TY - JOUR
T1 - Treatment Trials in Young Patients with Chronic Obstructive Pulmonary Disease and Pre-Chronic Obstructive Pulmonary Disease Patients
T2 - Time to move forward
AU - Martinez , Fernando J
AU - Agusti, Alvar
AU - Celli, Bartolome R
AU - Han, MeiLan K.
AU - Allinson , James
AU - Bhatt, Surya P
AU - Calverley, Peter
AU - Chotirmall, Sanjay H
AU - Chowdhury, Bradul
AU - Darken, Patrick
AU - Da Silva, Carla A
AU - Donaldson, Gavin
AU - Dorinsky, Paul
AU - Dransfield, Mark
AU - Faner, Rosa
AU - Halpin, David MG
AU - Jones, Paul
AU - Krishnan, Jerry A
AU - Locantore, Nicholas
AU - Martinez, Fernando D.
AU - Müllerová, Hana
AU - Price, David
AU - Rabe, Klaus F
AU - Reisner, Colin
AU - Singh, Dave
AU - Vestbo, Jørgen
AU - Vogelmeier, Claus F
AU - Wise, Robert A.
AU - Tal-Singer, Ruth
AU - Wedzicha, Jadwiga A
N1 - Supported by NIH/NHLBI grants 1R01 HL136682, U01 HL137880, R01 HL 182622, and P01 HL114501 (F.J.M.).
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - COPD
KW - Early
KW - young age
KW - pre-COPD
KW - Clinical Trials
U2 - 10.1164/rccm.202107-1663SO
DO - 10.1164/rccm.202107-1663SO
M3 - Article
C2 - 34672872
SN - 1073-449X
VL - 205
SP - 275
EP - 287
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 3
ER -