Sodium Cromoglycate and Eformoterol Attenuate Sensitivity and Reactivity to Inhaled Mannitol in Subjects with Bronchiectasis

Background And Objective: Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis. A reduction in FEV1 has been recorded in some subjects with bronchiectasis after inhaling mannitol. The aim of this study was to investigate if pre-medicating with either sodium cromoglycate (SCG) or eformoterol could inhibit this reduction in FEV1.

Methods: A double-blind, placebo-controlled, randomized cross-over study was conducted. Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo, SCG and eformoterol in nine subjects. Sensitivity to mannitol, expressed as the dose required to induce a 15% fall in FEV1 (PD15), and reactivity to mannitol, expressed as the % fall in FEV1 per mg of mannitol (response-dose ratio, RDR), are reported.

Results: Subjects had an FEV1 of 68 ± 14% predicted, FVC of 97 ± 15% predicted and FEV1 /FVC of 71 ± 8%. They were mildly hypoxemic and the SpO2 was 95 ± 2%.They had a PD15 to mannitol of 235 mg (95% CI: 150-368 mg) and a RDR of 0.057% fall in FEV1 per mg (95% CI: 0.038-0.085). After pre-medication with SCG, PD15 increased (773 mg, P < 0.05) and RDR was reduced (0.013, P < 0.05). Pre-medication with eformoterol also resulted in an increased PD15 (1141 mg, P < 0.01) and a reduced RDR (0.009, P < 0.01). A small but significant decrease in SpO2 from baseline was noted after mannitol in the presence of SCG (P < 0.05).

Conclusions:   Pre-medication with either SCG or eformoterol protects patients with bronchiectasis from developing a significant reduction in FEV1 after inhaling mannitol.