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

Fernando J Martinez * (Corresponding Author), Alvar Agusti, Bartolome R Celli, MeiLan K. Han, James Allinson , Surya P Bhatt, Peter Calverley, Sanjay H Chotirmall, Bradul Chowdhury, Patrick Darken, Carla A Da Silva, Gavin Donaldson, Paul Dorinsky, Mark Dransfield, Rosa Faner, David MG Halpin, Paul Jones, Jerry A Krishnan, Nicholas Locantore, Fernando D. MartinezHana Müllerová, David Price, Klaus F Rabe, Colin Reisner, Dave Singh, Jørgen Vestbo, Claus F Vogelmeier, Robert A. Wise, Ruth Tal-Singer, Jadwiga A Wedzicha

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)275-287
Number of pages13
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number3
Early online date21 Oct 2021
Publication statusPublished - 1 Feb 2022

Bibliographical note

Supported by NIH/NHLBI grants 1R01 HL136682, U01 HL137880, R01 HL 182622, and P01 HL114501 (F.J.M.).

Data Availability Statement

This article has an online supplement, which is accessible from this issue’s table of contents at


  • COPD
  • Early
  • young age
  • pre-COPD
  • Clinical Trials


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