Asthma: the importance of epithelial mesenchymal communication in pathogenesis. Inflammation and the airway epithelium in asthma.
Asthma is a disorder of the airways in which Th-2-mediated inflammation is considered to provide the basis for altered structure and function that leads to bronchial hyper-responsiveness (BHR) and variable airflow obstruction. This linear progression underpinning asthma pathophysiology is questioned on the basis of observations on the pathology of the disease in early childhood, the independent genetic factors that influence atopy and BHR, incomplete responses to treatment with corticosteroids despite powerful anti-inflammatory effects and the recent disappointing results with targeted therapies that almost abolish eosinophilia in the blood and airways and yet produce little effect on the clinical outcomes of asthma. An alternative hypothesis is put forward in which atopy/airway inflammation and altered structure and function of the formed airway elements are parallel but interacting factors. For asthma to develop as a chronic disease, genetic and environmental factors that drive each of these components are required. Fundamental to this is the concept of aberrant signalling between the airway epithelium and underlying mesenchyme and persistent activation of the epithelial mesenchymal trophic unit.
Davies
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Respiratory Cell and Molecular Biology Division, Southampton General Hospital, University of Southampton School of Medicine, Southampton SO16 6YD, UK.
Holgate
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D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological