Objective-To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease.Design and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0-22 litre (0.02 to 0.42) reduction in adult FEVI.

Background:Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.Methods:Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age.Results:Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.Conclusions:The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ≤ 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10−12), 4q24 in GSTCD (2.18 × 10−23), 5q33 in HTR4 (P = 4.29 × 10−9), 6p21 in AGER (P = 3.07 × 10−15) and 15q23 in THSD4 (P = 7.24 × 10−15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Background-Impaired fetal growth may be a risk factor for asthma although evidence in children is conflicting and there are few data in adults. Little is known about risk factors which may influence asthma in late childhood or early adult life. Whilst there are clues that fatness may be important, this has been little studied in young adults. The relations between birth weight and childhood and adult anthropometry and asthma, wheeze, hayfever, and eczema were investigated in a nationally representative sample of young British adults. Methods-A total of 8960 individuals from the 1970 British Cohort Study (BCS70) were studied. They had recently responded to a questionnaire at 26 years of age in which they were asked whether they had suVered from asthma, wheeze, hayfever, and eczema in the previous 12 months. Adult body mass index (BMI) was calculated from reported height and weight. Results-The prevalence of asthma at 26 years fell with increasing birth weight. After controlling for potential confounding factors, the odds ratio comparing the lowest birth weight group (<2 kg) with the modal group (3-3.5 kg) was 1.99 (95% CI 0.96 to 4.12). The prevalence of asthma increased with increasing adult BMI. After controlling for birth weight and other confounders, the odds ratio comparing highest with lowest quintile was 1.72 (95% CI 1.29 to 2.29). The association between fatness and asthma was stronger in women; odds ratios comparing overweight women (BMI 25-29.99) and obese women (BMI >30) with those of normal weight (BMI <25) were 1.51 (95% CI 1.11 to 2.06) and 1.84 (95% CI 1.19 to 2.84), respectively. The BMI at 10 years was not related to adult asthma. Similar associations with birth weight and adult BMI were present for wheeze but not for hayfever or eczema. Conclusions-Impaired fetal growth and adult fatness are risk factors for adult asthma.