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Asthma is a chronic respiratory disease characterized by bronchial hyperreactivity. There are several endotypes of which allergic asthma is the most common. Severe eosinophilic asthma is prevalent in approximately 5% of asthmatics and its phenotype overlaps with allergic asthma and type 2 inflammation. Patients with refractiveness to corticosteroids underline the difficulty in controlling persistent inflammation in severe eosinophilic asthma. The focus of biological therapies is geared towards the understanding of the intricate interplay of the cytokines that drive the eosinophil’s ability to induce chronic inflammation with airway obstruction. This chapter takes the reader down a historical journey of initial studies that were performed using mouse helper T cell clones for reconstitution experiments to unravel the mechanism of the role T helper 2 cytokines play in allergic asthma. We then reviewed the classic in vivo experiments that demonstrated how antibodies to IL5 can down regulate eosinophils in the blood and their progenitors in the bone marrow of mice. We also delve into the complex interaction of the alarmins on the cytokines triggers of allergic inflammation with elevated eosinophils. Finally, we review the clinical literature on the beneficial effects of humanized monoclonal antibodies in use for treatment of patients suffering from severe eosinophilic asthma.
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Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma
Abstract Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical classic microbiome M. nonliquefaciens inflammation IFN-intermediate , B) clinical atopic microbiome S. pneumoniae / M. catarrhalis inflammation IFN-high , C) clinical severe microbiome mixed inflammation IFN-low , and D) clinical non-atopic microbiome M.catarrhalis inflammation IL-6 . Particularly, compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.
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- Award ID(s):
- 2028280
- PAR ID:
- 10332930
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 12
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41467-021-23859-6
