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Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease\/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.<\/jats:p>","DOI":"10.1183\/16000617.0001-2024","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T08:45:26Z","timestamp":1726649126000},"page":"240001","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target"],"prefix":"10.1183","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane 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