Bronchoconstriction and airway biology: potential impact and therapeutic opportunities.
Recent work has demonstrated that mechanical forces occurring in the airway as a consequence of bronchoconstriction are sufficient to not only induce symptoms but also influence airway biology. Animal and human in vitro and in vivo work demonstrates that the airways are structurally and functionally altered by mechanical stress induced by bronchoconstriction. Compression of the airway epithelium and mechanosensing by the airway smooth muscle trigger the activation and release of growth factors, causing cell proliferation, extracellular matrix protein accumulation, and goblet cell differentiation. These effects of bronchoconstriction are of major importance to asthma pathophysiology and appear sufficient to induce remodeling independent of the inflammatory response. We review these findings in detail and discuss previous studies in light of this new evidence regarding the influence of mechanical forces in the airways. Furthermore, we highlight potential impacts of therapies influencing mechanical forces on airway structure and function in asthma.
Groningen Research Institute for Asthma and COPD, Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands. Electronic address: r.gosens@rug.nl.
Reinoud
R
Gosens
Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
Chris
C
Grainge
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D012137:Respiratory System / Q000473:pathology / Q000503:physiopathology*; D013314:Stress, Mechanical
D018927:Anti-Asthmatic Agents; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins