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

Tidal expiratory flow limitation (EFL_T) 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 EFL_T with 6-minute walk distance (6MWD), exacerbations, and mortality.

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 [Formula: see text], measured over several breaths at baseline, calculated as mean inspiratory-mean expiratory reactance over the sampling period. In addition to the established threshold of EFL_T, an upper limit of normal (ULN) was defined using the 97.5th percentile of [Formula: see text], of the healthy controls in the study; 6MWDs were compared according to [Formula: see text], as normal, ≥ ULN < EFL_T, or ≥ EFL_T. 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.

In patients with COPD and baseline [Formula: see text] below the ULN (0.09 kPa·s·L^-1), 6MWD was stable. 6MWD declined significantly in patients with [Formula: see text]. Worse lung function and more exacerbations were found in patients with COPD with [Formula: see text], and patients with [Formula: see text] had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with [Formula: see text] and FEV₁ >50%.

Patients with baseline [Formula: see text] had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. [Formula: see text] is a novel independent marker of outcome in COPD.