A number of chronic respiratory diseases including chronic bronchitis, asthma, cystic fibrosis and bronchiectasis are characterized by mucus hypersecretion. Following damage to the airway epithelium, a repair process of dedifferentiation, regenerative proliferation and redifferentiation takes place that is invariably accompanied by mucus hypersecretion as a key element in the host defence mechanism. In chronic respiratory diseases, however, excessive mucus production leads to a pathological state with increased risk of infection, hospitalization and morbidity. An understanding of the mechanisms that underlie and maintain this hypersecretory phenotype is therefore crucial for the development of rational approaches to therapy. Despite a high and increasing prevalence and cost to healthcare services and society, mucus hypersecretion in chronic respiratory disease has received little attention until recently, probably because of the difficulties inherent in studying this pathology. Only in the last few years have some of the genes involved in mucus secretion been characterized. The recent availability of genomic sequence information and specific antibodies has led to an explosion of interest in this area making this publication particularly timely. This book draws together contributions from an international and interdisciplinary group of experts, whose work is focused on both basic and clinical aspects of the problem. Coverage includes epidemiology, airways infection and mucus hypersecretion, the genetics and regulation of mucus production, models of mucus hypersecretion, and the implications of new knowledge for the development of novel therapies.

A number of chronic respiratory diseases including chronicbronchitis, asthma, cystic fibrosis and bronchiectasis arecharacterized by mucus hypersecretion. Following damage to theairway epithelium, a repair process of dedifferentiationregenerative proliferation and redifferentiation takes place thatis invariably accompanied by mucus hypersecretion as a key elementin the host defence mechanism. In chronic respiratory diseaseshowever, excessive mucus production leads to a pathological statewith increased risk of infection, hospitalization and morbidity. Anunderstanding of the mechanisms that underlie and maintain thishypersecretory phenotype is therefore crucial for the developmentof rational approaches to therapy.Despite a high and increasing prevalence and cost to healthcareservices and society, mucus hypersecretion in chronic respiratorydisease has received little attention until recently, probablybecause of the difficulties inherent in studying this pathology.Only in the last few years have some of the genes involved in mucussecretion been characterized. The recent availability of genomicsequence information and specific antibodies has led to anexplosion of interest in this area making this publicationparticularly timely.This book draws together contributions from an international andinterdisciplinary group of experts, whose work is focused on bothbasic and clinical aspects of the problem. Coverage includesepidemiology, airways infection and mucus hypersecretion, thegenetics and regulation of mucus production, models of mucushypersecretion, and the implications of new knowledge for thedevelopment of novel therapies.

Chair's Introduction (C. Basbaum).Epidemiological studies in mucus hypersecretion (J. Vestbo).Post-secretory fate of host defence components in mucus (M.Salathe, et al.).Mechanisms of submucosal gland morphogenesis in the airway (M.Filali, et al.).Mucin-producing elements and inflammatory cells (P. Jeffery andJ. Zhu).Respiratory tract mucins: structure and expression patterns (J.Davies, et al.).Development and validation of a lectin-based assay for thequantitation of rat respiratory mucin (A. Jackson, et al.).Regulation of mucin secretion from in vitro cellularmodels (C. Davis).Oscillations of pH inside the secretory granule control the gainof Ca¯2+ release for signal transduction in goblet cellsexocytosis (W. Chin, et al.).A calcium-activated chloride channel blocker inhibits gobletcell metaplasia and mucus overproduction (Y. Zhou, et al.).Mechanisms by which Gram-positive bacteria and tobacco smokestimulate mucin induction through the epidermal growth factorreceptor (EGFR) (C. Basbaum, et al.).Non-allergic models of mu cous cell metaplasia and mucushypersecretion in rat nasal and pulmonary airways (J. Harkema andJ. Wagner).Cytokine regulation of mucus production in a model of allergicasthma (L. Cohn, et al.).The role of apoptotic regulators in metaplastic mucous cells (Y.Tesfaigzi).Current and future therapies for airway mucus hypersecretion (P.Barnes).Clinical evaluation of new therapies for treatment of mucushypersecretion in respiratory diseases (B. Disse).Final general discussion.Index of contributors.Subject index.