Research ArticleAsthma

Eosinophils increase airway sensory nerve density in mice and in human asthma

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Science Translational Medicine  05 Sep 2018:
Vol. 10, Issue 457, eaar8477
DOI: 10.1126/scitranslmed.aar8477

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Remodeling airway innervation in asthma

Asthma is a widespread chronic airway disease characterized by airway obstruction, inflammation, and hyperresponsiveness. Symptoms such as bronchoconstriction and cough range from mild intermittent to severe persistent. In eosinophilic asthma, the most common form of asthma, eosinophils in the airway alter nerve function and exacerbate the disease. However, whether eosinophils also affect airway nerve structure is unclear. Now, Drake et al. show that in specimens from patients with severe eosinophilic asthma, airway innervation was increased and positively correlated with symptom severity. In mice, eosinophilia increased airway innervation and triggered bronchoconstriction and airway hyperresponsiveness. The results suggest that structural remodeling of airway innervation contributes to symptom severity in eosinophilic asthma.

Abstract

In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airway innervation and substance P expression were increased in moderate persistent asthmatics compared to mild intermittent asthmatics and healthy subjects. Increased innervation was associated with a lack of bronchodilator responsiveness and increased irritant sensitivity. In a mouse model of eosinophilic airway inflammation, the increase in nerve density and airway hyperresponsiveness were mediated by eosinophils. Our results implicate airway nerve remodeling as a key mechanism for increased irritant sensitivity and exaggerated airway responsiveness in eosinophilic asthma.

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