The clinical relevance of the emphysema-hyperinflated phenotype in COPD

Abstract

The classification of chronic pulmonary obstructive disease (COPD) into clinical and pathophysiological subsets is not new, but increasing data is available on the relation of these different phenotypes to clinically meaningful outcomes. This review focuses on the “emphysema-hyperinflation” (EH) phenotype, which is characterised by a prominent loss of lung elastic recoil and hyperinflation burden that translates into marked exercise intolerance and a heightened sense of dyspnoea. Although no single genetic profile has been associated with the EH phenotype, recent data have shown that certain single nucleotide polymorphisms, such as DNAH5, appear to have an effect on the preferential development of hyperinflation in smokers. Static and dynamic hyperinflation are hallmarks of the EH phenotype, and abnormal increases in resting lung function indices such as total lung capacity (TLC), functional residual capacity (FRC) and inspiratory to TLC ratio (IC/TLC) seem more associated with the clinical EH phenotype than others markers of gas trapping. An increased level of dyspnoea on exertion and exercise intolerance are also characteristic of the EH presentation and are likely related in part to critical mechanical constraints imposed on tidal volume expansion in situations where ventilatory demands are increased, but also possibly on cardiac and hemodynamic anomalies related to emphysema and hyperinflation. Importantly, the clinical relevance of the EH phenotype is underlined by the finding that indices of hyperinflation such as IC/TLC and residual volume (RV) can be used as independent predictors of mortality in patients with COPD. Treatment of patients with the EH phenotype should primarily focus on smoking cessation and maximal bronchodilator therapy. New long-acting combined bronchodilators options provide clinicians with safe and effective ways to address the hyperinflation issue in this population. Pulmonary rehabilitation also has a positive impact on exercise tolerance, quality of life and hyperinflation, and should be routinely considered in patients with EH presentation that remain symptomatic despite optimal treatment, whereas as lung volume reduction techniques should be reserved for highly selected patients.