title: Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.
abstract: Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown.
  
  
  
  To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up.
  
  
  
  We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV1decline based on reported exacerbations or acute respiratory events.
  
  
  
  In subjects with COPD, exacerbations were associated with excess FEV1decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV1decline.
  
  
  
  Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
authors.affiliation: 1 Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.|2 Birmingham VA Medical Center, Birmingham, Alabama.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: 3 Minneapolis VA Health Care System, Minneapolis, Minnesota.|4 University of Minnesota, Minneapolis, Minnesota.
authors.forename: Ken M
authors.initials: KM
authors.lastname: Kunisaki
authors.affiliation: 5 National Jewish Health, Denver, Colorado.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Strand
authors.affiliation: 6 Pulmonary/Critical Care, University of Texas Health Science Center, San Antonio, Texas.|7 South Texas Veterans Health Care System, San Antonio, Texas.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.affiliation: 1 Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Surya P
authors.initials: SP
authors.lastname: Bhatt
authors.affiliation: 5 National Jewish Health, Denver, Colorado.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.affiliation: 8 Temple University, Philadelphia, Pennsylvania.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.affiliation: 9 University of Michigan, Ann Arbor, Michigan.|10 VA Ann Arbor Health Care System, Ann Arbor, Michigan.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.affiliation: 11 Baylor College of Medicine, Houston, Texas.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.affiliation: 1 Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Hrudaya
authors.initials: H
authors.lastname: Nath
authors.affiliation: 12 Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Putcha
authors.affiliation: 9 University of Michigan, Ann Arbor, Michigan.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Roark
authors.affiliation: 13 Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.affiliation: 13 Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Washko
authors.affiliation: 1 Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama.|2 Birmingham VA Medical Center, Birmingham, Alabama.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wells
authors.affiliation: 3 Minneapolis VA Health Care System, Minneapolis, Minnesota.|4 University of Minnesota, Minneapolis, Minnesota.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wendt
authors.affiliation: 5 National Jewish Health, Denver, Colorado.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
mesh_terms: D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013147:Spirometry; D014797:Vital Capacity / Q000502:physiology
keywords: chronic obstructive pulmonary disease; exacerbations; spirometry