Screening for bronchial hyperresponsiveness using methacholine and adenosine monophosphate - Relationship to asthma severity and beta(2)-receptor genotype

Bronchial hyperresponsiveness (BHR) Is a key feature of asthma and may be m easured by direct methacholine challenge or indirect adenosine monophosphat e (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 relation ships between BHR and disease severity markers or beta(2)-adrenoceptor geno type. Of these subjects, 258 had a methacholine challenge, 259 an AMP chall enge and 185 both. Of subjects having both, 140 (76%) were methacholine res ponsive with PD20 < 500 mu g (PC20 < 5 mg/ml) and 92 (50%) were AMP respons ive with PC20 < 200 mg/ml. For those who were AMP unresponsive 57% were met hacholine responsive, whereas for the methacholine nonresponders 11% were A MP responsive. Methacholine (but not AMP)-responsive patients had a signifi cantly (p < 0.05) lower % predicted FEV1 and FEF25-75 and higher inhaled co rticosteroid dose than unresponsive patients. Finally, subjects with a glyc ine allele at codon 16 had significantly (p < 0.05) increased BHR to methac holine but not AMP. Our results suggest that methacholine is a more appropr iate screening tool for BHR than AMP as it was more sensitive in our popula tion and was also related to asthma severity. In addition, we have demonstr ated an association between the glycine allele (codon 16) and increased BHR to methacholine.