The association of tidal EFL with exercise performance, exacerbations, and death in COPD

Abstract

Background: Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is ≥0.28 kPa·s·L-1. The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality. Methods: In 425 patients, spirometry and forced oscillation technique measurements were obtained on eight occasions over 3 years. 6MWD was assessed at baseline and at the 3-year visit. Respiratory symptoms, exacerbations, and hospitalizations were recorded. A total of 5-year mortality statistics were retrieved retrospectively. We grouped patients according to the mean within-breath reactance (ΔXrs), measured over several breaths at baseline, calculated as mean inspiratory–mean expiratory reactance over the sampling period. In addition to the established threshold of EFLT, an upper limit of normal (ULN) was defined using the 97.5th percentile of ΔXrs of the healthy controls in the study; 6MWDs were compared according to ΔXrs, as normal, ≥ ULN < EFLT, or ≥ EFLT. Annual exacerbation rates were analyzed using a negative binomial model in the three groups, supplemented by time to first exacerbation analysis, and dichotomizing patients at the ULN. Results: In patients with COPD and baseline ΔXrs below the ULN (0.09 kPa·s·L-1), 6MWD was stable. 6MWD declined significantly in patients with ΔXrs ≥ ULN. Worse lung function and more exacerbations were found in patients with COPD with ΔXrs ≥ ULN, and patients with ΔXrs ≥ ULN had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with ΔXrs ≥ ULN and FEV1 >50%. Conclusion: Patients with baseline ΔXrs ≥ ULN had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. ΔXrs is a novel independent marker of outcome in COPD.