AUTHOR=Reynaud Paul , Ahmed Engi , Serre Isabelle , Knabe Lucie , Bommart Sébastien , Suehs Carey , Vachier Isabelle , Berthet Jean Philippe , Romagnoli Micaela , Vernisse Charlotte , Mallet Jean Pierre , Gamez Anne Sophie , Bourdin Arnaud 

TITLE=Club Cell Loss as a Feature of Bronchiolization in ILD

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.630096

DOI=10.3389/fimmu.2021.630096

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1<sup>+</sup> bronchiolar-specific club cell may play a role in this aberrant regenerative process.</p><p><bold>Objective:</bold> To assess the presence of club cells in the small airways of patients suffering from ILD.</p><p><bold>Methods:</bold> Small airways (internal diameter &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.</p><p><bold>Results:</bold> Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1<sup>+</sup> cells [0.064 (0.020–0.172)] as compared to controls' sample's small airways [0.393 (0.082–0.698), <italic>p</italic> &lt; 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1/EH &lt;0.025): UIP (18/33; 55%) as compared with non-UIP patterns (4/31; 13%) or controls (0/29; 0%): <italic>p</italic> &lt; 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho −0.63, <italic>p</italic> &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 <italic>p</italic> &lt; 0.001) as markers of fibrotic changes.</p><p><bold>Conclusion:</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.</p>