Although the pharmacologic challenges with methacholine and histamine have been used to assess treatment of asthma with steroids, they cannot be used to assess the effects of sodium cromoglycate. While it is common to use exercise to assess the benefits of sodium cromoglycate, challenge with hyperosmolar saline aerosol is superior to exercise testing in that a dose-response curve can be obtained, and it requires little cooperation from the patient. It is also superior to a bronchial provocation testing with histamine because sensitivity to histamine, although reduced, may be expected to remain during treatment with corticosteroids, as histamine will act directly via Hl receptors causing the bronchial smooth muscle to contract. Some investigators have reported that the responsiveness to histamine and methacholine may take years to return to the normal range. Thus, a pharmacologic challenge while useful to assess the potential for the bronchial smooth muscle to contract is not as useful as hyperosmolar saline aerosol for assessing the effects of anti-inflammatory drugs on reducing the amount or availability of endogenous mediators. canadian drug mall
This study was initiated as a result of our findings in a double-blind placebo controlled trial of the inhibitory effect of nebulized nedocromil sodium (Tilade) on responses to 4.5 percent saline aerosol. We noted that six of the eight subjects who had a complete block or who recorded a plateau after saline aerosol in the presence of nedocromil were using beclomethasone on a daily basis. As nedocromil sodium is not marketed in Australia, we wished to investigate if sodium cromoglycate given in the same way, by nebulization, had a similar effect in subjects given budesonide.
This study did not use a placebo controlled doubleblind study as it was carried out during the normal course of laboratory assessment and medical treatment of asthma. We were fortunate in being able to study the subjects before they commenced their treatment with steroids. We were careful not to carry out a challenge if there had been a respiratory tract infection in the last 4 weeks. If the subjects had experienced symptoms of asthma in the previous 24 h, they were asked to reschedule their appointment. This resulted in a variation in the time between visits.
The subjects were required to attend the laboratory on five separate occasions with visits 2 and 3 being separated by about 4 weeks. Some normal variation in the PD20 to hyperosmolar saline aerosol would be expected to occur over this time. We have repeated challenges 1 to 37 days apart and found the PD20 to be within 2 ml. This variation occurred both at low and high values of PD20, but there were both increases and decreases between study days. In this study by contrast, the PD20 continued to increase and the improvement from 2.76 ml to 16.7 ml to 44.1 ml, over time and, in response to budesonide and sodium cromoglycate was 3 to 20 times more than the expected by normal variation.