Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma

Kaharu Sumino, Elizabeth A. Sugar, Charles G. Irvin, David A. Kaminsky, Dave Shade, Christine Y. Wei, Janet T. Holbrook, Robert A. Wise, Mario Castro

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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 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.

Original languageEnglish
Pages (from-to)354-360.e1
JournalAnnals of Allergy, Asthma and Immunology
Volume112
Issue number4
DOIs
StatePublished - Apr 2014

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    Sumino, K., Sugar, E. A., Irvin, C. G., Kaminsky, D. A., Shade, D., Wei, C. Y., Holbrook, J. T., Wise, R. A., & Castro, M. (2014). Variability of methacholine bronchoprovocation and the effect of inhaled corticosteroids in mild asthma. Annals of Allergy, Asthma and Immunology, 112(4), 354-360.e1. https://doi.org/10.1016/j.anai.2014.01.013