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This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10–15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2high asthma (N = 4) compared to T2low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies. [ABSTRACT FROM AUTHOR]

Introduction: Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) is linked to childhood asthma development. Despite a growing understanding of risk factors for developing post‐bronchiolitis asthma, protective factors remain unclear. In this study, we aimed to investigate whether exposure to residential greenness between birth and bronchiolitis hospitalization is associated with asthma and atopic asthma development by age 6 years. Methods: We analyzed a US severe bronchiolitis cohort from hospitalization to age 6 years, investigating how the normalized difference vegetation index (NDVI) and chlorophyll index green (CI green), measured in small (100 m) and large (500 m) radiuses around homes, relate to asthma and atopic asthma by age 6 years. We also explored whether maternal antibiotic use, daycare attendance, and respiratory virus type during hospitalization act as effect modifiers. Results: The study cohort included 861 infants, with 239 (28%) developing asthma by age 6 years—152 atopic, 17 nonatopic, and 70 unclassified. Early life residential exposure to high NDVI and CI green levels was associated with lower odds of asthma (ORAdj for NDVI within a 100 m radius, 0.18; 95% CI, 0.05–0.78; and ORAdj for CI green levels within a 100 m radius, 0.53; 95% CI, 0.31–0.90). Associations also were significant for the development of atopic asthma (ORAdj 0.16; 95% CI, 0.03–0.96; and ORAdj 0.46; 95% CI, 0.25–0.92; respectively). Results were similar for the 500 m radius exposures. No effect modification was noted. Conclusion: In a U.S. bronchiolitis cohort, exposure to residential greenness between birth and bronchiolitis hospitalization is linked to lower asthma and atopic asthma risk by age 6 years. [ABSTRACT FROM AUTHOR]

Background: Infants hospitalized for bronchiolitis are at high risk for developing recurrent wheeze in childhood. The role of airway lipids in the link between these two conditions remains unclear. This study aimed to identify the association between airway lipids in infants hospitalized for bronchiolitis and the development of recurrent wheeze, with a focus on immunoglobulin E (IgE) sensitization. Methods: In a multicenter prospective cohort study of 919 infants (age <1 year) hospitalized for bronchiolitis, we performed lipidomic profiling of nasopharyngeal airway specimens collected at hospitalization. We first identified lipid modules composed of highly correlated lipids by performing weighted correlation network analysis. We then examined the longitudinal association of those lipid modules with the rate of recurrent wheeze by age 3 years after discharge from hospitalization for bronchiolitis. We also examined the associations of lipid modules with IgE non‐sensitized (i.e., neither sensitized at admission nor at age 3 years) and IgE‐sensitized (i.e., sensitized at admission and/or at age 3 years) recurrent wheeze by age 3 years, respectively. Results: Our analysis identified 15 distinct lipid modules in the nasopharyngeal airway lipidome data. Overall, lipid modules composed of triacylglycerols (hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.26–2.51, FDR < 0.01) and sphingolipids (HR 1.74, 95% CI 1.25–2.44, FDR <0.01) had the strongest associations with recurrent wheeze development. Stratification by IgE sensitization revealed differential associations. For example, the module composed of triacylglycerols was significantly associated with IgE non‐sensitized recurrent wheeze, whereas the module composed of sphingolipids was significantly associated with IgE‐sensitized recurrent wheeze (both FDR <0.05). Conclusion: Distinct nasopharyngeal airway lipid modules are associated with recurrent wheeze development following severe bronchiolitis, with different patterns based on IgE sensitization status. [ABSTRACT FROM AUTHOR]

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45–7.98, p =.38), 2.87 (95% CI: 1.38–5.95, p <.05), and 3.38 (95% CI: 1.72–6.64, p <.05) for cutoff values in the <300, 300–449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association. [ABSTRACT FROM AUTHOR]

Author(s): Marie Toussaint [1, 2]; David J Jackson [1, 2, 3, 4]; Dawid Swieboda [1, 2]; Anabel Guedán [1, 2]; Theodora-Dorita Tsourouktsoglou [5]; Yee Man Ching [1, 2]; Coraline Radermecker [...], Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or by degrading NETs with DNase protects mice from type-2 immunopathology. Furthermore, the injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type-2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations.