Lung function in early adulthood and health in later life: a transgenerational cohort analysis

Background Early life events can affect health in later life. We hypothesised that low lung function (FEV1 <80% predicted) in early adulthood (25–40 years) is associated with higher prevalence and earlier incidence of respiratory, cardiovascular, and metabolic abnormalities, and premature death. Methods In this cohort analysis, we tested this hypothesis using data from the Framingham Offspring Cohort (FOC) and validated our observations in CARDIA (an independent cohort) and GenIII (which includes the direct descendants of FOC participants). These were three general population cohorts that included men and women, who were regularly and prospectively followed up to collect extensive clinical, physiological, biological, and imaging information. Main outcomes were prevalence (in early adulthood) and incidence (during follow-up) of comorbidity, and all-cause mortality. χ2 test, unpaired t test, Fisher's exact test, and Cox proportional hazards models were used for data analysis. Differential dropout rates during follow-up were regarded as a potential source of bias. Findings We found that 111 (10%) of 1161 participants in FOC, 338 (13%) of 2648 participants in CARDIA, and 71 (4%) of 1912 participants in GenIII had FEV1 of less than 80% predicted at the age of 25–40 years. These individuals also had higher prevalence of respiratory, cardiovascular, and metabolic abnormalities in early adulthood; higher and earlier (about a decade) incidence of comorbidities during follow-up (39 years vs 47 years in FOC; 30 years vs 37 years in CARDIA, p<0·0001); and higher all-cause mortality than individuals with normal lung function in early adulthood (in FOC, hazard ratio 2·3 [95% CI 1·4–3·7], p=0·001), which was independent of, but additive with, cumulative smoking exposure. In GenIII, we observed that individuals with at least one parent stratified as having low lung function in early adulthood in FOC (n=115) had lower FEV1 in early adulthood (10% had FEV1 of less than 80% predicted; this proportion was 3% in those with both parents classified as normal in FOC [n=248]; p<0·0001); and early adulthood FEV1 of GenIII participants was related (R2=0·28, p<0·0001) to FOC parents' average FEV1 in early adulthood. Interpretation Low peak lung function in early adulthood is common in the general population and could identify a group of individuals at risk of early comorbidities and premature death. Funding Fondo de Investigacion Sanitaria, Sociedad Española de Neumologia y Cirurgia Torácica, Formació Personal Investigador, Agencia de Gestió d'Ajuts de Recerca 2016, and AstraZeneca Foundation Young Researcher Award.