TY - JOUR T1 - Inhibition of mast cell PGD<sub>2</sub> release protects against mannitol-induced airway narrowing JF - European Respiratory Journal JO - Eur Respir J SP - 944 LP - 950 DO - 10.1183/09031936.06.00078205 VL - 27 IS - 5 AU - J. D. Brannan AU - M. Gulliksson AU - S. D. Anderson AU - N. Chew AU - J. P. Seale AU - M. Kumlin Y1 - 2006/05/01 UR - http://erj.ersjournals.com/content/27/5/944.abstract N2 - Mannitol inhalation increases urinary excretion of 9α,11β-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that β2-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 ≥25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 µg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9α,11β-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 9α,11β-prostaglandin F2 concentration from 61 to 92 ng·mmol creatinine−1, but no significant increase in 9α,11β-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. ER -