The Journal of asthma : official journal of the Association for the Care of Asthma
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Phospholipases mediate the release of arachidonic acid from membrane phospholipids, enabling the subsequent metabolism to potent inflammatory mediator products of cyclooxygenase and lipoxygenase enzymes, such as prostaglandins and leukotrienes. Cytosolic phospholipase A₂ has long been recognized as important, but newly characterized are secreted A₂ isoenzymes. These secretory phospholipases are released into the extracellular compartment on cell activation. ⋯ Utilizing secretory phospholipase knockout mice, group X deficiency significantly diminished the airway goblet cell metaplasia, mucus hypersecretion, increased airway smooth muscle mass, and subepithelial fibrosis observed in wild type mice after allergen challenge. The mechanism is likely through impaired generation of cysteinyl leukotrienes in the knockout mice. Recent human investigation in patients with exercise induced bronchoconstriction is supportive of a role of secretory phospholipase, directing attention to these enzymes as particularly attractive pharmacologic targets in asthma.
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Asthma and mental health conditions often coexist and studies support a link between the two disorders. Indeed, an increase in the incidence of depression and anxiety has been reported in children with asthma compared to those without asthma. ⋯ There is support for a working hypothesis, linking inner-city violence and the development of childhood asthma via pathways that include parental mental health conditions, parental nicotine addiction, environmental tobacco smoke, and Th2 skewing in infants. It is anticipated that a better understanding of the above relationships will lead to the development of new targeted treatment strategies for childhood asthma in the future.