1. A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze.
- Author
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Teague WG, Griffiths CD, Boyd K, Kellams SC, Lawrence M, Offerle TL, Heymann P, Brand W, Greenwell A, Middleton J, Wavell K, Payne J, Spano M, Etter E, Wall B, and Borish L
- Subjects
- Humans, Male, Female, Child, Child, Preschool, Bronchoalveolar Lavage Fluid virology, Bronchoalveolar Lavage Fluid immunology, Biomarkers, Syndrome, Recurrence, Infant, Granulocytes immunology, Adolescent, Respiratory Sounds, Rhinovirus immunology, Picornaviridae Infections immunology, Picornaviridae Infections complications
- Abstract
Background: Rhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important., Objectives: This study sought to examine the associations of RV on bronchoalveolar lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n = 616)., Methods: Children underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers., Results: Despite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children. Compared to children with no BAL pathogens (n = 341), those with RV alone (n = 127) had greater (P < .05) isolated neutrophilia (43% vs 16%), mixed eosinophils and neutrophils (26% vs 11%), and less pauci-granulocytic (27% vs 61%) BAL. Children with RV alone furthermore had biomarkers of active infection with higher total blood neutrophils and serum C-reactive protein, but no differences in blood eosinophils or total IgE. With advancing age, the log odds of BAL RV alone were lower, 0.82 (5th-95th percentile CI: 0.76-0.88; P < .001), but higher, 1.58 (5th-95th percentile CI: 1.01-2.51; P = .04), with high-dose daily corticosteroid treatment., Conclusions: Children with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation. The syndrome is less prevalent by school age and is not informed by markers of type-2 inflammation. The investigators speculate that dysregulated mucosal innate antiviral immunity is a responsible mechanism., Competing Interests: Disclosure Statement W.G. Teague has received funding from the UVA Ivy Foundation Distinguished Chair, National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases grants 1RO1AI 176171 and 5R21AI151496, NIH/National Heart, Lung, and Blood Institute grant 5UG1HL139126, NIH/integrated Translational Health Research Institute of Virginia Clinical and Translational Science Award UL1TR003015, and NIH/Small Business Innovation Research grant RFA-MD-22-004. L. Borish has received funding from the NIH/National Institute of Allergy and Infectious Diseases (grants UO1 AI123337 and R56 AI 158519). C.D. Griffiths has received funding from the Human Frontier Science Program Fellowship LT000469/2021-L. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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