Determinants of the bronchodilation response to salbutamol on histamine-induced bronchoconstriction.
Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.
Department of Respiratory Medicine, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland. heikki.koskela@kuh.fi
Heikki O
HO
Koskela
Vesa
V
Kiviniemi
Minna K
MK
Purokivi
Antti H
AH
Taivainen
Hannu O
HO
Tukiainen
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019819:Budesonide / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D019819:Budesonide; D006632:Histamine; D000420:Albuterol