Search

Hyperosmolar aerosols are used to assess airway responsiveness in subjects with asthma. Using a 10% NaCl aerosol, we investigated airway responsiveness in 23 cystic fibrosis (CF) subjects (12 females, 11 males; 19.1 +/- 3.3 years) who had asthma-like symptoms. The pre-challenge predicted forced expiratory volume in 1 second (FEV1) was 74.7 +/- 21.5. The aerosol was generated by a MistO2gen 143A ultrasonic nebulizer and inhaled for 0.5, 1, 2, 4, 8, 8, and 8 minutes or part thereof. Spirometry was performed before and 1 minute after each inhalation period. The challenge was stopped when a > or = 20% fall from the baseline FEV1 was recorded, after the last inhalation period, or when requested by the subject. We recorded different responses to 10% NaCl among subjects. In 7, the FEV1 fell progressively throughout the challenge in a manner similar to asthmatics. By contrast, in 15 subjects the FEV1 was higher at the completion of challenge compared to during challenge, i.e., the fall in FEV1 was transient. In 7 of these subjects, the final FEV1 at the end of the challenge was higher than the pre-challenge FEV1. We conclude that inhaled 10% hyperosmolar saline causes either progressive and sustained or transient airway narrowing during challenge in the majority of CF subjects. The cause of the transient airway narrowing requires further investigation.

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 FEV1 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 micrograms/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 FEV1 (PD20). Reactivity was measured as the dose-response slope by taking the percent fall in FEV1 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.

Asthmatic subjects were challenged with aerosols of hyper- and hypotonic saline 15 min (Group A) and 90 min (Group B) after inhaling clemastine. Measurements were made of forced expiratory volume in one second (FEV1) before and after medication and after challenge. When the FEV1 values (% predicted) were compared on the active and placebo days they were higher 15 min after clemastine (p less than 0.05) for both challenges and higher 90 min after clemastine inhalation (p less than 0.05) for the hypertonic challenge. The % fall in FEV1 was compared after the same concentration of saline aerosol had been given on both active and placebo days. In Group A the % fall in FEV1 on the clemastine day was reduced after challenge with hypertonic (p less than 0.02) and hypotonic (p less than 0.03) aerosol. In Group B there was a reduction in the % fall in FEV1 on the clemastine day only after hypertonic challenge (p less than 0.04). The protective effect afforded by clemastine was unrelated to change in baseline lung function. We conclude that histamine is an important mediator of the airway response to non-isotonic aerosols and suggest that the aerosol route of administration may be useful for delivering antihistamines.