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Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing
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2006 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 5, 944-50 p.Article in journal (Refereed) Published
Abstract [en]

Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.

Place, publisher, year, edition, pages
2006. Vol. 27, no 5, 944-50 p.
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Medical and Health Sciences
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URN: urn:nbn:se:shh:diva-60DOI: 10.1183/09031936.06.00078205PubMedID: 16707393OAI: oai:DiVA.org:shh-60DiVA: diva2:301316
Available from: 2010-03-03 Created: 2010-02-23 Last updated: 2014-10-15Bibliographically approved

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CiteExportLink to record
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