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* From the Research Center (Drs. Cartier and Labrecque, and Ms. Barone), Division of Chest Medicine, Hôpital du Sacré-C
ur de Montréal; Department of Psychology (Dr. Lavoie), University of Quebec at Montreal; Department of Exercise Science (Dr. Bacon), Concordia University; and Department of Psychology (Dr. Ditto), McGill University, Montreal, QC, Canada.
Correspondence to: Kim L. Lavoie, PhD, Research Center, Division of Chest Medicine, J-3190, 5400 Gouin West, Montreal, QC, H4J 1C5, Canada; e-mail: k-lavoie{at}crhsc.rtss.qc.ca
Abstract
Background: The high burden of asthma appears to be related to poor asthma control. Although previous studies have reported associations between depressive disorders (DDs) and anxiety disorders (ADs) and worse asthma control and quality of life, the relative impact of these disorders on asthma control and quality of life has not been explored. This study evaluated the relative impact of having a DD and/or AD on asthma control and quality of life.
Method: Five hundred four consecutive adults with confirmed, physician-diagnosed asthma underwent a brief, structured psychiatric interview using the Primary Care Evaluation of Mental Disorders. Asthma control and asthma-related quality of life were assessed using the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ). All patients underwent standard spirometry.
Results: Thirty-one percent of patients (n = 157) met the diagnostic criteria for one or more psychiatric disorders (8% had DD only, 12% had AD only, and 11% had both). Analyses revealed independent effects for DDs on total ACQ scores (p < 0.01), and for DDs and ADs on total AQLQ scores and all four AQLQ subscales (p < 0.05). There were no interaction effects.
Conclusions: Results suggest that DDs and ADs are associated with worse asthma-related quality of life, but only DDs are associated with worse asthma control. Interestingly, having both a DD and an AD did not confer additional risk for worse asthma control or quality of life. Physicians may want to consider the differential impact of negative mood states when assessing levels of asthma control and quality of life.
Key Words: anxiety disorders asthma control depression depressive disorders quality of life
Asthma is among the four most common chronic disorders affecting adults.12 Despite important advances in diagnosis and treatment, the prevalence of asthma has increased among all age, sex, and racial groups to affect approximately 100 to 150 million people worldwide.2 Asthma is a multifactorial lung disease that is associated not only with significant medical morbidity, but also has important personal, social, and economic impacts. Asthma has been directly related to impaired asthma-related quality of life including increased work and school absences, an inability to perform household chores, and restriction of social activities.13 The total costs of caring for asthma have been calculated by the World Health Organization to exceed those of AIDS/HIV and tuberculosis combined,2 with costs reaching nearly $13 billion annually in the United States alone.4
The availability of effective treatments suggests asthma can be well controlled in most patients.56 However, current trends in asthma prevalence rates and morbidity indicate that asthma remains poorly controlled in the vast majority of patients.789 Criteria for classifying poorly controlled asthma have been published extensively elsewhere51011 but are generally ascribed when patients exhibit one or more of the following: symptom exacerbations (eg, wheezing, nocturnal waking, shortness of breath), functional impairment (eg, difficulties engaging in physical activity), reduced pulmonary function, and/or increased bronchodilator use (more than four times in the past week).5
Achieving optimal asthma control relies on several behavioral factors (eg, self-monitoring, treatment adherence, and managing environmental triggers) that may be influenced by chronic negative mood states.121314 Chronic negative mood states such as depression may interfere with daily self-monitoring abilities and treatment adherence,1315 which may result in worse levels of asthma control. Interestingly, rates of psychiatric disorders (particularly depressive disorders [DDs] and anxiety disorders [ADs]) have been shown to be up to six times more prevalent among asthma patients (16 to 52% for ADs, and 14 to 41% for DDs) compared to rates observed in the general population.16171819202122 We16 and others1217 have previously reported associations between DDs and ADs and worse asthma control and/or asthma-related quality of life. However, the relative impact of these chronic negative mood states on asthma control and asthma-related quality of life was not explored in our previous report, or in any previous studies linking these disorders to worse asthma morbidity. The goal of the present study was to assess the prevalence of DDs and ADs in a sample of adult asthmatics, and to evaluate the relative impact of having a DD only, an AD only, or both, on levels of asthma control and asthma-related quality of life.
Materials and Methods
Study Subjects
A total of 504 consecutive adult patients with physician-diagnosed asthma were recruited from the asthma clinic of Hôpital du Sacré-Coeur de Montréal from June 2003 to March 2005. Patients were eligible if they had a primary diagnosis of asthma, were between the ages of 18 and 75 years, and were fluent in either English or French. A total of 1,243 patients presented to the asthma clinic, of whom 1,094 subjects (88%) were screened for inclusion in the study (the remaining 149 subjects had insufficient medical information with which to conduct prescreening). A total of 550 subjects were excluded (n = 187 due to existence of comorbid disease that conferred greater risk for morbidity than asthma [n = 107 with COPD] or the presence of severe psychopathology or substance abuse [n = 8 had psychoses]; n = 126 due to new or unconfirmed asthma; n = 48 due to primary diagnosis of occupational asthma; n = 142 due to age criteria; and n = 31 due to language criteria), resulting in 553 eligible patients who were contacted to participate in the study. Only 40 patients declined to participate, which yielded a sample of 513 patients (93% participation rate). Nine patients were excluded from analysis due to incomplete or missing data, yielding a final sample of 504 patients. All patients gave written, informed consent, and this project was approved by the Human Ethics Committee of Hôpital du Sacré-C
ur de Montréal.
Study Design
All patients were screened on the day of their asthma clinic visit to verify eligibility. Participants underwent a sociodemographic and medical history interview, including asking patients to report the frequency of bronchodilator use and alcohol consumption in the past week, followed by a brief, structured psychiatric interview (Primary Care Evaluation for Mental Disorders [PRIME-MD]) administered by a trained clinical research assistant. Patients completed an Asthma Control Questionnaire (ACQ) and an Asthma Quality of Life Questionnaire (AQLQ) and underwent standard spirometry23 to measure pulmonary function. Asthma diagnoses were confirmed by chart evidence of a 20% fall in FEV1 after methacholine challenge and/or bronchodilator reversibility in FEV1
20% predicted.24 Asthma severity was classified according to International Global Initiative for Asthma guidelines.5 Medical history, including medication status and dosage, was self-reported and verified by chart medical review.
Measures
Psychiatric Assessment:
The PRIME-MD25 is a well-validated screening instrument designed to detect the most common disorders listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)26 seen in primary and tertiary care settings. The PRIME-MD uses diagnostic algorithms to generate current diagnoses based on DSM-IV criteria that have been shown to be of comparable reliability, sensitivity, and specificity as longer structured interviews.25 The interview begins with a series of screening questions followed by structured interview questions that are used to follow-up patient responses. The PRIME-MD takes from 10 and 20 min to administer and score, and has been used successfully in previous studies1727 assessing the prevalence of psychiatric disorders in asthma patients. A trained clinical research assistant with > 5 years experience administering psychiatric interviews administered the mood disorders and ADs modules of the PRIME-MD. The mood disorders module yields diagnoses for current major DD, minor DD, dysthymia, and bipolar disorder; and the ADs module yields diagnoses for current panic disorder, generalized AD, and AD not otherwise specified. Due to the relative frequency of social AD in asthma samples,2022 we also administered questions from the Anxiety Disorders Interview Schedule for DSM-IV28 to evaluate diagnoses of social AD.
In order to validate DD and AD diagnoses, patients also completed the Beck depression inventory-II (BDI-II)2930 and the anxiety sensitivity index (ASI),31 which measure levels of depressive symptomatology and panic-like anxiety (or fear of anxiety symptoms), respectively. Both have demonstrated excellent psychometric properties including construct validity and test-retest reliability.293031
Asthma Control and Quality of Life Assessment:
To assess asthma control, participants completed the ACQ,10 reported the frequency of bronchodilator use in the last week, and underwent standard spirometry23 to assess pulmonary function (FEV1). The ACQ evaluates levels of asthma control according to standard criteria specified by international guidelines.5 Respondents are asked to recall their symptoms (shortness of breath, wheezing, waking dyspnea, and nocturnal dyspnea), activity limitations, and bronchodilator use in the last week. One additional question assessing spirometry results (FEV1 percentage of predicted) is completed by the research assistant. The ACQ contains seven items rated on a 7-point scale (0, good control; to 6, poor control) to yield a mean score out of 6. To assess asthma quality of life, participants completed the AQLQ.32 The AQLQ evaluates asthma quality of life across four life domains that may be negatively impacted by asthma: activity limitation (how asthma limits ability to carry out daily activities), symptoms (nature and frequency of asthma symptoms such as wheezing, shortness of breath), emotional distress (how emotionally stressful the disease is), and environmental stimuli (how difficult it is for the patient to manage or avoid environmental triggers of asthma, such as pollution, smoke, dust). The AQLQ contains 32 items rated on a 7-point scale (1, maximal impairment; to 7, no impairment) to yield a mean score out of 7. Both the ACQ and AQLQ have demonstrated very good measurement properties, including high intraclass correlation coefficients between 0.90 and 0.95 and good construct, cross-sectional and longitudinal validity,10323334 and have been validated in Quebec French.35
Pulmonary Function Testing:
All patients underwent standard pulmonary function testing according to American Thoracic Society guidelines.2336 Rescue medication was withheld for at least 4 h (but up to 8) before pulmonary function tests. Predicted values of FEV1 and FVC were calculated from reference values for patients < 70 years old37 and > 70 years old,38 respectively, yielding percentage of predicted FEV1 and percentage of predicted FEV1/FVC ratio.
Statistical Analysis
Group differences in categorical variables were examined using
2 test statistics. Group differences in continuous variables were examined using general linear models. All tests were two sided, and significance was set at 0.05. The main effects of the presence of a DD and presence of an AD, and their interaction on bronchodilator use, total ACQ scores, and AQLQ scores (total and subscales), were examined using general linear models controlling for age, sex, and asthma severity (determined a priori). To assess extent of the relative impact of DDs vs ADs on ACQ and AQLQ scores, we performed multiple linear regression, and included age, sex, and asthma severity in the model. Data analysis was performed using statistical software (SAS v.8.2; SAS Institute; Cary, NC).
Results
Sample Characteristics
A total of 504 adult asthma participated in the present study. Participants were 61% female and had a mean ± SD age of 50 ± 14.4 years.
Prevalence of Psychiatric Disorders
A total of 31% of patients (n = 157) met the diagnostic criteria for one or more psychiatric disorders (Table 1
). A total of 23% of patients (n = 117) met the diagnostic criteria for one or more ADs, the most common of which was panic disorder (11%; n = 53). A total of 20% of patients (n = 97) met the diagnostic criteria for one or more DDs, the most common of which was major DD (14%; n = 72). A total of 12% of patients (n = 60) met the criteria for an AD only (ie, with no comorbid depressive disorder), compared to 8% (n = 40) with a DD only, and 11% (n = 57) with anxiety and depressive disorders (ADDs) [Table 1].
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Discussion
The results of the present study indicate a high rate of both DDs and ADs among adult asthmatics. Compared to point prevalence rates in the general population, rates of both DDs and ADs were at least double those observed in the general population (20% and 23% vs 2 to 9% and 1 to 13%, respectively2640). More importantly, results suggest DDs and ADs may exert distinct effects on important measures of asthma morbidity. Our findings revealed that both DDs and ADs were independently associated with worse asthma-related quality of life, but that only DDs were independently associated with worse levels of asthma control. The lack of any significant interaction effects suggests that there is no incremental risk associated with having both a DD and an AD on asthma control and quality of life.
To our knowledge, this is the first study to examine the independent contributions of distinct chronic negative mood states on measures of asthma control and asthma-related quality of life. Results of worse asthma control in patients with DDs such as major depression or dysthymia may occur because these patients may have more difficulty initiating and maintaining complex treatment regimens that require sustained effort, self-monitoring, and self-administration. Cardinal features of chronic depression include decreased energy and fatigue, reduced interest in performing daily activities, and difficulties making decisions.26 All of these symptoms may seriously impair a patients ability to achieve optimal asthma control, which may ultimately result in worse asthma outcomes. In fact, there is evidence to suggest that asthma patients who are depressed are less likely to adhere to asthma medication regimens12 and more likely to require emergency services,41 compared to asthmatics without depression.
Poor asthma control in patients with DDs, rather than ADs, may also occur through autonomic and immunologic pathways. For example, there is preliminary evidence to suggest a link between negative mood states and increased cholinergically mediated airway reactivity in asthmatics,424344 although this link still remains the subject of much debate. Other research454647 has documented the role of proinflammatory cytokines (eg, interleukin-1, tumor necrosis factor-
, and interferon-
), key mediators of inflammatory responses in asthmatics, in the etiology and pathophysiology of DDs such as major depression. Although the extent to which depression is associated with increased production of proinflammatory cytokines remains to be determined, there is evidence to suggest a link between the experience of chronic psychological stress (examination stress) and increased production of proinflammatory cytokines in asthmatics.484950
The lack of an independent association between ADs and asthma control may be due to the tendency of AD patients to be higher self-monitors, making them more likely to detect asthma symptoms and intervene relative to depressed patients. However, AD patients hypervigilance to bodily sensations that may signal danger (eg, shortness of breath) may also lead them to overperceive symptoms and/or misinterpret normal fluctuations in respiratory parameters as symptoms of asthma.515253 This phenomenon may have accounted for our finding, although not significant, of a trend indicating greater bronchodilator use in patients with ADs, despite having better overall levels of asthma control than patients with DDs. An alternative explanation is that anxious patients may be more likely to fear exacerbations, which may make them more likely to adhere to daily controller medications (inhaled corticosteroids). This may have increased their overall level of control independent of their bronchodilator use. Although we did not assess controller (inhaled corticosteroids) medication adherence in the present study, there is evidence from previous studies14 that at least moderate anxiety may be beneficial for medication adherence in asthmatics. The fact that so many symptoms of anxiety (eg, shortness of breath, hyperventilation, dizziness) overlap with many symptoms related to asthma may also make accurate symptom perception, and appropriate self-management, a unique challenge for patients with ADs.
Our findings indicating worse asthma-related quality of life in patients with either a DD or an AD suggests that the impact of psychiatric comorbidity on quality of life measures may be more general than specific. This finding is consistent with at least one study17 that reported an association between actual DDs (rather than subclinical symptoms of depression) and asthma-related quality of life. However, the present study strengthens previous reports by evaluating the unique contributions of DDs vs ADs on multiple measures of asthma morbidity. Additional strengths of the present study include having a large, consecutive sample of patients with moderate-to-severe asthma who, by virtue of being treated in a tertiary care setting, may be at greatest risk of poorly controlled asthma and worse outcomes. Finally, it is important to note that our findings for the AQLQ, including all four subscale domains, revealed not only statistically significant differences between groups, but clinically significant differences that were independent of age, sex, and asthma severity.
The present study may be limited by the fact that measures of asthma control and quality of life were based primarily on self-report assessments, which may be subject to recall bias. However, the established clinical validity of the measures used1034 suggests findings are clinically valid. An additional limitation may be that the sample was drawn from a tertiary asthma clinic; as such, findings may not generalize to asthmatics treated in primary care. We also instructed patients to refrain from taking bronchodilators for at least 4 h (but up to 8 h) prior to pulmonary function testing, which is somewhat shorter than the period recommended by the American Thoracic Society guidelines.23 However, given that all patients received the same instructions, we are confident this did not bias the results. It is also important to note that even though our model for asthma control explained 29% of the total variance, only 3% was accounted for by having a DD. Nonetheless, this finding suggests a greater role for depressive (rather than anxious) mood states in achieving control of asthma. Our model for quality of life similarly explained 22% of the total variance, of which only 3% and 2% were accounted for by having a DD and an AD, respectively. However, our findings were independent of important confounders (age, sex, asthma severity) and highlight the differential impact of separate classes of psychiatric disorders on important asthma management variables. Finally, the cross-sectional nature of this study may also be considered a limitation. Prospective studies are needed to better delineate the directionality of the DD/AD-asthma morbidity relationship, as we cannot exclude the possibility that poorly controlled asthma and/or asthma-related quality of life confer risk for the development of psychiatric disorders.
In conclusion, the results of this study highlight the high prevalence of DDs and ADs in adult asthmatics, and that there may be distinct pathways by which depressive and ADs impact asthma outcomes. Physicians may want to consider the potential impact of negative mood states when assessing levels of asthma control and functional impairment due to asthma, and when implementing and evaluating treatment strategies. Given that < 20% of patients meeting criteria for one or more psychiatric disorder were receiving some form of psychological treatment (psychotherapy or pharmacotherapy) at the time of their entry into the study also suggests a need to improve both detection and treatment of these patients. Although we cannot rule out the possibility that patients had a previous diagnosis (from their physician) and refused treatment, these findings highlight a need to improve both detection and treatment of these patients in nonpsychiatric tertiary care settings. What is not known is the extent to which treatment of psychiatric disorders may impact (improve) asthma control and quality of life. Further studies are needed to assess this.
Acknowledgements
The authors thank Drs. Catherine Lemière, Dr. Jean-Luc Malo, and Mr. Guillaume Lacoste for their invaluable assistance with data collection.
Footnotes
Abbreviations: ACQ = Asthma Control Questionnaire; AD = anxiety disorder; ADD = anxiety plus depressive disorder; AQLQ = Asthma Quality of Life Questionnaire; ASI = anxiety sensitivity index; BDI-II = Beck Depression Inventory-II; DD = depressive disorder; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; ND = no disorder; PRIME-MD = Primary Care Evaluation of Mental Disorders
This study was supported by a fellowship grant from the Canadian Institutes of Health Research (Dr. Lavoie) and a Young Investigators grant from the Auger Foundation of Hôpital du Sacré-Coeur de Montréal.
Dr. Lavoie has been paid professional honorariums from GlaxoSmithkline and Pfizer Canada.
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Received for publication January 6, 2006. Accepted for publication April 7, 2006.
References
This article has been cited by other articles:
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