ACUTE EFFECT OF SODIUM CROMOGLYCATE ON AIRWAY NARROWING INDUCED BY 4.5-PERCENT SALINE AEROSOL - OUTCOME BEFORE AND DURING TREATMENT WITH AEROSOL CORTICOSTEROIDS IN PATIENTS WITH ASTHMA

Study objective: To investigate the acute effect of sodium cromoglycate on airway responses to 4.5 percent saline aerosol challenge, before and during treatment with inhaled budesonide-a corticosteroid. Design: Open study, with a total of five visits, two before budesonide treatment, and three follow-up visits, two between 5 and 6 weeks and one at more than 11 weeks. Setting: Referral-based Respiratory Investigation Unit at Royal Prince Alfred Hospital, a major Sydney-based teaching hospital. Patients: Eleven patients with asthma (ten atopic), with a PD20 FEV(1) to 4.5 percent saline aerosol challenge and about to commence inhaled budesonide for treatment of their asthma. Interventions: The 40 mg of sodium cromoglycate was inhaled before a 4.5 percent NaCl challenge, both before and after regular (36 +/- 9 d) treatment with budesonide (1,000 mu g/d). The final challenge was repeated in ten subjects after 11 weeks or more of treatment with budesonide. Measurements and results: Sensitivity to 4.5 percent saline aerosol was measured as the dose of saline aerosol required to induce a 20 percent fall in FEV(1) (PD20). Reactivity was measured as the dose-re-sponse slope by taking the percent fall in FEV(1) and dividing it by the dose required to induce the fall. On the control day the geometric mean PD20 (95 percent CI) for 4.5 percent saline aerosol was 2.8 (1.4 to 5.4) and the dose response slope (DRS) 5.6 (2.9 -11.1). An acute dose of sodium cromoglycate reduced sensitivity (PD20) by 8-fold and reactivity (DRS) 12.3-fold. This effect was similar in magnitude to that measured after regular treatment with budesonide alone. When sodium cromoglycate was given during treatment with budesonide, the PD20 was reduced 16-fold and the DRS 42-fold, and this was greater than the reduction with budesonide taken for 3 months (p < 0.03, p < 0.05 respectively). Conclusions: Sodium cromoglycate inhibits responses to 4.5 percent saline aerosol and has additional benefits to those conferred by aerosol steroids. The mechanism for responsiveness to saline aerosol and efficacy of these drugs may relate to alteration in chloride ion channel regulation by inflammation.