A population-based birth cohort study of the association between childhood-onset asthma and exposure to industrial air pollutant emissions.

BACKGROUND: Studies of the association between air pollution and asthma onset have mostly focused on urban and traffic-related air pollution. We investigated the associations between exposure to industrial emissions and childhood-onset asthma in a population-based birth cohort in Quebec, Canada, 2002-2011. METHODS: The cohort was built from administrative health databases. We developed separately for PM2.5 and SO2 different metrics representing children's time-varying residential exposure to industrial emissions: 1) yearly number of tons of air pollutant emitted by industries located within 2.5 km of the residence; 2) distance to the nearest "major emitter" (≥100 tons) of either PM2.5 and SO2 within 7.5 km of the residence, and; 3) tons of air pollutant emitted by the nearest "major emitter" within 7.5 km, weighted by the inverse of the distance and the percentage of time that the residence was downwind. To handle the large number of zeros (i.e., children unexposed) we decomposed the exposure variable into two covariates simultaneously included in the regression model: a binary indicator of exposure and a continuous exposure variable centered at the mean value among exposed children. We performed Cox models using age as the time axis, adjusted for gender, material and social deprivation and calendar year. We indirectly adjusted for unmeasured secondhand smoke. RESULTS: The cohort included 722,667 children and 66,559 incident cases of asthma. Across the different exposure metrics, mean percentage changes in the risk of asthma onset in children exposed to the mean relative to those unexposed ranged from 4.5% (95% CI: 2.8, 6.3%) to 10.6% (95% CI: 6.2, 15.2%) for PM2.5 and, from 1.1% (95% CI: -0.1, 3.3%) to 8.9% (95% CI: 7.1, 11.1%) for SO2. Indirect adjustment for secondhand smoke did not substantially affect the associations. In children exposed, the risk of asthma onset increased with the magnitude of the exposure for all metrics, except the distance to the nearest major emitter of SO2. CONCLUSIONS: In this population-based birth cohort, residential exposure to industrial air pollutant emissions was associated with childhood-onset asthma. Additional studies with improved models for estimating exposure to industrial point-sources are needed to further support the observed associations.

Incidence, Prevalence, and Mortality Trends in Chronic Obstructive Pulmonary Disease over 2001 to 2011: A Public Health Point of View of the Burden.

Background. An increase of chronic obstructive pulmonary disease (COPD) prevalence was reported in Canada despite the decline of the main risk factor. Objectives. To estimate incidence, prevalence, and mortality of COPD from 2001 to 2011 and establish the COPD burden by the evaluation of the age-period-cohort effects on incidence trends and the comorbidities prevalence estimations. Methods. A retrospective population-based cohort was built using Quebec health administrative data. Change in trends was measured by relative percentage of changes and by joinpoint regression. After a descriptive analysis of the trends, an age-period-cohort analysis was performed on incidence rates. Results. Overall increase in prevalence along with a decrease of incidence and all-cause mortality was observed. Over time, all age-standardized trends were higher in men than women. Despite higher rates, the number of incident and prevalent cases in women exceeds men since 2004. The curve analysis by age groups showed over time a downshift for both sexes in incidence and all-cause mortality. Further analysis showed the presence of a cohort effect in women. Conclusion. The burden of COPD has risen over time. Women younger than 65 years old have been identified as at-risk group for healthcare planning.

Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants.

BACKGROUND: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). METHOD: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child's residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. RESULTS: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 µg/m³) of 1.095 (95% CI 1.058-1.131), 1.052 (95% CI 1.037-1.066) and 1.025 (95% CI 1.017-1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. CONCLUSIONS: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth.

Childhood Exposure to Ambient Air Pollutants and the Onset of Asthma: An Administrative Cohort Study in Québec.

BACKGROUND: Although it is well established that air pollutants can exacerbate asthma, the link with new asthma onset in children is less clear. OBJECTIVE: We assessed the association between the onset of childhood asthma with both time of birth and time-varying exposures to outdoor air pollutants. METHOD: An open cohort of children born in the province of Québec, Canada, was created using linked medical-administrative databases. New cases of asthma were defined as one hospital discharge with a diagnosis of asthma or two physician claims for asthma within a 2 year period. Annual ozone (O3) levels were estimated at the child's residence for all births 1999-2010, and nitrogen dioxide (NO2) levels during 1996-2006 were estimated for births on the Montreal Island. Satellite based concentrations of fine particles (PM2.5) were estimated at a 10 km × 10 km resolution and assigned to residential postal codes throughout the province (1996-2011). Hazard ratios (HRs) were assessed with Cox models for the exposure at the birth address and for the time-dependent exposure. We performed an indirect adjustment for secondhand smoke (SHS). RESULTS: We followed 1,183,865 children (7,752,083 person-years), of whom 162,752 became asthmatic. After controlling for sex and material and social deprivation, HRs for an interquartile range increase in exposure at the birth address to NO2 (5.45 ppb), O3 (3.22 ppb), and PM2.5 (6.50 µg/m3) were 1.04 (95% CI: 1.02, 1.05), 1.11 (95% CI: 1.10, 1.12), and 1.31 (95% CI: 1.28, 1.33), respectively. Effects of O3 and PM2.5 estimated with time-varying Cox models were similar to those estimated using exposure at birth, whereas the effect of NO2 was slightly stronger (HR = 1.07; 95% CI: 1.05, 1.09). CONCLUSIONS: Asthma onset in children appears to be associated with residential exposure to PM2.5, O3 and NO2. CITATION: Tétreault LF, Doucet M, Gamache P, Fournier M, Brand A, Kosatsky T, Smargiassi A. 2016. Childhood exposure to ambient air pollutants and the onset of asthma: an administrative cohort study in Québec. Environ Health Perspect 124:1276-1282; http://dx.doi.org/10.1289/ehp.1509838.

Understanding the evolution of multimorbidity: evidences from the North West Adelaide Health Longitudinal Study (NWAHS).

OBJECTIVE: The aim of this study is to describe the evolution of multimorbidity. STUDY DESIGN AND SETTING: Data from 1854 South Australians who participated in the North West Adelaide longitudinal Health Study (NWAHS) was collected between baseline (2000-2002) and follow-up (2008-2010). Status for eight chronic diseases (CDs) was determined by biomedical measurement or self-report. Chronic disease (CD) mean age of occurrence and order of appearance was investigated. RESULTS: The prevalence of multimorbidity increased from 32% to 64% during the 7.8±1.1 years of follow-up. The estimated mean age of onset of a new CD was significantly older for hypertension, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) and younger for hypercholesterolemia, asthma and other mental problem. Hypercholesterolemia was more likely to develop as a first than as a subsequent CD (39%vs.16%, p<0.0001) while CVD (1%vs.5%, p<0.0001), diabetes (5%vs.11%, p<0.001) and COPD (6%vs.16%, p<0.0001) were less likely. The presence of mood disorders at baseline was associated with an increased risk of developing other mental disorders (36%vs.12%, p<0.0001), diabetes (18%vs.9%, p<0.01) and asthma (30%vs.21%, p<0.05). CONCLUSION: Longitudinal data could be used to study the evolution of multimorbidity and could provide information on CDs mean age of occurrence, order of appearance and impact on the development of future CDs.

Atrophy and hypertrophy signalling of the quadriceps and diaphragm in COPD.

BACKGROUND: Factors involved in the regulation of muscle mass in chronic obstructive pulmonary disease (COPD) are still poorly understood. Comparing the signalisation involved in muscle mass regulation between two muscles with different levels of activation within the same subjects is an interesting strategy to tease out the impact of local (muscle activity) versus systemic factors in the regulation of muscle mass. A study was undertaken to measure and compare the protein levels of p-AKT, AKT, Atrogin-1, p-p70S6K, p-4E-BP1, p-GSK3ß as well as the mRNA expression of Atrogin-1, MuRF1 and FoxO-1 in the quadriceps and the diaphragm of 12 patients with COPD and 7 controls with normal lung function. METHODS: Diaphragm biopsies were obtained during thoracic surgery and quadriceps samples were obtained from needle biopsies. Protein content and mRNA expression were measured by western blot and quantitative PCR, respectively. RESULTS: Increased mRNA expressions of Atrogin-1, MuRF1 and FoxO-1 were found in the quadriceps compared with the diaphragm only in patients with COPD. The quadriceps/diaphragm ratio for MuRF1 was higher in COPD. The protein level of p-p70S6K was decreased in the quadriceps compared with the diaphragm in patients with COPD. The quadriceps/diaphragm ratios of p-p70S6K and p-GSK3ß were lower in patients with COPD than in controls. CONCLUSIONS: These results indicate a greater susceptibility to a catabolic/anabolic imbalance favouring muscle atrophy in the quadriceps compared with the diaphragm in patients with COPD. The balance between the atrophy and hypertrophy signalling is inhomogeneous between respiratory and lower limb muscles, suggesting that local factors are likely to be involved in the regulation of muscle mass in COPD.

Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease.

RATIONALE: The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways. OBJECTIVES: To measure the protein expression of AKT, forkhead box class O (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70(S6K) glycogen synthase kinase-3beta (GSK-3beta), eukaryotic translation initiation factor 4E binding protein-1 (4E-BP1), and the mRNA expression of atrogin-1, muscle ring finger (MuRF) protein 1, and FoxO-1 and -3 in the quadriceps of 12 patients with COPD with muscle atrophy and 10 healthy control subjects. Five patients with COPD with preserved muscle mass were subsequently recruited and were compared with six patients with low muscle mass. METHODS: Protein contents and mRNA expression were measured by Western blot and quantitative polymerase chain reaction, respectively. MEASUREMENTS AND MAIN RESULTS: The levels of atrogin-1 and MuRF1 mRNA, and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins, were increased in patients with COPD with muscle atrophy compared with healthy control subjects, whereas atrogin-1, p70(S6K), GSK-3beta, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70(S6K), GSK-3beta, and 4E-BP1 compared with patients with COPD with preserved muscle mass. CONCLUSIONS: An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps of patients with COPD. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT. The overexpression of the muscle hypertrophic signaling pathways found in patients with COPD with muscle atrophy could represent an attempt to restore muscle mass.

Chronic obstructive pulmonary disease in women.

BACKGROUND: Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women's response to pulmonary rehabilitation. OBJECTIVES: To compare lung function, disability, mortality and response to pulmonary rehabilitation between women and men with COPD. METHODS: In the present retrospective study, 68 women (mean age 62.5+/-8.9 years) and 168 men (mean age 66.3+/-8.4 years) were evaluated by means of pulmonary function testing and an incremental symptom-limited cycle exercise test. Forty women and 84 men also participated in a 12-week pulmonary rehabilitation program. A 6 min walking test and the chronic respiratory questionnaire were used to assess the effects of pulmonary rehabilitation. Survival status was also evaluated. RESULTS: Compared with men, women had a smaller tobacco exposure (31+/-24 versus 48+/-27 pack-years, P<0.05), displayed better forced expiratory volume in 1 s (44+/-13 versus 39+/-14 % predicted, P<0.05), a higher functional residual capacity (161+/-37 versus 149+/-36 % predicted, P<0.05) and total lung capacity (125+/-20 versus 115+/-19 % predicted, P<0.001). Peak oxygen consumption was not different between women and men when expressed in predicted values but lower in women when expressed in absolute values. Pulmonary rehabilitation resulted in significant improvements in 6 min walking test and quality of life in both sexes, but women had a greater improvement in chronic respiratory questionnaire dyspnea. Survival status was similar between sexes, but predictors of mortality were different between sexes. CONCLUSIONS: Women may be more susceptible to COPD than men. The clinical expression of COPD may differ between sexes with greater degree of hyperinflation in women, who also benefit from pulmonary rehabilitation.

The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies.

Sedentary lifestyles and increased pollution brought about by industrialization pose major challenges to the prevention of both obesity and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, obstructive sleep apnea and obesity hypoventilation syndrome. Obesity has emerged as an important risk factor for these respiratory diseases, and in many instances weight loss is associated with important symptomatic improvement. Moreover, obesity may influence the development and presentation of these diseases. In this article, we review the current understanding of the influence of obesity on chronic respiratory diseases and the clinical management of obesity concurrent with asthma, COPD, obstructive sleep apnea or obesity hypoventilation syndrome.