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What Is Worse for Asthma Control and Quality of Life
Original Research ASTHMA
What Is Worse for Asthma Control and Quality of Life* Depressive Disorders, Anxiety Disorders, or Both? Kim L. Lavoie, PhD; Simon L. Bacon, PhD; Silvana Barone, BSc; Andre Cartier, MD; Blaine Ditto, PhD; and Manon Labrecque, MD, MSc, FCCP
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 ⴝ 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. (CHEST 2006; 130:1039 –1047) Key words: anxiety disorders; asthma control; depression; depressive disorders; quality of life 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
is among the four most common chronic A sthma disorders affecting adults. Despite important 1,2
advances in diagnosis and treatment, the prevalence of asthma has increased among all age, sex, and racial *From the Research Center (Drs. Cartier and Labrecque, and Ms. Barone), Division of Chest Medicine, Hoˆpital du Sacre´Cœur de Montre´al; 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. 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 Hoˆpital du Sacre´-Coeur de Montre´al. Dr. Lavoie has been paid professional honorariums from GlaxoSmithkline and Pfizer Canada. www.chestjournal.org
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 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. Manuscript received January 6, 2006; revision accepted April 7, 2006. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Kim L. Lavoie, PhD, Research Center, Division of Chest Medicine, J-3190, 5400 Gouin West, Montreal, QC, H4J 1C5, Canada; e-mail: [email protected] DOI: 10.1378/chest.130.4.1039 CHEST / 130 / 4 / OCTOBER, 2006
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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.1,3 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.5,6 However, current trends in asthma prevalence rates and morbidity indicate that asthma remains poorly controlled in the vast majority of patients.7–9 Criteria for classifying poorly controlled asthma have been published extensively elsewhere5,10,11 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.12–14 Chronic negative mood states such as depression may interfere with daily self-monitoring abilities and treatment adherence,13,15 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.16 –22 We16 and others12,17 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 physiciandiagnosed asthma were recruited from the asthma clinic of 1040
Hoˆpital du Sacre´-Coeur de Montre´al 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 Hoˆpital du Sacre´-Cœur de Montre´al. 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 ⱖ 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 studies17,27 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,20,22 we also adminisOriginal Research
tered 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)29,30 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.29 –31 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,10,32–34 and have been validated in Quebec French.35 Pulmonary Function Testing: All patients underwent standard pulmonary function testing according to American Thoracic Society guidelines.23,36 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. www.chestjournal.org
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]. Sociodemographic and General Medical Characteristics Sociodemographic and general medical characteristics are presented in Table 2 as a function of patient group (no disorder [ND], AD only, DD only, and ADD). There were significantly more women in all three psychiatric groups compared to the ND group. Moreover, significantly fewer patients in the ADD group were employed compared to all other groups. Significantly fewer patients in the ADD and DD groups were married or cohabitating compared to patients in the AD or ND groups. With the exception of a nonsignificant trend suggesting a greater proportion of current smokers in all three psychiatric groups compared to the ND group, there were no other significant differences in general medical characteristics between groups. Levels of depressive (BDI-II) and anxious (ASI) symptomatology were significantly greater in all three psychiatric groups
Table 1—Prevalence of DSM-IV Psychiatric Disorders Presented as a Percentage of the Total Sample (n ⴝ 504) Variables
% (No.)
No DD or AD Any DD or AD Only an AD Only a DD ADD Any AD* Panic disorder Generalized AD Social AD Other AD Any DD* Major DD Minor DD Dysthymia Bipolar disorder
69 (347) 31 (157) 12 (60) 8 (40) 11 (57) 23 (117) 11 (53) 5 (26) 4 (19) 10 (51) 20 (97) 14 (72) 5 (25) 4 (20) 1 (1)
*Comorbidities are summarized. CHEST / 130 / 4 / OCTOBER, 2006
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Table 2—Sociodemographics and General Medical Characteristics as a Function of Psychiatric Group* Variables Sociodemographics Age, yr Female gender White race Cohabitating Education, yr Employed Medical characteristics Hypertension Diabetes Hyperlipidemia BMI, kg/m2 Current smoker Pack-years† Psychological distress BDI-II ASI Psychopharmacologic or psychotherapeutic treatment Benzodiazepines Antidepressants Seeing a mental health professional‡
ND (n ⫽ 347)
AD (n ⫽ 60)
DD (n ⫽ 40)
ADD (n ⫽ 57)
2/F Statistic
51 ⫾ 14 56 (195) 93 (321) 71 (235) 13 ⫾ 4 64 (213)
50 ⫾ 14 78 (47) 95 (57) 73 (44) 13 ⫾ 4 62 (37)
50 ⫾ 12 68 (27) 95 (38) 63 (25) 13 ⫾ 5 65 (26)
47 ⫾ 15 68 (39) 92 (52) 51 (29) 12 ⫾ 4 44 (25)
0.74 12.98 0.98 10.02 2.61 8.54
0.495 0.005 0.806 0.018 0.216 0.036
25 (86) 7 (25) 18 (64) 27 (5) 8 (28) 12 ⫾ 19
22 (13) 8 (5) 28 (11) 27 (5) 15 (9) 13 ⫾ 23
30 (12) 5 (2) 25 (15) 28 (5) 15 (6) 10 ⫾ 14
18 (10) 5 (3) 19 (11) 27 (5) 18 (10) 14 ⫾ 18
2.39 0.70 2.88 0.35 7.30 0.38
0.496 0.874 0.410 0.792 0.062 0.766
6.4 (6.0) 12.3 (9.0)
11.3 (7.2) 21.9 (12.0)
16.1 (8.9) 16.2 (10.1)
21.5 (9.6) 25.2 (12.1)
75.17 35.81
⬍ 0.001 ⬍ 0.001
11 (31) 5 (14) 3 (11)
26 (9) 20 (7) 20 (8)
19 (10) 18 (10) 13 (8)
25 (12) 31 (15) 12 (7)
10.81 34.41 25.13
0.013 ⬍ 0.001 ⬍ 0.001
p Value
*Data are presented as mean ⫾ SD or % (No.). †Pack-years are the average number of packs (20 cigarettes per pack) smoked per day ⫻ the number of years smoked. ‡A psychiatrist or psychologist.
(DD, AD, and ADD) compared to the ND group. Moreover, BDI-II scores were significantly higher in patients with a DD (DD and ADD groups) vs without a DD (ND and AD groups); and ASI scores were significantly higher in patients with an AD (AD and ADD groups) vs without an AD (ND and DD groups), providing validation for PRIME-MD diagnoses. Finally, a greater proportion of patients in all three psychiatric groups were receiving benzodiazepines and antidepressants and were being seen by a mental health professional (psychiatrist or psychologist), compared to the ND group. However, it is noteworthy that ⬍ 20% (n ⫽ 32) of all psychiatric patients were receiving antidepressants, and ⬍ 15% (n ⫽ 23) were under the care of a mental health professional at the time of their evaluation. Pulmonary Function, Asthma Characteristics, and Asthma Medications Pulmonary function, asthma characteristics, and asthma medications are presented in Table 3. There were no significant group differences in pulmonary function, asthma characteristics (including asthma duration, atopy assessed using skin-prick tests, and severity classification), or in the proportion of patients receiving various asthma medications (including daily dose of inhaled corticosteroids). There were also no significant group differences in the frequency of emergency department visits or hospitalizations in the past year. 1042
Asthma Control Analyses on group differences in total score on the ACQ revealed a significant main effect of DD on total ACQ score, indicating that patients with a DD (DD and ADD groups; corrected mean ⫾ SEM, 2.1 ⫾ 0.1) had significantly higher total ACQ scores (indicating worse control) compared to patients without a DD (ND and AD groups; corrected mean ⫾ SEM, 1.6 ⫾ 0.1), independent of age, sex, and asthma severity (F ⫽ 14.98, p ⬍ 0.0001; Fig 1). It is noteworthy that the differences observed between patients with vs without a DD was 0.5, which is considered clinically significant for asthma populations.11 There was no significant main effect for having an AD or for an interaction effect. A multiple regression model containing asthma severity, sex, age, DD, AD, and the interaction of ADDs accounted for 29% of the variance in total ACQ score (Table 4). As expected, there was a significant, independent effect for having a DD, which accounted for 2% of the variance in total ACQ score. There were no significant main effects for having an AD or for an interaction effect. Bronchodilator Use We assessed group differences in the frequency of bronchodilator use in the last week (Fig 2) because it is an important clinical measure of asthma control. The analyses revealed a trend for having an AD on Original Research
Table 3—Pulmonary Function, Asthma Characteristics, and Asthma Medications as a Function of Psychiatric Group* Variables FEV1, L FEV1, % predicted FEV1/FVC, % predicted Asthma severity Mild intermittent Mild persistent Moderate persistent Severe persistent Asthma duration, yr Atopic Emergency department visits in last year Hospitalizations in last year Asthma medications Short-acting 2-agonists Long-acting 2-agonists Inhaled corticosteroids Inhaled corticosteroids dose, g† Oral corticosteroids Antileukotrienes
ND (n ⫽ 347)
AD (n ⫽ 60)
DD (n ⫽ 40)
ADD (n ⫽ 57)
2.34 ⫾ 0.88 72 ⫾ 21 71 ⫾ 19
2.27 ⫾ 0.75 80 ⫾ 23 72 ⫾ 12
2.49 ⫾ 0.93 82 ⫾ 22 75 ⫾ 10
2.28 ⫾ 0.72 77 ⫾ 17 73 ⫾ 11
1 (3) 13 (42) 55 (177) 31 (98) 20 ⫾ 16 63 (215) 0.29 (0.91) 0.10 (0.37)
0 15 (5) 56 (19) 29 (10) 17 ⫾ 14 58 (34) 0.35 (0.90) 0.10 (0.35)
0 7 (4) 59 (34) 34 (20) 17 ⫾ 15 72 (28) 0.30 (0.61) 0.10 (0.30)
98 (338) 76 (242) 94 (321) 665 (525) 12 (33) 15 (42)
98 (55) 70 (40) 98 (58) 675 (424) 13 (7) 17 (9)
95 (38) 69 (27) 90 (35) 729 (664) 6 (2) 9 (3)
F Statistic/2
p Value
0.65 0.82 1.47 7.02
0.580 0.483 0.221 0.636
0 6 (3) 53 (28) 42 (22) 21 ⫾ 17 70 (40) 0.53 (1.05) 0.25 (0.76)
0.72 3.23 1.09 2.02
0.542 0.357 0.351 0.110
98 (56) 71 (39) 93 (53) 849 (535) 19 (9) 12 (6)
2.00 1.60 3.42 1.58 3.01 1.35
0.571 0.660 0.356 0.194 0.390 0.715
*Data are presented as mean ⫾ SD or % (No.). †Median (range) fluticasone propionate equivalent.
the frequency of bronchodilator use in the last week, indicating that patients with an AD (AD and ADD patients; corrected mean ⫾ SEM, 13.0 ⫾ 1.5) used their bronchodilator more times in the last week compared to patients without an AD (ND and DD patients; corrected mean ⫾ SEM, 9.3 ⫾ 1.4). There were no significant main effects for having a DD or for an interaction effect. Asthma Quality of Life Analyses on group differences in total score on the AQLQ revealed significant main effects of DD
(F ⫽ 38.5, p ⬍ 0.001) and AD (F ⫽ 18.06, p ⬍ 0.001) on total AQLQ score, indicating that patients with a DD (DD and ADD patients; corrected mean ⫾ SEM, 4.41 ⫾ 0.14) had lower total scores than patients without a DD (ND and AD patients; corrected mean ⫾ SEM, 5.05 ⫾ 0.09), and patients with an AD (AD and MAD patients; corrected mean ⫾ SEM, 4.56 ⫾ 0.12) had significantly lower total AQLQ scores compared to patients without an AD (ND and DD patients; corrected mean ⫾ SEM, 4.90 ⫾ 0.11; Fig 3). However, there was no significant interaction effect. It
Table 4 —Linear Regression Models for Total Scores on ACQ and AQLQ Variables
Figure 1. Total ACQ scores (mean ⫾ SEM) presented as a function of psychiatric group (higher scores indicate worse control). No Psych ⫽ no psychiatric disorder. www.chestjournal.org
ACQ, total score Severity Sex Age DD AD DD ⫻ AD Model AQLQ, total score Severity Sex Age DD AD DD ⫻ AD Model
R2
F Statistic
t Test
p Value
0.23 0.00 0.01 0.02 0.00 0.00 0.29
139.48 1.06 4.67 9.82 2.66 0.27 30.59
11.81 1.03 ⫺ 2.16 3.15 1.63 ⫺ 0.52
⬍ 0.001 0.304 0.031 0.002 0.103 0.604 ⬍ 0.001
0.09 0.01 0.01 0.03 0.02 0.00 0.22
42.70 4.46 4.09 14.64 10.43 1.93 17.81
⫺ 6.53 2.11 2.02 ⫺ 3.83 ⫺ 3.23 1.39
⬍ 0.001 0.035 0.044 ⬍ 0.001 0.001 0.165 ⬍ 0.001
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symptom subscale could explain 20% of the variance (F ⫽ 17.17, p ⬍ 0.001), of which having a DD accounted for 2% (F ⫽ 11.44, p ⬍ 0.001) and having an AD accounted for 2% (F ⫽ 8.14, p ⫽ 0.005). The model for the emotional distress subscale could explain 19% of the variance (F ⫽ 16.37, p ⬍ 0.001), of which DD accounted for 2% (F ⫽ 8.21, p ⫽ 0.004) and AD accounted for 3% (F ⫽ 14.47, p ⬍ 0.001). Finally, the model for the environmental limitations subscale could explain 12% of the variance (F ⫽ 9.54, p ⬍ 0.001), of which DD accounted for 2% (F ⫽ 10.08, p ⫽ 0.002) and AD accounted for 2% (F ⫽ 6.66, p ⫽ 0.010). Figure 2. Bronchodilator use in the last week (mean ⫾ SEM) presented as a function of psychiatric group. See Figure 1 legend for expansion of abbreviation.
is noteworthy that the AQLQ score differences observed between patients with vs without a DD was 0.64, which is considered clinically significant for asthma populations.39 A multiple regression model containing asthma severity, sex, age, DD, AD, and the interaction of ADD accounted for 22% of the variance in total AQLQ score (Table 4). There were significant independent effects for having a DD (accounting for 3% of the variance in total AQLQ score) and for having an AD (accounting for 2% of the variance in total AQLQ score). There was no significant interaction effect. Separate regression models were also conducted for each subscale of the AQLQ, containing asthma severity, sex, age, DD, AD and their interaction. The model for the activity limitation subscale could explain 17% of the variance (F ⫽ 13.98, p ⬍ 0.001), of which having a DD accounted for 3% (F ⫽ 14.66, p ⬍ 0.001) and having an AD accounted for 1% (F ⫽ 6.11, p ⫽ 0.014). The model for the
Figure 3. Total AQLQ score (mean ⫾ SEM) presented as a function of psychiatric group (higher scores indicate better quality of life). See Figure 1 legend for expansion of abbreviation. 1044
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%, respectively26,40). 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 selfadministration. 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 patient’s 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 preOriginal Research
liminary evidence to suggest a link between negative mood states and increased cholinergically mediated airway reactivity in asthmatics,42– 44 although this link still remains the subject of much debate. Other research45– 47 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.48 –50 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.51–53 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 www.chestjournal.org
on multiple measures of asthma morbidity. Additional strengths of the present study include having a large, consecutive sample of patients with moderateto-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 used10,34 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 CHEST / 130 / 4 / OCTOBER, 2006
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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. ACKNOWLEDGMENT: The authors thank Drs. Catherine Lemie`re, Dr. Jean-Luc Malo, and Mr. Guillaume Lacoste for their invaluable assistance with data collection.
References 1 CDC, National Center for Health Statistics. Asthma prevalence, heath care use and mortality, 2002. Available at: www.cdc.gov/ nchs/products/pubs/pubd/hestats/asthma/asthma.htm. Accessed July 4, 2005 2 World Health Organization. Fact sheet 206: Bronchial asthma. Available at: www.who.int/mediacentre/factsheets/ fs206/en/print.html. Accessed July 4, 2005 3 Krahn MD, Berka C, Langlois P, et al. Direct and indirect costs of asthma in Canada, 1990. Can Med Assoc J 1996; 154:821– 831 4 Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. N Engl J Med 1992; 326:862– 866 5 Global strategy for asthma management and prevention. Washington, DC: National Institutes of Health, National Heart, Lung, and Blood Institute, 2002; NIH publication 02-3659 6 Bateman ED, Boushey HA, Bousquet J, et al. Can guidelinedefined asthma control be achieved? The Gaining Optimal Asthma Control Study. Am J Respir Crit Care Med 2004; 170:836 – 844 7 Chapman KR, Ernst P, Grenville A, et al. Control of asthma in Canada: failure to achieve guideline targets. Can Respir J 2001; 8(suppl A):35A– 40A 8 Chapman KR, Boulet LP, FitzGerald MJ, et al. Patient factors associated with suboptimal asthma control in Canada: results from the Reality of Asthma Control Study [abstract]. Am J Respir Crit Care Med 2005; 172:A678 9 Chapman KR, Rea RM, Boulet LP. Primary care assessment of asthma control: discordance with guideline recommendations [abstract]. Am J Respir Crit Care Med 2005; 171:A549 10 Juniper EF, O’Byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999; 14:902–907 11 Juniper EF, Stahl E, Mork AC, et al. Minimal important difference for the asthma control questionnaire. Eur Respir J 2004; 24:460s 12 Cluley S, Cochrane GM. Psychological disorder is asthma is associated with poor control and poor adherence to inhaled steroids. Respir Med 2001; 95:37–39 13 Bosley CM, Fosbury JA, Cochrane GM. The psychological factors associated with poor compliance with treatment in asthma. Eur Respir J 1995; 8:899 –904 1046
14 Schmaling KB, Hernandez DV, Giardino ND, eds. Provider and patient adherence with asthma evaluation and treatment. Basel, Switzerland: Basel, Karger, 2003 15 DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: metaanalysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000; 160:2101–2107 16 Lavoie KL, Cartier A, Labrecque M, et al. Are psychiatric disorders associated with worse asthma control and quality of life in asthma patients? Respir Med 2005; 99:1249 –1257 17 Goldney RD, Ruffin R, Fisher LJ, et al. Asthma symptoms associated with depression and lower quality of life: a population survey. Med J Aust 2003; 178:437– 441 18 Netjeck V, Brown E, Khan D, et al. Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic. Ann Allergy Asthma Immunol 2001; 87:129 –133 19 Perna G, Bertani A, Politi E, et al. Asthma and panic attacks. Biol Psychiatry 1997; 42:625– 630 20 Naciemento I, Nardi AE, Valenca AM, et al. Psychiatric disorders in asthmatic outpatients. Psychiatry Res 2002; 110:73– 80 21 Goodwin RD. Asthma and anxiety disorders. Adv Psychosom Med 2003; 24:51–71 22 Goodwin RD, Jacobi F, Thefeld W. Mental disorders and asthma in the community. Arch Gen Psychiatry 2003; 60: 1125–1130 23 American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995; 152:1107– 1136 24 American Thoracic Society. Definition and classification of chronic bronchitis, asthma, and pulmonary emphysema. Am Rev Respir Dis 1962; 85:62– 68 25 Spitzer RL, Williams JB, Kroenke K, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 Study. JAMA 1994; 272:1749 –1756 26 American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Washington DC: American Psychiatric Press, 1994 27 Goodwin RD, Olfson M, Shea S, et al. Asthma and mental disorders in primary care. Gen Hosp Psychiatry 2003; 25: 479 – 483 28 DiNardo PA, Barlow DH. Anxiety disorders interview schedule-Revised (ADIS-R). Albany, NY: Phobia and Anxiety Disorders Clinic, 1988 29 Beck AT, Steer RA, Garbin MG. Psychometric properties of the Beck depression inventory: twenty-five years of evaluation. Clin Psychol Rev 1988; 6:77–100 30 Beck AT, Steer RA, Ball R, et al. Comparison of Beck depression inventories-IA and -II in psychiatric outpatients. J Pers Assess 1996; 67:588 –597 31 Reiss S, Peterson RA, Gursky DM, et al. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther 1986; 24:1– 8 32 Juniper EF, Guyatt GH, Ferrie PJ, et al. Measuring quality of life in asthma. Am Rev Respir Dis 1993; 147:832– 838 33 Juniper EF, O’Byrne PM, Ferrie PJ, et al. Measuring asthma control: clinic questionnaire or daily diary? Am J Respir Crit Care Med 2000; 162:1330 –1334 34 Leidy NK, Coughlin C. Psychometric performance of the Asthma Quality of Life Questionnaire in a US sample. Qual Life Res 1998; 7:127–134 35 Juniper EF. Measurement of health-related quality of life. 2005. Available at: www.qoltech.co.uk/index.htm. Accessed July 1, 2006 36 Brusasco V, Crapo R, Viegi G. Coming together: the ATS/ Original Research
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ERS consensus on clinical pulmonary function testing. Eur Respir 2005; J26:1–2 Knudson RJ, Lebowitz MD, Holberg CJ, et al. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983; 127:725–734 Enright PL, Kronmal RA, Higgins M, et al. Spirometry reference values for women and men 65 to 85 years of age: Cardiovascular Health Study. Am Rev Respir Dis 1993; 147:125–133 Juniper EF, Guyatt GH, Willan A, et al. Determining a minimal important change in a disease-specific quality of life questionnaire. J Clin Epidemiol 1994; 47:81– 87 Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51:8 –19 Mancuso CA, Rincon M, McCulloch CE, et al. Self-efficacy, depressive symptoms, and patients’ expectations predict outcomes in asthma. Med Care 2001; 39:1326 –1338 Lehrer PM. Emotionally triggered asthma: a review of research literature and some hypotheses for self-regulation therapies. Appl Psychophysiol Biofeedback 1998; 23:13– 41 Miller BD, Wood BL. Psychophysiologic reactivity in asthmatic children: a cholinergically mediated confluence of pathways. J Am Acad Child Adolesc Psychiatry 1994; 33: 1236 –1245 Miller BD, Wood DL. Influence of specific emotional states on autonomic reactivity and pulmonary function in asthmatic children. J Am Acad Child Adolesc Psychiatry 1997; 36:669 – 677
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45 Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:201–217 46 Anisman H, Merali Z, Poulter MO, et al. Cytokines as a precipitant of depressive illness: animal and human studies. Curr Pharm Des 2005; 11:963–972 47 Simmons DA, Broderick PA. Cytokines, stressors, and clinical depression: augmented adaptation responses underlie depression pathogenesis. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:793– 807 48 Kang DH, Coe CL, McCarthy DO, et al. Immune responses to final exams in healthy and asthmatic adolescents. Nurs Res 1997; 46:12–19 49 Kang DH, Coe CL, McCarthy DO. Academic examinations significantly impact immune responses, but not lung function, in healthy and well-managed asthmatic adolescents. Brain Behav Immun 1996; 10:164 –181 50 Liu LY, Coe CL, Swenson CA, et al. School examinations enhance airway inflammation to antigen challenge. Am J Respir Crit Care Med 2002; 165:1062–1067 51 Katon WJ, Richardson L, Lozano P, et al. The relationship of asthma and anxiety disorders. Psychosom Med 2004; 66:349 – 355 52 Rietveld S, Everaerd W, Vanbeest I. Can biased symptom perception explain false-alarm choking sensations? Psychol Med 1999; 29:121–126 53 Spinhoven P, van Peski-Oosterbaan AS, Van der Does AJ, et al. Association of anxiety with perception of histamine induced bronchoconstriction in patients with asthma. Thorax 1997; 52:149 –152
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What Is Worse for Asthma Control and Quality of Life* Depressive Disorders, Anxiety Disorders, or Both? Kim L. Lavoie, PhD; Simon L. Bacon, PhD; Silvana Barone, BSc; Andre Cartier, MD; Blaine Ditto, PhD; and Manon Labrecque, MD, MSc, FCCP
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 ⴝ 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. (CHEST 2006; 130:1039 –1047) Key words: anxiety disorders; asthma control; depression; depressive disorders; quality of life 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
is among the four most common chronic A sthma disorders affecting adults. Despite important 1,2
advances in diagnosis and treatment, the prevalence of asthma has increased among all age, sex, and racial *From the Research Center (Drs. Cartier and Labrecque, and Ms. Barone), Division of Chest Medicine, Hoˆpital du Sacre´Cœur de Montre´al; 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. 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 Hoˆpital du Sacre´-Coeur de Montre´al. Dr. Lavoie has been paid professional honorariums from GlaxoSmithkline and Pfizer Canada. www.chestjournal.org
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 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. Manuscript received January 6, 2006; revision accepted April 7, 2006. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Kim L. Lavoie, PhD, Research Center, Division of Chest Medicine, J-3190, 5400 Gouin West, Montreal, QC, H4J 1C5, Canada; e-mail: [email protected] DOI: 10.1378/chest.130.4.1039 CHEST / 130 / 4 / OCTOBER, 2006
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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.1,3 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.5,6 However, current trends in asthma prevalence rates and morbidity indicate that asthma remains poorly controlled in the vast majority of patients.7–9 Criteria for classifying poorly controlled asthma have been published extensively elsewhere5,10,11 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.12–14 Chronic negative mood states such as depression may interfere with daily self-monitoring abilities and treatment adherence,13,15 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.16 –22 We16 and others12,17 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 physiciandiagnosed asthma were recruited from the asthma clinic of 1040
Hoˆpital du Sacre´-Coeur de Montre´al 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 Hoˆpital du Sacre´-Cœur de Montre´al. 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 ⱖ 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 studies17,27 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,20,22 we also adminisOriginal Research
tered 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)29,30 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.29 –31 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,10,32–34 and have been validated in Quebec French.35 Pulmonary Function Testing: All patients underwent standard pulmonary function testing according to American Thoracic Society guidelines.23,36 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. www.chestjournal.org
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]. Sociodemographic and General Medical Characteristics Sociodemographic and general medical characteristics are presented in Table 2 as a function of patient group (no disorder [ND], AD only, DD only, and ADD). There were significantly more women in all three psychiatric groups compared to the ND group. Moreover, significantly fewer patients in the ADD group were employed compared to all other groups. Significantly fewer patients in the ADD and DD groups were married or cohabitating compared to patients in the AD or ND groups. With the exception of a nonsignificant trend suggesting a greater proportion of current smokers in all three psychiatric groups compared to the ND group, there were no other significant differences in general medical characteristics between groups. Levels of depressive (BDI-II) and anxious (ASI) symptomatology were significantly greater in all three psychiatric groups
Table 1—Prevalence of DSM-IV Psychiatric Disorders Presented as a Percentage of the Total Sample (n ⴝ 504) Variables
% (No.)
No DD or AD Any DD or AD Only an AD Only a DD ADD Any AD* Panic disorder Generalized AD Social AD Other AD Any DD* Major DD Minor DD Dysthymia Bipolar disorder
69 (347) 31 (157) 12 (60) 8 (40) 11 (57) 23 (117) 11 (53) 5 (26) 4 (19) 10 (51) 20 (97) 14 (72) 5 (25) 4 (20) 1 (1)
*Comorbidities are summarized. CHEST / 130 / 4 / OCTOBER, 2006
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Table 2—Sociodemographics and General Medical Characteristics as a Function of Psychiatric Group* Variables Sociodemographics Age, yr Female gender White race Cohabitating Education, yr Employed Medical characteristics Hypertension Diabetes Hyperlipidemia BMI, kg/m2 Current smoker Pack-years† Psychological distress BDI-II ASI Psychopharmacologic or psychotherapeutic treatment Benzodiazepines Antidepressants Seeing a mental health professional‡
ND (n ⫽ 347)
AD (n ⫽ 60)
DD (n ⫽ 40)
ADD (n ⫽ 57)
2/F Statistic
51 ⫾ 14 56 (195) 93 (321) 71 (235) 13 ⫾ 4 64 (213)
50 ⫾ 14 78 (47) 95 (57) 73 (44) 13 ⫾ 4 62 (37)
50 ⫾ 12 68 (27) 95 (38) 63 (25) 13 ⫾ 5 65 (26)
47 ⫾ 15 68 (39) 92 (52) 51 (29) 12 ⫾ 4 44 (25)
0.74 12.98 0.98 10.02 2.61 8.54
0.495 0.005 0.806 0.018 0.216 0.036
25 (86) 7 (25) 18 (64) 27 (5) 8 (28) 12 ⫾ 19
22 (13) 8 (5) 28 (11) 27 (5) 15 (9) 13 ⫾ 23
30 (12) 5 (2) 25 (15) 28 (5) 15 (6) 10 ⫾ 14
18 (10) 5 (3) 19 (11) 27 (5) 18 (10) 14 ⫾ 18
2.39 0.70 2.88 0.35 7.30 0.38
0.496 0.874 0.410 0.792 0.062 0.766
6.4 (6.0) 12.3 (9.0)
11.3 (7.2) 21.9 (12.0)
16.1 (8.9) 16.2 (10.1)
21.5 (9.6) 25.2 (12.1)
75.17 35.81
⬍ 0.001 ⬍ 0.001
11 (31) 5 (14) 3 (11)
26 (9) 20 (7) 20 (8)
19 (10) 18 (10) 13 (8)
25 (12) 31 (15) 12 (7)
10.81 34.41 25.13
0.013 ⬍ 0.001 ⬍ 0.001
p Value
*Data are presented as mean ⫾ SD or % (No.). †Pack-years are the average number of packs (20 cigarettes per pack) smoked per day ⫻ the number of years smoked. ‡A psychiatrist or psychologist.
(DD, AD, and ADD) compared to the ND group. Moreover, BDI-II scores were significantly higher in patients with a DD (DD and ADD groups) vs without a DD (ND and AD groups); and ASI scores were significantly higher in patients with an AD (AD and ADD groups) vs without an AD (ND and DD groups), providing validation for PRIME-MD diagnoses. Finally, a greater proportion of patients in all three psychiatric groups were receiving benzodiazepines and antidepressants and were being seen by a mental health professional (psychiatrist or psychologist), compared to the ND group. However, it is noteworthy that ⬍ 20% (n ⫽ 32) of all psychiatric patients were receiving antidepressants, and ⬍ 15% (n ⫽ 23) were under the care of a mental health professional at the time of their evaluation. Pulmonary Function, Asthma Characteristics, and Asthma Medications Pulmonary function, asthma characteristics, and asthma medications are presented in Table 3. There were no significant group differences in pulmonary function, asthma characteristics (including asthma duration, atopy assessed using skin-prick tests, and severity classification), or in the proportion of patients receiving various asthma medications (including daily dose of inhaled corticosteroids). There were also no significant group differences in the frequency of emergency department visits or hospitalizations in the past year. 1042
Asthma Control Analyses on group differences in total score on the ACQ revealed a significant main effect of DD on total ACQ score, indicating that patients with a DD (DD and ADD groups; corrected mean ⫾ SEM, 2.1 ⫾ 0.1) had significantly higher total ACQ scores (indicating worse control) compared to patients without a DD (ND and AD groups; corrected mean ⫾ SEM, 1.6 ⫾ 0.1), independent of age, sex, and asthma severity (F ⫽ 14.98, p ⬍ 0.0001; Fig 1). It is noteworthy that the differences observed between patients with vs without a DD was 0.5, which is considered clinically significant for asthma populations.11 There was no significant main effect for having an AD or for an interaction effect. A multiple regression model containing asthma severity, sex, age, DD, AD, and the interaction of ADDs accounted for 29% of the variance in total ACQ score (Table 4). As expected, there was a significant, independent effect for having a DD, which accounted for 2% of the variance in total ACQ score. There were no significant main effects for having an AD or for an interaction effect. Bronchodilator Use We assessed group differences in the frequency of bronchodilator use in the last week (Fig 2) because it is an important clinical measure of asthma control. The analyses revealed a trend for having an AD on Original Research
Table 3—Pulmonary Function, Asthma Characteristics, and Asthma Medications as a Function of Psychiatric Group* Variables FEV1, L FEV1, % predicted FEV1/FVC, % predicted Asthma severity Mild intermittent Mild persistent Moderate persistent Severe persistent Asthma duration, yr Atopic Emergency department visits in last year Hospitalizations in last year Asthma medications Short-acting 2-agonists Long-acting 2-agonists Inhaled corticosteroids Inhaled corticosteroids dose, g† Oral corticosteroids Antileukotrienes
ND (n ⫽ 347)
AD (n ⫽ 60)
DD (n ⫽ 40)
ADD (n ⫽ 57)
2.34 ⫾ 0.88 72 ⫾ 21 71 ⫾ 19
2.27 ⫾ 0.75 80 ⫾ 23 72 ⫾ 12
2.49 ⫾ 0.93 82 ⫾ 22 75 ⫾ 10
2.28 ⫾ 0.72 77 ⫾ 17 73 ⫾ 11
1 (3) 13 (42) 55 (177) 31 (98) 20 ⫾ 16 63 (215) 0.29 (0.91) 0.10 (0.37)
0 15 (5) 56 (19) 29 (10) 17 ⫾ 14 58 (34) 0.35 (0.90) 0.10 (0.35)
0 7 (4) 59 (34) 34 (20) 17 ⫾ 15 72 (28) 0.30 (0.61) 0.10 (0.30)
98 (338) 76 (242) 94 (321) 665 (525) 12 (33) 15 (42)
98 (55) 70 (40) 98 (58) 675 (424) 13 (7) 17 (9)
95 (38) 69 (27) 90 (35) 729 (664) 6 (2) 9 (3)
F Statistic/2
p Value
0.65 0.82 1.47 7.02
0.580 0.483 0.221 0.636
0 6 (3) 53 (28) 42 (22) 21 ⫾ 17 70 (40) 0.53 (1.05) 0.25 (0.76)
0.72 3.23 1.09 2.02
0.542 0.357 0.351 0.110
98 (56) 71 (39) 93 (53) 849 (535) 19 (9) 12 (6)
2.00 1.60 3.42 1.58 3.01 1.35
0.571 0.660 0.356 0.194 0.390 0.715
*Data are presented as mean ⫾ SD or % (No.). †Median (range) fluticasone propionate equivalent.
the frequency of bronchodilator use in the last week, indicating that patients with an AD (AD and ADD patients; corrected mean ⫾ SEM, 13.0 ⫾ 1.5) used their bronchodilator more times in the last week compared to patients without an AD (ND and DD patients; corrected mean ⫾ SEM, 9.3 ⫾ 1.4). There were no significant main effects for having a DD or for an interaction effect. Asthma Quality of Life Analyses on group differences in total score on the AQLQ revealed significant main effects of DD
(F ⫽ 38.5, p ⬍ 0.001) and AD (F ⫽ 18.06, p ⬍ 0.001) on total AQLQ score, indicating that patients with a DD (DD and ADD patients; corrected mean ⫾ SEM, 4.41 ⫾ 0.14) had lower total scores than patients without a DD (ND and AD patients; corrected mean ⫾ SEM, 5.05 ⫾ 0.09), and patients with an AD (AD and MAD patients; corrected mean ⫾ SEM, 4.56 ⫾ 0.12) had significantly lower total AQLQ scores compared to patients without an AD (ND and DD patients; corrected mean ⫾ SEM, 4.90 ⫾ 0.11; Fig 3). However, there was no significant interaction effect. It
Table 4 —Linear Regression Models for Total Scores on ACQ and AQLQ Variables
Figure 1. Total ACQ scores (mean ⫾ SEM) presented as a function of psychiatric group (higher scores indicate worse control). No Psych ⫽ no psychiatric disorder. www.chestjournal.org
ACQ, total score Severity Sex Age DD AD DD ⫻ AD Model AQLQ, total score Severity Sex Age DD AD DD ⫻ AD Model
R2
F Statistic
t Test
p Value
0.23 0.00 0.01 0.02 0.00 0.00 0.29
139.48 1.06 4.67 9.82 2.66 0.27 30.59
11.81 1.03 ⫺ 2.16 3.15 1.63 ⫺ 0.52
⬍ 0.001 0.304 0.031 0.002 0.103 0.604 ⬍ 0.001
0.09 0.01 0.01 0.03 0.02 0.00 0.22
42.70 4.46 4.09 14.64 10.43 1.93 17.81
⫺ 6.53 2.11 2.02 ⫺ 3.83 ⫺ 3.23 1.39
⬍ 0.001 0.035 0.044 ⬍ 0.001 0.001 0.165 ⬍ 0.001
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symptom subscale could explain 20% of the variance (F ⫽ 17.17, p ⬍ 0.001), of which having a DD accounted for 2% (F ⫽ 11.44, p ⬍ 0.001) and having an AD accounted for 2% (F ⫽ 8.14, p ⫽ 0.005). The model for the emotional distress subscale could explain 19% of the variance (F ⫽ 16.37, p ⬍ 0.001), of which DD accounted for 2% (F ⫽ 8.21, p ⫽ 0.004) and AD accounted for 3% (F ⫽ 14.47, p ⬍ 0.001). Finally, the model for the environmental limitations subscale could explain 12% of the variance (F ⫽ 9.54, p ⬍ 0.001), of which DD accounted for 2% (F ⫽ 10.08, p ⫽ 0.002) and AD accounted for 2% (F ⫽ 6.66, p ⫽ 0.010). Figure 2. Bronchodilator use in the last week (mean ⫾ SEM) presented as a function of psychiatric group. See Figure 1 legend for expansion of abbreviation.
is noteworthy that the AQLQ score differences observed between patients with vs without a DD was 0.64, which is considered clinically significant for asthma populations.39 A multiple regression model containing asthma severity, sex, age, DD, AD, and the interaction of ADD accounted for 22% of the variance in total AQLQ score (Table 4). There were significant independent effects for having a DD (accounting for 3% of the variance in total AQLQ score) and for having an AD (accounting for 2% of the variance in total AQLQ score). There was no significant interaction effect. Separate regression models were also conducted for each subscale of the AQLQ, containing asthma severity, sex, age, DD, AD and their interaction. The model for the activity limitation subscale could explain 17% of the variance (F ⫽ 13.98, p ⬍ 0.001), of which having a DD accounted for 3% (F ⫽ 14.66, p ⬍ 0.001) and having an AD accounted for 1% (F ⫽ 6.11, p ⫽ 0.014). The model for the
Figure 3. Total AQLQ score (mean ⫾ SEM) presented as a function of psychiatric group (higher scores indicate better quality of life). See Figure 1 legend for expansion of abbreviation. 1044
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%, respectively26,40). 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 selfadministration. 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 patient’s 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 preOriginal Research
liminary evidence to suggest a link between negative mood states and increased cholinergically mediated airway reactivity in asthmatics,42– 44 although this link still remains the subject of much debate. Other research45– 47 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.48 –50 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.51–53 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 www.chestjournal.org
on multiple measures of asthma morbidity. Additional strengths of the present study include having a large, consecutive sample of patients with moderateto-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 used10,34 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 CHEST / 130 / 4 / OCTOBER, 2006
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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. ACKNOWLEDGMENT: The authors thank Drs. Catherine Lemie`re, Dr. Jean-Luc Malo, and Mr. Guillaume Lacoste for their invaluable assistance with data collection.
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