Journal Article

P166 External validation of the minimal clinically important difference of fractional exhaled nitric oxide using the asthma control questionnaire: a secondary analysis of two RCTs in mild or moderate asthma

Beasley, R, Weatherall, M, Bean, O, Noble, J

2023

Overview

IntroductionThe utility of fractional exhaled nitric oxide (FeNO) in randomised controlled trials (RCTs) of asthma, particularly the minimal clinical important difference (MCID), is uncertain. The American Thoracic Society recommends that the MCID for FeNO is a relative change of ≥20%. However, this effect size has not been validated against other clinical outcomes. Here we report the relationship between FeNO and a patient reported outcome measure of asthma control, for which the MCID is known, in a secondary analysis of two RCTs in mild-moderate asthma.MethodsThe PRACTICAL and Novel-START studies were 52-week open-label RCTs comparing as-required SABA with or without maintenance ICS versus as-required ICS-formoterol. This analysis includes participants with measurements of both FeNO and the Asthma Control Questionnaire-5 item (ACQ-5). FeNO was analysed on the logarithm (log) scale, and associations between change in log FeNO and ACQ-5 were estimated. The MCID for the ACQ-5 is 0.5. Associations were assessed with Spearman’s rank correlation coefficient, t-tests, and logistic regression. A sub-group analysis was performed for those participants with ‘active uncontrolled’ asthma, baseline FeNO ≥25ppb and ACQ ≥1.5.ResultsA total of 1398 participants had FeNO and ACQ-5 data and, of these, 242 had ‘active uncontrolled’ asthma. There was a weak association between change in log FeNO and ACQ-5; correlation coefficient 0.08 (P=0.002) and 0.14 (P=0.026) for the total and sub-group respectively (figure 1). In the total group the mean (SD) change in log FeNO for those with an ACQ-5 improvement of < 0.5 was -0.14 (0.60), N=820; and -0.25 (0.64), N=530 for those with ACQ-5 improvement ≥0.5; representing geometric mean ratios of 0.87 and 0.78 respectively. In the sub-group these values were -0.33 (0.57), N=69; and -0.52 (0.61), N=173; representing geometric mean ratios of 0.72 and 0.59 respectively. AUC-ROC in the two groups for FeNO versus an improvement in ACQ-5 ≥0.5 was 0.54 overall and 0.59 in the sub-group.DiscussionFeNO changes are a poor surrogate for the ACQ-5. However, the magnitude of the changes in FeNO in those with an improvement in ACQ-5 ≥ 0.5 supports that the MCID for FeNO may be about a 20% relative change.Please refer to page A291 for declarations of interest related to this abstract.Abstract P166 Figure 1Change in ACQ-5 versus log FeNO in ‘active uncontrolled’ sub-group.

• Publisher: BMJ Publishing Group Ltd and British Thoracic Society,BMJ Publishing Group LTD
• Subject: Asthma / Nitric oxide / Questionnaires / ‘Two Way Traffic’ – Challenging the status quo in asthma