Child Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Beirne Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, Va; Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.
Department of Biomedical Engineering, University of Virginia, Charlottesville, Va.
J Allergy Clin Immunol. 2024 Sep;154(3):571-579.e6. doi: 10.1016/j.jaci.2024.04.027. Epub 2024 May 16.
Rhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important.
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).
Children underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers.
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.
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.
鼻病毒（RV）感染会引发儿童喘息发作。因此，了解喘息儿童肺部对 RV 的炎症反应非常重要。
本研究旨在探讨治疗后复发喘息儿童（n=616）中 RV 对支气管肺泡灌洗液（BAL）中粒细胞模式和炎症标志物与年龄的关系。
对儿童进行 BAL 检查，以检测病毒核酸序列、细菌培养、粒细胞计数以及为一般和 2 型炎症标志物采集血样。
尽管没有感冒症状，但 RV 是最常见的病原体（30%），当存在时，75%的儿童 BAL 中存在粒细胞增多。与无 BAL 病原体的儿童（n=341）相比，仅 RV 感染的儿童（n=127）的单纯中性粒细胞增多（43% vs. 16%）、混合嗜酸性粒细胞和中性粒细胞增多（26% vs. 11%）和少粒细胞增多（27% vs. 61%）更为显著（P<0.05）。仅 RV 感染的儿童还有更高的全身感染生物标志物，包括总血中性粒细胞和血清 C 反应蛋白，但血嗜酸性粒细胞和总 IgE 无差异。随着年龄的增长，单独 RV 感染的 BAL 发生的可能性降低，0.82（5 至 95 百分位 CI：0.76-0.88；P<0.001），但在高剂量每日皮质激素治疗时，BAL 中单独 RV 感染的可能性更高，1.58（5 至 95 百分位 CI：1.01-2.51；P=0.04）。
严重反复发作性喘息的儿童常有（22%）肺部 RV 感染的沉默综合征，表现为粒细胞性细支气管炎和全身性炎症标志物升高。该综合征在学龄期时不常见，也不受 2 型炎症标志物的影响。研究人员推测，黏膜固有抗病毒免疫失调是一个负责的机制。
