Background Children with allergic asthma have more frequent and severe human rhinovirus (HRV)-induced wheezing and asthma exacerbations through unclear mechanisms. Objective To determine whether increased high-affinity IgE receptor (FcεRI) expression and cross-linking impairs innate immune responses to HRV, particularly in allergic asthmatic children. Methods Peripheral blood mononuclear cells (PBMC) were obtained from 44 children and surface expression of FcεRI on plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), monocytes, and basophils was assessed using flow cytometry. Cells were also incubated with rabbit anti-human IgE to cross-link FcεRI, followed by stimulation with HRV-16, and interferon (IFN)-α and -λ1 were measured by Luminex. The relationships among FcεRI expression and cross-linking, HRV-induced IFN-α and -λ1 production, and childhood allergy and asthma were subsequently analyzed. Results FcεRIα expression on pDCs was inversely associated with HRV-induced IFN- α and IFN-λ1 production. Cross-linking FcεRI prior to HRV stimulation further reduced PBMC IFN-α (47% relative reduction, 95% confidence interval [CI], 32–62%, p<0.0001) and IFN-λ1 (81% relative reduction, 95% CI, 69–93%, p<0.0001) secretion. Allergic asthmatic children had higher surface expression of FcεRIα on pDCs and mDCs when compared to non-allergic non-asthmatic children. Further, after FcεRI cross-linking, allergic asthmatic children had significantly lower HRV-induced IFN responses than allergic non-asthmatics (IFN-α, p=0.004; IFN-λ1, p=0.02) and non-allergic non-asthmatics (IFN-α, p=0.002; IFN-λ1, p=0.01). Conclusions Allergic asthmatic children have impaired innate immune responses to HRV that correlate with increased FcεRI expression on pDCs and are reduced by FcεRI cross-linking. These effects likely increase susceptibility to HRV-induced wheezing and asthma exacerbations.

Unlike with smoking cigarettes, electronic nicotine delivery systems do not cause CYP450 1A2 induction as there is a lack of combustion and polycyclic aromatic hydrocarbon production. Changing to the use of an electronic nicotine delivery system from cigarettes can result in the deinduction of CYP450 1A2 and the increase of certain medication serum concentrations, including clozapine. A case is reported in which the switch from smoking to an electronic nicotine delivery system resulted in increased clozapine serum concentration and constipation, necessitating pharmacologic management. The patient ultimately transitioned back to cigarettes, which resulted in the emergence of psychiatric symptoms. An evaluation of longitudinal serum concentrations and clinical correlation is provided. It is important that patients and health care professionals have knowledge not only about the impact of smoking cigarettes on clozapine metabolism, but also the effects of switching to or from an electronic nicotine delivery system.

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