Although nicotinic acetylcholine receptors (nAChRs) are commonly associated with neurons in the brain and periphery, recent data indicate they are also expressed in non-neuronal tissues. We recently found the alpha7 (α7nAChR) subunit is highly expressed in human airway smooth muscle (hASM) with substantial increase in asthmatics, but their functionality remains unknown. We investigated the location and functional role of α7nAChRs in hASM cells from normal vs. mild-moderate asthmatic patients. Immunostaining and protein analyses showed α7nAChR in the plasma membrane including in asthmatics. Patch clamp recordings showed functional homomeric α7nAChR channels at are significantly higher in asthmatic hASM. Real-time fluorescence imaging showed nicotine, via α7nAChR, increases intracellular Ca2+ ([Ca2+]i) independent of ACh effects, particularly in asthmatic hASM, while cellular traction force microscopy showed nicotine-induced contractility including in asthmatics. These results indicate functional homomeric and heteromeric nAChRs that are increased in asthmatic hASM, with pharmacology that likely differ owing to different subunit interfaces that form the orthosteric sites. nAChRs may represent a novel target in alleviating airway hyperresponsiveness in asthma. New and Noteworthy Cigarette smoking and vaping exacerbate asthma. Understanding mechanisms of nicotine effects in asthmatic airways is important. This study demonstrates functional alpha7 nicotinic acetylcholine receptors (α7nAChRs) are expressed in human airway smooth muscle, including from asthmatics, and enhance intracellular calcium and contractility. Although a7nAChRs are associated with neuronal pathways, α7nAChR in smooth muscle suggests inhaled nicotine (e.g. vaping) can directly influence airway contractility. Targeting α7nAChR may represent a novel approach to alleviating airway hyperresponsiveness in asthma.

Chronic airway diseases, such as wheezing and asthma, remain significant sources of morbidity and mortality in the pediatric population. This is especially true for preterm infants who are impacted both by immature pulmonary development as well as disproportionate exposure to perinatal insults that may increase the risk of developing airway disease. Chronic pediatric airway disease is characterized by alterations in airway structure (remodeling) and function (increased airway hyperresponsiveness), similar to adult asthma. One of the most common perinatal risk factors for development of airway disease is respiratory support in the form of supplemental oxygen, mechanical ventilation, and/or CPAP. While clinical practice currently seeks to minimize oxygen exposure to decrease the risk of bronchopulmonary dysplasia (BPD), there is mounting evidence that lower levels of oxygen may carry risk for development of chronic airway, rather than alveolar disease. In addition, stretch exposure due to mechanical ventilation or CPAP may also play a role in development of chronic airway disease. Here, we summarize the current knowledge of the impact of perinatal oxygen and mechanical respiratory support on the development of chronic pediatric lung disease, with particular focus on pediatric airway disease. We further highlight mechanisms that could be explored as potential targets for novel therapies in the pediatric population.

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