Bronchial responsiveness to beta-adrenergic stimulation and enhanced beta-blockade in asthma.
OBJECTIVE
Beta-adrenergic blocking drugs have no effect on the airways of normal subjects but in asthma even small doses may cause severe deterioration. A seemingly obvious explanation for this abnormal sensitivity is that asthmatic airways, but not normal airways, are tonically dilated by the sympatho-adrenal system. However, studies suggest that sympatho-adrenal activity is normal in asthma, as is bronchial sensitivity to beta-agonists. The present study re-examines bronchial beta-adrenergic sensitivity in asthma and also measures antagonism produced in normal and asthmatic bronchi by a beta-blocking drug.


METHODS
The threshold bronchodilator doses of inhaled isoprenaline (dose required for a 35% increase in specific airway conductance 'PD35') was measured in 11 normal and 14 asthmatic adults on two separate occasions. After administering propranolol (inhaled or intravenously) PD35 was remeasured.


RESULTS
Sensitivity to isoprenaline was greater in symptomatic asthmatics (PD35 = 0.003 micromol) than in asymptomatic asthmatics (PD35 = 0.021 micromol) and in non-asthmatics (PD35 = 0.123 micromol; P < 0.001 in each case). Symptomatic asthmatics also showed 66-fold more antagonism than non-asthmatics when they were given propranolol by inhalation (P < 0.001) and sixfold more with intravenous propranolol (P = 0.005).


CONCLUSIONS
The increased sensitivity of asthmatics to inhaled isoprenaline suggests that they may also be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways. Taken with enhanced antagonism by propranolol, this provides insight into the aggravation of asthma by beta-blocking drugs.
Boskabady
M H
MH
Department of Physiology, Ghaem Medical Centre, Mashhad University of Medical Sciences, Iran.
Snashall
P D
PD
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D011433:Propranolol; D007545:Isoproterenol