STUDY OBJECTIVE: It has been suggested that the defective cyclic AMP-dependent Cl- secretion and the increased Na+ absorption from airway epithelia in cystic fibrosis (CF) may lead to dehydrated secretions and impaired mucociliary clearance. Beta 2-adrenergic agonists are unable to stimulate the Cl- transport in the airways in CF while being able to do so in normal airways. Thus, we questioned whether the beta 2-adrenergic agonist, terbutaline, would improve mucociliary clearance in patients with CF as it does in healthy subjects. DESIGN: A double-blind, randomized cross-over trial. SETTING: Whole lung and regional mucociliary clearance of a radioaerosol was measured for 3 h by gamma camera. One minute of cough clearance was measured at 3 h. Pulmonary function was measured before and after the gamma camera study. PATIENTS: Ten young patients with CF were studied; three were heterozygous for deletion of the phenylalanine at position 508 (delta F508), and seven were delta F508 homozygous. INTERVENTIONS: Inhalation of 1 mg of terbutaline (4 puffs) and placebo via a metered-dose inhaler by spacer. MEASUREMENTS AND RESULTS: The largest differences in tracheobronchial retention (percent) in the whole lung and regional lung zones were generally observed within 1 h after terbutaline and placebo treatment: whole lung (mean +/- SD), 60 +/- 22 percent and 63 +/- 20 percent; central zone, 41 +/- 19 percent and 50 +/- 25 percent; midzones, 65 +/- 27 percent and 63 +/- 19 percent; and peripheral zones, 77 +/- 28 percent and 72 +/- 28 percent, respectively [p > 0.1]. Whereas none of these differences was statistically significant, subanalyses suggested an improvement in mucociliary clearance by terbutaline in the three delta F508 heterozygous patients but not in the seven delta F508 homozygous patients. One minute of voluntary coughing resulted in clearance of less than 8 percent of the initial radioactivity, with a trend of more peripheral zone clearance after terbutaline compared with placebo. A small significant decrease in airway resistance was detected 3 h after terbutaline. CONCLUSIONS: We conclude that 1 mg of terbutaline did not improve mucociliary clearance significantly in the patients with CF. Also, the effect of terbutaline was much less than demonstrated earlier in healthy subjects. This is consistent with earlier findings of a lack of beta-adrenergic modulation of Cl- transport in CF. Thus, no rehydration of the dry mucus in CF is expected, and a possible beta 2-agonist-induced increase in ciliary beating would have only a minor effect on overall mucociliary clearance.
RCT Entities:
STUDY OBJECTIVE: It has been suggested that the defective cyclic AMP-dependent Cl- secretion and the increased Na+ absorption from airway epithelia in cystic fibrosis (CF) may lead to dehydrated secretions and impaired mucociliary clearance. Beta 2-adrenergic agonists are unable to stimulate the Cl- transport in the airways in CF while being able to do so in normal airways. Thus, we questioned whether the beta 2-adrenergic agonist, terbutaline, would improve mucociliary clearance in patients with CF as it does in healthy subjects. DESIGN: A double-blind, randomized cross-over trial. SETTING: Whole lung and regional mucociliary clearance of a radioaerosol was measured for 3 h by gamma camera. One minute of cough clearance was measured at 3 h. Pulmonary function was measured before and after the gamma camera study. PATIENTS: Ten young patients with CF were studied; three were heterozygous for deletion of the phenylalanine at position 508 (delta F508), and seven were delta F508 homozygous. INTERVENTIONS: Inhalation of 1 mg of terbutaline (4 puffs) and placebo via a metered-dose inhaler by spacer. MEASUREMENTS AND RESULTS: The largest differences in tracheobronchial retention (percent) in the whole lung and regional lung zones were generally observed within 1 h after terbutaline and placebo treatment: whole lung (mean +/- SD), 60 +/- 22 percent and 63 +/- 20 percent; central zone, 41 +/- 19 percent and 50 +/- 25 percent; midzones, 65 +/- 27 percent and 63 +/- 19 percent; and peripheral zones, 77 +/- 28 percent and 72 +/- 28 percent, respectively [p > 0.1]. Whereas none of these differences was statistically significant, subanalyses suggested an improvement in mucociliary clearance by terbutaline in the three delta F508 heterozygous patients but not in the seven delta F508 homozygous patients. One minute of voluntary coughing resulted in clearance of less than 8 percent of the initial radioactivity, with a trend of more peripheral zone clearance after terbutaline compared with placebo. A small significant decrease in airway resistance was detected 3 h after terbutaline. CONCLUSIONS: We conclude that 1 mg of terbutaline did not improve mucociliary clearance significantly in the patients with CF. Also, the effect of terbutaline was much less than demonstrated earlier in healthy subjects. This is consistent with earlier findings of a lack of beta-adrenergic modulation of Cl- transport in CF. Thus, no rehydration of the dry mucus in CF is expected, and a possible beta 2-agonist-induced increase in ciliary beating would have only a minor effect on overall mucociliary clearance.
Authors: Brian M Peters; Mary Ann Jabra-Rizk; Graeme A O'May; J William Costerton; Mark E Shirtliff Journal: Clin Microbiol Rev Date: 2012-01 Impact factor: 26.132
Authors: Abhiram R Bhashyam; Peter J Mogayzel; Jeffrey C Cleary; Bradley J Undem; Marian Kollarik; James Fox; Beth L Laube Journal: Auton Neurosci Date: 2010-01-03 Impact factor: 3.145