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Journal of Investigational Allergology... Jun 2023Bronchial asthma is a chronic inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underlying... (Review)
Review
Bronchial asthma is a chronic inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underlying pathophysiological mechanisms (endotypes). The definition of phenotype/endotype is crucial, given the availability of novel biologic agents for patients who do not respond to conventional therapies. Although patients with type 2 severe asthma benefit significantly from treatment with biologics, nonresponders have been identified. Comorbidities worsen the symptoms of asthma and complicate management of the disease. The assessment and treatment of comorbidities is a crucial step, and appropriate management may improve asthma symptoms and morbidity. Among comorbidities, those with a marked negative impact on control despite appropriate treatment include chronic rhinosinusitis with nasal polyps, obesity, bronchiectasis, and immune deficiency. Although asthma is frequently characterized by increased blood eosinophils that release mediators and cytokines and are involved in inflammation of the airway wall, in patients with very high blood eosinophil levels, we must differentiate between isolated severe eosinophilic asthma and asthma in eosinophilic granulomatosis with polyangiitis. In addition, hypereosinophilia may result from specific biological treatment, as in the case of dupilumab. We outline the clinical features of patients with severe asthma whose disease is complex to manage.
Topics: Humans; Biological Products; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Asthma; Cytokines; Chronic Disease; Pulmonary Eosinophilia
PubMed: 36059229
DOI: 10.18176/jiaci.0856 -
Frontiers in Immunology 2023Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several... (Review)
Review
Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several decades. Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction that is self-resolving or remits with treatment. Around half of asthma patients are "Type-2-high" asthma with overexpression of type 2 inflammatory pathways and elevated type 2 cytokines. When stimulated by allergens, airway epithelial cells secrete IL-25, IL-33, and TSLP to derive a Th2 immune response. First ILC2 followed by Th2 cells produces a series of cytokines such as IL-4, IL-5, and IL-13. T cells control IgE synthesis by secreting IL-4 to allergen-specific B cells. IL-5 promotes eosinophil inflammation, while IL-13 and IL-4 are involved in goblet cell metaplasia and bronchial hyperresponsiveness. Currently, "Type-2 low" asthma is defined as asthma with low levels of T2 biomarkers due to the lack of reliable biomarkers, which is associated with other Th cells. Th1 and Th17 are capable of producing cytokines that recruit neutrophils, such as IFN-γ and IL-17, to participate in the development of "Type-2-low" asthma. Precision medicine targeting Th cells and related cytokines is essential in the management of asthma aiming at the more appropriate patient selection and better treatment response. In this review, we sort out the pathogenesis of Th cells in asthma and summarize the therapeutic approaches involved as well as potential research directions.
Topics: Humans; Cytokines; Immunity, Innate; Interleukin-13; Interleukin-4; Interleukin-5; Asthma; Inflammation; Allergens; Th17 Cells
PubMed: 37377958
DOI: 10.3389/fimmu.2023.1149203