{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:02:41Z","timestamp":1791428561652,"version":"4.3.3"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1<jats:sup>+<\/jats:sup> bronchiolar-specific club cell may play a role in this aberrant regenerative process.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To assess the presence of club cells in the small airways of patients suffering from ILD.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Small airways (internal diameter &amp;lt;2 mm) in lung samples [surgical lung biopsy (SLB) and\/or transbronchial lung cryobiopsy (TBLC)] from 14 patients suffering from ILD and 10 controls were morphologically assessed and stained for SCGB1A1. SCGB1A1 was weighted by epithelial height as a marker of airway generation (SCGB1A1\/EH). Correlations between clinical, functional, and high-resolution CT (HRCT) prognostic factors and histomorphometry were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1<jats:sup>+<\/jats:sup> cells [0.064 (0.020\u20130.172)] as compared to controls' sample's small airways [0.393 (0.082\u20130.698), <jats:italic>p<\/jats:italic> &amp;lt; 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1\/EH &amp;lt;0.025): UIP (18\/33; 55%) as compared with non-UIP patterns (4\/31; 13%) or controls (0\/29; 0%): <jats:italic>p<\/jats:italic> &amp;lt; 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho \u22120.63, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and a positive relationship with both forced vital capacity (FVC) and Hounsfield unit (HU)-distribution pattern in kurtosis (Rho 0.38 and 0.50, respectively, both <jats:italic>p<\/jats:italic> &amp;lt; 0.001) as markers of fibrotic changes.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Compared with controls, the small airways of patients with ILD more often lack SCGB1A1, especially so in UIP. Low densities of SCGB1A1-marked cells correlate with bronchiectasis and fibrotic changes. Further research investigating SCGB1A1 staining as a pathological feature of the bronchiolization process is merited.<\/jats:p>","DOI":"10.3389\/fimmu.2021.630096","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T06:15:44Z","timestamp":1614320144000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Club Cell Loss as a Feature of Bronchiolization in 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