A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze - 07/06/24

Doi : 10.1016/j.jaci.2024.04.027

W. Gerald Teague, MD ^a,^b,^c,^⁎ , Cameron D. Griffiths, PhD ^d, Kelly Boyd, MD ^e, Stella C. Kellams, BA ^a, Monica Lawrence, MD ^e, Thomas L. Offerle, MD ^e, Peter Heymann, MD, MPH ^a,^c, William Brand, MD ^f, Ariana Greenwell, MD ^f, Jeremy Middleton, MD ^g, Kristin Wavell, BS ^a,^c, Jacqueline Payne, BS ^c, Marthajoy Spano, MS ^b,^e, Elaine Etter, PhD ^e, Brittany Wall, MD ^c, Larry Borish, MD ^b,^e,^h
^a Child Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va
^c Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va
^g Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va
^b Beirne Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Va
^e Division of Asthma, Allergy, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va
^f Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Va
^h Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Va
^d Department of Biomedical Engineering, University of Virginia, Charlottesville, Va

^∗Corresponding author: W. Gerald Teague, MD, Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908.Division of Respiratory MedicineAllergyImmunology, and SleepDepartment of PediatricsUniversity of Virginia School of MedicineCharlottesvilleVA22908

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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.

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Key words : Rhinovirus, recurrent wheeze, severe asthma, bronchoalveolar lavage, BAL granulocyte patterns, type-2 inflammation

Abbreviations used : BAL, CRP, ICS, RSV, RV