Trajectory and mortality of preserved ratio impaired spirometry: the Rotterdam Study

Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ≥0.7, FEV₁  ≥80%), PRISm (FEV₁/FVC ≥0.7, FEV₁ <80%) and chronic obstructive pulmonary disease (COPD) (FEV₁/FVC <0.7) at two study visits. Hazard ratios with 95% confidence intervals for mortality (until December 30, 2018) were adjusted for age, sex, body mass index, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9 years; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of the re-examined PRISm subjects, 15.7% transitioned to normal spirometry and 49.4% to COPD. Median lung function decline was highest in subjects with incident PRISm (FEV₁ -92.8 mL·year^-1, interquartile range (IQR) -131.9- -65.8 mL·year^-1; FVC -93.3 mL·year^-1, IQR -159.8- -49.1 mL·year^-1), but similar in persistent PRISm (FEV₁ -30.2 mL·year^-1, IQR -67.9- -7.5 mL·year^-1; FVC -20.1 mL·year^-1, IQR -47.7-21.7 mL·year^-1) and persistent controls (FEV₁ -39.6 mL·year^-1, IQR -64.3--12.7 mL·year^-1; FVC -20.0 mL·year^-1, IQR -55.4-18.8 mL·year^-1). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2-4 had increased all-cause mortality (PRISm: HR 1.6, 95% CI 1.2-2.0; COPD GOLD 2-4: HR 1.7, 95% CI 1.4-2.1) and cardiovascular mortality (PRISm: HR 2.8, 95% CI 1.5-5.1; COPD 2-4: HR 2.1, 95% CI 1.2-3.6). Mortality within <1 year was highest in PRISm, with patients often having cardiovascular comorbidities (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.