Interactions between SERPINA1 PiMZ genotype, occupational exposure and lung function decline.

OBJECTIVES: We evaluated interactions between SERPINA1 PiMZ genotype, associated with intermediate α1-antitrysin deficiency, with outdoor particulate matter ≤10 µm (PM10), and occupational exposure to vapours, dusts, gases and fumes (VGDF), and their effects on annual change in lung function. METHODS: Pre-bronchodilator spirometry was performed in 3739 adults of the Swiss Cohort Study on Air Pollution and Lung Disease in Adults (SAPALDIA) for whom SERPINA1 genotypes were available. At baseline in 1991, participants were aged 18-62 years; follow-up measurements were conducted from 2001 to 2003. In linear mixed regression models of annual change in lung function, multiplicative interactions were evaluated between PiMZ genotype (PiMM as reference) and change in PM10 (µg/m(3)), and VGDF exposure (high-level, low-level or no exposure as reference) during follow-up. RESULTS: Annual declines in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) (-82 mL/s, 95% CI -125 to -39) and forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) (-0.3%, 95% CI -0.6% to 0.0%) in association with VGDF exposure were observed only in PiMZ carriers (Pinteraction<0.0001 and Pinteraction=0.03, respectively). A three-way interaction between PiMZ genotype, smoking and VGDF exposure was identified such that VGDF-associated FEF25-75% decline was observed only in ever smoking PiMZ carriers (Pinteraction=0.01). No interactions were identified between PiMZ genotype and outdoor PM10. CONCLUSIONS: SERPINA1 PiMZ genotype, in combination with smoking, modified the association between occupational VGDF exposure and longitudinal change in lung function, suggesting that interactions between these factors are relevant for lung function decline. These novel findings warrant replication in larger studies.

Effect modification of immunoglobulin E-mediated atopy and rhinitis by glutathione S-transferase genotypes in passive smokers.

BACKGROUND: Experimental studies suggest that glutathione S-transferase (GST) genotypes modify nasal allergen responses induced by secondhand smoke (SHS) exposure. OBJECTIVE: We aimed to investigate whether GSTs affected systemic IgE and allergic rhinitis (AR) in SHS-exposed individuals from a population-based cohort. METHODS: Analyses comprised 2309 never-smokers from the Swiss study on air pollution and health in adults cohort, reporting SHS status at baseline and 11 years later. Outcomes were defined by total serum IgE≥100 kU/L, specific serum IgE determined by Phadiatop® ≥0.35 kU/L and self-reported AR. GSTP1 Ile105Val, GSTM1 and GSTT1 gene deletion genotypes were identified at the follow-up survey. RESULTS: After adjustment for relevant covariates, the homozygous GSTP1 105-Val genotype was negatively associated with high total IgE and high-specific IgE by Phadiatop®, notably in subjects persistently exposed to SHS (OR: 0.20, 95% CI 0.05-0.75; P=0.02, for high total IgE and OR: 0.29, 95% CI 0.10-0.89; P=0.03, for high specific IgE by Phadiatop®). Carrying at least one copy of the GSTM1 gene (non-null) showed a similar association for high specific IgE by Phadiatop® (OR: 0.41, 95% CI 0.22-0.76; P=0.004). No significant associations were found between GSTs and rhinitis. CONCLUSION AND CLINICAL RELEVANCE: In this large cohort, homozygosity for GSTP1 105-Val or carrying the GSTM1 non-null genotype decreased the risk of high total IgE or high specific IgE using Phadiatop® by nearly half in subjects exposed to SHS, as compared with subjects carrying opposite alleles. These findings underline the value of genetic susceptibility when evaluating the effects of environmental exposure on allergic illness. The potential long-term effects of persistent SHS exposure in genetically vulnerable individuals may be of public health relevance.

Traffic-related air pollution correlates with adult-onset asthma among never-smokers.

BACKGROUND: Traffic-related pollution is associated with the onset of asthma in children. Its effect on adult-onset asthma is poorly investigated. The SAPALDIA cohort study was used to investigate associations between the 11-year change (1991-2002) in home outdoor traffic-related particulate matter up to 10 microm in diameter (TPM(10)) and the incidence of asthma. METHODS: Never-smokers without asthma at baseline aged 18-60 years in 1991 were eligible for inclusion in the study. Subjects reporting doctor-diagnosed asthma at follow-up were considered incident cases. TPM(10) at baseline and follow-up was predicted and interpolated to subjects' place of residence by dispersion models using emission and meteorological data. Cox proportional hazard models for time to asthma onset were adjusted (age, gender, baseline atopy, body mass index, bronchial reactivity, maternal allergies). RESULTS: Of 2725 never-smokers, 41 reported asthma onset in 2002. Home outdoor TPM(10) concentrations improved during the interval (mean -0.6; range -9 to +7.2; IQR 0.6 microg/m(3)). The incidence of asthma was associated with a change in TPM(10). The hazard ratio (1.30; 95% CI 1.05 to 1.61) per 1 microg/m(3) change in TPM(10) (IQR) was not sensitive to further adjustments (education, workplace exposure, passive smoking, parental asthma or allergies, random area effects, lung function or co-pollutants such as regional, secondary, total PM(10) or proximity to busy roads). CONCLUSION: The data suggest a role for traffic-related pollution in adult-onset asthma. Space, time and source-specific individual assignment of exposure to traffic-related pollution is a key strength of SAPALDIA. It may explain why findings were statistically significant despite the limited number of new cases. As traffic-related pollution prevails, the finding may be of substantial public health relevance.