Hordvik and coworkers found that bronchodilator responsiveness in CF decreases during acute pulmonary exacerbations. Our patients were in stable condition, with no history of admission to hospital for the previous 3 months, and no pulmonary exacerbation up to 4 weeks prior to the study. Fattishal studied the response to bronchodilators in CF patients in a longitudinal and cross-sectional manner by using pulmonary function data over an 8-year period. A proportion of patients (40 percent) presented a positive response to inhaled adrenergic agents; however, there was a lack of consistent response. Zinman and coworkers found a mean of 8 percent increase in FEVX after isoeth-arine (p2-sympathomimetic) in a group of 12 CF patients, but also found an increase in the degree of non-homogeneous lung emptying after the inhalation of the drug. Van Haren et al recently found, in a group of 20 adult CF patients, that both inhalation of terbu-taline and IB caused dose-related bronchodilation.
Avital and coworkers found an increase in PC20 without a change in baseline FEVX following S and an even greater change after IB, suggesting that the adrenergic agent altered the smooth muscle contractile mechanism and that muscarinic pathway appeared to be important in the pathogenesis of expiratory airflow obstruction in a proportion of CF patients. Furthermore, we have shown a positive relationship between airways hyperreactivity and the changes in lung function after bronchodilator; we found that a change in FEV! >6 percent from baseline after inhaled S was suggestive of nonspecific airways hyperreactivity with a high specificity if tested within a 2-week period. The adrenergic bronchodilator response in normal subjects has been published previously. Dales and coworkers found that the average increase in FEVi in normal subjects (children and adults) was only 2.1 percent. These results are similar to the data presented by Ekwo et al, who found an increase of 1.3±0.4 percent (mean ± SE) after isoproterenol in 182 healthy white children from 6 to 12 years of age.
Do high doses of (3-adrenergic and anticholinergic drugs have an additive effect in CF patients? To our knowledge, there are no previously published data in this population. In adult patients with chronic obstructive pulmonary disease, the effectiveness of both S and IB have been demonstrated.