In the lungs, parasympathetic nerves provide the dominant control of airway smooth muscle with release of acetylcholine onto M3 muscarinic receptors. Treatment of airway disease with anticholinergic drugs that block muscarinic receptors began over 2000 years ago. Pharmacologic data all indicated that antimuscarinic drugs should be highly effective in asthma but clinical results were mixed. Thus, with the discovery of effective b-adrenergic receptor agonists the use of muscarinic antagonists declined. Lack of effectiveness of muscarinic antagonists is due to a variety of factors including unwanted side effects (ranging from dry mouth to coma) and the discovery of additional muscarinic receptor subtypes in the lungs with sometimes competing effects. Perhaps the most important problem is ineffective dosing due to poorly understood differences between routes of administration and no effective way of testing whether antagonists block receptors stimulated physiologically by acetylcholine. Newer muscarinic receptor antagonists are being developed that address the problems of side effects and receptor selectivity that appear to be quite promising in the treatment of asthma and chronic obstructive pulmonary disease.

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Background Because of the coronavirus disease (COVID-19) pandemic, graduate medical education programs adopted virtual interviews (VIs) as the default modality for the 2020 recruitment season. It is unknown whether VIs allowed applicants to effectively evaluate programs, and the best interview format for the future is unclear. Objective To 1 ) assess pulmonary and critical care applicants’ perceived ability to evaluate programs using VIs, 2 ) determine the attitudes of applicants toward the components of VIs, and 3 ) identify applicants’ preferences for the future fellowship interview format. Methods After the National Residency Matching Program medical subspecialty match, an electronic survey was sent to 1,067 applicants to pulmonary and critical care medicine programs asking them to compare their fellowship VI experience with their residency in-person interview (IPI) experience. Results Three hundred six (29%) applicants responded to the survey, and 289 completed it (27%). There were 117 (40%) women and 146 (51%) White individuals. Most respondents believed that VIs hindered their ability to evaluate programs’ culture, faculty–fellow relationships, location, facilities, and their own fit within the program. They believed they were able to evaluate the clinical experience, curriculum, and potential for academic development equally well compared with IPIs. The most helpful elements of VIs were the interview with the program director, meetings with the fellows, and interviews with faculty members. Less helpful elements included conference access, prerecorded program director presentations, virtual hospital and city tours, and video testimonials. One hundred twenty-three respondents (43%) chose VIs with an optional visit as their preferred future interview format, 85 (29%) chose IPIs, 54 (19%) wanted a choice between VIs and IPIs, and 27 (9%) chose VIs only. Conclusion Most pulmonary and critical care medicine applicants preferred future interviews to include both VIs and the option of an in-person visit or interview. This study can assist programs in designing their future interview formats in a trainee-centric fashion.

Ozone causes persistent airway hyperreactivity in humans and animals. One day after ozone exposure, airway hyperreactivity is mediated by release of eosinophil major basic protein that inhibits neuronal M(2) muscarinic receptors, resulting in increased acetylcholine release and increased smooth muscle contraction in guinea pigs. Three days after ozone, IL-1β, not eosinophils, mediates ozone-induced airway hyperreactivity, but the mechanism at this time point is largely unknown. IL-1β increases NGF and the tachykinin substance P, both of which are involved in neural plasticity. These experiments were designed to test whether there is a role for NGF and tachykinins in sustained airway hyperreactivity following a single ozone exposure. Guinea pigs were exposed to filtered air or ozone (2 parts per million, 4 h). In anesthetized and vagotomized animals, ozone potentiated vagally mediated airway hyperreactivity 24 h later, an effect that was sustained over 3 days. Pretreatment with antibody to NGF completely prevented ozone-induced airway hyperreactivity 3 days, but not 1 day, after ozone and significantly reduced the number of substance P-positive airway nerve bundles. Three days after ozone, NK(1) and NK(2) receptor antagonists also blocked this sustained hyperreactivity. Although the effect of inhibiting NK(2) receptors was independent of ozone, the NK(1) receptor antagonist selectively blocked vagal hyperreactivity 3 days after ozone. These data confirm mechanisms of ozone-induced airway hyperreactivity change over time and demonstrate 3 days after ozone that there is an NGF-mediated role for substance P, or another NK(1) receptor agonist, that enhances acetylcholine release and was not present 1 day after ozone.