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Lancet Respir Med. 2017 Aug;5(8):619-626. doi: 10.1016/S2213-2600(17)30207-2. Epub 2017 Jun 28.

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

Author information

1
Division of Pulmonary and Critical Care, Michigan Medicine, Ann Arbor, MI, USA. Electronic address: mrking@med.umich.edu.
2
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
3
Department of Medicine, Columbia University, New York, NY, USA.
4
Center for Genomics and Personalized Medicine Research, Department of Medicine, Wake Forest University, Winston-Salem, NC, USA.
5
Division of Pulmonary and Critical Care, National Jewish, Denver, CO, USA.
6
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
7
Division of Pulmonary and Critical Care, University of Iowa, Iowa City, IA, USA.
8
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.
9
Department of Thoracic Medicine, Temple University, Philadelphia, PA, USA.
10
Division of Pulmonary and Critical Care, University of Alabama, Birmingham, AL, USA.
11
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
12
Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
13
Department of Medicine, Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
14
Division of Pulmonary and Critical Care, University of Illinois, Chicago, IL, USA.
15
Division of Pulmonary and Critical Care, Michigan Medicine, Ann Arbor, MI, USA.
16
Department of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Early Clinical Development, AstraZeneca, Cambridge, UK.
17
Department of Respiratory Medicine, Imperial College, London, UK.
18
Cardiovascular Research Institute, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
19
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.
20
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

Abstract

BACKGROUND:

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.

METHODS:

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 FEV1. 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.

FINDINGS:

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.

INTERPRETATION:

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.

FUNDING:

National Institutes of Health, and National Heart, Lung, and Blood Institute.

Comment in

PMID:
28668356
PMCID:
PMC5558856
DOI:
10.1016/S2213-2600(17)30207-2
[Indexed for MEDLINE]
Free PMC Article

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