Maximal response plateau to adenosine 5'-monophosphate in asthma. Relationship with the response to methacholine, exhaled nitric oxide, and exhaled breath condensate pH

Chest. 2009 Jun;135(6):1521-1526. doi: 10.1378/chest.08-2392. Epub 2009 Feb 18.

Abstract

Background: No information is available on the plateau in response to adenosine 5'-monophosphate(AMP). The aims of the present study were (1) to determine whether plateau can be detected with AMP and the relation with the plateau in response to methacholine, and (2) to identify the relation between the plateau and indirect markers of airway inflammation, such as exhaled nitric oxide (ENO) and exhaled breath condensate (EBC) pH.

Methods: Airway responsiveness to high concentrations of methacholine and AMP, ENO levels, and EBC pH values were obtained in 31 subjects with well-controlled asthma. Concentration-response curves were characterized by their concentration of agonist that produces a decrease in FEV(1) of 20% and, if possible, by the level of plateau.

Results: Although the prevalence of plateau with methacholine (48%) and AMP (58%) was similar, the two challenges did not identify plateau in exactly the same individuals. In 14 subjects who showed plateau with both bronchoconstrictor agents, the mean plateau level for methacholine was 26.0% (95% confidence interval [CI], 21.3 to 30.8), compared with 16.5% (95% CI, 12.2 to 20.8; p < 0.0001) for AMP. Both ENO and EBC pH values were similar in subjects with plateau and in those without plateau.

Conclusions: In well-controlled asthmatics, the plateau in response to AMP can be identified at a milder degree of obstruction than the plateau in response to methacholine, but the two agonists are not identifying the same airway abnormalities. Furthermore, if ENO and EBC pH are markers of inflammation, the determination of the presence or level of plateau is not a reliable method to identify airway inflammation in asthma.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Adenosine Monophosphate / pharmacology*
  • Administration, Inhalation
  • Adult
  • Asthma / diagnosis*
  • Asthma / drug therapy
  • Breath Tests
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests / methods
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Forced Expiratory Volume
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Male
  • Maximum Tolerated Dose
  • Methacholine Chloride* / metabolism
  • Middle Aged
  • Nitric Oxide / analysis*
  • Nitric Oxide / metabolism
  • Probability
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Spirometry

Substances

  • Methacholine Chloride
  • Nitric Oxide
  • Adenosine Monophosphate