MOLECULAR BIOTECHNOLOGY Volume 22, 2002 Airway Inflammation and Remodeling in Asthma 179 REVIEW 179 Molecular Biotechnology 2002 Humana Press Inc. All rights of any nature whatsoever reserved. 1073–6085/2002/22:2/179–189/$12.75 *Author to whom all correspondence and reprint requests should be addressed: Respiratory Cell and Molecular Biology, Infection, Inflamma- tion, and Repair Division, Mail Point 810, Level D. Centre Block, Southampton General Hospital, Southampton SO166YD, UK Abstract Airway Inflammation and Remodeling in Asthma: Current Concepts Stephen T. Holgate* 1. Introduction Asthma is an heterogeneous disorder of the airways with intermittent airflow obstruction fre- quently accompanied by increased responsive- ness of the bronchi to a wide variety of exogenous and endogenous stimuli. A number of different clinical patterns of asthma have been described, largely based on the clinical manifestations of, or factors precipitating, the airflow obstruction. As the disease becomes more severe and chronic, air- flow obstruction progressively loses some of its reversibility to resemble some aspects of chronic obstructive pulmonary disease (COPD). How- ever, in a small proportion of patients with life- threatening asthma, the airways are highly labile on account of greatly enhanced bronchial hyper- responsiveness. At the other end of the disease severity spectrum, there are many patients with mild intermittent asthma or cough variant asthma with little evidence of variable airflow obstruc- tion, whose disease only manifests when exposed to particular sensitizing allergens to which they are sensitive, e.g., outdoor allergens during the pollen season. Over the last 50 years, accumulated evidence indicates that the prevalence of asthma and allied allergic disorders have progressively increased on a worldwide scale, in both developed and devel- oping countries. In addition to an increase in asthma-related symptoms, there is evidence of in- creased medication usage and a rise in hospital ad- missions. The reasons for these rising trends are likely to be multiple. Suggestions include 1. Increased allergen exposure (especially within the domestic setting). 2. Reduced exposure to childhood infections or bacterial products in the environment. 3. Changes to the diet, e.g., reduced antioxidant and δ13 polyunsaturated fatty acids. 4. Alterations to the bowel flora possibly linked to a “Westernized” diet and to increased antibiotic prescribing in infancy. Whatever the underlying causes for these ris- ing trends, asthma has now become a public health issue. Therefore, it is of the utmost importance that a clear understanding of underlying cell and molecular mechanisms is obtained in order that appropriate biomarkers can be identified to detect the disease earlier and to follow its outcome. In childhood and early adulthood, asthma occurs in association with atopy characterized by elevated circulating allergen-specific IgE levels and posi- tive skin prick test responses to allergen extracts. However, in adults, asthma tends to lose its close Asthma is a chronic inflammatory disorder of the airways interacting with altered structure and function of the formed elements including smooth muscle. While atopy and polarization of the airway T-cell response toward a Th-2 phenotype are important factors in asthma pathogenesis, there is increasing realization that remodeling events are also important. Evidence is presented that inflammation and altered airway structure in asthma interact through the epithelium and underlying mesenchyme. As in other chronic inflammatory disorders, a dynamic interplay between mediators, cytokines, and growth factors provides a broader base on which to identify novel preventative and therapeutic strategies in asthma. Index Entries: Asthma; mediators, inflammation, remodeling.