PEF: Changes from baseline in morning and evening PEF measurements are shown in Figure 2. During the first four weeks of the treatment phase, PEF increased by 30 L/min in the nedocromil sodium group, whereas there was a slight decrease from baseline (5 L/min) in the placebo group. When the theophylline dose was reduced, there was a marked decrease in PEF in the placebo group while the improvement over baseline PEF was maintained, at a sjightly reduced level, for the nedocromil sodium group. comments
When theophylline therapy was withdrawn, there was a large decrease from baseline in the placebo group (morning, 73 L/min; evening, 41 L/min) compared with a slight decrease in the nedocromil sodium group (16 and 6 L/min, morning and evening, respectively). Between-treatment differences were highly significant (p<0.001) throughout (p<0.01; evening PEF weeks 7 to 8).Inhaled Bronchodilator Usage: During the period when the theophylline dosage was unchanged (Fig 3), there was a significant reduction in day (p<0.001; weeks 1 to 2, 3 to 4) and nighttime (p<0.05; weeks 3 to 4) inhaled bronchodilator use in the nedocromil sodium group (a total day plus night decrease of 1.5 inhalations) compared with the placebo group (increase of 0.5 inhalation). When theophylline intake was reduced, use of inhaled bronchodilator remained lower than baseline for the nedocromil sodium group (1.0 inhalation per 24 h) whereas there was a 50 percent increase in day and a 200 percent increase in nighttime use in the placebo group. When theophylline therapy was withdrawn, there was a slight increase above baseline for the nedocromil sodium group (0.75 inhalation) compared with a total increase of over 4.0 inhalations per day (p<0.01) and night (p<0.001) use for the placebo group.
Opinion of Efficacy: Patient and clinician opinion of treatment efficacy significantly (p<0.001) favored nedocromil sodium over both the first (clinicians; p<0.01) and second four-week treatment periods. Over the first four weeks, 72 percent of the nedocromil sodium-treated patients (13 of 18) compared with 17 percent (3 of 17) of the placebo-treated patients considered their additional treatment to be very or moderately effective. The clinicians considered that 56 percent of the nedocromil sodium-treated patients (n = 10) and 12 percent of the placebo-treated patients (n = 2) had received a very or moderately effective treatment. Over the final four weeks of treatment, when theophylline use was phased out, patient and clinician opinions were very similar. Twelve nedocromil sodium-treated patients (11 in the opinion of the clinicians) were in the very/moderately effective category. Only one patient receiving placebo considered or was adjudged to have received a moderately effective treatment.
|Morning PEF||Evening PEF|
|Nedocromil sodium ■||372.5 ±22.3||430.4 ±21.5|
|Placebo ■||397.9 ± 25.5||435.9 ±26.9|
Downward black and white arrow = theophylline reduction; downward open arrow = theophylline withdrawal; three asterisks = p<0.001; two asterisks = p<0.01. Error bars are standard error of the mean.
Figure 2. Change from baseline (liters/minute) in diary card morning and evening peak expiratory flow rate.
|Nighttime Use||Daytime Use|
|Nedocromil sodium ■||1.23 ± 0.39||3.30 ±0.40|
|Placebo ■||0.49 ±0.19||2.65 ±0.49|
Downward black and white arrow = theophylline reduction; downward open arrow = theophylline withdrawal; three asterisks = p<0.001; two asterisks = p<0.01; one asterisk = p<0.05. Error bars are standard error of the mean.
Ficure 3. Change from baseline (number of inhalations) in diary card day and nighttime inhaled (J2-bronchodilator use.