Which pulmonary function tests best differentiate between COPD phenotypes?

We are still at the early phase of finding useful phenotypes in COPD that can guide therapy. However, in a simple sense, "sick patients die." Many phenotypic measurements of severity correlate with mortality in COPD: FEV(1), the ratio of inspiratory capacity to total lung capacity (IC/TLC), diffusing capacity of the lung for carbon monoxide (D(LCO)), 6-min walk distance, and maximum oxygen (O(2)) consumption or maximum watts on exercise testing. However, composite parameters, such as the BODE index (body mass index, air flow obstruction, dyspnea, exercise capacity), perform better, likely because they capture different aspects of severity that affect functional impairment and risk of death. Bronchodilator responsiveness is just a relative feature that aids in distinction of asthma and COPD but is not diagnostic in this use. A normal D(LCO) helps to rule out exercise-induced O(2) desaturation, but those with a low D(LCO) and COPD need exercise measurements to confirm desaturation. Currently, pulmonary function tests (PFTs) alone do not define subsets who respond to particular therapies. The presence of air flow obstruction and its severity increase the risk of lung cancer in COPD patients. Inflammatory biomarkers (exhaled nitric oxide and eosinophilia in sputum or bronchoalveolar lavage fluid) help distinguish asthma from COPD. Genetics is a promising area to elucidate pathophysiology and treatment for asthma and COPD, but currently alpha-1 antitrypsin deficiency is the only genetically-determined phenotype that has relevance for COPD management. The best promise for the future seems to be in composite phenotypes or scores, both for distinguishing asthma from COPD, and for guiding therapeutic options. It may be better to throw out the old, limiting diagnostic concepts. If, instead, we start from outcomes of interest, perhaps we can work back to predictors of these outcomes, and organize new diagnostic entities that have predictive relevance for treatment choices, functional outcomes, and mortality.