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Review: medication adjustment based on fractional exhaled nitric oxide did not prevent asthma exacerbations

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H Petsky

Ms H Petsky, Royal Children's Hospital, Brisbane, Queensland, Australia; helen_petsky{at}


In adults and children with asthma, does medication adjustment based on fractional exhaled nitric oxide (FeNO) concentration prevent asthma exacerbations more than adjustment based on clinical symptoms?


Included studies compared adjustment of asthma medication based on FeNO concentrations with adjustment based on clinical symptoms (with or without spirometry) in adults or children with “classical” asthma. Outcomes were asthma exacerbations, symptom scores, and final and cumulative dose of inhaled corticosteroids.


Cochrane Airways Group Specialised Register of Trials, Cochrane Central Register of Controlled Trials (Issue 4, 2006), Medline and EMBASE/Excerpta Medica (to Dec 2006), Old Medline (1950–65), and references were searched for randomised controlled trials (RCTs). Authors of included trials were consulted. 4 RCTs (n = 356) met the selection criteria: 2 RCTs in children (n = 141, mean age 12 y, 63% boys), 1 RCT in adults (n = 118, median age 51 y, 54% women), and 1 RCT in mainly adults (n = 97, age 12–73 y). 1 RCT was double-blinded, and outcome assessors were blinded in 2 other RCTs. The FeNO cut point for change in therapy varied by study (20, 26, 30, or 35 ppb). Duration of follow-up ranged from 6 months to 2 years.


Basing medication adjustment on FeNO concentrations did not reduce asthma exacerbations (table) or improve symptom scores in either children or adults. At the final follow-up visit for adults, mean dose (but not cumulative dose) of inhaled corticosteroids was lower in the FeNO group than in the clinical symptoms group (weighted mean difference −282 μg, 95% CI −422 to −143). Use of FeNO concentrations did not reduce inhaled corticosteroid use in children.


In adults and children with asthma, medication adjustment based on fractional exhaled nitric oxide concentration did not prevent asthma exacerbations more than adjustment based on clinical symptoms.


Petsky HL, Cates CJ, Li AM, et al. Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev 2008;(2):CD006340.

Medication adjustment based on fractional exhaled nitric oxide (FeNO) concentration v clinical symptoms to reduce asthma exacerbations in patients with asthma at 12−24 months*

Clinical impact ratings: Allergy and immunology 6/7; Respirology/Pulmonology 5/7


The systematic review by Petsky et al showed that FeNO measurement may have a place in the management of asthma in adults for whom inhaled corticosteroid reduction is considered clinically important, but not in children. In patients for whom local or systemic effects of corticosteroids are of concern, any efforts that can reduce inhaled corticosteroid dose may be worthwhile. This recommendation needs to be made with caution because it is based on post hoc analysis, and 1 of the 2 trials in adults showed a non-significant 11% increase in cumulative inhaled corticosteroid use in the FeNO group compared with the control group during 12 months of follow-up. The 2 trials in children were even less convincing of a benefit of FeNO measurement in reducing inhaled corticosteroid dose.

The primary outcome of interest in this review was asthma exacerbations. This outcome was not improved nor was benefit shown for several other symptomatic and objective outcome measures. Given the expense and ongoing requirement for calibration and maintenance of a nitric oxide analyser, this review indicates relatively little benefit associated with routine measurement of exhaled nitric oxide.

Patients with atopy are known to have higher FeNO concentrations, which might suggest a potential role for FeNO measurement in these patients; however, no trial has specifically set out to assess this issue. Similarly, potentially greater benefits in patients with eosinophilic asthma or with high initial inhaled corticosteroid requirements have not been evaluated. Preplanned subgroup evaluations of such patients are required in future trials.

Evidence-based recommendations for management of asthma, including “difficult” asthma, have recently been published.1 Sputum eosinophilia may provide an alternative evidence-based strategy to guide medication adjustment in asthma. Titration based on sputum eosinophils has been shown to reduce asthma exacerbations in adults, although this requires patients to have hypertonic saline nebulisation.2 Currently, neither FeNO nor sputum eosinophilia is sufficiently well proven or practical to become mainstream clinical practice in the management of asthma.


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  • Source of funding: National Health and Medical Research Council.

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