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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.