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Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1318-1322

Screening for Bronchial Hyperresponsiveness Using Methacholine and Adenosine Monophosphate
Relationship to Asthma Severity and beta 2-Receptor Genotype

STEPHEN J. FOWLER, OWEN J. DEMPSEY, ERIKA J. SIMS, and BRIAN J. LIPWORTH

Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom

Bronchial hyperresponsiveness (BHR) is a key feature of asthma and may be measured by direct methacholine challenge or indirect adenosine monophosphate (AMP) challenge. We performed a retrospective analysis of our database (n = 487) of patients with asthma with the aim first, to compare methacholine and AMP challenge as screening tools, and second, to identify any relationships between BHR and disease severity markers or beta 2-adrenoceptor genotype. Of these subjects, 258 had a methacholine challenge, 259 an AMP challenge and 185 both. Of subjects having both, 140 (76%) were methacholine responsive with PD20 < 500 µg (PC20 < 5 mg/ml) and 92 (50%) were AMP responsive with PC20 < 200 mg/ ml. For those who were AMP unresponsive 57% were methacholine responsive, whereas for the methacholine nonresponders 11% were AMP responsive. Methacholine (but not AMP)-responsive patients had a significantly (p < 0.05) lower % predicted FEV1 and FEF25-75 and higher inhaled corticosteroid dose than unresponsive patients. Finally, subjects with a glycine allele at codon 16 had significantly (p < 0.05) increased BHR to methacholine but not AMP. Our results suggest that methacholine is a more appropriate screening tool for BHR than AMP as it was more sensitive in our population and was also related to asthma severity. In addition, we have demonstrated an association between the glycine allele (codon 16) and increased BHR to methacholine.




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