Significant spirometric transitions and Preserved Ratio Impaired Spirometry (PRISm) among ever-smokers.

ABSTRACT Background Emerging data from longitudinal studies suggest that PRISm, defined by proportionate reductions in FEV1 and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (e.g., whether transitions merely reflect measurement variability or "noise"). Research Question Are individuals with PRISm enriched for transitions associated with substantial changes in lung function? Study Design and Methods Current and former smokers enrolled in COPDGene with spirometry available at Phases 1-3 (enrollment, 5-year, and 10-year follow-up) were analyzed. Post-bronchodilator lung function categories were: PRISm=FEV1 10% change in FEV1% and/or FVC% predicted between consecutive visits. "Ever-PRISm" was present if a subject had PRISm at any visit. Logistic regression examined the association between "significant-transitions" and "ever-PRISm" status, adjusted for age, sex, race, FEV1% predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response. Results Among subjects with complete data (n=1,775) over 10.1±0.4 years of follow-up, the prevalence of PRISm remained consistent (10.4%-11.3%) between P1-P3, but nearly half of subjects with PRISm transitioned into or out of PRISm at each visit. 19.7% of subjects had a “significant transition”; “ever-PRISm” was a significant predictor of “significant transitions” (ORunadjusted=10.3, 95%CI=7.9-13.5, ORadjusted=14.9, 95%CI=10.9-20.7). Results were similar with additional adjustment for radiographic emphysema and gas trapping, when lower limit of normal criteria were used to define lung function categories, and when FEV1 alone (regardless of change in FVC%) was used to define "significant transitions" . Interpretation PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time.