Kaharu Sumino1, Elizabeth A Sugar2, Charles G Irvin3, David A Kaminsky3, Dave Shade4, Christine Y Wei4, Janet T Holbrook4, Robert A Wise5, Mario Castro6. 1. Washington University School of Medicine, St Louis, Missouri; St Louis VA Medical Center, St Louis, Missouri. Electronic address: ksumino@dom.wustl.edu. 2. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. University of Vermont College of Medicine, Burlington, Vermont. 4. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. 5. Johns Hopkins University School of Medicine, Baltimore, Maryland. 6. Washington University School of Medicine, St Louis, Missouri.
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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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: S Lim; A Jatakanon; M John; T Gilbey; B J O'connor; K F Chung; P J Barnes Journal: Am J Respir Crit Care Med Date: 1999-01 Impact factor: 21.405
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