Epithelial Barrier Dysfunction in Chronic Respiratory Diseases.

Mucosal surfaces are lined by epithelial cells, which provide a complex and adaptive module that ensures first-line defense against external toxics, irritants, antigens, and pathogens. The underlying mechanisms of host protection encompass multiple physical, chemical, and immune pathways. In the lung, inhaled agents continually challenge the airway epithelial barrier, which is altered in chronic diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis. In this review, we describe the epithelial barrier abnormalities that are observed in such disorders and summarize current knowledge on the mechanisms driving impaired barrier function, which could represent targets of future therapeutic approaches

Secretory Immunoglobulin A Immunity in Chronic Obstructive Respiratory Diseases.

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. In this review, we summarize the current knowledge regarding alterations of the IgA/pIgR system observed in those major obstructive airway diseases and discuss their implication for disease pathogenesis

Immunoglobulines A sécrétoires et maladies respiratoires chroniques

La bronchopneumopathie chronique obstructive (BPCO), l’asthme et la mucoviscidose constituent des maladies respiratoires chroniques, caractérisées par une atteinte obstructive des (petites) voies aériennes, et dont l’évolution clinique est marquée par des épisodes d’exacerbation fréquemment en lien avec des déclencheurs infectieux. Au niveau des muqueuses, la production d’immunoglobuline (Ig) A, relâchée dans les sécrétions (sous sa forme dimérique) grâce à l’intervention du récepteur épithélial des immunoglobulines polymériques (pIgR), est un mécanisme de défense crucial permettant l’exclusion immune et l’élimination des pathogènes des voies respiratoires. Cette revue résume les altérations du système pIgR/IgA dans les maladies respiratoires chroniques et évalue le rôle potentiel de telles altérations dans leur expression clinique

Secretoire immunoglobulines A en chronische ademhalingsziekten

Chronische obstructieve longziekte (COPD), astma en mucoviscidose zijn chronische ademhalingsziekten die gekenmerkt worden door obstructie van de (kleine) luchtwegen en die klinisch gekenmerkt worden door exacerbaties, vaak veroorzaakt door infecties. De productie van immunoglobuline (Ig) A in het slijmvlies, die in de vorm van dimeren wordt afgegeven in de secreties via de epitheliale polymere immunoglobulinereceptor (pIgR), is een cruciaal verdedigingsmechanisme dat pathogenen in de luchtwegen uitschakelt. Dit overzichtsartikel vat de afwijkingen van het pIgR/IgA-systeem bij chronische ademhalingsziekten samen en evalueert de mogelijke rol van die afwijkingen bij de klinische expressie ervan

Ventilatory capacity in CLAD is driven by dysfunctional airway structureResearch in context

Summary: Background: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. Methods: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014–2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. Findings: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. Interpretation: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. Funding: This research was funded with the National research fund Flanders (G060322N), received by R.V