Treatment Trials in Young Patients with Chronic Obstructive Pulmonary Disease and Pre-Chronic Obstructive Pulmonary Disease Patients: Time to Move Forward

Abstract

Chronic obstructive pulmonary disease (COPD) 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: "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" patients with 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 controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT 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.

Keywords: COPD; clinical trials; early; pre-COPD; young age.

Figure 1.

Examples of lung function trajectories from birth to death. The red shaded area highlights the population of young adults with chronic obstructive pulmonary disease to be included in treatment trials. Gray shaded areas indicate that these age limits are somewhat arbitrary (based on normal peak + plateau lung function), and therefore some age variability may be acceptable. Note also that this age range includes trajectories with normal peak lung function (100% reference) as well as those with reduced peak lung function (<80% reference) and that both can have a normal or an enhanced decline with time. For further explanations, see the main text.

Figure 2.

Prevalence of chronic obstructive pulmonary disease in young individuals (20–49 years) in the general population in China. Data are from Reference . GOLD = Global Initiative for Chronic Obstructive Lung Disease.