Ambient air pollution increases the risk of respiratory mortality, but evidence for impacts on lung function and chronic obstructive pulmonary disease (COPD) is less well established. The aim was to evaluate whether ambient air pollution is associated with lung function and COPD, and explore potential vulnerability factors.We used UK Biobank data on 303 887 individuals aged 40–69 years, with complete covariate data and valid lung function measures. Cross-sectional analyses examined associations of land use regression-based estimates of particulate matter (particles with a 50% cut-off aerodynamic diameter of 2.5 and 10 µm: PM_2.5and PM₁₀, respectively; and coarse particles with diameter between 2.5 μm and 10 μm: PM_coarse) and nitrogen dioxide (NO₂) concentrations with forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), the FEV₁/FVC ratio and COPD (FEV₁/FVC <lower limit of normal). Effect modification was investigated for sex, age, obesity, smoking status, household income, asthma status and occupations previously linked to COPD.Higher exposures to each pollutant were significantly associated with lower lung function. A 5 µg·m⁻³increase in PM_2.5concentration was associated with lower FEV₁(−83.13 mL, 95% CI −92.50– −73.75 mL) and FVC (−62.62 mL, 95% CI −73.91– −51.32 mL). COPD prevalence was associated with higher concentrations of PM_2.5(OR 1.52, 95% CI 1.42–1.62, per 5 µg·m⁻³), PM₁₀(OR 1.08, 95% CI 1.00–1.16, per 5 µg·m⁻³) and NO₂(OR 1.12, 95% CI 1.10–1.14, per 10 µg·m⁻³), but not with PM_coarse. Stronger lung function associations were seen for males, individuals from lower income households, and “at-risk” occupations, and higher COPD associations were seen for obese, lower income, and non-asthmatic participants.Ambient air pollution was associated with lower lung function and increased COPD prevalence in this large study.

Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health. We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide significance at p<5 × 10(-8). UK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50,008 unique samples: 10,002 individuals with low FEV1, 10,000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2.29 × 10(-16)) and between individuals with and without doctor-diagnosed asthma (p=6.06 × 10(-11)). We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with COPD, including in individuals with no history of smoking. The number of copies of a 150 kb region containing the 5' end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1. We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue. By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour. These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease. Medical Research Council.

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE).Residential exposure to nitrogen oxides (NO₂, NO_x) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis.We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m⁻³increase in NO₂exposure was associated with lower levels of FEV₁(−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m⁻³in PM₁₀, but not other PM metrics (PM_2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁(−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons.This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.

BACKGROUND Little is known of the epidemiology of pneumothorax. Routinely available data on pneumothorax in England are described. METHODS Patients consulting in primary care with a diagnosis of pneumothorax in each year from 1991 to 1995 inclusive were identified from the General Practice Research Database (GPRD). Emergency hospital admissions for pneumothorax were identified for the years 1991–4 from the Hospital Episode Statistics (HES) data. Mortality data for England & Wales were obtained for 1950–97. Analyses of pneumothorax rates by age and sex were performed for all data sources. Seasonal and geographical analyses were carried out for the HES data. RESULTS The overall person consulting rate for pneumothorax (primary and secondary combined) in the GPRD was 24.0/100 000 each year for men and 9.8/100 000 each year for women. Hospital admissions for pneumothorax as a primary diagnosis occurred at an overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and women, respectively. Mortality rates were 1.26/million per year for men and 0.62/million per year for women. The age distribution in both men and women showed a biphasic distribution for both GP consultations and hospital admissions. Deaths showed a single peak with highest rates in the elderly. There was an urban-rural trend observed for hospital admissions in the older age group (55+ years) with admission rates in the conurbations significantly higher than in the rural areas. Analysis for trends in mortality data for 1950–97 showed a striking increase in the death rate for pneumothorax in those aged 55+ years between 1960 and 1990, with a steep decline in the 1990s. Mortality in the younger age group (15–34 years) remained low and constant. CONCLUSION There is evidence of two epidemiologically distinct forms of spontaneous pneumothorax in England. The explanation for the rise and fall in mortality for secondary pneumothorax is obscure.