Chronic Obstructive Pulmonary Disease Phenotypes

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.

Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives

“…COPD is a major contributor of healthcare costs due to frequent hospitalisation, loss of productivity and disability [4]. COPD is a heterogeneous collection of syndromes with complex pathophysiological mechanisms and different clinical phenotypes, which negatively affect accurate diagnosis, as well as the design and validation of effective studies and therapies [5][6][7].…”

Addressing unmet needs in the treatment of COPD

“…COPD is a complex, multicomponent disease in which heterogeneity exists in a range of factors, including lung function decline, exacerbation frequency and the contribution of emphysema and small airways disease to airflow limitation [1,[8][9][10]98]. Addressing this heterogeneity is an unmet need in COPD management.…”

“…Heterogeneity in exacerbation frequency and other factors, such as the severity of airflow limitation, rate of lung function decline and presence of comorbidities, means individualised treatment may be desirable and effective for the management of patients with COPD [1,[8][9][10].…”

Personalised medicine: are we ready?

“…The last century saw an exponential increase in our understanding of health and disease, clinical phenotypes [8,9], biological endotypes and targeted biologics, as illustrated in the field of asthma and allergic diseases [10] although not yet for COPD, the other most frequent chronic bronchial disease [11]. But the end of this road is not yet visible on the horizon: the size of what we still need to learn is probably much larger than our current knowledge.…”