From triggers to asthma: a narrative review on epithelium dysfunction

Abstract

It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Birch pollen—The unpleasant herald of spring

“…More than 80% of all DEPs belong to the ultrafine particle range, i.e., they have a diameter of less than 0.1 µm and can therefore easily enter the respiratory tract, including the lower airways ( 90 , 91 ). In addition, these ultrafine particles have been shown to penetrate the lipid bilayer of alveolar epithelial cell membranes and to be translocated transcellularly by diffusion ( 92 ) and are thus capable of causing airway inflammation and tissue damage [as reviewed in ( 93 )]. Even worse, DEPs could also be a vehicle for birch pollen allergens, a similar effect has already been described for Lol p 1, an important grass pollen allergen from Lolium perenne ( 94 ).…”

Airway Epithelial-Derived Immune Mediators in COVID-19

“…Targeting airway inflammation and modulating the release of epithelial-derived cytokines using inhaled corticosteroids (ICSs) can reduce the secretion of epithelial-derived cytokines and chemokines. ICSs remain a mainstay therapeutic in the management of asthma, a disease characterized by chronic airway inflammation, airway hyperresponsiveness, and epithelial alterations such as goblet cell hyperplasia and sub- and intra-epithelial inflammatory cell accumulation [ 163 ]. Glucocorticoids exert their anti-inflammatory effect within the airways by suppressing inflammatory leukocyte migration and activation through the induction of the apoptosis of eosinophils and T cells [ 164 ].…”

Interleukin-4 (C590T) Gene Polymorphism in Association with Asthma Severity

“…3 The main causes of asthma are not known; however, several factors trigger the pathogenesis cascade of asthma, which include environmental triggers such as pollutants, tobacco smoking, allergens, viral and bacterial infection, and genetic variations. 4,5 The interaction between all these underlying risk factors increases the possibility of asthma presentation and even could determine the disease severity and control. 5 The pathogenesis of asthma is complex, and several immune cells and biomarkers are involved including T-lymphocyte, mast cells and eosinophils, and cytokines such as IL-4, IL-5, and IL-13 plus the immunoglobulin-E (IgE).…”

“…4,5 The interaction between all these underlying risk factors increases the possibility of asthma presentation and even could determine the disease severity and control. 5 The pathogenesis of asthma is complex, and several immune cells and biomarkers are involved including T-lymphocyte, mast cells and eosinophils, and cytokines such as IL-4, IL-5, and IL-13 plus the immunoglobulin-E (IgE). 6,7 calculated sample size would be 170 for a control: case ratio of 1:1 (85 in each limb) and 183 for a control: case ratio of 2:1 (minimum case=61 and minimum control=122).…”