Depression in children with asthma: Testing a cholinergically mediated “endotype”

Background: Asthma is not a single uniform disease; instead, it comprises various disease sub entities, or “endotypes,” with different etiologies and pathophysiologies. As asthma endotypes are discerned, individuals with asthma can be matched with optimal therapies for their specific asthma subtype. Depression is common in persons with asthma and associated with increased asthma-related morbidity and mortality. Depression in child asthma is associated with a predominance of parasympathetic/cholinergic activation over sympathetic activation. Cholinergic activity mediates airway smooth muscle constriction and has effects on airway inflammatory cells and mucus-secreting goblet cells. Objective: The goal of the current study was to examine whether children with asthma who have more depressive symptoms have cholinergically mediated disease that is differentially responsive to short-acting anticholinergic therapy. Methods: A total of 39 children with asthma (aged 7-17 years) and baseline obstruction on spirometry were evaluated for depressive symptoms by using the Children's Depression Inventory. Spirometry was used to evaluate the children for improvement in airway function following treatment with a short-acting anticholinergic medication. Inflammation was assessed by determining fractional exhaled nitric oxide levels and peripheral blood eosinophil counts, and atopic status was assessed by skin prick testing and measurement of total serum IgE level. Results: There was a statistically significant positive correlation between depressive symptoms and increase in FEV1 percent predicted value in response to ipratropium administration (rs = 0.344; P = .032). Conclusion: Higher depressive symptom scores are associated with increased airway responsiveness to inhaled ipratropium in children with asthma and active airway obstruction. These findings suggest the potential for definition of an endotype of asthma with comorbid depression that may benefit from anticholinergic asthma therapies.