title: Severe asthma in adults: what are the important questions?
abstract: The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.
authors.affiliation: INSERM U454 and Clinique des Maladies Respiratoires, Montpellier, France. chanez@montp.inserm.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Gary P
authors.initials: GP
authors.lastname: Anderson
authors.forename: Josep M
authors.initials: JM
authors.lastname: Anto
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Bel
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Babro
authors.initials: B
authors.lastname: Dahlen
authors.forename: Sven Erik
authors.initials: SE
authors.lastname: Dahlen
authors.forename: Leo M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Mina
authors.initials: M
authors.lastname: Gaga
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
authors.forename: Bruce
authors.initials: B
authors.lastname: Levy
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000818:Animals; D001249:Asthma / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000276:immunology; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones