Relationships of methacholine and adenosine 5'-monophosphate (AMP) responsiveness to the postbronchodilator FEV1/FVC ratio in children with asthma.

ABSTRACT

BACKGROUND: Airway remodeling has been assumed to cause bronchial hyperresponsiveness (BHR). A low postbronchodilator FEV1/FVC ratio has been suggested to be a functional surrogate marker of airway remodeling in asthma. BHR is commonly assessed by bronchial challenges using direct or indirect stimuli. OBJECTIVE: The aim of this study was to compare BHR to methacholine and adenosine 5'-monophosphate (AMP) with regard to their relationship with a marker of airway remodeling in children with asthma. METHODS: Methacholine and AMP challenge tests were performed in 129 children with asthma, aged 12 years, and a provocative concentration causing a 20% fall in FEV1 (PC20) was calculated for each challenge. All subjects also underwent pre- and postbronchodilator spirometry. A postbronchodilator FEV1/FVC ratio below the lower limits of normal was used as a marker of airway remodeling. RESULTS: A low postbronchodilator FEV1/FVC ratio was found in 17 subjects (13.2%). These subjects had a significantly lower methacholine PC20 (geometric mean 0.63 mg/mL, range of 1 SD 0.17-2.29) than those (n = 112) with a normal postbronchodilator FEV1/FVC ratio (2.42 mg/mL, 0.57-10.32, p = .000), whereas AMP PC20 was similar between the two groups (22.1 mg/mL, 3.9-125.9 vs. 27.7 mg/mL, 4.2-183.5, p = .231). In the whole group of subjects, methacholine PC20, but not AMP PC20, correlated significantly with the postbronchodilator FEV1/FVC ratio (r = 0.340, p = .000, and r = 0.056, p = .526, respectively). CONCLUSIONS: Our results provide evidence, though indirect, that BHR to methacholine is related to airway remodeling in children with asthma and suggest that BHR to methacholine may be a better marker of airway remodeling than BHR to AMP.