Eformoterol fumarate & sodium cromoglycate (SCG) inhibit the airway response to inhaled mannitol in asthmatics by mast cell inhibition

Mannitol is an osmotic stimulus that causes mast cell activation (Brannan et al. ERJ 2003; 22:491-96). We wanted to know if eformoterol & SCG inhibit the airway response to inhaled mannitol by preventing release of mast cell mediators. Mannitol was administered in progressively increasing doses to 14 asthmatics (6M,8F 19-37yr, FEV 1 >70% predicted). Following a control challenge a reduction of 25% in FEV 1 or greater was achieved. The dose to cause this response was administered again after eformoterol (24μg), SCG (40mg) or placebo (P), all given by inhalation 15min before the mannitol challenge in a double-blind cross over design. Urine was collected 60min before and for 90min after challenge. The mast cell marker used was the prostaglandin (PG) D 2 metabolite 9α,11β-PGF 2 and this was measured by enzyme immunoassay. Results are presented as mean ± SD. In the presence of placebo, the %fall in FEV 1 after mannitol was 31.8 ± 10.2% in response to a cumulative dose of 252 ± 213 mg. This response was associated with a significant increase in urinary 9α,11β PGF 2, (ng/mmol creatinine) compared to baseline (75.8 ± 38.0 vs 97.5 ± 41.6, p=0.004). Eformoterol afforded 95% protection (1.9 ± 2.7 %fall FEV 1) and SCG afforded 63% protection (11.4 ± 6.3 %fall FEV1) against the response to mannitol. This inhibition of the airway response was associated with unchanged levels in urinary 9α,11β PGF 2 for either eformoterol (70.1 ± 29.6 vs 66.8 ± 19.4, p=0.47) or SCG (72.1 ± 25.1 vs 71.4 ± 29.5, p=0.89). Eformoterol and SCG are effective at inhibiting the airway response to mannitol, likely by inhibition of mast cell mediator release.