Impact of Airway-Occluding Mucus Plugs on Mortality in Patients with COPD According to Disease Severity: A Subset Analysis of Data From COPDGene

Paola Rogliani,1 Luigino Calzetta2 1Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, ItalyCorrespondence: Paola Rogliani, Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, Rome, 00133, Italy, Tel +39 06 2090 4656, Email [email protected]: Chronic mucus hypersecretion (CMH) in chronic obstructive pulmonary disease (COPD) is associated with severe outcomes, but its impact on mortality across COPD stages is not well understood. This study evaluated the risk of mortality according to mucus plugs and COPD severity.Methods: A subset analysis was performed using secondary unadjusted data from published figures of a study on the COPDGene cohort. Data on mortality rates and mucus plug scores were extracted and classified by the GOLD stages. The mortality risk was calculated based on the number of mucus plugs occluding lung segments and GOLD stage, using calibration curves and best-fitting non-linear regression curve analysis.Results: The risk of all-cause mortality was significantly increased for GOLD stage 1 patients with ≥ 1 occluded lung segments (1.48, 95% CI 1.10– 1.86; P< 0.01) compared to those with no occlusions. Patients with GOLD stage 1 and ≥ 3 occluded lung segments had a significantly higher mortality risk (1.89, 95% CI 1.43– 2.36; P< 0.001). No increased mortality risk resulted for patients with 1– 2 occluded lung segments and those at GOLD stage 2– 4. The number needed to harm analysis indicated that 6 patients with ≥ 3 occluded segments at GOLD stage 1 were required to observe one death, compared to 26 patients at GOLD stage 4.Conclusion: The significant mortality risk associated with multiple mucus-plugged segments at GOLD stage 1 supports the potential benefit of thiol-based mucolytic therapy. Targeted interventions to reduce mucus plugs could be crucial in improving survival outcomes for early-stage COPD patients.Keywords: COPD, mucus plugs, mortality risk, GOLD stages, mucolytic therapy