODS:  A total of 798 patients with physician-diagnosed asthma were recruited from the outpatient asthma clinic at Hôpital du Sacré-Cœur de Montréal. Patients provided demographic and medical history information and completed a battery of questionnaires, including the Beck Depression Inventory (BDI)-II and the Asthma Control Questionnaire (ACQ). BMI was calculated from self-reported height and weight.

RESULTS:  Analyses adjusted for age, sex, years of education, cohabitation, and inhaled corticosteroid dose revealed an association between BMI and ACQ (β = 0.017, P = .026), between BMI and BDI-II (β = 0.189, P = .002), and between BDI-II and ACQ (β = 0.044, P < .001). However, when both BDI-II and BMI were entered into the same model, BDI-II (β = 0.044, P < .001) but not BMI (β = 0.009, P = .226) remained significantly associated with ACQ.

CONCLUSIONS:  The results indicate that depression and a high BMI are both associated with worse asthma control. However, consistent with our hypotheses, the relationship between BMI and worse asthma control was mediated by depressive symptoms. Future studies should examine the precise role of depressive symptoms in both weight and asthma control.

Figures in this Article

Obesity is highly prevalent, with nearly 35% of US adults and up to 30% of Canadian adults defined as obese.13 Obesity has important and varied health consequences, including increasing one’s risk for hypertension, cardiovascular disease, diabetes, cancer, lung disease, and sleep apnea.4,5

Similar to obesity, asthma is one of the four most common chronic disorders in adults and affects > 300 million people worldwide.6 Symptoms of asthma can be well controlled, and achieving optimal asthma control remains the primary treatment goal.7 However, high rates of uncontrolled asthma are observed in Canada, where nearly 60% of patients have poor asthma control.8 Poor asthma control has many consequences, including higher rates of health-care service use, worse quality of life, and decreased work productivity.9 Many studies among community samples indicate that asthma and obesity tend to co-occur.10 Moreover, epidemiologic studies have shown that increasing BMI may be related to increased asthma incidence, may cause a physiologic deterioration in lung function in individuals with11,12 and without13 asthma, and is associated with worse asthma control and quality of life.9,11,14

The high rates of obesity among patients with asthma have raised questions about risk factors for obesity in this population. Obesity may be heavily influenced by negative mood states, such as depression, likely through behavioral pathways that lead individuals to overeat and seek out high-fat foods during times of psychologic distress.15 Negative mood states may also affect obesity through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Individuals with depression are 60% more likely to be obese than those without depression,16 and rates of depression among obese individuals are about 1.5 to two times those of individuals with normal weight.1618

Negative mood states are common not only among patients with obesity but also among patients with asthma.19,20 We and others have previously reported a disproportionately high rate of depressive disorders (20%) among adults with asthma.19,21 Furthermore, depressive disorders have been linked to worse asthma control and quality of life.19,22 However, despite associations between depression and poor health behaviors,16,23 increased body weight and obesity, and asthma,10,12,24 the mechanisms underlying these associations remains unclear. Most previous studies showing an association between BMI and asthma control did not take into account other possible mechanisms that contribute to asthma morbidity, such as depression. The aim of the present study was to assess the association among BMI, depressive symptoms, and asthma control in a sample of adults with asthma and the extent to which depressive symptoms mediated any association between higher BMI and worse asthma control.

Participants

The current results are a subanalysis of a larger project (the Psychological Risk Factors for Asthma Longitudinal study) that examined the psychologic risk factors for asthma morbidity. Details of the methodology are described elsewhere.19,20 Briefly, consecutive adult patients with asthma presenting to the asthma clinic of the Hôpital du Sacré-Cœur de Montréal were recruited. Participants had to have been given a primary diagnosis of asthma as demonstrated by methacholine challenge, bronchodilator reversibility, or both.7 Participants also had to be aged between 18 and 75 years and be fluent in either English or French. Patients were excluded if they had a comorbid disorder conferring greater risk of morbidity than asthma.

Between June 2003 and December 2008, 801 patients were recruited. For the current analyses, three patients had missing data for the independent (BMI), dependent (Asthma Control Questionnaire [ACQ]), and mediator (Beck Depression Inventory [BDI]-II) variables and were excluded, yielding a final sample of 798 patients. This project was approved by the Research Ethics Board, Hôpital du Sacré-Cœur de Montréal (# 2003-10-198; 2010-95), and all participants provided written consent.

Study Design and Procedure

This cross-sectional study investigated the association among BMI, the severity of depressive symptoms, and asthma control in a sample of adults with asthma. Patients provided self-reported demographic and medical history information and completed a battery of questionnaires, including the BDI-II and ACQ.

To assess FEV1 and FVC, all patients underwent standard pulmonary function testing. Medical history, including information on medications and atopic status (determined from the results of previous skin prick tests documented in the patients’ hospital files), was self-reported and verified by chart review. If discrepancies between self-report measures and chart review existed, data from the chart review were used.

Measures
BMI:

BMI (kg/m2) was calculated from self-reported height and weight. Consistent with data from the National Health and Nutrition Examination Survey,25 we previously demonstrated that self-reported height and weight in tertiary care patients with asthma are reliable and accurate compared with measured data.26 In addition, based on Canadian normative data and a predetermined sex-specific algorithm,27 we adjusted self-reported measures of BMI to more closely represent measured values of BMI and, thus, the true nature of the relationships under examination. It should be noted that all analyses used the adjusted BMI variable.

Depressive Symptoms:

The BDI-II28 is used to detect the presence and severity of depressive symptoms. This 21-item self-report questionnaire yields a score out of 63, where higher scores indicate worse depressive symptoms. The BDI-II has demonstrated good psychometric properties28,29 and has been validated in Canadian French.30

Asthma Control:

All patients completed the ACQ,31 a self-report questionnaire assessing the prevalence of the six most common asthma symptoms over the past week, and an additional objective question asked for the results of pulmonary function testing (eg, FEV1 % predicted). Higher scores on the ACQ indicate worse asthma control. The ACQ has strong measurement properties, has been validated for use in both clinical practice and trials,31 and is validated in Canadian French.32

Statistical Analyses
Imputation of Missing Data:

Multiple imputation is the method of choice for studies with missing values that affect < 60% of the sample.33 In the present study, 19% of the sample (n = 148) had some missing data, and it was assumed that the data were missing at random. Following the rules of Rubin34 and using the PROC MIANALYZE method of multiple multivariate imputation in SAS (SAS Institute Inc), we independently generated and analyzed five copies of the data, each with missing values suitably imputed. PROC MIANALYZE was used to average estimates of the variables to give a single mean estimate and adjusted SEs and CIs according to guidelines by Harrell.35 Details on the amount of missing data per variable are shown in Tables 1 and 2.

Table Graphic Jump Location
TABLE 1  ] Participant Sociodemographic and Clinical Characteristics (N = 798)

Data are presented as mean ± SD or % (No.) unless otherwise indicated. BDI = Beck Depression Inventory.

a 

Variables included in the multiple imputation.

b 

Average number of packs (25 cigarettes/pack) smoked per day over 10 y.

Table Graphic Jump Location
TABLE 2  ] Participant Asthma History and Medication Characteristics (N = 798)

Data are presented as mean ± SD or % (No.) unless otherwise indicated. All categorical variables were coded as follows: 0 = no; 1 = yes. ACQ = Asthma Control Questionnaire; ICS = inhaled corticosteroid.

a 

Variable included in the multiple imputation.

Main Analyses:

The first procedure followed the Baron and Kenny37 process, which uses four steps of multiple regression to establish the mediation. To confirm these results, we conducted a Sobel test in the subsample of 528 participants who had complete data for all variables in the model. Because the Sobel test is known to have several limitations, a multiple mediation model with bootstrapping18 was used to confirm the Sobel results in the subsample. As per the CONSORT (Consolidated Standards of Reporting Trials) guidelines38 and because of their established influences on the main variables of interest, age, sex, cohabitation, years of education, and inhaled corticosteroid (ICS) dose (which was used as a proxy for asthma severity39) were included as a priori covariates in all the analyses. Significance was set at 0.05, and data analysis was performed with SAS version 9.3 (SAS Institute Inc) statistical software.

Participant Characteristics

Participant characteristics are presented as counts and percentages or mean ± SD for categorical and continuous variables, respectively (Tables 1, 2). The overall sample was predominantly female and middle aged. Most were married or cohabitating, were employed, and had a high school education. Few were current smokers, although more than one-half had a history of smoking. Overall, the sample was moderately overweight (BMI adjusted, 28.3 ± 5.2 kg/m2; range, 17.0-46.8 kg/m2) and minimally depressed (BDI-II score, 9.0 ± 8.4; range, 0-53). The distributions of BMI and BDI-II categories are shown in Table 1.

Mean duration of asthma was 19 years, and the majority of participants were atopic. Regarding pulmonary function, the sample characteristics are consistent with those of a tertiary care asthma population. Almost all participants were prescribed short-acting bronchodilators and ICSs, and the majority was prescribed long-acting bronchodilators, often in combination with ICSs. The average daily dose of ICS (either alone or in combination with a long-acting bronchodilator) was relatively high but consistent with doses prescribed to patients receiving tertiary care. The average score on the ACQ31 indicated that the sample as a whole had poorly controlled asthma.

Mediation Models
Main Analysis 1: Baron and Kenny Steps:

This mediation model is summarized in Figure 1. First, there was a significant association between the main independent variable (BMI) and the outcome variable (ACQ) such that participants with higher BMIs had worse asthma control after adjusting for covariates. Second, there was an effect for BMI on the mediator variable (BDI-II) such that patients with higher BMIs had significantly more depressive symptoms. Third, there was an association between the mediator variable (BDI-II) and the dependent variable (ACQ), showing that participants with more depressive symptoms had significantly worse asthma control. Fourth, when BMI, BDI-II, and ACQ were included in the same model, BDI-II but not BMI remained significantly associated with ACQ.

Figure Jump LinkFigure 1  Baron and Kenny model for the effects of BMI on asthma control mediated by depressive symptoms. ACQ = Asthma Control Questionnaire; BDI = Beck Depression Inventory.Grahic Jump Location
Main Analysis 2: Sobel Test:

As per the Baron and Kenny analyses, BMI was significantly associated with worse asthma control (β = 0.023, SE = 0.008, P = .006), as was BMI and BDI-II (β = 0.219, SE = 0.069, P = .002) and BDI-II and ACQ adjusting for BMI (β = 0.040, SE = 0.005, P < .001). Furthermore, the association between BMI and ACQ was significantly reduced when BDI-II was included in the model (β = 0.015, SE = 0.008, P = .070) (Sobel test, t = 2.938, SEM = 0.037, P = .003), indicating significant mediation.

Main Analysis 3: Multiple Mediation With Mediators Operating in Parallel Using Bootstrapping:

Results from 1,000 bootstrapping samples18 indicated that the total indirect effect of BMI on asthma control through depressive symptoms was statistically significant (β = 0.090; CI, 0.004-0.014; P = .004). The direct effect of BMI on ACQ was not significant (β = 0.015, SE = 0.008, t = 1.820, P = .070). The direction of the effect supports the hypothesis that higher BMIs are associated with higher BDI-II scores, which in turn is related to worse asthma control as indicated by significant point estimates and the bootstrapping 90% CIs.

The purpose of this study was to clarify the nature of the relationship between BMI and asthma control by concurrently examining the mediational role of depressive symptoms. As predicted, having a higher BMI was associated with worse asthma control. Results also indicated that patients with high levels of depressive symptoms had worse asthma control. Consistent with expectations, the relationship between BMI and asthma control was completely and uniquely mediated by depressive symptoms. That is, although previous research has established that higher BMIs are associated with worse asthma control, findings from the present study suggest that it is the association between BMI and depressive symptoms and not BMI per se that contributes the most to worse asthma control. To our knowledge, this study is the first to show such a relationship in asthma.

The findings are consistent with previous studies showing associations among BMI, depressive symptoms, and health outcomes in nonasthmatic populations.8,17,22 Increased attention to the role of depressive symptoms in adults with asthma is an important precursor to identifying the particular mechanisms that lead patients who are obese to have worse asthma control. For example, increased depressive symptoms are associated with decreased motivation and interest in daily activities, extreme fatigue, decreased energy, and appetite disturbances through activation of the HPA axis. Studies have shown that higher levels of proinflammatory cytokines are found in patients with depression and that those cytokines can induce somatic symptoms common in depression, such as fatigue and appetite disturbances, which in turn contribute to asthma and obesity.40 These high levels of inflammatory cytokines are associated with the dysregulation of the HPA axis in patients with depression and chronic inflammatory diseases, such as obesity and asthma.41

Moreover, depressive symptoms may influence asthma outcomes by affecting the perception and management of asthma. Patients with asthma and depression may have difficulty with accurately appraising asthma symptoms and detecting deteriorations in lung function. Furthermore, the impact of depression on cognitive functioning and increased feelings of hopelessness may also affect decision-making abilities, leading to poorer health behaviors and low confidence in one’s ability to self-manage their asthma.42 Poor health behaviors in patients with depression may also include increased exposure to asthma triggers, such as smoking.43

This study has several important strengths, including testing a large and consecutive sample of adults with asthma, the inclusion of patients with objectively confirmed physician-diagnosed asthma, the use of valid and reliable measures of depressive symptoms and asthma variables, statistical adjustment of important covariates, and robust tests of mediation. Despite the strengths of the study, the findings should be interpreted with caution due to some limitations. First, BMI was calculated based on self-reported height and weight, which may underestimate the prevalence of obesity.44 However, we have previously demonstrated that such self-reports are accurate in this population,26 leaving us confident that the BMI values reflect the true BMIs of the sample. Moreover, the fact that BMI, if biased, tends to be underestimated rather than overestimated indicates that the findings would most likely represent conservative estimates of the association among BMI, depressive symptoms, and asthma control.25 Second, the use of a cross-sectional design limits any inferences regarding the direction of the relationship. Finally, the results may not generalize to patients with asthma treated in primary care or community settings because the present sample comprised patients treated in a tertiary care setting.

In conclusion, the findings of this study indicate that higher BMI and more depressive symptoms are both independently associated with significantly worse asthma control, but mediation analyses revealed that the association between BMI and worse asthma control was completely mediated by depression. Investigations of the mechanisms underlying these associations are needed as well as longitudinal studies examining the temporal relationship among these variables. Professional health-care providers should consider the negative impact of depressive symptoms when assessing levels of asthma control and pulmonary function in patients who are overweight. These findings could lead to the development of targeted interventions in cohorts of patients with asthma identified as depressed to prevent associated weight gain and weight-related asthma morbidity. Clinical training could be offered to physicians and health-care professionals not accustomed to assessing psychiatric disorders to better detect the presence of depressive symptoms. Moreover, given the association between obesity and asthma in childhood,45 more research is needed to assess whether depression is having a similar impact on this relationship and the direction of this relationship.

Author contributions: K. L. L. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. M. B., S. L. B., and K. L. L. contributed to the study concept and design; M. B. and S. L. B. contributed to the data analysis and interpretation; and M. B., S. L. B., K. O., A. J., and K. L. L. contributed to the drafting and review of the manuscript for important intellectual content.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Bacon has received investigator-initiated funding from federal (Canadian Institutes of Health Research and Social Sciences and Humanities Research Council) and provincial (Fonds de la Recherche du Quebec: Sante) agencies as well as from Concordia University and Research Centre, Hôpital du Sacré-Cœur de Montréal, to conduct work looking at the behavioral aspects of asthma. In addition, he has been a paid consultant for Kataka Medical Communication in the development of behavior change continuing medical education programs. Dr Lavoie has served as a consultant on continuing medical education activities for Takeda Pharmaceutical Co Limited, AbbVie Inc, Boehringer Ingelheim GmbH, and Kataka Medical Communication. Mss Boudreau, Ouellet, and Jacob have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: The authors thank Guillaume Lacoste, BA, for invaluable assistance with data collection.

ACQ

Asthma Control Questionnaire

BDI

Beck Depression Inventory

HPA

hypothalamic-pituitary-adrenal

ICS

inhaled corticosteroid

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Figures

Figure Jump LinkFigure 1  Baron and Kenny model for the effects of BMI on asthma control mediated by depressive symptoms. ACQ = Asthma Control Questionnaire; BDI = Beck Depression Inventory.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1  ] Participant Sociodemographic and Clinical Characteristics (N = 798)

Data are presented as mean ± SD or % (No.) unless otherwise indicated. BDI = Beck Depression Inventory.

a 

Variables included in the multiple imputation.

b 

Average number of packs (25 cigarettes/pack) smoked per day over 10 y.

Table Graphic Jump Location
TABLE 2  ] Participant Asthma History and Medication Characteristics (N = 798)

Data are presented as mean ± SD or % (No.) unless otherwise indicated. All categorical variables were coded as follows: 0 = no; 1 = yes. ACQ = Asthma Control Questionnaire; ICS = inhaled corticosteroid.

a 

Variable included in the multiple imputation.

References

Clerisme-Beaty E, Rand CS. The effect of obesity on asthma incidence: moving past the epidemiologic evidence. J Allergy Clin Immunol. 2009;123(1):96-97. [CrossRef] [PubMed]
 
Ford ES. The epidemiology of obesity and asthma. J Allergy Clin Immunol. 2005;115(5):897-909. [CrossRef] [PubMed]
 
Shields M, Tremblay MS, Laviolette M, Craig CL, Janssen I, Connor Gorber S. Fitness of Canadian adults: results from the 2007-2009 Canadian Health Measures Survey. Health Rep. 2010;21(1):21-35. [PubMed]
 
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