Acute Effect of Sodium Cromoglycate on Airway Narrowing Induced by 4.5 Percent Saline Aerosol: Conclusion

Sensitivity to 4.5 percent saline aerosol has been shown to relate to mast cell number and corticosteroids reduce mast cell numbers, so it is not surprising that corticosteroids reduce sensitivity to 4.5 percent saline aerosol. What is more surprising is that only 1 of 11 patients had a PD20 greater after 24 to 56 days of treatment with budesonide than they did after a single treatment with sodium cromoglycate. Furthermore, in the seven patients who remained responsive to 4.5 percent saline aerosol after treatment with budesonide, sodium cromoglycate gave significant additional protection. The magnitude of the reduction in sensitivity was similar after a single acute dose of sodium cromoglycate as it was after 24 to 54 days of treatment with budesonide, 1,000 |ig per day, and the responses were closely related. Measuring the response to 4.5 percent saline aerosol after the acute administration of sodium cromoglycate may provide a useful guide to demonstrate the capacity to which airway hyperresponsiveness may be reduced. The duration of the protective action of sodium cromoglycate from 4.5 percent saline aerosol is not known. On the basis of studies using exercise as the stimulus, it is unlikely to be more than 2 h.

The dose of sodium cromoglycate was probably higher than that normally delivered by jet nebulizer, as 4 ml (40 mg) rather than 2 ml (20 mg) was used in the ultrasonic nebulizer. We have found the Fisoneb ultrasonic nebulizer to be very effective for delivering drugs to prevent the airway narrowing provoked by hyperosmolarity. The reason we used 40 mg of sodium cromoglycate was to expedite the delivery of 20 mg of the drug over 5 min. For practical purposes, the standard dose of 20 mg could be used and a volume of 2 to 3 ml of saline solution added. In this situation, the nebulization time would need to be longer. The dose would be reduced relative to the dead volume of the nebulizer, which for jet and small ultrasonic nebulizers is usually 1 ml. We would expect that four inhalations of 5 mg cromoglycate from a metered-dose inhaler (Intal Forte) would give the same results as those reported here.
The major aim in treating asthma with corticosteroids is to achieve normal lung function, reduce symptoms, and decrease bronchial responsiveness. It seems from this and other studies that, to reduce symptoms and achieve normal lung function, the dose of corticosteroid needed is less, and the duration for which it is given shorter compared with the dose required to reduce bronchial responsiveness. Patients may be unwilling to comply with a regimen of high dose and long duration of treatment with steroids once they have achieved good lung function and have few symptoms. The side-effects observed at higher doses may not be warranted if bronchial responsiveness to stimuli such as exercise can be acutely inhibited with the addition of sodium cromoglycate. If the bronchial responsiveness to hyperosmolar saline aerosol does reflect the presence of airway inflammation, then the important question is whether the dose of steroid should be increased until a plateau or complete inhibition is achieved. At present, questions relating to exercise tolerance are often used, by physicians, as a guide to efficacy and dose of corticosteroids. We think that a formal bronchial provocation testing using hyperosmolar saline aerosol would provide objective information. While acknowledging the deficiencies of a trial which is not placebo controlled or blinded to the investigator, we think that the techniques described here are useful in assessing the benefits of both chronic and acute treatment for asthma. The challenge and protocol carried out here could be easily carried out in routine lung function laboratories with the facility to measure bronchial responsiveness.

This entry was posted in Airway Narrowing and tagged airway narrowing, corticosteroid, hyperosmolar saline, responsiveness, sodium cromoglycate.