Comparison of Bronchial Hyperresponsiveness to Methacholine and Adenosine and Airway Inflammation Markers in Patients with Suspected Asthma

Abstract

Background. Bronchial hyperresponsiveness is usually measured by bronchial challenge test with direct (e.g., methacholine) and indirect (e.g., adenosine) agonists. There are few studies comparing both types of agents and they have had conflicting concordance. Objective. We sought to compare the results of both tests in a population with symptoms suggestive of asthma so as to determine their relationship with bronchial inflammatory markers. Methods. Seventy-nine patients whose age ranged from 14 to 81 years were recruited for this study. Challenge tests were performed using the tidal volume method. PC₂₀ methacholine and PC₁₅ and PC₂₀ adenosine were calculated. Induced sputum and fraction of exhaled nitric oxide measurements were also performed. Results. Atopy was found in 69% of the patients. Methacholine PC₂₀ and adenosine PC₁₅ were positive in 32 patients (40.5%), both having a sensitivity of 73%. Percentage of agreement was 45.45% and κ index was only 0.369. Adenosine PC₂₀ elicited lower sensitivity and agreement. No correlation between methacholine PC₂₀ and adenosine PC₁₅ was observed. Higher fraction of exhaled nitric oxide values and sputum eosinophil counts were seen in patients with positive adenosine challenge results. The use of adenosine PC₁₅ or PC₂₀ did not alter the association with inflammatory markers. Conclusions. The concordance between both techniques was low. Methacholine is not a reliable predictor of hyperresponsiveness to adenosine, leading us to conclude that the two tests are complementary but not interchangeable in clinical practice. Additionally, responsiveness to the two bronchoconstrictor stimuli does not indicate presence of the same airway abnormality. Indirect stimuli provide a better reflection of bronchial inflammation.

Keywords:

• adenosine
• asthma
• bronchial challenge
• bronchial hyperresponsiveness
• fraction of exhaled nitric oxide
• induced sputum
• methacholine

Acknowledgments

Oliver Shaw for editorial assistance and Ignacio Mahillo for statistical assistance.

Funding. This study was performed at FUNDACIÓN JIMÉNEZ DÍAZ. This study was supported by CIBERES (CIBER de Enfermedades Respiratorias) and fellowship grants from the Conchita Rábago Foundation (M.M.).

Declaration of Interest

Luis Manso, Mauro Madero, Mónica Ruiz-García, and Mar Fernández-Nieto declare not to have any conflict of interest.

Joaquín Sastre reports having served as a consultant to Phadia, Schering-Plough, Merck, and GSK; having been paid lecture fees by Novartis, GSK, Stallergenes, Merck, and UCB; and having received grant support from Phadia, GSK, and ALK-Abello.