News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2019)

Criner et al (N Engl J Med 2019; https://doi.org/10.1056/NEJMoa1905248) recently examined the effect of eosinophil depletion mediated by the IL-5 receptor α–blocking mAb benralizumab on the exacerbation rate of patients with chronic obstructive pulmonary disease (COPD) and high blood eosinophil counts in 2 large, complementary, phase 3, randomized controlled trials (GALATHEA and TERRANOVA). In both trials no statistically significant differences in annualized exacerbation rates were observed at any dose of benralizumab compared with placebo, despite substantial depletion of blood and sputum eosinophils. Overall, these findings demonstrate no effect of eosinophil depletion on the frequency of COPD exacerbations and indicate a need for continued investigation into alternative therapeutic strategies.No effect of eosinophil depletion on the frequency of COPD exacerbations No effect of eosinophil depletion on the frequency of COPD exacerbations Leyva-Castillo et al (Immunity 2019;50:1262-75, e4; https://doi.org/10.1016/j.immuni.2019.03.023) have recently identified that mechanical skin injury, in addition to its known roles promoting cutaneous sensitization to food allergens, also mediates a unique skin-to-gut crosstalk regulating intestinal mast cell activity. Tape stripping the skin of mice, which mimics scratching by patients, led to expansion and activation of mast cells within the small intestine and promoted food-induced anaphylaxis in sensitized mice without cutaneous allergen delivery. Mechanistically, tape stripping released IL-33 from the skin, which synergized with IL-25 derived from tuft cells within the gut to induce IL-4 and IL-13 production from group 2 innate lymphoid cells, and this caused subsequent intestinal mast cell expansion. Collectively, these results show that mechanical skin injury expands intestinal mast cells to promote food-induced anaphylaxis, which provides a plausible mechanism linking atopic dermatitis characterized by scratching that inflicts mechanical skin injury and food allergy.Mechanical skin injury expands intestinal mast cells to promote food-induced anaphylaxis Mechanical skin injury expands intestinal mast cells to promote food-induced anaphylaxis We asked senior author Raif S. Geha, MD, the James L. Gamble Professor of Pediatrics at Harvard Medical School and Children’s Hospital, Boston, Mass, to comment on the study. He writes: “Food-specific IgE antibodies are not always associated with food-induced anaphylaxis. Atopic dermatitis (AD), a disease characterized by intense pruritus, is highly associated with food-induced anaphylaxis. Our studies show that in addition to promoting cutaneous sensitization to foods, mechanical skin injury inflicted by scratching might play an important role in IgE-mediated food-induced anaphylaxis in patients with AD by expanding and activating intestinal mast cells.” Although narrowing of the small airways in asthmatic patients has become increasingly appreciated, its clinical significance and the best approach for its clinical measurement are currently unclear. Through combined computational modeling and statistical analysis of a cohort of patients with asthma, Foy et al (Am J Respir Crit Care Med 2019; https://doi.org/10.1164/rccm.201812-2322OC) determined that narrowing of the small airways worsened both disease control and quality of life and was reversed with treatment with type 2 inflammation–targeting biologic therapies. Additionally, accurate determination of the degree of small-airways narrowing in patients was achieved by means of forced oscillation, a simple respiratory technique that uses small pressure changes superimposed on normal breathing to measure respiratory mechanics and airway resistance. In total, the authors have identified both a high importance of small-airways disease in asthmatic patients and a clinically relevant method for its measurement.High importance of small-airways disease in asthmatic patients High importance of small-airways disease in asthmatic patients In light of growing evidence that patients without eosinophilic inflammation might not adequately respond to inhaled glucocorticoids, Lazarus et al (N Engl J Med 2019;380:2009-19; https://doi.org/10.1056/NEJMoa1814917) performed a crossover trial to assess the efficacy of standard treatment with mometasone or the long-acting muscarinic antagonist tiotropium in patients with mild persistent asthma and low sputum eosinophil counts. Compared with placebo, no statistically significant differences were observed with either treatment in a composite outcome consisting of treatment failure, days of asthma control, and FEV1, although tiotropium trended toward significance. These results are significant because current guidelines recommend initiation of inhaled glucocorticoid therapy with failure of as-needed short-acting β2-agonists and underscore a need for further investigation into the optimal treatment of patients without eosinophilic inflammation.No statistically significant differences were observed with either treatment No statistically significant differences were observed with either treatment We asked first author Stephen C. Lazarus, MD, of the University of California, San Francisco, to comment on the study. Dr Lazarus writes: “We were very surprised to find that nearly three quarters of these patients with mild persistent asthma had low sputum eosinophil counts. Going forward, we hope that biomarkers will enable us to predict the best treatment for each patient.” In a study of healthy volunteers, Matta et al (JAMA 2019; https://doi.org/10.1001/jama.2019.5586) recently identified systemic absorption of avobenzone, oxybenzone, and octocrylene with regular use of commercially available sunscreen. The maximum plasma concentrations of these chemicals were greater than the threshold set by the US Food and Drug Administration, requiring toxicologic assessment. Further study is needed to determine the clinical significance of these findings, including in patients with a disrupted skin barrier function. However, it is still recommended to wear sunscreen and be vigilant with other sun control measures, including seeking shade and wearing protective clothing, sunglasses, and hats, according to the Centers for Disease Control and Prevention. Chan et al (Sci Transl Med 2019; https://doi.org/10.1126/scitranslmed.aav1102) have developed a novel system for detecting middle-ear fluid, a key diagnostic feature of otitis media, using smartphones. This approach exhibited 85% sensitivity and 82% specificity in diagnosing otitis media in a clinical study of 98 pediatric patients. In combination with the fact that parents had similar performance as trained clinicians, this system could be a low-barrier and effective screening tool for detecting otitis media. Figure attribution: Public Domain at Wikimedia Commons by user Tim Parkinson [CC BY 2.0 (https://creativecommons.org/licenses/by/2.0)].News items were written by medical writer Jared Travers, MD, PhD. News items were written by medical writer Jared Travers, MD, PhD.