Relationships of Methacholine and Adenosine 5′-monophosphate (AMP) Responsiveness to the Postbronchodilator FEV₁/FVC Ratio in Children with Asthma

Article Outline

• Background
• Methods
• Results
• Conclusions
• Copyright

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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. BHR is commonly assessed by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare BHR to methacholine and adenosine 5′-monophosphate (AMP) with regard to the relationship with airway remodeling.

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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.

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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 = 0.000), 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 = 0.231). In the whole group of subjects, methacholine PC₂₀, but not AMP PC₂₀, correlated significantly with the postbronchodilator FEV₁/FVC ratio (r = 0.340, p = 0.000, and r = 0.056, p = 0.526, respectively).

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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.