Effectiveness of FeNO‐guided treatment in adult asthma patients: A systematic review and meta‐analysis

Objective Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta‐analysis to obtain summary estimates of the effectiveness of FeNO‐guided asthma treatment. Design We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse‐variance random‐effects meta‐analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. Data Sources The Cochrane Airways Group Trials Register was searched on 9 May 2023. Eligibility Criteria We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO‐guided treatment versus usual (symptom‐guided) treatment in adult asthma patients. Results We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO‐guided treatment probably reduces the number of patients having ≥1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = −0.10; 95%CI −0.18 to −0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. Conclusions FeNO‐guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes. In this systematic review, we included 12 RCTs (2,116 patients) comparing FeNO‐guided with usual (symptom‐guided) treatment in adult asthma patients, all showing high or unclear risk of bias. FeNO‐guided asthma treatment probably reduces the number of exacerbations. It may also slightly improve ACQ score, although the difference of 0.1 points compared to usual care is generally considered clinically irrelevant.