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  • The study was approved by the institutional review board of the vancouver coastal health research institute (project approval number: H08-01306). Writing informed consent was obtained from all patients. This is a cross-sectional study of subjects diagnosed with WRCA by standardized plicatic acid challenge test at a provincial referral centre at Vancouver General Hospital since 1972. A total of 47 lower mainland residents of British Columbia who were diagnosed with WRCA were eligible and agreed to participate. Methacholine challenge testing could not be successfully performed for one subject; therefore 46 subjects finished the study. The ATS asthma impairment score was assessed and impairment class determined based on post-bronchodilator FEV1, AHR and minimum medication needed [13]. According to the validated schema, the class of impairment was expressed as class 0, 1, 2, 3, and 4 (total asthma severity score 0, 1–3, 4–6, 7–9 and 10–11). Health-related Quality of Life Scores: All interviews were performed in person by the study coordinator. HRQL scores were assessed with the Short Form 36 (SF-36) [14], one of the most commonly used and validated generic health status questionnaires in adults. Total score and eight domains of HRQL were quantified: physical functioning, physical health, emotional problem, vitality (energy/fatigue), emotional well-being, social functioning, bodily pain, and general health perception. A higher asthma HRQL score reflects better functioning. Values close to 100 indicate excellent overall health and functioning. A methacholine challenge test was performed according to the method of Cockcroft et al [15] and the provocative concentration of methacholine that induces a 20% fall in FEV1 (PC20) was calculated from the following standard formula [16]:where C1 = second-to-last concentration, R1 = second-to-last response, C2 = last concentration, and R2 = last response. In cases where the FEV1 dropped between 15% and 20%, the same formula was applied [17], [18]. In cases where the FEV1 didn’t drop 15% by the last concentration of methacholine, the last concentration of methacholine was assigned as PC20 [17], [18]. The bronchial responsiveness index (BRI) was determined using the method described by Burrows et al [19]. The percentage decline in FEV1 was divided by the log of the last concentration of methacholine and then 10 was added to the resultant value to eliminate negative values, before log-transformation. FEV1% decline was defined as the decline in FEV1 from the post-diluent baseline value after the final methacholine was administrated, and the concentration of final dose was defined as the concentration of methacholine in mg/dl. The relationships between the HRQL total score and scores from its eight domains with methacholine-stimulated airway hyperresponsiveness (PC20 and BRI) were analyzed by Pearson correlation. Then multiple linear regressions were performed to adjust for age, ethnicity, years since diagnosis, years since last exposure and inhaled corticosteroid usage. P-values of ≤ 0.05 were considered significant and p-values of 0.05 to 0.10 were considered of borderline significance. All tests were performed using the JMP5.0 Statistics software package (SAS Institute Inc., Cary, NC).
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