Airway dysfunction and IgA immunity in COVID-unrelated and COVID-related ARDS - 17/02/23

Airway dysfunction and airway morphological changes have been reported in ARDS patients, and were associated with adverse outcomes [1Volta C.A., Dalla Corte F., Ragazzi R., et al. Expiratory flow limitation in intensive care: prevalence and risk factors Crit Care 2019 ;  23 : 395

Cliquez ici pour aller à la section Références]. However, airway functionality has been poorly characterized during ARDS, particularly in terms of IgA immunity, one of the frontline protection of the lung against pathogens. Besides, airway functionality and morphology have never been compared between COVID-unrelated ARDS and COVID-related ARDS (CARDS). Our objective was to assess the structure and functionality (with a specific focus on IgA immunity) of distal airways in patients with ARDS and with CARDS.

Samples of lung tissue from patients with ARDS (n=25), CARDS (n=18) and controls (n=15) were retrospectively compared in terms of morphological changes in distal airways. Broncho-epithelial functionality and IgA immunity were studied and quantified in a selected subset of lung samples by multiplex fluorescence immunohistochemistery. Production of Secretory Component (SC, the extracellular part of the Polymeric Immunoglobulin Receptor [pIgR], the carrier of IgA through the airway epithelium), IgAs, secretory (S) IgAs (IgA linked to SC) were prospectively assessed in the broncho-alveolar lavage (BAL) fluid from controls (n=5) and from patients with ARDS (n=24) as well as in the blood of controls (n=5), patients with CARDS (n=89) and with ARDS (n=24).

In comparison with controls, airways of ARDS and CARDS patients were characterized by increased epithelial denudation (P=0.0078 and P<0.0001) and increased epithelial inflammation, mainly with neutrophils (P<0.0001). The tissue expression of pIgR (Fig. 1) was significantly lower in patients with ARDS in comparison with controls (P=0.048) and with CARDS (P=0.0052). The expression of S-IgA was selectively lower in ARDS compared with CARDS (P=0.023) whereas there was no difference in terms of IgA expression. Besides, the concentrations of the Secretory component (SC), IgAs and S-IgAs in BAL fluid were not different between ARDS and controls. Conversely, SC, S-IgA1 and S-IgA2 serum concentrations were increased in both ARDS and CARDS compared with controls (P<0.0001 and P=0.002; P<0.0001 and P=0.0005; P=0.0025 and P=0.0465 respectively), the increase being significantly larger in ARDS than in CARDS for s-IgA1 (P=0.0039) and SC (P=0.0022). There was no difference in serum concentrations of IgAs, suggesting that the observed increase in S-IgAs and SC reflected a conCtamination of the blood from the airway lumen through a damaged epithelium.

Structural and inflammatory changes in distal airways of patients with ARDS and CARDS were identified. A specific pattern of airway epithelial dysfunction and defective IgA epithelial transport was suggested in ARDS unrelated to COVID-19.