Airway Mucus Occlusions in Ex-Smokers with and Without COPD

In patients with moderate-to-severe COPD, airway mucus-occlusions correlate with airflow limitation, exacerbation and mortality-risk. However, the clinical relevance of mucus-plugs in milder COPD is not well-understood. We evaluated pulmonary function, six-minute-walk-distance (6MWD), emphysema and airway mucus-plugs at baseline and 31 ± 7 months later (follow-up), in ex-smokers with COPD, and those at risk of COPD, but with normal spirometry. Ninety-three ex-smokers with (n = 54) and without COPD (n = 39) underwent spirometry, plethysmography, the six-minute-walk-test (6MWT),¹²⁹Xe MRI, and CT at a baseline visit and 31 ± 7 months later. Baseline and follow-up FEV₁, FVC, RV/TLC, DL_CO, mucus-score, -count, -volume, -length, airway wall-thickness%, total-airway-count (TAC), relative-area-of-lung-with-attenuation ≤-950 Hounsfield Units (RA₉₅₀), and ¹²⁹Xe MRI ventilation-defect-percent (VDP) were measured. A Sankey plot was generated to follow mucus-plug dynamics at follow-up. At follow-up, there was significantly worse 6MWD, RV/TLC (COPD, p ≤ 0.04), VDP, CT RA₉₅₀, airway WT% and TAC in participants with (p ≤ 0.002) and without COPD (p ≤ 0.03), but there was no change in FEV₁, mucus-score, count, volume or length (all p > 0.07). At baseline, there were 289 plugs in 58 participants; at FU, 94/289 (33%) mucus-plugs persisted and there were 193 new plugs for a total of 287 mucus-plugs (Δmucus-score = 0, p = 0.7; Δmucus-count = -2, p = 0.5). In COPD and participants at-risk for COPD, there was significantly worse airway remodelling, emphysema, gas-trapping, exercise capacity, and ventilation defects. While two thirds of plugs resolved, new plugs, in new locations were observed at follow-up; mucus-count and score did not change. The temporal dynamics of mucus-plugs should be considered when evaluating their clinical relevance in COPD patients.Clinical Trial Registration: www.clinicaltrials.gov NCT02279329.