Adenosine dry powder inhalation for bronchial challenge testing, part 2: Proof of concept in asthmatic subjects

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 88; no. 1; pp. 148 - 152
• Main Authors: Lexmond, Anne J., van der Wiel, Erica, Hagedoorn, Paul, Bult, Wouter, Frijlink, Henderik W., ten Hacken, Nick H.T., de Boer, Anne H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2014
• Subjects: Adenosine; Adenosine - administration & dosage; Adenosine 5′-monophosphate; Adenosine Monophosphate - chemistry; Administration, Inhalation; Adult; Asthma; Asthma - drug therapy; Bronchi - drug effects; Bronchial challenge test; Bronchial Hyperreactivity - diagnosis; Bronchial hyperresponsiveness; Bronchial Provocation Tests; Bronchoconstrictor Agents - administration & dosage; Dry powder inhaler; Dry Powder Inhalers; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride - administration & dosage; Middle Aged; Pilot Projects; Powders; Dry powder inhaler; Bronchial hyperresponsiveness; Adenosine 5′-monophosphate; Adenosine; Bronchial challenge test; Asthma
• ISSN: 0939-6411; 1873-3441; 1873-3441
• DOI: 10.1016/j.ejpb.2014.04.008

[Display omitted] Adenosine is an indirect stimulus to assess bronchial hyperresponsiveness (BHR2BHR: Bronchial hyperresponsiveness.2) in asthma. Bronchial challenge tests are usually performed with nebulised solutions of adenosine 5′-monophosphate (AMP3AMP: Adenosine 5′-monophosphate.3). The nebulised AMP test has several disadvantages, like long administration times and a restrictive maximum concentration that does not result in BHR in all patients. In this study, we investigated the applicability of dry powder adenosine for assessment of BHR in comparison to nebulised AMP. Dry powder adenosine was prepared in doubling doses (0.01–80mg) derived from the nebulised AMP test with addition of two higher doses. Five asthmatic subjects performed two bronchial challenge tests, one with nebulised AMP following the 2-min tidal breathing method; the second with dry powder adenosine administered with an investigational inhaler and single slow inhalations (inspiratory flow rate 30–40L/min). All subjects reached a 20% fall in FEV14FEV1: Forced expiratory volume in 1s.4 with the new adenosine test (PD205PD20: Provocative dose causing a 20% fall in the forced expiratory volume in 1s (FEV1).5) compared to four subjects with the AMP test (PC206PC20: Provocative concentration causing a 20% fall in the forced expiratory volume in 1s (FEV1).6). Dry powder adenosine was well tolerated by all subjects and better appreciated than nebulised AMP. In conclusion, this new bronchial challenge test appears to be a safe and convenient alternative to the nebulised AMP test to assess BHR in asthmatic subjects.