Genes and pathways regulating decline in lung function and airway remodeling in asthma

Gyu Young Hur, David H. Broide

    Research output: Contribution to journalReview articlepeer-review

    24 Citations (Scopus)

    Abstract

    Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.

    Original languageEnglish
    Pages (from-to)604-621
    Number of pages18
    JournalAllergy, Asthma and Immunology Research
    Volume11
    Issue number5
    DOIs
    Publication statusPublished - 2019 Sep 1

    Keywords

    • Airway remodeling
    • Gene polymorphisms
    • Lung function tests

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Pulmonary and Respiratory Medicine

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