News beyond our pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2023)

Neuromedin U (NMU) is a neuron-derived soluble mediator that activates group 2 innate lymphoid cells to promote type 2 immunity. Li et al (Science 2023;381:1189-96; https://doi.org/10.1126/ science.ade4177) identified an important role for NMU-mediated eosinophil activation in epithelial cell differentiation within the small intestine. More specifically, transcriptome profiling of murine small intestinal eosinophils revealed expression of NMU receptor 1 (NMUR1) on a subset of small intestinal eosinophils. NMUR1 expression was induced after extended residence within the small intestine and was enhanced during helminth infection or exposure to dextran sulfate sodium. Finally, NMU-mediated eosinophil activation induced goblet cell differentiation in vivo and in co-cultures of eosinophils and small intestinal organoids. Collectively, these results identify NMU-induced eosinophil activation as an important regulator of homeostatic goblet cell differentiation. We asked corresponding author Heping Xu, PhD, Assistant Professor, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China, to comment on the study. He writes, “This work elaborates a previously unrecognized pathway that enables neuropeptides-immune system-epithelium crosstalk, implying that the nervous system constantly regulates epithelial homeostasis through modulating the activity of eosinophils in the small intestine.” This summer, Canadian wildfires dramatically worsened air quality in wide swaths of both Canada and the United States. Chen et al (JAMA 2023;e2318768; https://doi.org/10.1001/jama.2023.18768) identified a pronounced impact of the Canadian wildfire exposure on lung function in New York City, which is hundreds of kilometers away from the source, using records from New York City’s syndromic surveillance system. During the height of the Canadian wildfires, elevated ambient air fine particulate matter concentrations were observed throughout the city with concurrent increases in asthma-related emergency department visits as compared to periods without smoke. Notably, the effect was sustained in all 5 boroughs of New York City and across a wide spectrum of ages. Given that most work has focused on the impacts of wildfires on populations within close proximity, these results highlight the need for further study into the impacts of wildfire smoke on distant populations, especially vulnerable ones. Figure reproduced under Creative Commons license CC-BY_SA 4.0, attribution: user Salam2009, via Wikimedia Commons.Concurrent increases in asthma-related emergency department visits Concurrent increases in asthma-related emergency department visits Once-weekly treatment with the IL-4 and IL-13-inhibiting mAb dupilumab reduced symptoms and improved disease control in patients with eosinophilic esophagitis as compared to placebo at 24 weeks in the 3-part phase 3 LIBERTY EoE TREET clinical trial. Parts A and B were independent 24-week trials, and parts A-C and B-C extended active treatment to 52 weeks upon completion of parts A and B, respectively. Clinical improvements with dupilumab were maintained up to 52 weeks in 77 patients in parts A-C of the study. Rothenberg et al (Lancet Gastroenterol Hepatol 2023 Aug 31; https://doi.org/10.1016/S2468-1253(23)00204-2) reports the results of extended treatment to 52 weeks upon completion of parts B-C of the trial, which involved a larger cohort of 227 subjects. The clinical, endoscopic, and histologic improvements were maintained up to 52 weeks in the part B-C cohort. Notably, dupilumab every 2 weeks did not improve symptoms to the same degree as weekly dosing despite similar endoscopic and histologic improvements. In total, these results reinforce the long-term efficacy of dupilumab in eosinophilic esophagitis and support weekly, rather than biweekly, dosing. Figure reproduced under Creative Commons license CC-BY_SA 3.0, attribution: user Nephron, via Wikimedia Commons. We asked corresponding author Marc Rothenberg MD, PhD, from the Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, to comment on the study. He writes, “This is an important paper as it shows the durability of dupilumab therapy for EoE over the course of 52 weeks. In addition, the importance of weekly dosing compared to biweekly dosing for improvement of dysphagia was replicated.” Inappropriate attribution of penicillin allergy is rampant throughout health systems and remedying this involves labor-intensive, specialized testing involving skin prick and intradermal testing with a confirmatory oral challenge if skin testing is negative. Copaescu et al (JAMA Intern Med 2023; 183:944-52; https://doi.org/10.1001/jamaiternmed.2023.2986) compared traditional penicillin allergy testing and direct oral penicillin challenge alone in an international randomized trial involving 382 patients with reported low-risk penicillin allergy as determined by the point-of-care PEN-FAST decision tool. The oral challenge alone was noninferior to traditional testing and the assessment time was shorter. Importantly, similar safety profiles were observed between the 2 treatment arms. These results suggest that direct oral challenge may facilitate penicillin allergy delabeling in low-risk patients. We asked corresponding author Ana Copaescu, MD, FAAAI, FRCP, from the Division of Allergy and Clinical Immunology, Department of Medicine, McGill University Health Centre (MUHC), McGill University, Montreal, Quebec, Canada, to comment on the study. She writes, “The biggest takeaway from the PALACE study is that patients with a low-risk penicillin allergy, as defined by the PEN-FAST score, can safely receive a direct penicillin oral challenge to see if they are still allergic. The results from our research aim to simplify delabeling, making penicillin allergy removal more universally available and acceptable regardless of the setting and social and economic circumstances.” Peters et al (Lancet Child Adolesc Health 2023;7:636-47; https://doi.org/10.1016/S2352-4642(23)00133-5) conducted a population-based longitudinal study with a cohort of over 5000 infants to assess the relationship between infant food allergy and lung function later in childhood. The presence of food allergies at age 1 year imparted a 3.7-fold increased risk of developing asthma at age 6 years. A greater effect was observed in children who remained food allergic at age 6 as compared to those who had outgrown their food allergies, however even children with resolved food allergies had a greater risk of asthma compared with those who never had a food allergy. Notably, food-allergic infants were also more likely to have reduced lung function, specifically FEV1 and FVC, as measured by spirometry, at age 6, and this association was not mediated by the presence of asthma. Together, these findings demonstrate a link between infant food allergy and subsequent asthma and reduced lung function later in childhood. We asked corresponding author Rachel L. Peters, PhD, from the Murdoch Children’s Research Institute, Parkville, Victoria, Australia, to comment on the study. She writes, “This is the first time that we have been able to show that infant food allergy, even if it resolves, is associated with both a higher risk of asthma and reduced lung function later in childhood. Further follow-up of the HealthNuts cohort is essential to see whether these poorer respiratory outcomes persist into adolescence and beyond.”News items were written by medical writer Jared Travers, MD, PhD. News items were written by medical writer Jared Travers, MD, PhD.