Screening for Bronchial Hyperresponsiveness Using Methacholine and Adenosine Monophosphate

Abstract

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 PD(20) < 500 microgram (PC(20) < 5 mg/ml) and 92 (50%) were AMP responsive with PC(20) < 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 FEV(1) and FEF(25-75) 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.

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

“…This may appear high, but is considered clinically relevant, since ''borderline'' AHR (PC20 4-16 mg?mL -1 ), defined according to the American Thoracic Society guidelines [14], was demonstrated by a considerable proportion (5/30, 16.7%) of asthma patients. A cut-off point of 200 mg?mL -1 was chosen for AMP PC20, because this allowed asthma patients and healthy controls to be discriminated in previous studies [15,20]. In fact, all but two asthmatic patients in the present study responded positively to AMP ,200 mg?mL -1 , which suggests that this concentration represents an appropriate upper limit for the evaluation of AHR.…”

The effect of adiposity measured by dual-energy X-ray absorptiometry on lung function

“…Inclusion criteria were being healthy and 20-50 yrs of age. To decrease the likelihood of subclinical airways disease, exclusion criteria were: current respiratory symptoms; history of respiratory disease; ex-smokers with a smoking history of .10 pack-yrs or who had smoked in the last year; cardiac or neurological comorbidity; structural abnormalities of the chest wall; and an exhaled nitric oxide concentration of .35 ppb [15] or a positive methacholine challenge [16]. The study was approved by the Lower South Ethics Committee (Dunedin, New Zealand) and all participants gave written informed consent.…”

Autonomic Nervous System Pharmacogenomics: A Progress Report

“…Numerous association studies have been carried out with respect to ␤ 2 -AR SNPs and asthma (Liggett, 2000a;Silverman et al, 2001;Fenech and Hall, 2002;Joos and Sandford, 2002;Palmer et al, 2002;Taylor and Kennedy, 2002;Small et al, 2003). Overall, the data suggest that ␤ 2 -AR polymorphisms, especially Arg16Gly, may play a role in airway hyperresponsiveness, bronchodilator sensitivity and response to ␤-agonist, long-term use of ␤-agonist, and tolerance (Table 11) Martinez et al, 1997;Tan et al, 1997;D'Amato et al, 1998;Kotani et al, 1999;Fowler et al, 2000;Israel et al, 2000;Lima et al, 2000;Taylor et al, 2000a). Future studies will need to identify individuals at risk for the development of asthma in addition to patient populations that are likely or unlikely to respond to treatment or experience adverse side effects (Silver- Albuterol-evoked FEV 1 was higher and more rapid in Arg16 homozygotes vs. Gly16 carriers Lima et al, 1999 Arg16Gly Lower airway responsiveness to salbutamol in Gly16 vs. Arg16 homozygotes or Arg16Gly heterozygotes Kotani et al, 1999 Arg16Gly, Gln27Glu No association between genotype and desensitization to short-or long-acting ␤ 2 -agonists (formoterol vs. terbutaline) Lipworth et al, 1999a Arg16Gly Poor FEV 1 vs. albuterol concentration relationship associated with Gly16 Lima et al, 2000 Arg16Gly No association between functional antagonism of methacholine-induced bronchoconstriction with formoterol or salmeterol and genotype Lipworth et al, 2000 Arg16Gly Decline in peak expiratory flow with regular albuterol use in Arg16 vs. Gly16 homozygotes Israel et al, 2000 Arg16Gly No association between tolerance to regular salmeterol and genotype Taylor et al, 2000b Arg16Gly More frequent exacerbations during salbutamol treatment of Arg16 vs. Gly16 homozygotes or Arg16Gly heterozygotes Taylor et al, 2000a Haplotype pairs Albuterol-evoked FEV 1 improvement related to haplotype pairs (i.e., Arg19Cys (Ϫ47), Arg16Gly, Gln27Glu) …”