Clinical Phenotypes and Prognostic Heterogeneity of Mild-to-Moderate Chronic Obstructive Pulmonary Disease: A...

The clinical phenotypes, prognosis, and heterogeneity of mild-to-moderate chronic obstructive pulmonary disease (COPD) have not been systematically evaluated.

Do different clinical phenotypes of mild-to-moderate COPD have different prognoses?

We analysed the baseline and 3-year follow-up data of participants with mild-to-moderate COPD from a prospective community-based cohort study. Mild-to-moderate COPD was defined as a forced expiratory volume in 1 second (FEV₁) / forced vital capacity ratio of < 0.70 and FEV₁ ≥ 50% of the predicted value. The clinical phenotypes included respiratory symptoms, exacerbation history, emphysema, air trapping, and airway remodelling. Respiratory health outcomes included exacerbations and lung function decline over the 3-year follow-up.

Overall, 806 participants with mild-to-moderate COPD were included, of whom 712 (88%) completed the 3-year follow-up. Participants with mild-to-moderate COPD had more severe emphysema, air trapping, and airway remodelling; increased exacerbation risk; and faster annual FEV₁ decline than those with preserved spirometry. The severity of airflow obstruction, respiratory symptoms, emphysema, and air trapping, as well as the eosinophilic phenotype, had low overlap in mild-to-moderate COPD. There was significant individual variation in the annual FEV₁ decline rate and exacerbation incidence among participants with mild-to-moderate COPD. Emphysema and air trapping were associated with faster FEV₁ decline and higher exacerbation risk. Respiratory symptoms and exacerbations in the previous year were associated with a higher acute exacerbation risk but not with faster lung function decline.

Mild-to-moderate COPD exhibited distinct clinical phenotypes with significant prognostic heterogeneity. Accurate phenotype identification is essential for targeted intervention, clinical precision management, and prognostic improvement.