Young and middle-aged adults with airflow limitation according to lower limit of normal but not fixed ratio have high morbidity and poor survival: a population-based prospective cohort study

A presumed consequence of using a fixed ratio for the definition of airflow limitation (AFL) has been overdiagnosis among older individuals and underdiagnosis among younger individuals. However, the prognosis of younger individuals with potentially underdiagnosed AFL is poorly described. We hypothesised that potential underdiagnosis of AFL at a younger age is associated with poor prognosis. We assigned 95 288 participants aged 20-100 years from the Copenhagen General Population Study into the following groups: individuals without AFL with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) >= 0.70 and >= lower limit of normal (LLN) (n=78 779, 83%); individuals with potentially underdiagnosed AFL with FEV1/FVC >= 0.70 and < LLN (n=1056, 1%); individuals with potentially overdiagnosed AFL with FEV1/FVC < 0.70 and >= LLN (n=3088, 3%); and individuals with AFL with FEV1/FVC < 0.70 and < LLN (n=12 365, 13%). We assessed risk of exacerbations, pneumonias, ischaemic heart disease, heart failure and all-cause mortality. Median follow-up was 6.0 years (range: 2 days-11 years). Compared to individuals without AFL, individuals with potentially underdiagnosed AFL had an increased risk of morbidity and mortality with age-and sex-adjusted hazard ratios (HR) of 2.7 (95% CI: 1.7-4.5) for pneumonias, 2.3 (95% CI: 1.2-4.5) for heart failure, and 3.1 (95% CI: 2.1-4.6) for all-cause mortality. Young and middle-aged adults with AFL according to LLN but not fixed ratio experience increased respiratory and cardiovascular morbidity and early death.