A Study on COPD Phenotypes, Endotypes and Treatable Traits

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes.

The prevalence of COPD varied from 11.4 to 26.1% according to a multi-city study that surveyed the population with spirometry. The economic burden of COPD on society is enormous. In 2005, COPD ranked second as a respiratory cause for hospitalization and inpatient bed days in Hong Kong. In those >75 years of age, the hospitalization rate for COPD was as high as 2,225/100,000. The prevalence of moderate COPD, using the spirometric reference of FEV1/FVC ratio of <70%, among 1,008 elderly HK Chinese (age ≥60 years) in the community, were 19.6% and 11.9% in the male and female subjects respectively.

The concept of "phenotype" is defined as the physical appearance or biochemical characteristic resulting from the interaction between the genotype and the environment.

It is the observable characteristics of a disease, such as morphology, development, biochemical or physiological properties, or behaviour. Some phenotypes have a significant impact on prognosis, including symptoms, exacerbations, response to therapy, and rate of disease progression or mortality.1 On the other hand, an endotype is a subtype of disease defined functionally and pathologically by a distinct molecular/ pathophysiological mechanism or by distinct treatment responses. An example is type 2 high inflammation.

The recognition of COPD phenotypes and endotypes has significantly impacted the management of the disease. Using biomarkers to identify specific COPD phenotypes has dramatically improved the success rate of novel drug development, increasing the probability of success in phase IIa trials from approximately 29% to 82%. This combined approach, incorporating COPD phenotypes and new biomarkers, is expected to revolutionize the management of COPD in the coming years. An example is a recent phase 3 clinical trial on Dupilumab in COPD patients. Dupilumab is a fully human monoclonal antibody which blocks the shared receptor component for interleukin-4 and interleukin-13. In COPD patients who had evidence of type 2 airway inflammation, as indicated by elevated blood eosinophil levels, those who received dupilumab experienced fewer disease exacerbations, improved lung function and quality of life, and less severe respiratory symptoms compared to those who received a placebo.8