• Emily S Wan, Spyridon Fortis, Elizabeth A Regan, John Hokanson, MeiLan K Han, Richard Casaburi, Barry J Make, James D Crapo, Dawn L DeMeo, Edwin K Silverman, and COPDGene Investigators.
• 1 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
• Am. J. Respir. Crit. Care Med. 2018 Dec 1; 198 (11): 139714051397-1405.

RationaleIncreasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lung Disease (GOLD)-unclassified spirometry, has expanded the body of knowledge on cross-sectional risk factors. However, longitudinal studies of PRISm remain limited.ObjectivesTo examine longitudinal patterns of change in lung function, radiographic characteristics, and mortality of current and former smokers with PRISm.MethodsCurrent and former smokers, aged 45 to 80 years, were enrolled in COPDGene (phase 1, 2008-2011) and returned for a 5-year follow-up (phase 2, 2012-2016). Subjects completed questionnaires, spirometry, chest computed tomography scans, and 6-minute-walk tests at both study visits. Baseline characteristics, longitudinal change in lung function, and mortality were assessed by post-bronchodilator lung function categories: PRISm (FEV1/FVC < 0.7 and FEV1 < 80%), GOLD0 (FEV1/FVC > 0.7 and FEV1 > 80%), and GOLD1-4 (FEV1/FVC < 0.7).Measurements And Main ResultsAlthough the prevalence of PRISm was consistent (12.4-12.5%) at phases 1 and 2, subjects with PRISm exhibited substantial rates of transition to and from other lung function categories. Among subjects with PRISm at phase 1, 22.2% transitioned to GOLD0 and 25.1% progressed to GOLD1-4 at phase 2. Subjects with PRISm at both phase 1 and phase 2 had reduced rates of FEV1 decline (-27.3 ± 42.1 vs. -33.0 ± 41.7 ml/yr) and comparable proportions of normal computed tomography scans (51% vs. 52.7%) relative to subjects with stable GOLD0 spirometry. In contrast, incident PRISm exhibited accelerated rates of lung function decline. Subjects with PRISm at phase 1 had higher mortality rates relative to GOLD0 and lower rates relative to the GOLD1-4 group.ConclusionsPRISm is highly prevalent, is associated with increased mortality, and represents a transitional state for significant subgroups of subjects. Additional studies to characterize longitudinal progression in PRISm are warranted.

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