External Validation of the Minimal Clinically Important Difference of FeNO Using the Asthma Control Questionnaire.

BACKGROUND

The minimal clinically important difference (MCID) for fractional exhaled nitric oxide (FeNO) in asthma is uncertain. The American Thoracic Society (ATS) suggests this may be a relative change ≥ 20%; however, this recommendation is not validated against a clinical outcome measure. A secondary analysis of two randomised controlled trials (RCTs) examining associations between changes in FeNO and the Asthma Control Questionnaire-5 (ACQ-5) may help estimate the MCID.

METHODS

The PRACTICAL and Novel START were 52-week RCTs that compared as-required short-acting beta-agonists with or without maintenance inhaled corticosteroids (ICS) versus as-required ICS-formoterol in mild-moderate asthma. In this secondary analysis, participants with measurements of FeNO and ACQ-5 were included. FeNO was analysed on the logarithm transformed scale. Logistic regression assessed associations between FeNO and ACQ-5 changes from baseline to end of study, relative to the ACQ-5 MCID (0.5 points). A t-test was used to compare the difference in log FeNO for those whose ACQ-5 fell by the MCID for an improvement in ACQ.

RESULTS

Data from 1553 participants were included. There was a weak association between the change in FeNO and change in ACQ-5; correlation coefficient was 0.08 (p = 0.002). The mean (SD) change in log FeNO for those with a clinically important improvement in ACQ-5 was -0.25 (0.64), N = 530; geometric mean ratio was 0.78, representing a 22% change in the geometric mean of FeNO. The change in log FeNO was -0.14 (0.60) for those without an improvement in ACQ-5, N = 852; geometric mean ratio was 0.87. The sensitivity and specificity for a 20% change in geometric mean FeNO were 47% and 57%, respectively.

CONCLUSION

Changes in FeNO are a poor surrogate for changes in ACQ-5. The magnitude of FeNO changes in participants with an MCID improvement in ACQ-5 provides weak support for the ATS recommendation that the MCID for FeNO may be about a 20% relative change.