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As the efficacy of current therapies often declines with muco\u2010obstructive disease progression, contributing significantly to morbidity and mortality, there is a need for improved treatments that address underlying defects in mucus homeostasis and airway physiology. In this study, we evaluate the effects of carbocisteine, a mucoactive therapeutic, in the \u03b2ENaC\u2010transgenic (\u03b2ENaC\u2010Tg) model of muco\u2010obstructive lung disease. Short\u2010term carbocisteine administration significantly reduced airway mucus obstruction, potentially through decreased concentrations of Muc5ac and Muc5b. Notably, carbocisteine treatment modulated key inducers of mucus production, such as interleukin (IL)\u201013 and the upstream promoter cytokine IL\u201017, suggesting broader effects on mucoregulatory pathways. Carbocisteine administration was observed to alter mononuclear cell populations, impacting specific inflammatory subsets of CD11b alveolar macrophages and Ly6c monocytes, indicating immunomodulatory effects, either directly or secondary to improved mucus clearance. However, despite changes in immune cell populations, short\u2010term administration failed to mitigate lung damage and inflammation associated with established muco\u2010obstructive lung disease. These findings demonstrate the potent mucoactive effect of carbocisteine in established muco\u2010obstructive lung disease, through a broader mechanism of action than previously understood, with the potential to modulate inflammatory responses for preventive or long\u2010term treatment strategies.<\/jats:p>","DOI":"10.1111\/imcb.70156","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:00:56Z","timestamp":1786683656000},"page":"833-844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carbocisteine Reduces Airway Mucus Obstruction and Alters Inflammatory Cell Populations in a Model of Muco\u2010Obstructive Lung Disease"],"prefix":"10.1111","volume":"104","author":[{"given":"Peter","family":"Ferris","sequence":"first","affiliation":[{"name":"Airway Innate Immunity Group (AiiR), School of Medicine, Dentistry and Biomedical Sciences, Wellcome\u2010Wolfson Institute for 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