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

Emily S Wan; Peter J Castaldi; Michael H Cho; John E Hokanson; Elizabeth A Regan; Barry J Make; Terri H Beaty; MeiLan K Han; Jeffrey L Curtis; Douglas Curran-Everett; David A Lynch; Dawn L DeMeo; James D Crapo; Edwin K Silverman; COPDGene Investigators

doi:10.1186/s12931-014-0089-y

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

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

Emily S Wan, Peter J Castaldi, Michael H Cho, John E Hokanson, Elizabeth A Regan, Barry J Make, Terri H Beaty, MeiLan K Han, Jeffrey L Curtis, Douglas Curran-Everett, …

Respiratory research, Vol.15(1), pp.89-89

2014

DOI: 10.1186/s12931-014-0089-y

PMCID: PMC4256936

PMID: 25096860

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Abstract

Background 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. Methods 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. Results 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”. Conclusions PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted

Spirometry

Restriction

Research

Lung diseases

Smoking

Details

Title: Subtitle: Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene
Creators: Emily S Wan - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, 4th floor, Boston, MA 2115 USA
Peter J Castaldi - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, 4th floor, Boston, MA 2115 USA
Michael H Cho - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, 4th floor, Boston, MA 2115 USA
John E Hokanson - Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, CO USA
Elizabeth A Regan - National Jewish Health, Denver, CO USA
Barry J Make - National Jewish Health, Denver, CO USA
Terri H Beaty - Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD USA
MeiLan K Han - Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, MI USA
Jeffrey L Curtis - Pulmonary and Critical Care Section, Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, MI USA
Douglas Curran-Everett - Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO USA
David A Lynch - National Jewish Health, Denver, CO USA
Dawn L DeMeo - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, 4th floor, Boston, MA 2115 USA
James D Crapo - National Jewish Health, Denver, CO USA
Edwin K Silverman - Channing Division of Network Medicine, Brigham and Women’s Hospital, 181 Longwood Avenue, 4th floor, Boston, MA 2115 USA
COPDGene Investigators
Contributors: Alejandro Comellas (Contributor) - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: Respiratory research, Vol.15(1), pp.89-89
DOI: 10.1186/s12931-014-0089-y
PMID: 25096860
PMCID: PMC4256936
NLM abbreviation: Respir Res
ISSN: 1465-9921
eISSN: 1465-993X
Publisher: BioMed Central
Language: English
Date published: 2014
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9984094770802771

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