Adenosine dry powder inhalation for bronchial challenge testing, part 2: proof of concept in asthmatic subjects.
Adenosine is an indirect stimulus to assess bronchial hyperresponsiveness (BHR(2)) in asthma. Bronchial challenge tests are usually performed with nebulised solutions of adenosine 5'-monophosphate (AMP(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 (0.01-80 mg) 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 30-40 L/min). All subjects reached a 20% fall in FEV₁(4) with the new adenosine test (PD20(5)) compared to four subjects with the AMP test (PC₂₀(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.
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands. Electronic address: a.j.lexmond@rug.nl.
Anne J
AJ
Lexmond
University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: e.van.der.wiel@umcg.nl.
Erica
E
van der Wiel
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands. Electronic address: p.hagedoorn@rug.nl.
Paul
P
Hagedoorn
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands. Electronic address: w.bult@umcg.nl.
Wouter
W
Bult
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands. Electronic address: h.w.frijlink@rug.nl.
Henderik W
HW
Frijlink
University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: n.h.t.ten.hacken@umcg.nl.
Nick H T
NH
ten Hacken
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands. Electronic address: a.h.de.boer@rug.nl.
Anne H
AH
de Boer
D000241:Adenosine / Q000008:administration & dosage*; D000249:Adenosine Monophosphate / Q000737:chemistry; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D011208:Powders
D016085:Bronchoconstrictor Agents; D011208:Powders; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D000241:Adenosine
Adenosine; Adenosine 5′-monophosphate; Asthma; Bronchial challenge test; Bronchial hyperresponsiveness; Dry powder inhaler