Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

MeiLan K Han; Pedro M Quibrera; Elizabeth E Carretta; R Graham Barr; Eugene R Bleecker; Russell P Bowler; Christopher B Cooper; Alejandro Comellas; David J Couper; Jeffrey L Curtis; Gerard Criner; Mark T Dransfield; Nadia N Hansel; Eric A Hoffman; Richard E Kanner; Jerry A Krishnan; Carlos H Martinez; Cheryl B Pirozzi; Wanda K O'Neal; Stephen Rennard; Donald P Tashkin; Jadwiga A Wedzicha; Prescott Woodruff; Robert Paine III; Fernando J Martinez

doi:10.1016/S2213-2600(17)30207-2

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Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

Journal article

Peer reviewed

Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort

MeiLan K Han, Pedro M Quibrera, Elizabeth E Carretta, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Christopher B Cooper, Alejandro Comellas, David J Couper, Jeffrey L Curtis, …

The lancet respiratory medicine, Vol.5(8), pp.619-626

08/2017

DOI: 10.1016/S2213-2600(17)30207-2

PMCID: PMC5558856

PMID: 28668356

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Abstract

Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas 567 (51%) had none. 82 (7%) of 1105 patients had at least one acute exacerbation each year, whereas only 23 (2%) had two or more acute exacerbations in each year. An inconsistent pattern (both years with and without acute exacerbations) was common (456 [41%] of the group), particularly among GOLD stages 3 and 4 patients (256 [56%] of 456). In logistic regression, consistent acute exacerbations (≥1 event per year for 3 years) were associated with higher baseline symptom burden, previous exacerbations, greater evidence of small airway abnormality on CT, lower interleukin-15 concentrations, and higher interleukin-8 concentrations, than were no acute exacerbations. Although acute exacerbations are common, the exacerbation status of most individuals varies markedly from year to year. Among patients who had any acute exacerbation over 3 years, very few repeatedly had two or more events per year. In addition to symptoms and history of exacerbations in the year before study enrolment, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, and interleukin-15 and interleukin-8 concentrations. National Institutes of Health, and National Heart, Lung, and Blood Institute.

Severity of Illness Index

Spirometry

Prospective Studies

Humans

Middle Aged

Interleukin-15 - blood

Logistic Models

Male

Tomography, X-Ray Computed

Pulmonary Disease, Chronic Obstructive - physiopathology

Biomarkers - blood

Disease Progression

Forced Expiratory Volume

Time Factors

Pulmonary Disease, Chronic Obstructive - blood

Aged, 80 and over

Adult

Female

Pulmonary Disease, Chronic Obstructive - diagnostic imaging

Aged

Interleukin-8 - blood

Longitudinal Studies

Details

Title: Subtitle: Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
Creators: MeiLan K Han - Division of Pulmonary and Critical Care, Michigan Medicine, Ann Arbor, MI, USA. Electronic address: mrking@med.umich.edu
Pedro M Quibrera - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Elizabeth E Carretta - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
R Graham Barr - Department of Medicine, Columbia University, New York, NY, USA
Eugene R Bleecker - Center for Genomics and Personalized Medicine Research, Department of Medicine, Wake Forest University, Winston-Salem, NC, USA
Russell P Bowler - Division of Pulmonary and Critical Care, National Jewish, Denver, CO, USA
Christopher B Cooper - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Alejandro Comellas - Division of Pulmonary and Critical Care, University of Iowa, Iowa City, IA, USA
David J Couper - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Jeffrey L Curtis - Division of Pulmonary and Critical Care, Michigan Medicine, Ann Arbor, MI, USA; Section of Pulmonary and Critical Care Medicine, Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
Gerard Criner - Department of Thoracic Medicine, Temple University, Philadelphia, PA, USA
Mark T Dransfield - Division of Pulmonary and Critical Care, University of Alabama, Birmingham, AL, USA
Nadia N Hansel - Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
Eric A Hoffman - Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Richard E Kanner - Department of Medicine, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Jerry A Krishnan - Division of Pulmonary and Critical Care, University of Illinois, Chicago, IL, USA
Carlos H Martinez - Division of Pulmonary and Critical Care, Michigan Medicine, Ann Arbor, MI, USA
Cheryl B Pirozzi - Department of Medicine, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Wanda K O'Neal - Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Stephen Rennard - Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Early Clinical Development, AstraZeneca, Cambridge, UK
Donald P Tashkin - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jadwiga A Wedzicha - Department of Respiratory Medicine, Imperial College, London, UK
Prescott Woodruff - Cardiovascular Research Institute, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA
Robert Paine III - Department of Medicine, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; Section of Pulmonary and Critical Care Medicine, Salt Lake City Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA
Fernando J Martinez - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
Resource Type: Journal article
Publication Details: The lancet respiratory medicine, Vol.5(8), pp.619-626
DOI: 10.1016/S2213-2600(17)30207-2
PMID: 28668356
PMCID: PMC5558856
NLM abbreviation: Lancet Respir Med
ISSN: 2213-2600
eISSN: 2213-2619
Publisher: England
Grant note: HHSN268200900017C / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS G1001365 / Medical Research Council HHSN268200900019C / NHLBI NIH HHS HHSN268200900020C / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS HHSN268200900015C / NHLBI NIH HHS I01 CX000911 / CSRD VA HHSN268200900013C / NHLBI NIH HHS RP-PG-0109-10056 / Department of Health R01 HL126838 / NHLBI NIH HHS G0800570 / Medical Research Council R01 HL122438 / NHLBI NIH HHS K24 HL137013 / NHLBI NIH HHS HHSN268200900016C / NHLBI NIH HHS HHSN268200900018C / NHLBI NIH HHS HHSN268200900014C / NHLBI NIH HHS G1001372 / Medical Research Council K23 HL130627 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 08/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9984051708102771

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