Treatment Trials in Young Patients with COPD and Pre-COPD Patients: Time to Move Forward.

Chronic Obstructive Pulmonary Disease is the end-result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts we propose therapeutic trials in two major groups of subjects: those "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized clinical trials (RCTs). We highlight the need of RCTs focused on young COPD or Pre-COPD patients to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCTs design including potential outcomes such as lung function, patient reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in (1) young adults with COPD and (2) those with pre-COPD at any age.