Epinephrine autoinjector prescribing following anaphylaxis presentation to the emergency department.

Background: Guidelines recommend patients with anaphylaxis are prescribed epinephrine autoinjectors (EAI), carry the EAI with them, and are referred to an allergist. There also are barriers to EAI administration, such as acquiring the medication, having it available, recognizing when to use it, and administering it appropriately. Objective: The objective was to describe how often patients with anaphylaxis discharged from the emergency department (ED) receive an EAI prescription and allergist referral; also, to assess the frequency of EAI pick-up by the patient from the outpatient pharmacy, out-of-pocket cost, change in EAI device during dispensing, and if patient training on EAI use and allergist follow-up occurred. Patient-specific factors associated with the occurrence of these variables were investigated. Methods: This was a retrospective, observational study of adult and pediatric ED patients who presented with anaphylaxis between July and December 2020. Data were collected from medical records and telephone calls to outpatient pharmacies and included patient demographics; ED treatment; EAI prescribing, EAI pick-up from the outpatient pharmacy, and cost; device changes; EAI training; and allergist referral and follow-up. Data are presented descriptively, and bivariate analyses were used for comparisons between patient-specific factors and incidence of EAI prescribing, patient pick-up, and allergist referral. Results: A total of 102 patients were included; mean age ± standard deviation 34 ± 7 years, 52% were < 18 years of age; and 54% had a history of allergy and/or anaphylaxis. EAI prescribing occurred in 79% of the patients. Of these, 71% picked up the EAI from the outpatient pharmacy, the median cost to the patient was $5 (range, $0-$379), 18% had an EAI device change at dispensing, and 23% received EAI training. Allergist referral occurred in 22%, and 28% followed up with an allergist within 60 days. Presenting symptoms of mucosal edema and respiratory stridor were associated with the occurrence of EAI prescribing. Presenting symptoms of respiratory wheezing, hoarseness, throat itching, skin flushing and allergist referral from the ED were associated with the occurrence of EAI pick-up from the outpatient pharmacy. Conclusion: Overall, 79% of ED patients with anaphylaxis had an EAI prescribed and 22% had an allergist referral; 71% picked up the EAI from the outpatient pharmacy, EAI dispensing changes occurred, and training was infrequent. Collaboration between emergency medicine clinicians, allergists, and pharmacists is needed to streamline treatment and follow-up.

Secondhand smoke exposure and serum cytokine levels in healthy children.

INTRODUCTION: Exposure to secondhand smoke (SHS) is associated with morbidity in children. Alterations in immune responses may explain this relationship, but have not been well-studied in children. Our objective was to determine the association between SHS exposure and serum cytokine levels in healthy children. METHODS: We recruited 1-6 year old patients undergoing routine procedures. A parent interview assessed medical history and SHS exposure. Children with asthma were excluded. Blood was collected under anesthesia. We used Luminex Multiplex Assays to test for a panel of cytokines; cotinine was determined using an enzyme-linked immunosorbent assay. Children were categorized as no, intermediate, or high exposure. A mixed-effects model was fit to determine differences in cytokines by exposure level. RESULTS: Of the 40 children recruited, 65% (N=26) had SHS exposure; 16 intermediate, and 10 high. There were no differences by demographics. In bivariate analyses, children exposed to SHS had lower concentrations of IL-1ß, IL-4, IL-5, and IFN-γ than those with no exposure. In the mixed-effects model, children with any SHS exposure had significantly lower concentrations of IL-1ß (0.554 pg/mL vs. 0.249 pg/mL) and IFN-γ (4.193 pg/mL vs. 0.816 pg/mL), and children with high exposure had significantly lower mean concentrations of IL-4 (8.141 pg/mL vs. 0.135 pg/mL) than children with no exposure. CONCLUSIONS: This study suggests that SHS exposure decreases expression of some pro-inflammatory cytokines in SHS exposed children, including IFN-γ. Further research to describe the acute and chronic effects of SHS on the immune systems of children is needed.

IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells.

Immune cells are key regulators of neoplastic progression, which is often mediated through their release of cytokines. Inflammatory cytokines such as IL-6 exert tumor-promoting activities by driving growth and survival of neoplastic cells. However, whether these cytokines also have a role in recruiting mediators of adaptive anticancer immunity has not been investigated. Here, we report that homeostatic trafficking of tumor-reactive CD8+ T cells across microvascular checkpoints is limited in tumors despite the presence of inflammatory cytokines. Intravital imaging in tumor-bearing mice revealed that systemic thermal therapy (core temperature elevated to 39.5°C ± 0.5°C for 6 hours) activated an IL-6 trans-signaling program in the tumor blood vessels that modified the vasculature such that it could support enhanced trafficking of CD8+ effector/memory T cells (Tems) into tumors. A concomitant decrease in tumor infiltration by Tregs during systemic thermal therapy resulted in substantial enhancement of Tem/Treg ratios. Mechanistically, IL-6 produced by nonhematopoietic stromal cells acted cooperatively with soluble IL-6 receptor-α and thermally induced gp130 to promote E/P-selectin- and ICAM-1-dependent extravasation of cytotoxic T cells in tumors. Parallel increases in vascular adhesion were induced by IL-6/soluble IL-6 receptor-α fusion protein in mouse tumors and patient tumor explants. Finally, a causal link was established between IL-6-dependent licensing of tumor vessels for Tem trafficking and apoptosis of tumor targets. These findings suggest that the unique IL-6-rich tumor microenvironment can be exploited to create a therapeutic window to boost T cell-mediated antitumor immunity and immunotherapy.