TY - JOUR
T1 - Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma
AU - Sumino, Kaharu
AU - Sugar, Elizabeth A.
AU - Irvin, Charles G.
AU - Kaminsky, David A.
AU - Shade, Dave
AU - Wei, Christine Y.
AU - Holbrook, Janet T.
AU - Wise, Robert A.
AU - Castro, Mario
N1 - Funding Information:
Disclosures: Dr Sumino has received funding from the American Lung Association. Dr Castro's institution received a grant from the American Lung Association Asthma Clinical Research Centers and he is a board member of the American Lung Association. Dr Irvin as principal investigator received grants from the American Lung Association and National Institutes of Health and participated in a leadership group for the American Lung Association. Dr Wise served on the clinical end-point committee of GlaxoSmithKline, the Data Monitoring Committee of Merck, and as a consultant to AstraZeneca. Dr Kaminsky as co-investigator received funding from the American Lung Association.
PY - 2014/4
Y1 - 2014/4
N2 - 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 PC 20 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 PC 20 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.
AB - 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 PC 20 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 PC 20 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.
UR - http://www.scopus.com/inward/record.url?scp=84897399875&partnerID=8YFLogxK
U2 - 10.1016/j.anai.2014.01.013
DO - 10.1016/j.anai.2014.01.013
M3 - Article
C2 - 24507830
AN - SCOPUS:84897399875
SN - 1081-1206
VL - 112
SP - 354-360.e1
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 4
ER -