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PGD2/DP2 Receptor Activation Promotes Severe Viral Bronchiolitis by Suppressing IFN- Λ Production Cheryl A

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PGD2/DP2 Receptor Activation Promotes Severe Viral Bronchiolitis by Suppressing IFN- Λ Production Cheryl A of wheezing and infantile colic in the first year of life. This compared with those from healthy subjects. RSV- association appears to be stronger with increasing antibi- infected cultured human primary airway epithelial otic duration. There was a trend toward allergic sensiti- cells also revealed increased PGD2 production. In a zation in infants who were treated with antibiotics. No neonatal mouse model of severe viral bronchiolitis, significant association was found with regard to the de- DP2 antagonism decreased viral load, promoted antiviral velopment of eczema. immunity, and ameliorated type 2 inflammation and bronchiolitis. This protective effect was replicated REVIEWER COMMENTS. The authors of this study demonstrate with a specific DP1 agonist and lost with DP1/DP2 that neonatal antibiotic administration may predispose antagonism. children to wheezing and colic. The authors of past studies have linked early-life antibiotics (not limited to CONCLUSIONS. The authors conclude that PGD2 contributes the neonatal period) with wheezing but report a link to disease severity by suppressing antiviral immunity and fl between antibiotic exposure and infantile colic. Further promoting type 2 in ammation. DP2 blockade or DP1 studies are needed to determine if these findings are agonism increased interferon-I expression and viral due to the alteration of gut microbiota during a critical clearance. Thus, DP2 antagonists or DP1 agonists may window. Optimization of indications for starting be a useful treatment of viral bronchiolitis and a antibiotics, early discontinuation if possible, and the possible preventive for asthma and other diseases with administration of probiotics may be indicated. pathogeneses related to viruses. REVIEWER COMMENTS. The authors of this study highlight the URL: www.pediatrics.org/cgi/doi/10.1542/peds.2018–2420RRR importance of PGD2 during RSV bronchiolitis and suggest Shazia Lutfeali, MD a similar role in the development of asthma after an RSV Christopher Parrish, MD infection. PGD2 suppression may boost immune defenses Dallas, TX against RSV bronchiolitis. The findings from this study could lead to clinical studies to determine if DP2 antag- onism and DP1 agonism could be used to treat viral PGD2/DP2 Receptor Activation Promotes bronchiolitis and perhaps prevent the subsequent de- Severe Viral Bronchiolitis by Suppressing velopment of asthma. IFN-l Production Werder RB, Lynch JP, Simpson JC, et al. Sci Transl Med. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2018–2420SSS 2018;10(440):eaao0052 Cheryl A. Steiman, MD PURPOSE OF THE STUDY. Respiratory syncytial virus (RSV) James E. Gern, MD bronchiolitis is a major risk factor for the development of Madison, WI asthma. Prostaglandin D2 (PGD2) is an established che- moattractant that signals via prostaglandin D2 receptor 2 Early-Life Home Environment and Risk of (DP2) on type 2 effector cells to promote asthma patho- Asthma Among Inner-city Children genesis. The purpose of this study is to understand the role O’Connor G, Lynch S, Bloomberg G, et al. J Allergy Clin of PGD2 during RSV bronchiolitis and investigate whether Immunol. 2018;141(4):1468–1475 DP2 antagonists or prostaglandin D2 receptor 1 (DP1) PURPOSE OF THE STUDY. The authors of this study aim to agonists are a useful treatment against viral bronchiolitis identify environmental risk factors in early life that are and a primary preventive against asthma development. correlated with asthma at age 7 years in high-risk, inner- STUDY POPULATION. The study included infants hospitalized city children. with RSV bronchiolitis and healthy subjects from the surgical STUDY POPULATION. Researchers in the Urban Environment ward without bronchiolitis or respiratory complications. and Childhood Asthma birth cohort study recruited METHODS. The authors collected nasopharyngeal samples pregnant woman aged $18 years in inner-city Baltimore, from infants with RSV bronchiolitis and healthy subjects Maryland; Boston, Massachusetts; New York, New York; and measured the PGD2 production in both groups. In and St Louis, Missouri, with a parental history of asthma, the study, the authors also used cultured human primary allergic rhinitis, or eczema. airway epithelial cells from healthy pediatric donors and a METHODS. Maternal questionnaires regarding smoking, neonatal mouse model of severe viral bronchiolitis. stress, and depression were collected prenatally and Specific DP1 and DP2 antagonists and agonists were used annually after each infant’s birth. Child health ques- in vivo and in vitro to measure effects on viral load, tionnaires were collected every 3 months through age 7 immunopathology, and phenotypic outcome. years. Annual visits began at age 1 year, and allergen- RESULTS. Nasopharyngeal samples from infants with RSV specific immunoglobulin E and skin prick tests for a bronchiolitis revealed an increased PGD2 production variety of food and aeroallergens were performed at PEDIATRICS Volume 142, Supplement 4, December 2018 S253 Downloaded from www.aappublications.org/news by guest on October 2, 2021 PGD2/DP2 Receptor Activation Promotes Severe Viral Bronchiolitis by Suppressing IFN- λ Production Cheryl A. Steiman and James E. Gern Pediatrics 2018;142;S253 DOI: 10.1542/peds.2018-2420SSS Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/142/Supplement_4/S253 .1 Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml Downloaded from www.aappublications.org/news by guest on October 2, 2021 PGD2/DP2 Receptor Activation Promotes Severe Viral Bronchiolitis by Suppressing IFN- λ Production Cheryl A. Steiman and James E. Gern Pediatrics 2018;142;S253 DOI: 10.1542/peds.2018-2420SSS The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/142/Supplement_4/S253.1 Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397. Downloaded from www.aappublications.org/news by guest on October 2, 2021.
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