Eosinophil activation status and corticosteroid responsiveness in severe asthma |
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Authors: | Bossé M Audette M Laflamme G Ferland C Boulet L P Laviolette M |
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Institution: | Unité de Recherche, Centre de Pneumologie de l'H?pital Laval, Centre Hospitalier Universitaire de Québec, Université Laval, Ste-Foy, Québec, Canada. |
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Abstract: | BACKGROUND: Since eosinophils are implicated in asthma pathogenesis, we investigated whether these cells were activated in severe asthma. METHODS: Twenty-six asthmatics with different clinical responses to oral corticosteroid (CS), i.e. sensitive change in forced expiratory volume in 1 s (DeltaFEV(1)) >/= 25% after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant (DeltaFEV(1) = 15%, n = 9) and dependent (>/= 20 mg oral prednisone daily for acceptable asthma control, n = 10), were studied. RESULTS: Calcium ionophore-induced leukotriene (LT) C(4) release of purified blood eosinophils was similar in the three groups. Cell incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced ionophore-induced LTC(4) release, and this effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7-fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two groups of subjects (p = 0.02) and decreased GM-CSF-enhanced LTC(4) release in CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily dose of oral CS (35 +/- 8 mg), blood counts of eosinophils from CS-dependent subjects were higher (p = 0.03) and GM-CSF enhancement of LTC(4) release was greater (2.8-fold) than in CS-sensitive (2. 1-fold) and CS-resistant (1.7-fold) subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM-CSF enhancement of LTC(4) release by eosinophils of CS-sensitive asthmatics (p = 0.001). CONCLUSIONS: Eosinophils from CS-dependent asthmatics have an impaired response to CS, whereas serum from CS-resistant subjects contains an inhibitor of eosinophil response to GM-CSF. |
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