Airways Disorders
Defining and treating early COPD: Can we make a difference?
There is growing evidence that early COPD—before currently accepted spirometric or symptomatic criteria are present—may be an important clinical entity. The primary pathobiologic mechanisms in early COPD development include both abnormal lung development and accelerated lung aging (Augustí et al. Am J Respir Crit Care Med. 2018 Oct 15;198:8:978).
Martinez and colleagues recently proposed defining early COPD as age <50 with 10+ pack-year smoking history and at least one of the following: (1) early airflow limitation (postbronchodilator FEV1/FVC < lower limit of normal), (2) compatible CT scan abnormalities, (3) rapid decline in FEV1 (≥60 mL/yr) that is accelerated relative to FVC (Martinez et al. Am J Respir Crit Care Med. 2018 Jun 15;197[12]:1540).
A novel multiresolution CT scan imaging protocol described by Koo and coworkers found that substantial loss of small airways— specifically the terminal and transitional bronchioles—occurs in patients with mild-to-moderate COPD even prior to the development of emphysema on CT scan. These findings show that significant destruction of the small airways has occurred prior to the development of mild COPD (Koo et al. Lancet Respir Med. 2018 Aug;6:591).
Pharmacologic treatment for COPD is targeted at the reduction of symptoms and risk of exacerbation, as there remains no conclusive evidence that existing therapies modify long-term decline in lung function. It is unknown if pharmacotherapy for “early COPD” will alter the disease course. While not directly addressing this subset, information may be gleaned from trials on younger, more mild GOLD Stage 1 or Stage 2 patients. The Tie-COPD trial, the largest powered study to date of mild-to-moderate COPD, found that among patients with GOLD stage 1 or 2 COPD treatment with tiotropium compared with placebo for 2 years resulted in significantly higher FEV1 before bronchodilator use (between group difference of 157 mL) and slowed annual decline in FEV1 after bronchodilator use (Zhou et al. N Engl J Med. 2017 Sep 7;377[10]:923).
As our understanding of heterogeneity within COPD increases, striving for improved outcomes from our therapies—an impact on lung function in addition to symptom and exacerbation risk—may need to begin with the study of earlier treatment.
Megan Conroy, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, DO, FCCP
Steering Committee Vice-Chair