Remodeling of the airway epithelium in asthma.
Several pathologic changes occur in the airway epithelium in asthma, but the relationship between these changes and the initiation and progression of asthma remains poorly understood. One possibility is that changes in the structure and function of the epithelium induced by environmental exposure in genetically susceptible subjects represent primary pivotal events that occur early in the pathogenesis of asthma. Alternatively, these epithelial changes may occur simply as a consequence of pivotal early events in other systems, such as immune deviation in childhood to a helper T cell type 2 (Th2) subtype of CD4(+) cells. Epithelial desquamation in asthma represents a pathologic change that is frequently cited as important for the mechanisms of airway remodeling and airway hyperresponsiveness. Desquamation of the epithelium may not represent true pathology, however, but may instead be an artifact of tissue sampling and handling. Evidence is more firm for other pathologic changes in the epithelium. For example, goblet cell numbers are increased in asthma, leading to increases in stored mucins in the epithelium and in secreted mucins in sputum. The functional consequences of these changes include sputum production and airway narrowing, which lead to asthma exacerbations. Currently available data suggest that an important mechanism for goblet cell hyperplasia in asthma is the action of Th2 cytokines. Improved understanding of epithelial goblet cell abnormalities in asthma will hopefully lead to novel therapies for mucin hypersecretion, which is an important cause of morbidity and mortality.
Fahy
J V
JV
Pulmonary and Critical Care Division, Department of Medicine and the Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143, USA. jfahy@itsa.ucsf.edu
D000818:Animals; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D016084:Bronchoconstriction; D002199:Capillary Permeability; D015550:Cell Degranulation; D048429:Cell Size; D004195:Disease Models, Animal; D015870:Gene Expression; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D006965:Hyperplasia; D007118:Immunoassay; D051379:Mice; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D009077:Mucins