Airway smooth muscle (ASM) displays a hyperresponsive phenotype at young age and becomes less responsive in adulthood. We hypothesized that allergic sensitization, which causes ASM hyperresponsiveness and typically occurs early in life, prevents the ontogenetic loss of the ASM hyperresponsive phenotype. We therefore studied whether neonatal allergic sensitization, not followed by later allergen challenges, alters the ontogenesis of ASM properties. We neonatally sensitized guinea pigs to ovalbumin and studied them at 1 week, 3 weeks, and 3 months (adult). A Schultz-Dale response in isolated tracheal rings confirmed sensitization. The occurrence of inflammation was evaluated in the blood and in the submucosa of large airways. We assessed ASM function in tracheal strips as ability to produce force and shortening. ASM content of vimentin was also studied. A Schultz-Dale response was observed in all 3-week or older sensitized animals. A mild inflammatory process was characterized by eosinophilia in the blood and in the airway submucosa. Early life sensitization had no effect on ASM force generation, but prevented the ontogenetic decline of shortening velocity and the increase in resistance to shortening. Vimentin increased with age in control but not in sensitized animals. Allergic sensitization at birth without subsequent allergen exposures is sufficient to prevent normal ASM ontogenesis, inducing persistence to adulthood of an ASM hyperresponsive phenotype.
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http://dx.doi.org/10.14814/phy2.12241 | DOI Listing |
Genome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype.
View Article and Find Full Text PDFClin Rev Allergy Immunol
January 2025
Postgraduate Program in Biochemistry, Federal University of Espírito Santo (UFES), Vitória, Espírito Santo, Brazil.
Asthma is a complex disease with varied clinical manifestations resulting from the interaction between environmental and genetic factors. While chronic airway inflammation and hyperresponsiveness are central features, the etiology of asthma is multifaceted, leading to a diversity of phenotypes and endotypes. Although most research into the genetics of asthma focused on the analysis of single nucleotide polymorphisms (SNPs), studies highlight the importance of structural variations, such as copy number variations (CNVs), in the inheritance of complex characteristics, but their role has not yet been fully elucidated in asthma.
View Article and Find Full Text PDFEBioMedicine
December 2024
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:
Background: There are important inter-relationships between miRNAs and metabolites: alterations in miRNA expression can be induced by various metabolic stimuli, and miRNAs play a regulatory role in numerous cellular processes, impacting metabolism. While both specific miRNAs and metabolites have been identified for their role in childhood asthma, there has been no global assessment of the combined effect of miRNAs and the metabolome in childhood asthma.
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J Pers Med
December 2024
Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK.
While the phenotypic diversity of childhood wheezing is well described, the subsequent life course of such phenotypes and their adult outcomes remain poorly understood. We hypothesized that different childhood wheezing phenotypes have varying longitudinal outcomes at age 26. We sought to identify factors associated with wheezing persistence, clinical remission, and new onset in adulthood.
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