Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene

• Published in: Respiratory research Vol. 15; no. 1; p. 89
• Main Authors: Wan, Emily S, Castaldi, Peter J, Cho, Michael H, Hokanson, John E, Regan, Elizabeth A, Make, Barry J, Beaty, Terri H, Han, MeiLan K, Curtis, Jeffrey L, Curran-Everett, Douglas, Lynch, David A, DeMeo, Dawn L, Crapo, James D, Silverman, Edwin K
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.08.2014; BioMed Central
• Subjects: Aged; Aged, 80 and over; Analysis; Body mass index; Care and treatment; Cluster Analysis; Cohort Studies; Colleges & universities; Cross-Sectional Studies; Epidemiology; Female; Genetic aspects; Genetic variance; Genetics; Genome-Wide Association Study - methods; Health aspects; Hospitals; Humans; Lung diseases; Male; Medicine; Middle Aged; Mortality; Pharmaceutical industry; Public health; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Respiratory tract diseases; Spirometry - methods; Womens health; United Kingdom; Switzerland
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-014-0089-y

Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported. Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering. The prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype". PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted. Clinicaltrials.gov Identifier: NCT000608764.