Original Title: Medición de la fracción exhalada de óxido nítrico (FeNO) en el diagnóstico y tratamiento de niños con asma

Authors' objectives: The aim of this report is to determine the usefulness of the measurement of FeNO in the diagnosis and monitoring of treatment with inhaled corticosteroids in children with asthma through the identification and the assessment of the quality of the available evidence.

Authors' results and conclusions: Following the search of CPGs, systematic reviews and reports, four CPGs, four assessment reports and a Cochrane SR were selected. The first question, on the usefulness of FeNO measurement in small children with wheezing problems in order to predict the diagnosis of asthma at school-age, was not considered in any of the guidelines, although one of the assessment reports had identified the only study that we finally selected to answer to the aforementioned question. This study concluded that when the level of FeNO is 1.95 times greater than the reference value, the OR of wheezing at eight years of age is 1.57 (95% CI 1.10 to 2.23). Nevertheless, due to study design limitations and imprecision of the results, the quality of the evidence is considered low. For the question on the FeNO measurement validity in the diagnosis of asthma in children aged over five, 10 individual studies of consecutive patients were selected. Following an analysis of the evidence, it is observed that for a pre-test probability of 48%, false positives and false negatives are 82 and 144, respectively, for every 1,000 patients with symptoms in which the FeNO level is determined. Even if the quality of the evidence was considered of high quality at the beginning of the process, finally the overall quality was considered low, due to indirectness, with most of the included studies carried out on adults and not on children, and to the statistical heterogeneity found in the overall estimates of sensitivity and specificity. Lastly, with regard to the efficacy of the FeNO measurement to guide treatment with inhaled corticosteroids (ICS) in children aged over five, all the guidelines and reports include this aspect-the most recent of these based on the Cochrane SR published in 2009. This review includes studies made on adults and children, but in order to answer to this question only the studies carried out on children were selected. This review concludes that the strategy that uses the FeNO measurement decreases the number of patients with one or more exacerbations (RD -0.063 (IC95% of -0.124 to 0.002)), but at the expense of using a larger final daily dose of ICS (MD 140.8 µg (IC 95% of 28.24 to 251.43)). Due to the risk of bias in the included studies and to the imprecision of the estimator to measure the final daily dose of ICS, the overall quality of the evidence was considered low. Contextualisation Almost all the hospitals in our context have a portable FeNO measuring device, although there are also hospitals that have stationary analysers. The organisational changes that require the implementation of these devices depend on the type of analyser. The stationary analyzer is the one that requires the highest level of experience. However, it is also the only one that allows performing those measurements in non-collaborating children. Conclusions The existing evidence to support the routine use of FeNO measurement to predict and/or diagnose asthma both in small children and in children aged more than five is of low quality. With regard to the use of FeNO measurement to guide the treatment with ICS in asthmatic children, the evidence is controversial and of low quality.

Authors' methods: Three clinical questions related to the measurement of FeNO and infant asthma were considered. These questions were structured in accordance with the PICO format. A search of Clinical Practice Guidelines (CPGs), systematic reviews (SRs) and assessment reports was made. When necessary, a search of individual studies was made from the beginning, or, when a report or review that dealt with the question was identified, from the date on which the search in those documents had concluded. The CPGs quality was assessed using the AGREE II instrument and the quality of SRs using the AMSTAR instrument. Individual studies were assessed by means of specific checklists for each type of study design (the Cocrhane’s Risk of Bias for RCT, the checklist of the Centre for Evidence Based Medicine for prognostic studies and the QUADAS II instrument for diagnostic studies). The quality of the evidence was evaluated following the GRADE system, and for this reason the relevant outcomes were defined and their importance was rated on a scale of 1 to 9 (from least to greatest importance). The evidence was summarised for each outcome and the quality of the evidence was assessed considering the following criteria established by GRADE: limitations in the study design or execution, inconsistent results, absence of direct evidence, imprecision and publication bias. Where appropriate, the strength of association, the presence of any dose-response gradient and the consideration of potential confounding factors were also considered. In order to assess the overall quality of the evidence for each question, the level of evidence of the critical outcome of the lowest quality was taken into account.

Project Status: Completed

Year Published: 2014

URL for published report: https://www.euskadi.eus/contenidos/informacion/2014_osteba_publicacion/es_def/adjuntos/medFeno_asmanino.pdf

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Spain

Organisation Name: Basque Office for Health Technology Assessment

Contact Address: C/ Donostia – San Sebastián, 1 (Edificio Lakua II, 4ª planta) 01010 Vitoria - Gasteiz

Contact Name: Lorea Galnares-Cordero

Contact Email: lgalnares@bioef.eus

Copyright: Osteba (Basque Office for Health Technology Assessment) Health Department of the Basque Government