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

Summary

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.

Introduction

Chronic obstructive pulmonary disease (COPD) is a major cause of disability and death around the globe.¹ COPD is generally considered to be a self-inflicted disease caused by tobacco smoking and characterised by an accelerated decline of lung function with age.² Yet, other COPD risk factors, including occupational exposures to organic and inorganic dusts; chemical agents and fumes; indoor pollution from biomass cooking and heating in poorly ventilated dwellings; and a history of severe childhood respiratory infection, HIV, or tuberculosis, have also been identified.¹ Furthermore, low peak lung function in early adulthood has been shown to increase the risk of COPD later in life, independently of the rate of lung function decline.³ A previous study showed that about half of patients diagnosed with COPD in late adulthood had evidence of low peak lung function in early adulthood.³ These observations suggest that abnormal lung development (in utero, after birth, or both) could be a novel risk factor for COPD.1, 3

Lung development is a complex process that can be altered by various genetic or environmental factors,⁴ including passive smoking, poor nutrition, and repeated infections.5, 6, 7 These factors (acting alone or in combination) might also compromise the development of other organ systems (eg, the cardiovascular and metabolic systems).8, 9, 10 We hypothesised that individuals with low lung function in early adulthood would also present a higher prevalence of respiratory, cardiovascular, and metabolic abnormalities, as well as a higher and earlier incidence of comorbid diseases and premature mortality during follow-up compared with individuals with normal lung function. Given that there is familial COPD aggregation,¹¹ and that lung function has been related to several environmental exposures and gene polymorphisms,¹² we also aimed to explore the transgenerational reproducibility of these traits.