Public Release: 

Exacerbations in COPD patients hasten lung function loss

American Thoracic Society

ATS 2016, SAN FRANCISCO -- In patients with chronic obstructive pulmonary disease (COPD), exacerbations accelerated lung function loss, according to a new study presented at the ATS 2016 International Conference. The effect was particularly prominent in those with mild disease.

The investigators embarked on their research because previous studies failed to adequately examine if exacerbations in patients with mild COPD, or similar acute respiratory events in current and former smokers without airflow obstruction, affect lung decline, said Ken M. Kunisaki, MD, MS, of the Minneapolis VA Health Care System in Minneapolis.

Investigators analyzed data from 2,861 patients in the COPDGene 5-year follow-up cohort study. All COPDGene participants were current or former smokers. Spirometry, used to diagnose COPD and assess lung function, was performed at study entry in all subjects and at follow-up in 2,000 subjects. Exacerbations were defined as acute respiratory symptoms that required antibiotics or systemic steroids; severe events were defined by the need for hospitalization. (In those without established COPD, the criteria were used to define acute respiratory events.)

Thirty-seven percent of patients reported at least one exacerbation/acute respiratory event. In patients with COPD, each exacerbation was associated with excess loss of lung function, as measured by FEV1--the amount of air a person can forcefully blow out of their lungs in one second.

The investigators saw the greatest excess loss of FEV1 in those with mild COPD. Acute respiratory events were not associated with additional FEV1 decline in subjects who did not have airflow obstruction.

"Our findings are particularly novel due to our large numbers of persons with mild COPD--a group that has not been well studied in previous investigations," Kunisaki said. The investigators recommend additional trials to test existing and novel therapies in subjects with early or mild COPD, to potentially reduce the risk for progression to more advanced lung disease.

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Abstract 3981

Effect of Acute Respiratory Events on Lung Function Decline in Current and Former Smokers with and Without COPD

K.M. Kunisaki1, M.T. Dransfield2, M. Strand3, S.P. Bhatt2, R.P. Bowler3, G.J. Criner4, J.L. Curtis5, N.A. Hanania6, H. Nath2, N. Putcha7, S.E. Roark8, E.S. Wan9, G. Washko10, J.M. Wells11, C. Wendt1, B.J. Make3

1Minneapolis VA Health Care System - Minneapolis, MN/US, 2University of Alabama at Birmingham - Birmingham, AL/US, 3National Jewish Health - Denver, CO/US, 4Temple University Hospital - Philadelphia, PA/US, 5University of Michigan/VAAAHS - Ann Arbor, MI/US, 6Baylor College of Medicine - Houston, TX/US, 7Johns Hopkins University - Baltimore, MD/US, 8University of Michigan - Ann Arbor, MI/US, 9Brigham and Women's Hospital - Boston, MA/US, 10Brigham and Women's Hospital - Harvard Medical School - Boston, MA/US, 11University of Alabama Birmingham (UAB) - Birmingham, AL/US COPDGene Investigators

Introduction/Rationale

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are critical events that increase the risk of death, impair quality of life and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. No study has adequately examined whether exacerbations in subjects with mild COPD, or similar acute respiratory events in current and former smokers without airflow obstruction, affect lung function decline.

Methods

We examined data from the first 2,000 subjects who returned for a second COPDGene visit, approximately 5 years after their initial visit. COPDgene study participants were current or former smokers and all performed spirometry at both study visits. Baseline data included demographics, smoking history and CT emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring use of 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 six-month intervals. Linear mixed models were used to fit FEV1 decline, stratified by GOLD group. Primary predictors included visit (baseline and follow-up), acute respiratory events/exacerbations and their interaction. Covariates included baseline race, sex, percent emphysema, smoking status, weight, age, height and bronchodilator response. Percent emphysema was evaluated at Visit 1 and the smoking status variable was created based on longitudinal follow-up information. An unstructured covariance structure was used for repeated measures. Total number of exacerbations and number of severe exacerbations were used as predictors in separate models.

Results

Among 1,937 study subjects with two FEV1 measures and exacerbation data (97% of the first 2,000 subject cohort), 35% reported at least one exacerbation/acute respiratory event. In subjects with COPD, exacerbations were associated with excess FEV1 decline, with the greatest effect in GOLD 1, where each exacerbation and severe exacerbation was associated with an additional -21 mL/year (95% CI: -43 to 0; p=0.047) and -75 mL/year (95% CI: -141,-10; p= 0.02) decline, respectively (Table). In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV1 decline.

Conclusions

Exacerbations accelerate lung function loss in subjects with established COPD, particularly those with mild disease. Our findings are particularly novel due to the lack of large numbers of persons with mild COPD in previous investigations. 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.

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