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 mUyear-1, IQR-159.8-49.1 mL.year(-1)), but similar in persistent PRISm (FEV1-30.2 mUyear-1, IQR-67.9-7.5 mLyear(-1); FVC-20.1 mL.year(-1), IQR-47.7 21.7 mL.year(-1)) and persistent controls (ITV,-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.