Airway responsiveness to adenosine after a single dose of fluticasone propionate discriminates asthma from COPD

Pulm Pharmacol Ther. 2014 Feb;27(1):70-5. doi: 10.1016/j.pupt.2013.05.002. Epub 2013 May 18.

Abstract

Background: Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5'-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP).

Aim: To determine whether this rapid protective effect of a single dose of FP is also present in COPD.

Methods: 23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 μg FP or matched placebo.

Results: In subjects with asthma, 1000 μg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3-116.3) to 81.5 (9.6-1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3-183.9) and 76.3 (21.0-445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma.

Conclusion: A single dose of 1000 μg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD.

Keywords: Adenosine 5′-monophosphate; Airway hyperresponsiveness; Asthma; COPD; Fluticasone propionate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate*
  • Administration, Inhalation
  • Adult
  • Aged
  • Androstadienes / administration & dosage
  • Androstadienes / pharmacology*
  • Asthma / diagnosis*
  • Asthma / drug therapy
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / etiology
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Fluticasone
  • Humans
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Sensitivity and Specificity

Substances

  • Androstadienes
  • Bronchodilator Agents
  • Methacholine Chloride
  • Adenosine Monophosphate
  • Fluticasone