Pulmonary mucus: Pediatric perspective

Airway mucus hypersecretion is a clinical feature of a number of childhood diseases, including asthma and bronchitis-associated conditions. However, compared with adults, there is relatively scarce information concerning mucus pathophysiology in respiratory diseases in children. The available evidence indicates many similarities between adult and childhood respiratory hypersecretory conditions, including goblet-cell hyperplasia and submucosal gland hypertrophy, and airway mucus plugging in asthma. Consequently, it is likely that treatments that are effective in adults would be effective in children. Numerous therapeutic targets are linked to the pathophysiology of airway mucus hypersecretion in experimental models and adults with respiratory disease. Whether or not these same targets are relevant in children is for the most part unclear. These targets include the inflammatory cells mediating the inflammatory response that generates the hypersecretory phenotype, and highly specific cellular elements such as epidermal growth factor receptor tyrosine kinase and calcium-activated chloride (CACL) channels. Identification of these factors is linked with the development of different classes of pharmacotherapeutic molecules directed at these targets. Compounds with a broader spectrum of anti-inflammatory activity are likely to be more effective than compounds with restricted activity. However, certain highly specific targets, such as human CACL1 channels, appear to be strongly associated with the development of an airway hypersecretory phenotype. Data from current clinical trials in adults with blockers of these specific targets are awaited with great interest. The hope is that, if effective, pediatric trials with these compounds could be initiated with a view to alleviation of the clinical impact of airway mucus hypersecretion in children. A significant challenge to the therapeutic progression of these new compounds is effective delivery to the airways in children, with the research effort into development of new compounds matched by advances in inhaler design.