Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impaired in asthma. Airway mucus is acting as a physical and a biological fluid between the environment and the epithelium, synergistically moved by the cilia. In asthma, excessive mucus production is a hallmark of airway remodeling. Since many years we tried to therapeutically target mucus hypersecretion, but actually this option is still not achieved. The present review discusses the dynamic processes regulating airway mucus production. Airway inflammation is central in current asthma management. Understanding of how the airway epithelium influences the TH2 paradigm in response to deleterious agents is improving. The multiple receptors expressed by the airway epithelium are the transducers of the biological signals induced by various invasive agents to develop the most adapted response. Airway remodeling is observed in severe chronic airway diseases and may result from ongoing disturbance of signal transduction and epithelial renewal. Chronic airway diseases such as asthma will require assessment of these epithelial abnormalities to identify phenotypic characteristics associated with predicting a clinical benefit for epithelial-directed therapies.
Keywords: AHR; ASM; Acetylcholine; Ach; Airway hyperresponsiveness; Airway smooth muscle; Airways; Asthma; BAL; BEC; Bronchial epithelial cell; Bronchoalveolar lavage; CF; CFTR; CHI3L1; COPD; COX; CSE; Chronic obstructive pulmonary disease; Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; DC; DHA; DLL-1; Delta like protein 1; Dendritic cell; Docosahexaenoic acid; EGF; EGFR; EMTU; ERK; ET; Endothelin; Epithelial cells; Epithelial growth factor; Epithelial growth factor receptor; Epithelial–mesenchymal trophic unit; Extracellular signal-regulated kinase; G protein coupled receptor; GCs; GPCR; GR; Glucocorticoid receptor; Glucocorticoids; HB-EGF; Heparin binding-EGF; ICS; IL; IL-R; IgA; IgE; Immunoglobulin A; Immunoglobulin E; Inhaled Corticosteroid; Interleukin; LABA; LAMA; LO; LPS; LTRA; LXs; Leukotrien agonist; Lipopolysaccharide; Lipoxins; Lipoxygenase; Long acting β2-agonist; MMP; MUC; NF-kB; NK2 homeobox 1; NO; Nkx2.1; Nuclear Factor-KappaB; OVA; PGE2; PKC; PM; Particulate matter; Prostaglandin E2; SABA; SAM pointed domain-containing Ets transcription factor; SP; SPDEF; STAT; Short acting β2-agonist; Signal transducer and activator of transcription; Structural changes; TACE; TGF; TLR; TNF; TSLP; Thymic stromal lymphopoietin; Toll like receptor; Transforming growth factor; Treatment; Tumor necrosis factor; chitinase 3 like protein 1; cigarette smoke extract; cyclooxygenase; interleukin receptor; long acting muscarinic receptor; matrix metalloproteinase; miR; microRNA; mucin; nitric oxide; ovalbumin; pIgR; phosphokinase C; polymeric immunoglobulin receptor; surfactant protein; tumor necrosis factor-alpha-converting enzyme.