Respiratory impairment and systemic inflammation in cedar asthmatics removed from exposure.

BACKGROUND: Prior research has shown that removing occupational asthmatics from exposure does not routinely lead to significant improvements in respiratory impairment. These studies were of limited duration and factors determining recovery remain obscure. Our objective was to evaluate residual respiratory impairment and associated sputum and blood biomarkers in subjects with Western red cedar asthma after exposure cessation. METHODS: Subjects previously diagnosed with cedar asthma, and removed from exposure to cedar dust for at least one year, were recruited. Subjects completed a questionnaire and spirometry. PC20 (methacholine concentration that produces 20% fall in FEV1 (forced expiratory volume at 1 second)) sputum cellularity and select Th1/Th2 (T helper cells 1 and 2) cytokine concentrations in peripheral blood were determined. The asthma impairment class was determined and multivariate analyses were performed to determine its relationship with sputum cell counts and serum cytokines. RESULTS: 40 non-smoking males (mean age 62) were examined at a mean interval of 25 years from cedar asthma diagnosis and 17 years from last cedar exposure. 40% were in impairment class 2/3. On average, the PC20 had increased by 2.0 mg/ml; the FEV1 decreased by 1.5 L, with greater decrease in those with greater impairment. Higher impairment was associated with serum interferon-gamma (mean = 1.3 pg/ml in class 2/3 versus 0.62 pg/ml in class 0/1, p = 0.04), mainly due to the FEV1 component (correlation with interferon-gamma = -0.46, p = 0.005). CONCLUSION: Years after exposure cessation, patients with Western red cedar asthma have persistent airflow obstruction and respiratory impairment, associated with systemic inflammation

Cotinine versus questionnaire: early-life environmental tobacco smoke exposure and incident asthma

Abstract Background The use of biomarkers has expanded considerably, as an alternative to questionnaire-based metrics of environmental tobacco smoke (ETS); few studies have assessed the affect of such alternative metrics on diverse respiratory outcomes in children, and we aimed to do so. Methods We evaluated various measures of birth-year ETS, in association with multiple respiratory endpoints early years of life, in the novel context of a birth cohort at high risk for asthma. We administered questionnaires to parents, both at the end of pregnancy and at one year of life, and measured cotinine in cord blood (CCot; in 275 children) and in urine (UCot; obtained at 12 months in 365 children), each by radioimmunoassay. Multiple logistic regression was used to assess the association of the various metrics with recurrent wheeze at age 2 and with bronchial hyperresponsiveness (BHR) and asthma at age 7. Results Self-reported 3rd trimester maternal smoking was associated with significantly increased risk for recurrent wheeze at age 2 (odds ratio 3.5 [95% confidence interval = 1.2,10.7]); the risks associated with CCot and 3rd trimester smoking in any family member were similar (OR 2.9 [1.2,7.0] and 2.6 [1.0,6.5], respectively). No metric of maternal smoking at 12 months appeared to significantly influence the risk of recurrent wheeze at age 2, and no metric of ETS at any time appeared to significantly influence risk of asthma or BHR at age 7. Conclusions Biomarker- and questionnaire-based assessment of ETS in early life lead to similar estimates of ETS-associated risk of recurrent wheeze and asthma.</p

Cotinine versus questionnaire: early-life environmental tobacco smoke exposure and incident asthma

Background: The use of biomarkers has expanded considerably, as an alternative to questionnaire-based metrics of environmental tobacco smoke (ETS); few studies have assessed the affect of such alternative metrics on diverse respiratory outcomes in children, and we aimed to do so. Methods We evaluated various measures of birth-year ETS, in association with multiple respiratory endpoints early years of life, in the novel context of a birth cohort at high risk for asthma. We administered questionnaires to parents, both at the end of pregnancy and at one year of life, and measured cotinine in cord blood (CCot; in 275 children) and in urine (UCot; obtained at 12 months in 365 children), each by radioimmunoassay. Multiple logistic regression was used to assess the association of the various metrics with recurrent wheeze at age 2 and with bronchial hyperresponsiveness (BHR) and asthma at age 7. Results Self-reported 3rd trimester maternal smoking was associated with significantly increased risk for recurrent wheeze at age 2 (odds ratio 3.5 [95% confidence interval = 1.2,10.7]); the risks associated with CCot and 3rd trimester smoking in any family member were similar (OR 2.9 [1.2,7.0] and 2.6 [1.0,6.5], respectively). No metric of maternal smoking at 12 months appeared to significantly influence the risk of recurrent wheeze at age 2, and no metric of ETS at any time appeared to significantly influence risk of asthma or BHR at age 7. Conclusions Biomarker- and questionnaire-based assessment of ETS in early life lead to similar estimates of ETS-associated risk of recurrent wheeze and asthma.Medicine, Department ofMedicine, Faculty ofNon UBCReviewedFacult

Odds of increased respiratory impairment given various subject characteristics (race, atopic status and inhaled steroid use [n (%)]; age and lung function [mean (SD)]).

<p><i>Italics</i> depicts the 3 components of the impairment score.</p>*<p>Odds of being in IC 2/3 versus IC 0/1 with given characteristic, from logistic regression model with, in each analysis, adjustment for age (except for fevpp, where age is already incorporated, and for race, atopy, inhaled steroids) and years since last exposure (except for race, atopy, inhaled steroids).</p>**<p>p<0.05</p

Serum and sputum cytokines and sputum cell counts, stratified by impairment status.

*<p>Odds of being in IC 2/3 versus IC 0/1 from logistic regression model appropriate to each variable, each adjusted for age and years since last exposure.</p>**<p>p = 0.04.</p

Serum interferon-gamma, stratified by higher versus lower respiratory impairment (IC = impairment class).

<p>Serum interferon-gamma, stratified by higher versus lower respiratory impairment (IC  =  impairment class).</p

Demographics and lung function (baseline and change from time of initial diagnosis with Western red cedar asthma).

*<p>10 subjects did not have PC₂₀ available from the time of initial diagnosis with Western red cedar asthma</p