title: Addressing corticosteroid insensitivity in adults with asthma.
abstract: Corticosteroids are the most effective treatment for asthma, but the therapeutic response varies markedly between individuals, with up to one third of patients showing evidence of insensitivity to corticosteroids. This article summarizes information on genetic, environmental and asthma-related factors as well as demographic and pharmacokinetic variables associated with corticosteroid insensitivity in asthma. Molecular mechanisms proposed to explain corticosteroid insensitivity are reviewed including alterations in glucocorticoid receptor subtype, binding and nuclear translocation, increased proinflammatory transcription factors and defective histone acetylation. Current therapies and future interventions that may restore corticosteroid sensitivity in asthma are discussed, including small molecule drugs and biological agents. In the future, biomarkers may be used in the clinic to predict corticosteroid sensitivity in patients with poorly controlled asthma.
authors.affiliation: a Institute of Infection, Immunity & Inflammation , University of Glasgow , Glasgow , UK.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000367:Age Factors; D056151:Airway Remodeling; D000485:Allergens / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D015992:Body Mass Index; D004351:Drug Resistance; D004731:Endotoxins / Q000009:adverse effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D055118:Medication Adherence; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012141:Respiratory Tract Infections / Q000150:complications; D012907:Smoking / Q000009:adverse effects; D014808:Vitamin D Deficiency / Q000150:complications
chemical_list: D000485:Allergens; D018927:Anti-Asthmatic Agents; D004731:Endotoxins; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid
keywords: Adherence; asthma; biological agents; biomarkers; cigarette smoking; corticosteroid insensitivity; corticosteroid resistance; corticosteroids; small molecule drugs