Dataset Information

Severe refractory asthma: an update.

ABSTRACT: Asthma is a heterogeneous disease in which adequate asthma control cannot be achieved in a substantial proportion despite currently available treatment possibilities. This subgroup has been defined as "severe refractory" asthma. Over the past years considerable progress has been made regarding a more exact definition of severe refractory asthma. A systematic approach to evaluate the asthma patient has been postulated. Further detailed classification into distinct phenotypes is ongoing to target the right treatment to the right patient. And, new therapeutic targeted treatment options are currently in development to provide possible new targets to improve disease state, symptoms and quality of life. This review will provide an update on the latest advancements with regard to all these domains.

SUBMITTER: Wener RR

PROVIDER: S-EPMC9487365 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Severe refractory asthma: an update.

Wener Reinier R L RR Bel Elisabeth H EH

European respiratory review : an official journal of the European Respiratory Society 20130901 129

Asthma is a heterogeneous disease in which adequate asthma control cannot be achieved in a substantial proportion despite currently available treatment possibilities. This subgroup has been defined as "severe refractory" asthma. Over the past years considerable progress has been made regarding a more exact definition of severe refractory asthma. A systematic approach to evaluate the asthma patient has been postulated. Further detailed classification into distinct phenotypes is ongoing to target ...[more]

PMID: 23997049

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Project description:BackgroundMast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma.MethodsWe conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy.ResultsAmong the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P=0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group.ConclusionsIn patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694 .).

Dataset Information

Severe refractory asthma: an update.

Publications

Severe refractory asthma: an update.

Similar Datasets

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