Miedinger, David MD; Lavoie, Kim L. PhD; L'Archevêque, Jocelyne MT; Ghezzo, Heberto PhD; Zunzunuegui, Maria Victoria PhD; Malo, Jean-Luc MD
Psychiatric disorders such as mood (depressive) and anxiety disorders are frequently associated with asthma, and patients with depressive disorders have been shown to have worse asthma control, impaired quality of life (QOL), and tend to use more health care than patients without psychiatric comorbidity.1–3
Only a handful of studies have attempted to assess QOL impacts and the prevalence of psychological and psychiatric disorders in patients with occupational asthma (OA), as stated in a recent review article.2 One can hypothesize that patients with OA would have a more-impaired QOL because of being removed from their workplace, resulting in lost income and personal status. We have shown that patients with OA have a significantly decreased QOL compared with asthma patients without OA.4
In a study assessing participants with OA 2 years after removal from exposure to the causal agent, we reported that 35% of patients with OA had anxiety disorders and about 23% had dysthymia (a chronic form of depression). We also found that patients with OA had elevated psychological distress (PD) and moderately impaired disease-specific QOL.5 Nevertheless, this study examined only psychological morbidity and disease-specific QOL 2 years postdiagnosis; therefore, we could not examine the risk factors that might influence the psychosocial and QOL outcomes of OA.
* Outline previous findings on the association between psychiatric disorders and asthma in general and occupational asthma in particular.
* Discuss the new follow-up data on psychologic distress and quality of life in workers with occupational asthma.
* Identify the most important factors associated with psychologic outcomes and disease-specific quality of life in this group of patients.
The aim of this study was to examine the association between anthropometric, clinical, functional, and socioeconomic variables assessed at the time of the OA diagnosis and 2 years thereafter on QOL and psychological outcomes in patients with OA. We expected that factors such as sex, age, the time interval since diagnosis, asthma severity, and being employed at follow-up would be associated with worse psychological outcomes, particularly the prevalence of mood and anxiety disorders. We also wanted to determine whether or not QOL and PD assessed at follow-up were associated with higher compensation costs for OA.
The interested reader will find a detailed account of all aspects of the methodology used in this study by consulting the supplemental digital content section (http://links.lww.com/JOM/A50).
Study Design, Setting, and Participants
This was a cross-sectional study investigating patients who claimed compensation for OA at the Workers' Compensation Agency of Quebec (Commission de la santé et sécurité du travail du Québec; CSST) in the years 2004 to 2006. Patients who were no longer exposed to the offending allergens causing OA for 2 years or more were evaluated by two of the four Quebec CSST medical committees in Montreal (Montreal Chest Institute and Hôpital du Sacré-Coeur) for a permanent disability indemnity. In Quebec, all patients who claim compensation for OA undergo specific inhalation testing to confirm a diagnosis of OA. The methods used for specific challenge testing using different work-related allergens have been described previously,6 and this method is considered to be the reference standard for the diagnosis of OA.7 Therefore, all of the patients included in this study showed a positive response to a specific inhalation test. In this study, the definition of asthma is therefore based on workplace-associated respiratory symptoms and a positive result in the specific inhalation test. All claimants scheduled for evaluation by the committees were asked to participate in this study on a voluntary basis.
Patients were assessed on two occasions: (1) when the initial OA diagnosis was made and the claim filed with the Workers' Compensation Board (WCB) (diagnosis) and (2) when the participants were reevaluated to determine compensation for permanent disability approximately 2 years later. Patients underwent the same testing protocol on both occasions, with the exception of skin-prick testing, which was performed only at diagnosis (see details later). Furthermore, questions regarding patients' employment status at the time, participation in rehabilitation programs, socioeconomic factors, and validated psychological and QOL questionnaires were added to their investigation at the 2-year reevaluation point.
Patients were assured that the medical committee would be informed neither of participation or decline of participation in this study nor of the test results. They were given compensation for their study participation to cover expenses like loss of salary and transportation or parking fees. All study participants gave written consent for their participation. The research protocol was approved by the research ethical committee of our hospital (CER de l'Hôpital Sacré-Coeur, Montreal).
Measures at Diagnosis
All patients investigated underwent standard spirometry, methacholine challenge testing, and induced sputum analysis. The type of agent causing OA, medication use, smoking status, and data on socioeconomic status, such as income, employment status, and company size, were recorded from the WCB's report (Fig. 1).
Measures at Reevaluation
Approximately 2 years after receiving their initial diagnosis, all patients investigated underwent standard spirometry, methacholine challenge testing, and if patients could produce sputum on induction examination, induced sputum analysis (Fig. 1). All patients completed a questionnaire on chest and upper airway symptoms, medication use, home allergen exposure, and smoking status. Patients also completed a questionnaire assessing whether they were still exposed to the offending agent, as well as a questionnaire assessing socioeconomic factors, including their employment at time, salary, education history, country of origin, number of children and family members dependant on the household income, and the nature of their participation in social rehabilitation programs offered by the WCB (eg, full- or part-time participation in job education, use of the employment agency). In addition, participants completed the validated French versions of the following questionnaires.
Asthma Quality of Life Questionnaire
The standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]) includes 32 items and evaluates asthma QOL across four life domains that may be negatively affected by asthma. The life domains include (1) asthma symptoms, (2) activity limitations, (3) emotional function, and (4) exposure to environmental stimuli. Every question is cored from one (extremely severe impairment of QOL) to seven (no impairment at all), and the total score is the mean of the four scores.8
St Georges Respiratory Questionnaire
For this study, we used the section on only respiratory symptoms from the St Georges Respiratory Questionnaire (SGRQ), which includes eight questions, and the total score represents the sum of these elements. The total score ranges from 0 to 100, and a higher score indicates a worse health-related QOL.9
Psychiatric Symptom Index
The Psychiatric Symptom Index (PSI) is a 29-item questionnaire elaborated to assess the presence and intensity of PD in the 2 weeks preceding the evaluation.10 Items are scored by using a four-point scale from zero (never) to three (very often). Total scores and subscale scores (depression, anxiety, anger, and cognitive disturbance) are calculated as a percentage of the total possible score out of 100. Scores of greater than 25 are considered to indicate clinically significant distress.10
Primary Care Evaluation of Mental Disorders
The Primary Care Evaluation of Mental Disorders (PRIME-MD) is a validated screening instrument designed to detect some of the most common Diagnostic and Statistical Manual (DSM) of Mental Disorders seen in community and medical settings.11 It consists of a 27-item patient's self-report section followed by a structured clinical interview that is used to follow up patient responses. The PRIME-MD evaluates five groups of mental disorders (mood, anxiety, somatoform, alcohol, and eating), and items are developed on the basis of criteria from the DSM, 3rd edition revised.12 It has demonstrated very good sensitivity (83%) for any psychiatric diagnosis and excellent specificity (88%) across diagnostic modules.11
Spirometry and Methacholine Provocation Testing
All patients underwent standard spirometry according to American Thoracic Society guidelines,13 using the reference values derived by Knudson et al.14 Methacholine challenge testing was performed according to a previously published protocol.15 Normal responsiveness was set at a concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) of greater than 16 mg/mL.16
Skin-prick tests were performed at diagnosis of OA to assess atopic status according to the method described by Pepys.17 Atopy was defined as having at least one positive result to an aeroallergen.
Induced Sputum Analysis
Patients underwent sputum induction by inhaling increasing concentrations (3%, 4%, and 5%) of hypertonic saline at diagnosis and at reevaluation.18 The samples were processed according to a previously published protocol.19
Compound Asthma Severity Score
Asthma severity was assessed at diagnosis and reevaluation. The asthma severity at diagnosis and reevaluation and the proportion of permanent disability that was allocated were calculated according to the Quebec WCB Scale for OA: 0%, low severity; and 100%, maximum severity.20 This scale incorporates three factors in the same way as the one proposed by the American Medical Association21: level of bronchial caliber, degree of bronchial responsiveness, and need for medication to control asthma.22
Direct Costs of Occupational Asthma
We consulted the patients' files at the Québec WCB to determine the costs of compensation for OA at the time of the reevaluation. We reported the compensation for loss of income (CLI) and compensation for functional impairment (CFI) in this study. The CLI corresponds mainly to compensation for lost wages during the rehabilitation period (up to 2 years) after the worker is removed from the workplace. The CFI is allocated at the time of reevaluation by the WCB, about 2 years after the confirmation of the initial diagnosis and subsequent removal from the workplace, and is calculated according to the WCB scale for OA.
Continuous data are reported as mean ± standard deviation or median and 25th and 75th percentiles. Proportions were compared by using chi-square or the Fisher exact test if the expected cell count was less than 5. Continuous variables were compared by using the Mann-Whitney U test. We calculated the Spearman ρ for correlation analysis between two continuous variables, and we conducted point-biserial correlations between continuous and categorical variables, but we did not correct the P values for multiplicity. Before performing linear regression, we performed logarithmic transformation and then applied the second power of the dependent variables, AQLQ(S) and the PSI total scores. Presence of psychiatric mood and anxiety disorders was assess by the PRIME-MD and coded as a dichotomous variable (yes, no).
Two models were fitted for each dependant variable. First, an a priori model, which included factors set in our hypotheses as likely associated with psychological outcomes (AQLQ[S], SGRQ, and PSI): sex (male vs female), age at reevaluation, time intervals since diagnosis, the asthma severity composite score at reevaluation, and the current employment status (working vs not working). Second, a full model that we have named “a posterior,” which included all significant covariates identified in the a priori model in whom the coefficients had a P < 0.2 and new socioeconomic covariates gathered at the time of diagnosis, as well as at the time of reevaluation. Linear regression was used for continuous dependant variables and logistic regression for the presence of mood and anxiety disorders according to the PRIME-MD. For all data analyses, we used the statistical software package SPSS V.16 (SPSS Inc, Chicago, IL). We considered a P < 0.05 as significant.
Seventy-three subjects were eligible to participate, as their claims were reviewed by the two committees in Montreal for a permanent disability indemnity during the study's recruitment period. Of these eligible individuals, we were unable to contact five subjects and eight subjects refused to participate, yielding a final sample of 60 subjects and a participation rate of 82%. Participants did not differ from nonparticipants with respect to sex, age at diagnosis, atopy, smoking status, lung function, hyperreactivity to methacholine, proportion of subjects with OA caused by low-molecular-weight agents, and the number of years at the workplace with symptoms (see results in the Supplemental Digital Content section of this journal, http://links.lww.com/JOM/A50).
Characteristics of the study sample at the time of their initial diagnosis and at reevaluation can be seen in Table 1. Fifty-five percent of participants were working at the time of reevaluation, 20% were retired, 20% were unemployed, and 5% were currently on retraining for another job. Thirty-one percent reported their overall health status as being fair or poor.
Disease-specific QOL, PD, and the frequency of psychiatric (mood and anxiety) disorders assessed at the reevaluation are shown in Table 2. Disease-specific QOL measured with the AQLQ(S) was moderately impaired, and participants had a score in the medium range of the SGRQ symptom subscale. Forty-seven percent of the participants had a total score of 25 or more on the PSI, indicating a clinically significant level of PD. Thirty-two percent of patients screened positive for a mood disorder, and 15% screened positive for anxiety disorder according to the PRIME-MD. Twelve percent had comorbid mood and anxiety disorders concomitantly, and 35% had mood and/or anxiety disorder(s).
As shown in Table 3, FEV1(%predicted) was positively correlated with all the AQLQ(S) subscale scores and total score, and negatively correlated with the SGRQ symptom subscale score and the PSI total score. Furthermore, and not shown in Table 3, change in FEV1%predicted (FEV1%predicted at diagnosis − FEV1%predicted at reevaluation) was negatively correlated with the symptom and emotional function subscale score (r = −0.266, P = 0.042 and r = −0.273, P = 0.036, respectively) and positively correlated with the SGRQ symptom score (r = 0.256, P = 0.050). Not shown in Table 3, inhaled steroid dose was positively correlated with the SGRQ symptom score (r = 0.398, P = 0.013) and the asthma severity compound score was negatively correlated with the AQLQ(S) total and subscale scores, the SGRQ symptom score, and all PSI subscale scores (with the exception of cognitive disturbances). For the induced sputum analysis, the total sputum cell count was negatively correlated with all the AQLQ(S) total and subscale scores (with the exception of environmental stimuli) and positively correlated with the SGRQ symptom score (Table 3). Not shown in Table 3, the proportion of eosinophils was negatively correlated with having a diagnosis of mood disorder and having a mood and/or anxiety disorder according to the PRIME-MD (r = −0.312, P = 0.035 and r = −0.368, P = 0.012, respectively). The proportion of neutrophils was negatively correlated with the AQLQ(S) activity limitation subscale score and positively correlated with the SGRQ symptom score (r = −0.389, P = 0.008 and r = 0.375, P = 0.010, respectively).
Participants receiving no treatment for asthma or taking only short-acting bronchodilators, as needed, had significantly less-impaired disease-specific QOL (total AQLQ[S] score 5.9 [Q1; Q3: 4.9; 6.4] vs 3.9 [Q1; Q3: 2.9; 5.1], P < 0.001; and a lower SGRQ symptom score 35.2 [21.1;40.8] vs 64.1 [36.8;81.7], P < 0.001), as well as less PD (total PSI score 17.5 [6.0;27.0] vs 28.5 [15.0;39.5], P = 0.028) compared with those on regular (daily) antiasthma treatment.
According to employment status, total asthma disease-specific QOL was significantly different at reevaluation: participants who were working at the time had better disease-specific QOL (AQLQ[S] score 5.3 [Q1; Q3: 4.2; 6.3] and SGRQ score 38 [Q1; Q3: 26; 53]) than those who were unemployed (AQLQ[S] score 3.9 [Q1; Q3: 3.1; 4.4] and SGRQ score 68 [40;86]) or retired (AQLQ[S] score 2.9 (Q1; Q3: 2.3; 5.3), P = 0.001; and SGRQ score 69 [39;79], P = 0.008) at the time of reevaluation. For PD levels, there was a similar trend for the PSI anxiety and depression scores: participants who were working at the time had less PD (anxiety score 21.0 [Q1; Q3: 9; 36] and depression score 17.0 [Q1; Q3: 3; 3]) than those who were unemployed (anxiety score 36.0 [Q1; Q3: 21; 48] and depression score 28.5 [Q1; Q3: 23; 33]) or retired (anxiety score 30 [Q1; Q3: 10.5; 43.5], P = 0.067; and depression score 26.5 [Q1; Q3: 11.8; 47], P = 0.088) at the time of reevaluation.
In the multivariate linear regression analysis, the AQLQ(S) total score was significantly negatively correlated to the compound asthma severity score at reevaluation in the a priori model (Table 4). After applying stepwise linear regression, the compound asthma severity score at the time of reevaluation and being married at the diagnosis of OA were associated with worse QOL in the AQLQ(S) score; however, the P values derived after applying stepwise regression modeling were only approximate values. The SGRQ symptom score was significantly positively associated to the compound asthma severity score in the a priori model. After applying stepwise linear regression to other socioeconomic variables, and retaining asthma severity within the model, being married, having low income, and being employed for more than 5 years with the same employer at the time of diagnosis were related to poorer QOL scores according to the SGRQ.
The total PSI score had no significant association with the covariates in the a priori model; however, being a labor union member at the time of diagnosis was associated with the PSI score at reevaluation in the “a posteriori” model (Table 4).
The median CLI cost was 55.6 × 103 Canadian dollars (CAD) (Q1;Q3: 25.3 × 103 CAD; 124.1 × 103 CAD), the median CFI cost was 12.0 × 103 CAD (2.5 × 103 CAD; 18.6 × 103 CAD), and the median total cost for compensation was 69.2 ×103 CAD (36.6 × 103 CAD; 135.5 × 103 CAD). The correlation of the asthma severity, disease-specific QOL, and PD scores with direct costs for compensation are shown in Table 5. All AQLQ(S) subscale scores and the total score had a significant negative correlation with CLI costs, and this correlation remained significant with total costs for the total score and all the subscores, with the exception of the emotional function score. The activity limitations subscale score had a small negative correlation with the CFI costs. The SGRQ symptom score had a small to medium positive correlation with the CLI and total cost. The PSI total and subscales scores did not correlate with costs for compensation, with the exception of the anger score (ρ = 0.285, P = 0.028).
Our study shows that high proportions of patients with OA have moderate impairment in disease-specific QOL, elevated levels of PD, and a high prevalence of psychiatric (mood and anxiety) disorders 2 years after their initial diagnosis.
Despite the fact that most of the study participants were no longer working at the workplace that caused OA at the time of reevaluation, participants had moderately impaired QOL measured according to the AQLQ(S). This is in accordance with past studies showing that more than 70% of subjects continue to have symptoms and use asthma medication despite being removed from the workplace for more than 2 years.23 Airway hyperresponsiveness to methacholine tends to improve more rapidly in the first 2.5 years but slows down afterward.24 In workers with different allergic manifestations due to natural latex, Al-Otaibi et al25 reported a decrease of disease-specific QOL impairment with increasing time since the diagnosis was made and symptoms duration. In our study, we did not investigate a control group, and, therefore, we cannot compare the level of QOL impairment with individuals without OA; however, as shown in the past, despite matching for disease severity, subjects with OA seem to be significantly more impaired in QOL than control subjects without OA.4
In our study, between 35% and 47% of participants had clinically significant levels of PD and 35% met criteria for one or more current mood or anxiety disorders according to the PRIME-MD. Without considering asthma severity, in non-OA patients seen in our hospital asthma clinic, the prevalence of anxiety or mood disorder is similar, that is, 31%.26 Suffering from a chronic illness is known to be associated with higher PD in cross-sectional population studies.27 In a World Health Organization study, the prevalence of depressive disorder was reported to be between 10.4% and 7.9% for generalized anxiety disorder.28 It has been demonstrated that physical disability is a risk factor for the development of depressive disorders, whereas other studies have shown in healthy cohorts at baseline that individuals with depression have an increased risk of developing a new disabilities in the following years.29
Our study shows that the principal factor associated with impact on QOL and psychological outcomes was the severity of asthma. There are conflicting findings concerning the correlation between objective parameters of asthma severity and anxiety levels. Some studies showed significant correlations between peak expiratory flow variability and self-reported anxiety in the Beck Anxiety Symptom Inventory,30 whereas other studies could not report a correlation between PD and lung function.31,32 Depression does not appear to be associated with objective measures of asthma severity. In a pilot study, asthmatic patients with a history of mood disorder seemed to have less-severe airway obstruction and less-severe asthma.33 Elevated depression scores were associated with perceived asthma severity and risk but not with intubation history, number of hospitalizations, or asthma medication history.34 Interestingly, we found a correlation between the proportion of sputum eosinophils and mood disorder. It has been shown that eosinophilic airway inflammation is more pronounced after antigen challenge during final examinations among college students and is associated with higher self-reported psychological stress.35
In the multivariate linear regression a priori model, the asthma severity compound score was the only factor significantly associated with the AQLQ(S) total score. Other covariates, such as sex, age, current employment status, and the time since diagnosis of OA and consequent removal from the causal allergen, found significant at a P < 0.2 level in the univariate analysis, were not significantly associated with disease-specific QOL. Nevertheless, in the a posteriori analysis, some socioeconomic factors were significantly associated with AQLQ(S) but not with psychological outcomes. Being married at the time of diagnosis was associated with more-severe QOL impairment, measured as the total AQLQ(S) and in the SGRQ symptom score. In general, married individuals often have better health status than their unmarried counterparts.36 Nevertheless, singles seem to have better health outcomes when compared with those in low-quality marriages, as shown in hypertension research studies.37 Job loss due to OA and resultant income and social status losses might influence QOL; this might be even more important in individuals who have a dependent spouse. Participants being labor union members at the time of diagnosis had lower PD levels at reevaluation. The mission of a labor union is to defend the economic, professional, and social interests of workers, especially in the workplace. Workers may thereby benefit from labor union help in terms of complying to the requirements of filing a claim for compensation. Moreover, they may receive support during the rehabilitation phase (eg, in finding a new workplace, exploring possibilities for reeducation programs, and receiving legal support), thereby explaining lower levels of PD at the time of reevaluation. Although employment status at the time of reevaluation was significantly related to QOL and psychological outcomes in the univariate analysis, this was not the case in the multivariate analysis, in contrast to asthma severity that was significantly correlated to QOL and psychological outcomes in both the univariate and multivariate analyses. Asthma severity has been shown in other studies to be a weak, although significant, determinant for employment status.38
Another important finding of this study is the association between direct costs and psychological outcomes. We found small to medium significant correlations between QOL measures and the anger subscale of the PSI questionnaire and compensation costs. The relation was strongest with the CFI compensation component, which reflected disease severity. As many factors influenced CLI costs (age and income at the time of diagnosis being the most important ones), it is not surprising that we could not find any association between QOL, PD, and costs for CLI.
We did not collect information about disease-specific QOL and PD and psychiatric morbidity (mood and anxiety disorders) at the time of diagnosis and therefore have no information about the interaction of OA with PD and psychiatric disorders and the progression of both conditions. Furthermore, we did not systematically collect information on medication used in treating psychiatric disorders. It is possible that some individuals were treated successfully for psychiatric disorders and that the results of our study underestimated impairment in QOL and PD in individuals with OA. In Quebec, a broad compensation system for OA is in place. Even when compensation systems appear to be effective, not all subjects with a high probability of asthma claim compensation from the WCB or change workplaces to avoid the causal agent(s).39 In countries such as the United States, where disputes about compensation are usually settled through litigation in an adversarial setting, the impact on QOL and PD may be even more pronounced. Compensation claims and costs for occupational injuries have shown to be influenced by economic cycles. Compensation claims tend to decline in recessions and increase in times of economic recovery.40 How these factors influence QOL and PD in individuals with OA is unknown.
A large proportion of patients with OA have significant impairment in disease-specific QOL with elevated levels of PD and psychiatric (mood and anxiety) disorders. Quality of life, as well as some PD parameters at reevaluation, correlates well with objective measures of disease activity, which seem to be the principal determinant. Nevertheless, besides the current asthma severity, socioeconomic factors, such as employment status, marital status, income, the number of years of employment at the time of diagnosis, also influence, though to a lesser degree, disease-specific QOL and psychological outcomes. Finally, disease-specific QOL correlates with the direct costs for compensation by the WCB. Therefore, our findings underline the importance of PD and comorbid psychiatric disorders in patients with OA. Nevertheless, further studies are needed to prospectively investigate patients in terms of the evolution of their QOL, PD levels, and psychiatric morbidity from the time of diagnosis to when patients are removed from the workplace and undergo rehabilitation. Furthermore, future studies are needed to investigate whether intervention programs can reduce PD and/or prevent the development of psychiatric morbidity in patients with OA and whether the same factors influence QOL and PD in countries with different medical and compensation systems.
The authors thank the administrative authorities of the Québec CSST, who provide cost information, and Cynthia Demedash for proofreading the manuscript. to the authors also thank Denyse Gautrin, PhD, for her valuable help regarding the elaboration of this manuscript.
The research was funded by Center for Asthma in the Workplace, Centre Léa-Robback sur les inégalités sociales de la santé, Canadian Institutes of Health Research. David Miedinger is the recipient of a research grant from the Swiss National Science Foundation (PBBSB-120767) and from the Center for Asthma in the Workplace (Canadian Institutes of Health Research). Kim Lavoie is supported by a salary award from the Fonds de la recherche en santé du Québec.
1. Eisner MD, Katz PP, Lactao G, Iribarren C. Impact of depressive symptoms on adult asthma outcomes. Ann Allergy Asthma Immunol. 2005;94:566–574.
2. Lavoie KL, Joseph M, Bacon SL. Psychological distress and occupational asthma. Curr Opin Allergy Clin Immunol. 2009;9:103–109.
3. Richardson LP, Russo JE, Lozano P, McCauley E, Katon W. The effect of comorbid anxiety and depressive disorders on health care utilization and costs among adolescents with asthma. Gen Hosp Psychiatry. 2008;30:398–406.
4. Malo JL, Boulet LP, Dewitte JD, et al.. Quality of life of subjects with occupational asthma. J Allergy Clin Immunol. 1993;91:1121–1127.
5. Yacoub MR, Lavoie K, Lacoste G, et al.. Assessment of impairment/disability due to occupational asthma through a multidimensional approach. Eur Respir J. 2007;29:889–896.
6. Vandenplas O, Malo JL. Inhalation challenges with agents causing occupational asthma. Eur Respir J. 1997;10:2612–2629.
7. Tarlo SM, Balmes J, Balkissoon R, et al.. Diagnosis and management of work-related asthma: American College Of Chest Physicians consensus statement. Chest. 2008;134:1S–41S.
8. Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest. 1999;115:1265–1270.
9. Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. 1991;85(suppl B):25–31.
10. Illfeld FW. Further validation of a psychiatric symptom index in a normal population. Psychol Rep. 1976;39:1215–1228.
11. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282:1737–1744.
12. American Psychological Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: American Psychological Association; 1987.
13. Standardization of spirometry, 1994 update. American Thoracic Society. Am J Respir Crit Care Med. 1995;152:1107–1136.
14. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127:725–734.
15. Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy. 1977;7:235–243.
16. Malo JL, Pineau L, Cartier A, Martin RR. Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population. Am Rev Respir Dis. 1983;128:8–11.
17. Pepys J. Skin tests for immediate, type I, allergic reactions. Proc R Soc Med. 1972;65:271–272.
18. Pizzichini MM, Popov TA, Efthimiadis A, et al.. Spontaneous and induced sputum to measure indices of airway inflammation in asthma. Am J Respir Crit Care Med. 1996;154:866–869.
19. Pizzichini E, Pizzichini MM, Efthimiadis A, et al.. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996;154:308–317.
20. Dewitte JD, Chan-Yeung M, Malo JL. Medicolegal and compensation aspects of occupational asthma. Eur Respir J. 1994;7:969–980.
21. American Medical Association. Guides to the Evaluation of Permanent Impairment. Chicago, IL: American Medical Association; 2001:102–104.
22. Bernstein IL, Keskinen H, Blanc PD, Chan-Yeung M, Malo JL. Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI. Medicolegal aspects, compensation aspects, and evaluation of impairment/disabilitiy. In: Asthma in the Workplace. New York, NY: Taylor & Francis; 2006:319–351.
23. Labrecque M, Khemici E, Cartier A, Malo JL, Turcot J. Impairment in workers with isocyanate-induced occupational asthma and removed from exposure in the province of Quebec between 1985 and 2002. J Occup Environ Med. 2006;48:1093–1098.
24. Malo JL, Ghezzo H. Recovery of methacholine responsiveness after end of exposure in occupational asthma. Am J Respir Crit Care Med. 2004;169:1304–1307.
25. Al-Otaibi S, Tarlo SM, House R. Quality of life in patients with latex allergy. Occup Med (Lond). 2005;55:88–92.
26. Lavoie KL, Bacon SL, Barone S, Cartier A, Ditto B, Labrecque M. What is worse for asthma control and quality of life: depressive disorders, anxiety disorders, or both? Chest. 2006;130:1039–1047.
27. Wells KB, Golding JM, Burnam MA. Psychiatric disorder in a sample of the general population with and without chronic medical conditions. Am J Psychiatry. 1988;145:976–981.
28. Üstün TB, Sartorius N. Mental Illness in General Health Care. An International Study. Chichester, West Sussex, England: John Wiley & Sons; 2005.
29. Penninx BW. Steptoe A. Depression and physical disability. In: Depression and Physical Illness. Cambridge, England: Cambridge University Press; 2007:125–144.
30. Hommel KA, Chaney JM, Wagner JL, McLaughlin MS. Asthma-specific quality of life in older adolescents and young adults with long-standing asthma: the role of anxiety and depression. J Clin Psychol Med Settings. 2002;9:185–192.
31. 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.
32. Rimington LD, Davies DH, Lowe D, Pearson MG. Relationship between anxiety, depression, and morbidity in adult asthma patients. Thorax. 2001;56:266–271.
33. Nejtek VA, Brown ES, Khan DA, Moore JJ, Van Wagner J, Perantie DC. 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.
34. Janson-Bjerklie S, Ferketich S, Benner P, Becker G. Clinical markers of asthma severity and risk: importance of subjective as well as objective factors. Heart Lung. 1992;21:265–272.
35. Liu LY, Coe CL, Swenson CA, Kelly EA, Kita H, Busse WW. School examinations enhance airway inflammation to antigen challenge. Am J Respir Crit Care Med. 2002;165:1062–1067.
36. Wyke S, Ford G. Competing explanations for associations between marital status and health. Soc Sci Med. 1992;34:523–532.
37. Holt-Lunstad J, Birmingham W, Jones BQ. Is there something unique about marriage? The relative impact of marital status, relationship quality, and network social support on ambulatory blood pressure and mental health. Ann Behav Med. 2008;35:239–244.
38. Vandenplas O, Toren K, Blanc PD. Health and socioeconomic impact of work-related asthma. Eur Respir J. 2003;22:689–697.
39. Provencher S, Labreche FP, De GL. Physician based surveillance system for occupational respiratory diseases: the experience of PROPULSE, Quebec, Canada. Occup Environ Med. 1997;54:272–276.
40. Institute for Work & Health. Workers' Compensation and the Business Cycle. Toronto, Ontario, Canada: Institute for Work & Health; 2009.