Jan 19, 2023

Disclosures: Bhatt reports receiving grants from the NIH; royalties/licenses from Springer Humana; consultant fees from Boehringer Ingelheim, Sanofi/Regeneron and Sunovion; lecture payments from GSK and IntegrityCE; and stock from Vigor Medical Systems. Please see the study for all other authors’ relevant financial disclosures. ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . Please try again later. If you continue to have this issue please contact customerservice@slackinc.com . Back to Healio Former smokers with COPD who experienced exacerbations had larger lung density declines than those without exacerbations, according to a letter to the editor published in Annals of the American Thoracic Society. “We found a stepwise greater loss of lung density with increasing exacerbation frequency, predominantly in former smokers who already had some preexisting emphysema,” Surya P. Bhatt, MD, MSPH, associate professor of medicine in the division of pulmonary, allergy and critical care medicine at the University of Alabama School of Medicine and medical director of the UAB Pulmonary Function and Exercise Physiology Lab, and colleagues wrote. Data were derived from Bhatt SP, et al. Ann Am Thorac Soc. 2022;doi:10.1513/AnnalsATS.202112-1385RL. Using data from the COPDGene study, Bhatt and colleagues analyzed 3,874 adults (mean age, 63.4 years; 50.2% women; 25% African American) with COPD, either current (n = 1,522) or former persistent (n = 2,352) smokers, to find out if acute exacerbations are related to quicker emphysema progression. Patients underwent spirometry and CT at study enrollment and after 5 years, and researchers tracked patients’ interval exacerbations every 3 to 6 months within the study period. Of the total cohort, 1,829 patients had Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0, 357 had GOLD stage 1, 756 had GOLD stage 2, 365 had GOLD stage 3 and 87 had GOLD stage 4 disease at baseline. Researchers characterized patients based on exacerbation frequency over 5 years: 2,590 (67%) patients had no exacerbations, 1,284 (33%) had at least one exacerbation, 864 (22%) had one to four exacerbations and 420 (11%) had at least five exacerbations. Adjusting for variables such as age, sex, race and BMI, researchers found that a higher number of exacerbations was linked to larger adjusted lung density declines among patients who formally smoked . Former smokers who had five or more exacerbations had a –5.22 g/L (95% CI, –6.23 to –4.21) change in lung density compared with a change of –4.16 g/L (95% CI, –4.91 to –3.41) among those who had one to four exacerbations and a change of –3.27 g/L (95% CI, –3.81 to –2.74) among those with no exacerbations (P < .0001 for all). Adjusted lung density estimates include aging effects, which researchers estimated to be 0.36 g/L per year. Researchers reported similar findings when evaluating former smokers with at least 5% emphysema (5 exacerbations, –5.92 g/L, 95% CI, –7.13 to –4.71; 1-4 exacerbations, –4.68 g/L, 95% CI –5.67 to –3.69; no exacerbations, –3.73 g/L, 95% CI, –4.6 to –2.87), although this association did not occur for those with less than 5% emphysema at baseline regardless of smoking status. On the other hand, patients who actively smoked had greater mean adjusted lung density changes than former smokers ( 5 exacerbations, –5.61 g/L, 95% CI, –7.39 to –3.83; 1-4 exacerbations, –5.58 g/L, 95% CI –6.84 to –4.32; no exacerbations, –4.89 g/L, 95% CI, –5.63 to –4.16), but researchers did not find the same effect modification that they found in the former smoker group. “Exacerbations are related to emphysema progression in a dose-dependent manner,” Bhatt and colleagues wrote. “Even low exacerbation frequency is associated with a high risk of emphysema progression, especially once emphysema has already set in. As emphysema is irreversible, these results underscore the importance of preventing exacerbations.” Perspective