Outdoor air pollution is associated with disease severity in α₁-antitrypsin deficiency

Abstract

The aim of this study was to determine whether long-term air pollution exposure is associated with clinical phenotype in a 1 -antitrypsin deficiency.In total, 304 PiZZ subjects underwent full lung function testing and quantitative high-resolution computed tomography to identify the presence and severity of the disease. Mean annual air pollutant data for 2006 was matched to the location of patients' houses and used in regression models to identify phenotypic associations with pollution, controlling for covariates. Relative trends in pollution levels were assessed to validate use of a single year's data to indicate longterm exposure.Pollutant levels correlated significantly with one another, with higher levels of primary particles, SO 2 and NO 2 being associated with lower ozone levels. Regression models showed that estimated higher exposure to ozone was associated with worse gas transfer and more severe emphysema. Regression parameters suggested that significance from other pollutants was due to collinearity with ozone. The 2006 pollutant levels showed linear relationships with cumulative years, thus validating the model.Higher exposures to ozone may be associated with worse respiratory status in a 1 -antitrypsin deficiency, identifying a group susceptible to ambient air pollution.

Smoke exposure as a determinant of autoantibody titre in α1-antitrypsin deficiency and COPD

“…We surmised that differences in elastin breakdown and subsequent anti-elastin generation might still occur between nonsmokers with and without AATD for this reason. This was not confirmed, perhaps because the effect sizes of agents other than cigarette smoke are small in both groups [22,23].…”

“…This, together with the recent suggestion that smoking may be a risk factor for autoimmunity [12], is important to note in future studies of the prevalence of other autoantibodies in COPD and control populations. Subjects with AATD may be more sensitive to other environmental influences on lung function, as shown by relationships between outdoor air pollution and lung function in this group [22]. We surmised that differences in elastin breakdown and subsequent anti-elastin generation might still occur between nonsmokers with and without AATD for this reason.…”

Outdoor air pollution is associated with rapid decline of lung function in α-1-antitrypsin deficiency

“…Air pollution also induces lung inflammation10 and we have shown that ozone exposure related to lung function in a cross-sectional study of subjects with AATD in the UK 11. Other environmental agents, predominantly relating to occupation, may also influence lung function in AATD,12 13 but it is not known whether they influence lung function decline in this group.…”

Polymerization and Oxidation of Alpha-1-Antitrypsin in Pathogenesis of Emphysema

“…Also, the single-nucleotide polymorphisms (SNPs) were identified in the six haplotypes of the SERPINA1 gene, which controls synthesis of A1AT (Chappell, et al, 2006). Several environmental factors that accelerate the onset of symptoms in A1ATD patients, such as personal and second hand exposure to tobacco smoke in childhood, respiratory infections (Mayer et al, 2006), and higher exposures to ozone (Wood et al, 2009) have been also identified. In addition to the low circulating levels of A1AT in hereditary A1ATD, the risk of emphysema includes reduced antielastase activity.…”