Deposition of inhaled nanoparticles is reduced in subjects with COPD and correlates with the extent of emphysema: Proof of concept for a novel diagnostic technique

Background: The diagnosis of chronic obstructive pulmonary disease (COPD) is often based on spirometry, which is not sensitive to early emphysema. We have recently described a method for assessing distal airspace dimensions by measuring recovery of nanoparticles in exhaled air after a single-breath inhalation followed by breath-hold. Recovery refers to the non-deposited particle fraction. The aim of this study was to explore differences in the recovery of exhaled nanoparticles in subjects with COPD and never-smoking controls. A secondary aim was to determine whether recovery correlates with the extent of emphysema. Method: A total of 19 patients with COPD and 19 controls underwent three repeats of single-breath nanoparticle inhalation followed by breath-hold. Particle concentrations in the inhaled aerosol, and in an alveolar sample exhaled after breath-hold, were measured to obtain recovery. Findings: The patients with COPD had a significantly higher mean recovery than controls, 0·128 ± 0·063 versus 0·074 ± 0·058; P = 0·010. Also, recovery correlated significantly with computed tomography (CT) densitometry variables (P<0·01) and diffusing capacity for carbon monoxide (D_L,CO; P = 0·002). Interpretation: Higher recovery for emphysema patients, relative to controls, is explained by larger diffusion distances in enlarged distal airspaces. The nanoparticle inhalation method shows potential to be developed towards a tool to diagnose emphysema.