Feature Article

Some Smokers With Early COPD Have a Higher Risk Than Others of Poor Outcomes (With Audio)
2012;17(7):1, 4.

Some Smokers With Early COPD Have a Higher Risk Thank Others of Poor Outcomes (With Audio)

Some, but not all, smokers with mild-to-moderate COPD have an accelerated rate of lung function decline, research suggests.

(Click here to listen to a Pulmonary Reviews audiocast in which M. Bradley Drummond, MD, MHS, discusses his research on lung function decline in smokers with mild-to-moderate COPD.)

Contrary to conventional wisdom, not all smokers experience a rapid decline in lung function over time. According to M. Bradley Drummond, MD, MHS, of Johns Hopkins University, Baltimore, and colleagues reporting in the June 15 American Journal of Respiratory and Critical Care Medicine, the current threshold used to define COPD (ie, FEV1/FVC < 0.70 or below the fifth percentile of the lower limit of normal) may be too high to identify those who are most at risk for poorer lung function and worse mortality.

“The historical model of lung function decline that was originally described by Fletcher and Peto was one of gradually accelerating lung function decline over time,” Drummond told Pulmonary Reviews. “Recent data from clinical trials of patients with established COPD have shown that there is substantial heterogeneity in lung function decline in smokers. Identifying individuals who are at risk earlier in the disease process is important from a clinical standpoint as this would help define who could benefit the most from early therapy.”

Lung Health Study Data
The researchers analyzed data from the longitudinal Lung Health Study (LHS). The LHS I (1986 to 1994) was a multicenter randomized trial of smoking cessation intervention combined with inhaled ipratropium or placebo versus usual care involving 5,887 smokers ages 35 to 60 (mean age, 49) who had mild-to-moderate airflow obstruction. Patients were not regularly using bronchodilators and their lung function was measured annually for five years. Nearly all (98.3%) underwent extended follow-up (14.5 years) for LHS III (1998 to 2001). Most patients (96%) were of white race, two-thirds were men, and all were active smokers at the time of enrollment with an average 41 pack-years’ smoking history.

Patients were stratified into bins based on baseline FEV1 to FVC ratio and separately into bins based on Z-score (ie, the difference between actual and predicted FEV1/FVC, normalized to the standard deviation of predicted FEV1/FVC).

Threshold Shift?
Two and one-half percent of the cohort had died at the five-year follow-up. At LHS III, 9.8% of the original cohort had died and by year 12, 7.2% of the cohort had died. By study completion, 46% were active smokers and 15.5% were sustained quitters.

“In general, individuals with lower lung function by any metric had more rapid adjusted FEV1 decline,” the researchers noted.

With the exception of participants in the highest bin of baseline FEV1/FVC ratio, the adjusted mean FEV1 slope was less than zero. There was a threshold for differential decline at an FEV1/FVC of less than 0.65 and a Z-score less than -2.0. Lower thresholds of each spirometric metric were associated with increasing adjusted hazard of death. “There was no statistical difference in annual FEV1 decline between participants whose baseline FEV1/FVC Z-score included the LLN 5th percentile threshold … compared with the next highest bin,” the researchers noted.

Stratified by smoking status, the association between lower baseline lung function and accelerated decline was present among continuous smokers and intermittent quitters, and present but attenuated among sustained quitters.

Spirometry is a useful prognostic tool in at-risk patients, Drummond said. “The thresholds that we observed that put patients at risk for excessive lung function decline and mortality are lower than the current levels to define COPD, and we think these data can inform future guideline development in how we define COPD.” While the current guidelines indicate that smokers who do not have symptoms should not be screened, these study results suggest that screening spirometry in smokers regardless of symptoms may help with risk stratification, he added.

—Adriene Marshall

Suggested Reading
Drummond MB, Hansel NN, Connett JE, et al. Spirometric predictors of lung function decline and mortality in early chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(12):1201-1306.
Fletcher P, Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1645-1648.

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