The geometric mean values for the PD20 and DRS are given in Table 2, together with the values for FEVj immediately measured before challenge on each study day. Individual data are shown in Figures 1 and 2.
The acute administration of a single dose of sodium cromoglycate significantly reduced the sensitivity and reactivity to 4.5 percent saline aerosol in this group of patients with asthma. The magnitude of the reduction in sensitivity (PD20) and reactivity (DRS) after a single dose of sodium cromoglycate, 8-fold and 12.3-fold, respectively, was similar to that observed after 24 to 56 days of treatment with budesonide when there was a reduction in PD20 and DRS from control of 6-fold and 14-fold, respectively. There was a significant relationship (r = 0.88, p < 0.01) between the fold change in PD20 after a single dose of sodium cromoglycate (visit 1) and after 24 to 56 days of treatment with budesonide (visit 3). A further reduction in sensitivity (16-fold) and reactivity (42-fold) to 4.5 percent saline aerosol compared with control was observed when sodium cromoglycate was given during treatment with aerosol corticosteroids. The sensitivity and reactivity in the ten subjects studied after 11 weeks or more of treatment was unchanged compared with their first visit after the commencement of budesonide.
While all patients had a PD20 recorded on the control day (range 0.47 to 16.4 ml), 5 of the 11 patients had less than a 20 percent fall in FEVl after a single dose of sodium cromoglycate. After 36 ± 9 days of treatment with budesonide, 4 patients had less than a 6.1 percent fall, but 7 of the 11 patients remained responsive to 4.5 percent saline aerosol, although sensitivity was reduced. When the challenge was repeated after a single acute dose of sodium cromoglycate, five of these seven patients had no PD20 recorded, and in four the fall in FEVj was less than 6.1 percent. In the remaining two there was a 20 percent fall in FEVj after challenge with saline aerosol but the PD20 values had increased 8-fold in one patient from 1.7 to 13.6 ml and 7-fold in the other from 1.6 to 11.0 ml. The values observed for PD20 and DRS were significantly different (p < 0.018, p < 0.037, respectively) when the values for these seven patients were compared with visits 3 (budesonide) and 4 (budesonide and sodium cromoglycate). Four of these seven patients remained responsive to 4.5 percent saline aerosol even after 11 or more weeks of treatment with budesonide (Fig 1).
Nine patients in this study had values for FEV, greater than 78 percent predicted on the control day. While four individuals had big changes in FEV, (up to 33 percent predicted) after treatment with steroids, the values for FEV, for the group were not significantly different on the five test days. Changes in PD20 were not related simply to improvement in FEV, for the group. There was no significant relationship (r = -0.4) between the ratio of FEV, percent predicted after budesonide treatment visit 3 to FEV, percent predicted on the control day visit 1 and the ratio of the PD20 visit 3 to PD20 visit 1. For some patients, however, the FEV, and PD20 improved at the same time.
Table 2 — Mean ± SD for FEVJ Measured Before Challenge
|Control||SCG||Budesonide, 3-8 wk||SCG + Budesonide, 3-8 wk||Budesonide >11 wk|
Figure 1. The FEV, expressed as a % pred, the DRS and dose of 4.5% saline aerosol required to induce a 20% fall in FEV, in the 11 subjects on the five test days (control: SCG = sodium cromoglycate, budes = budesonide 1,000 Hg/d).
Figure 2. Relationship between the fall in FEVp expressed as a percentage of the prechallenge value (%FalI), and the cumulative dose of 4.5% saline aerosol delivered to the inspiratory port of the two-wav valve.