Table 1.

Chronic obstructive pulmonary disease phenotypes. Numerous methods of patient phenotyping have been pursued, with varying levels of success. Although some methods do seem to distinguish between endotypes, some of them merely enrich for certain endotypes and some of them may select for subpopulations within multiple endotypes, thus ultimately failing to define useful underlying pathophysiology or direct therapy

Phenotype	Identifying characteristic	Predictive of response to specific therapy	Specific to COPD endotype (i.e. pathophysiology of airflow obstruction)	Predictive of clinical course?
A1AT deficiency	Genotype or low Al AT activity	A1AT replacement	Yes	Yes
Frequent exacerbator	Clinical	Azithromycin, PDE4 inhibition	No	↑ Exacerbations by definition
Upper lobe predominant emphysema	Radiographic	Lung volume reduction	No	↑ Survival (if LVRS)
Pure emphysema	Low sputum volume or purulence, ↓ BW:AW	No	No	↑ Spirometric decline
Chronic bronchitis	High sputum volume or purulence, ↑ BW:AW	PDE4 inhibition for FEV<50%	No	↑ Symptoms and mortality
Pulmonary vascular	↑ PAPm, PA:A	Unknown	No	↑ Exacerbations
High systemic inflammation	↑ Laboratory markers of serum inflammation	Unknown	Possibly	↑ Symptoms and mortality
Steroid responsive	May be predicted by: FEV1 variability, BDR, eosinophilia and other TH2 markers, ↑ Bronchial BM thickness	ICS, by definition	? Irreversible asthma	Unknown
ACOS	Varied definitions; often early onset fixed airflow obstruction	Disputed	May enrich for asthma/ICS responsive + early-onset COPD	↑ Symptoms and mortality

A1 AT, alpha 1 antitrypsin; ACOS, asthma-COPD overlap syndrome; BDR, bronchodilator responsiveness; BM, basement membrane; BW:AW, bronchial wall: artery wall thickness; CT, computed tomography; FEV1, forced xpiratory volume in 1-s; ICS, inhaled corticosteroid; LVRS, lung volume reduction surgery; PAPm, mean pulmonary arterial pressure; TH2, type-2 helper T-cell.