title: Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.
abstract: BACKGROUND
  In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway.
  
  
  METHODS
  Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed.
  
  
  RESULTS
  Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing).
  
  
  CONCLUSIONS
  Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.
  
  
  BACKGROUND
  Registered at clinicaltrials.gov: NCT01216748 .
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. educancado@uol.com.br.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Cancado
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. emendes@med.miami.edu.
authors.forename: Eliana S
authors.initials: ES
authors.lastname: Mendes
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. jarana@med.miami.edu.
authors.forename: Johana
authors.initials: J
authors.lastname: Arana
authors.affiliation: Department of Pulmonology, Semmelweis University School of Medicine, Budapest, Hungary. ghorvath.mail@gmail.com.
authors.forename: Gabor
authors.initials: G
authors.lastname: Horvath
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. MMonzonMedina@med.miami.edu.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Monzon
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. msalathe@med.miami.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Salathe
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL, 33136, USA. awanner@med.miami.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Wanner
mesh_terms: D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D000472:Alkalosis, Respiratory / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol