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

MS#: 
MS034
TitleFrequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.
Publication TypePublication
Year2017
AuthorsHan MK, Quibrera PM, Carretta EE, R Barr G, Bleecker ER, Bowler RP, Cooper CB, Comellas A, Couper DJ, Curtis JL, Criner G, Dransfield MT, Hansel NN, Hoffman EA, Kanner RE, Krishnan JA, Martinez CH, Pirozzi CB, O'Neal WK, Rennard S, Tashkin DP, Wedzicha JA, Woodruff P, Paine R, Martinez FJ
Corporate AuthorsSPIROMICS Investigators
JournalLancet Respir Med
Volume5
Issue8
Pagination619-626
Date Published2017 08
ISSN2213-2619
KeywordsAdult, Aged, Aged, 80 and over, biomarkers, Disease Progression, Female, Forced Expiratory Volume, Humans, Interleukin-15, Interleukin-8, Logistic Models, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Spirometry, Time Factors, Tomography, X-Ray Computed
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 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.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.

DOI10.1016/S2213-2600(17)30207-2
Alternate JournalLancet Respir Med
PubMed ID28668356
PubMed Central IDPMC5558856
Grant ListHHSN268200900019C / HL / NHLBI NIH HHS / United States
G0800570 / / Medical Research Council / United Kingdom
P30 ES005605 / ES / NIEHS NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
R01 HL126838 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
R01 HL122438 / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
P30 DK054759 / DK / NIDDK NIH HHS / United States
HHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
K23 HL130627 / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Michigan (University of Michigan)
ECI: 
Manuscript Status: 
Published