title: Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma.
abstract: BACKGROUND
  The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose-response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established.
  
  
  OBJECTIVE
  To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20.
  
  
  METHODS
  A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval.
  
  
  RESULTS
  Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements.
  
  
  CONCLUSIONS
  The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.
authors: Washington University School of Medicine, St Louis, Missouri; St Louis VA Medical Center, St Louis, Missouri. Electronic address: ksumino@dom.wustl.edu.
authors: Kaharu
authors: K
authors: Sumino
authors: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Elizabeth A
authors: EA
authors: Sugar
authors: University of Vermont College of Medicine, Burlington, Vermont.
authors: Charles G
authors: CG
authors: Irvin
authors: University of Vermont College of Medicine, Burlington, Vermont.
authors: David A
authors: DA
authors: Kaminsky
authors: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors: Dave
authors: D
authors: Shade
authors: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors: Christine Y
authors: CY
authors: Wei
authors: Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
authors: Janet T
authors: JT
authors: Holbrook
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Robert A
authors: RA
authors: Wise
authors: Washington University School of Medicine, St Louis, Missouri.
authors: Mario
authors: M
authors: Castro
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy*; D001985:Bronchial Provocation Tests / Q000706:statistics & numerical data; D002648:Child; D018592:Cross-Over Studies; D003951:Diagnostic Errors / Q000517:prevention & control; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D016210:Methacholine Chloride; D000068298:Fluticasone