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

Area of Science:

• Pulmonology
• Clinical Trials
• Biomarkers

Background:

• The minimal clinically important difference (MCID) for fractional exhaled nitric oxide (FeNO) in asthma remains uncertain.
• The American Thoracic Society (ATS) suggests a ≥20% relative change in FeNO, but this lacks validation against clinical outcomes.
• A secondary analysis of RCTs can help estimate the FeNO MCID by examining its association with asthma control.

Purpose of the Study:

• To estimate the minimal clinically important difference (MCID) for fractional exhaled nitric oxide (FeNO) in asthma.
• To assess the association between changes in FeNO and the Asthma Control Questionnaire-5 (ACQ-5).
• To evaluate the ATS recommendation for FeNO MCID against clinical outcome measures.

Main Methods:

• Secondary analysis of two randomized controlled trials (PRACTICAL and Novel START) involving 1553 participants with mild-moderate asthma.
• Logistic regression assessed associations between FeNO and ACQ-5 changes relative to the ACQ-5 MCID (0.5 points).
• A t-test compared log FeNO differences for participants achieving the ACQ-5 MCID.

Main Results:

• A weak association was found between changes in FeNO and ACQ-5 (correlation coefficient = 0.08, p=0.002).
• Participants with a clinically important improvement in ACQ-5 showed a 22% change in the geometric mean of FeNO (ratio=0.78).
• Sensitivity and specificity for a 20% FeNO change were 47% and 57%, respectively.

Conclusions:

• Changes in FeNO are a poor surrogate for changes in asthma control as measured by ACQ-5.
• The observed FeNO changes in patients with improved ACQ-5 provide only weak support for the ATS recommendation of a 20% MCID for FeNO.
• Further research is needed to establish a validated MCID for FeNO in asthma management.