Club Cell Loss as a Feature of Bronchiolization in ILD

Abstract

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

Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19

“…We also detected changes in the airway epithelium which were mostly driven by time rather than differences between PC groups. However, a common feature of IPF is the ectopic appearance of airway epithelial cells (bronchiolization), and their secretion of CC16/SCGB1A1 particularly in Club cells [39][40][41][42] . We had observed that similarly to IPF, some images from PC patients showed extensive secreted CC16 in peribronchial regions (Figure 2l).…”

Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases

“…In IPF samples, LGR6 expression was generally increased in the basal progenitor populations, reaching the highest protein levels in areas of bronchiolization and honeycombing, whereas in COPD tissues, LGR6-positive basal cells were observed in damaged and inflated bronchioles and in proliferative bronchiolar lesions, but not in airways proximal to emphysematous lesions. The presence of LGR6 in lung epithelial progenitors of damaged and proliferating bronchioles and in fibrotic alveoli may suggest a Wnt-mediated response in divergent chronic insults occurring in COPD and IPF [ 10 , 46 , 48 ].…”

Club Cells—A Guardian against Occupational Hazards

“…The population of club cells in the fibrotic tissue of patients with ILD is different and apparently more heterogeneous compared to that of healthy subjects. Some authors have found less club cells (identified by the SCGB1A1+ marker) in the small airways of ILD, particularly in areas with a UIP radiological pattern [66], and have explained the bronchiolization process by the migration of club cells to more proximal sites in the airways or by the blockade in replacement of these cells after lung injury.…”