Biomaterial Database

Reduced effect of inhaled beta 2-adrenergic agonists on lung mucociliary clearance in patients with cystic fibrosis. 1993

J Mortensen, and A Hansen, and M Falk, and I K Nielsen, and S Groth

Department of Clinical Physiology, Rigshospitalet, State University Hospital, Copenhagen, Denmark.

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. METHODS A double-blind, randomized cross-over trial. METHODS 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. METHODS 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. METHODS Inhalation of 1 mg of terbutaline (4 puffs) and placebo via a metered-dose inhaler by spacer. 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.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D009079	Mucociliary Clearance	A non-specific host defense mechanism that removes MUCUS and other material from the LUNGS by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers.	Mucociliary Transport,Clearance, Mucociliary,Clearances, Mucociliary,Mucociliary Clearances,Mucociliary Transports,Transport, Mucociliary,Transports, Mucociliary
D010919	Placebos	Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol.	Sham Treatment
D011877	Radionuclide Imaging	The production of an image obtained by cameras that detect the radioactive emissions of an injected radionuclide as it has distributed differentially throughout tissues in the body. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph.	Gamma Camera Imaging,Radioisotope Scanning,Scanning, Radioisotope,Scintigraphy,Scintiphotography,Imaging, Gamma Camera,Imaging, Radionuclide
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D003550	Cystic Fibrosis	An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.	Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases
D004311	Double-Blind Method	A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.	Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man