title: 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.
authors.affiliation: Department of Pediatrics, Seoul National University Hospital, Seoul, Korea.
authors.forename: Dong In
authors.initials: DI
authors.lastname: Suh
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Ju Kyung
authors.initials: JK
authors.lastname: Lee
authors.forename: Jin-Tack
authors.initials: JT
authors.lastname: Kim
authors.forename: Young Yull
authors.initials: YY
authors.lastname: Koh
mesh_terms: D000249:Adenosine Monophosphate; D056151:Airway Remodeling; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D013147:Spirometry; D014797:Vital Capacity
chemical_list: D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate