title: Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma.
abstract: BACKGROUND
  Airway hyperresponsiveness is a cardinal feature of asthma. Although the modulation of cholinergic neuroeffector transmission may play a role in airway responsiveness, in vivo evidence remains scarce. It is well known that histamine causes bronchoconstriction partly via vagal reflex, whereas methacholine does not. To investigate the significance of modulating neuroeffector transmission, we compared the effect of low-dose salbutamol-a β2-adrenoceptor agonist-on airway responsiveness to histamine with that to methacholine.
  
  
  METHODS
  We enrolled 12 subjects with stable asthma. After screening confirmed that inhalation of low-dose salbutamol (1μg) did not change their basic pulmonary function, subjects underwent measurement of airway responsiveness to inhaled histamine and methacholine with or without pretreatment with low-dose salbutamol, in a randomized, crossover fashion. Airway responsiveness was measured by an astograph by which respiratory conductance (Grs) was assessed by the forced oscillation method during continuous inhalation of histamine or methacholine in stepwise incremental concentrations. Airway responsiveness was calculated as the cumulative dose of bronchoconstrictors that induced a decrease of 35% in Grs.
  
  
  RESULTS
  Inhalation of 1μg of salbutamol significantly attenuated airway responsiveness to histamine but not methacholine. This selective attenuation was observed irrespective of disease severity or phenotype, namely atopy or non-atopy.
  
  
  CONCLUSIONS
  Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma. The present study may provide a novel insight into the bronchoprotective mechanism of β2-adorenoceptor agonist in clinical settings.
authors: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. koichi@kokyu.med.kyushu-u.ac.jp
authors: Koichiro
authors: K
authors: Matsumoto
authors: Hisamichi
authors: H
authors: Aizawa
authors: Satoru
authors: S
authors: Fukuyama
authors: Makoto
authors: M
authors: Yoshida
authors: Masashi
authors: M
authors: Komori
authors: Syohei
authors: S
authors: Takata
authors: Hiroshi
authors: H
authors: Koto
authors: Hiromasa
authors: H
authors: Inoue
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D016210:Methacholine Chloride; D006632:Histamine; D000420:Albuterol
keywords: ACh; Airway responsiveness; EFS; GSEM; Grs; LABA; MCh; Neuroeffector transmission; PD(35)-Grs; PGE(2); RAST; Rrs; SABA; Salbutamol; Vagal reflex; acetylcholine; electrical field stimulation; geometric standard errors of means; long-acting β(2)-adrenoceptor agonist; methacholine; prostaglandin E(2); radioallergosorbent test; respiratory conductance; respiratory resistance; short-acting β(2)-adrenoceptor agonist; the cumulative dose of bronchoconstrictor that induced a decrease of 35% in Grs