Chronic Obstructive Pulmonary Disease Phenotypes

TLDR

COPD exhibits marked heterogeneity in presentation and progression, and while FEV1 fails to capture this, no clear alternative metric exists, leading to confusion over the definition and use of phenotypes in the disease. The authors aim to refine COPD phenotyping by defining it as a single or combination of disease attributes that distinguish individuals in terms of symptoms, exacerbations, therapy response, progression, or death. They propose that phenotypes should be linked to shared underlying biology and validated iteratively by identifying candidate phenotypes and testing their association with clinical outcomes. Adopting the refined definition enables classification of COPD patients into distinct prognostic and therapeutic subgroups, and a common language will aid future research and management.

Abstract

Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.