Chronic obstructive pulmonary disease phenotypes: the future of COPD.
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.
University of Michigan-Pulmonary and Critical Care, 1500 E. Medical Center Drive, 3916 Taubman, Ann Arbor, MI 48109, USA. mrking@umich.edu
MeiLan K
MK
Han
Alvar
A
Agusti
Peter M
PM
Calverley
Bartolome R
BR
Celli
Gerard
G
Criner
Jeffrey L
JL
Curtis
Leonardo M
LM
Fabbri
Jonathan G
JG
Goldin
Paul W
PW
Jones
William
W
Macnee
Barry J
BJ
Make
Klaus F
KF
Rabe
Stephen I
SI
Rennard
Frank C
FC
Sciurba
Edwin K
EK
Silverman
Jørgen
J
Vestbo
George R
GR
Washko
Emiel F M
EF
Wouters
Fernando J
FJ
Martinez
D018450:Disease Progression; D005540:Forced Expiratory Flow Rates; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D013147:Spirometry