Analysis of variance was used to compare quantitative variables at baseline and after the different treatments for each subject and to compare the percentage of change after each drug (S and IB). Paired t tests (two-tailed) were applied to compare the values after the additive treatment doses. A p value ^0.05 was considered to be significant.
Baseline characteristics of the patients as well as baseline pulmonary function measurements (PFTs), oxygen saturation, and heart rate are presented in Table 1. All patients had previous evidence of a positive response to inhaled S on at least 1 occasion in the previous 2 years. There was no difference in the average baseline PFT between the 2 days of the protocol.
There was a significant improvement in FEV\ and a decrease in Raw after inhalation of high doses of S during sequence A or IB during sequence В compared with baseline (Table 2). The improvement in midex-piratory flows was not statistically significant. Lung volume measurements (RV and FRC) were decreased by 10 and 5 percent vs 12 and 7 percent after S200 + S400 in sequence A compared to after IBW, in sequence B. However, these decreases were not significantly different from baseline. There was no significant further improvement in expiratory flows, lung volumes, and Raw when IB was given after high doses of S (sequence A) or when S was given after a high dose of IB (sequence B) (Table 2). The PFTs at 4 and 8 h from baseline showed a significant increase in FEVt (p<0.05) and a decrease in Raw (p<0.01) compared with baseline with either sequence. Expiratory flows and lung volume measurements were not significantly different from baseline. canadian family pharmacy online
Several authors have demonstrated that patients with cystic fibrosis (CF) present with an increased airways responsiveness. The use of bronchodilator therapy in patients with CF still remains controversial and there is no consensus as to the efficacy of inhaled adrenergic medication in the treatment of the disease. The reason for the controversy is that previous studies have shown that inhaled p-adrenergic agents may have variable effects on expiratory airflows in CF, ranging from an increase, no effect, or even a decrease in flows. Furthermore, studies of inhaled anticholinergic bronchodilators in patients with CF are limited and even more controversial. It is known that because of the permanent airways inflammation and structural damage to the bronchial tree that are inherent and present in CF patients, airflow obstruction is predominantly irreversible, and the maximal possible improvement is slight. Recently, we demonstrated that the combination of a 0-adrenergic and an anticholinergic agent, compared with each drug alone, provides a greater improvement in FEVi and a more significant decrease in lung volumes and airway resistance (Raw) in young CF patients who have been shown previously to respond to inhaled salbutamol (S). From this study, we concluded that muscarinic pathways appeared to be important in the pathogenesis of expiratory airflow obstruction in CF patients with previous bronchodilator response. However, because we used single usual doses of bronchodilators (S and ipratropium bromide [IB]) by nebulization, we were not able to ascertain whether this additive effect could have been obtained by giving an extra dose of the same bronchodilator and whether by using larger doses of drug the additive effect would still have been present.
To our knowledge, the use of high doses of bronchodilator agents has not been tested in CF patients. Therefore, in the present study, we tested the hypothesis that in CF patients with known positive response to bronchodilators, an additive effect could be obtained by using large doses of S or IB.