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. Objectives 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.

Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma

“…We analysed methacholine challenge data from both paediatric and adult participants involved in one of the five different studies of the ALA-ACRC [9][10][11][12][13][14] (ClinicalTrials. gov Identifiers: NCT00069823, NCT00442013, NCT0 1118312, NCT00705341 and NCT01629823).…”

Mechanisms of airway hyper‐responsiveness in asthma: the past, present and yet to come

“…Furthermore, the measurement of AHR is confounded by its moderate repeatability, with estimates of within-subject repeatability ranging from 1–3 doubling doses (reviewed in (23)). Variability of AHR is further increased in those with non-atopic disease and those over 50 years of age (24). It is important to acknowledge that the variability of AHR is not only due to variability in the underlying mechanisms but also due to the imprecision of the measurement itself.…”

Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial

“…Regardless, there was a notable and statistically significant improvement in airway reactivity in all three treatment groups. This improvement of PC 20 was in excess of the variability of PC 20 that we reported in a previous study (34). The improvement in airway reactivity was approximately one doubling dose in the sham group and was accompanied by improvements in patient-reported outcomes, including asthma control scores, but no effect on FEV 1 was seen.…”

“…There are several potential explanations for decreased airway reactivity in all groups. One possibility is regression to the mean because we selected people who had high levels of airway reactivity; however, a previous study of patients with similar initial levels of airway reactivity did not show similar decreases (34).…”