The value of FeNO measurement in childhood asthma: uncertainties and perspectives

Abstract

Asthma is considered an heterogeneous disease, requiring multiple biomarkers for diagnosis and management. Fractional exhaled nitric oxide in exhaled breath (FeNO) was the first useful non-invasive marker of airway inflammation in asthma and still is the most widely used. The non-invasive nature and the relatively easy use of FeNO technique make it an interesting tool to monitor airway inflammation and rationalize corticosteroid therapy in asthmatic patients, together with the traditional clinical tools (history, physical examination and lung function tests), even if some controversies have been published regarding the use of FeNO to support the management of asthma in children. The problem of multiple confounding factors and overlap between healthy and asthmatic populations preclude the routine application of FeNO reference values in clinical practice and suggest that it would be better to consider an individual “best”, taking into account the context in which the measurement is obtained and the clinical history of the patient. Besides, there is still disagreement about the role of FeNO as a marker of asthma control, due to the complexity of balance among the different items involved in its determination and the lack of homogeneity in the population groups studied in the few studies conducted so far. Heterogeneity of problematic severe asthma greatly limits utility of FeNO alone as a biomarker of inflammation to optimize the disease management on an individual basis. None of the studies conducted so far demonstrated that the use of FeNO was better than current asthma guidelines in controlling asthma exacerbations. In summary, there is a large variation in FeNO levels between individuals, which may reflect the natural heterogeneity in baseline epithelial nitric oxide synthase activity and/or the contribution of other noneosinophilic factors to epithelial nitric oxide synthase activity. FeNO is a promising biomarker, but at present some limits are highlighted. We would recommend that further research can be carried out by organizing studies aimed to obtain reliable reference values of FeNO and in order to better interpret FeNO measurements in clinical settings, taking also into account the influence of genetic and environmental factors.

Immunological and toxicological risk assessment of e-cigarettes

“…On the downside, this study did not include a treatment group of individuals smoking conventional cigarettes only, making it hard to compare the safety of e-cigs with tobacco cigarettes. FeNO is a biomarker for lung inflammation, which is affected by multiple factors including duration of exposure, smoking habits and current medication of the user [50]. Thus, it is difficult to predict probable decline in lung inflammation due to vaping just by measuring the FeNO levels in the lungs.…”

Longitudinal study of lung function, exhaled nitric oxide and asthma control level in children and adolescents treated with inhaled beclomethasone

“…16 O nível da FeNO foi o primeiro e é o mais amplamente marcador de inflação das vias aéreas utilizado. 8 Segundo alguns autores o nível da FeNO prediz a probabilidade de responsividade a corticosteroides mais consistentemente que espirometria, resposta broncodilatadora, variabilidade do pico de fluxo expiratório (PFE) e hiperrresponsividade à metacolina. 22,23 Outros autores têm demonstrado que o nível da FeNO pode ser usado como marcador de controle da asma 16 e que este apresenta resposta rápida à modificação do tratamento (Grob et al, 2008).…”

“…Entretanto, este marcador inflamatório, além de ser modulado por diversos fatores como a idade, gênero, altura, etnia, heterogeneidade dos fenótipos da asma e doenças relacionadas à atopia, ele também é modulado por fatores ambientais (fumo, poluição ambiental, horário da medida, estação do ano). 8,30 Concluindo, este estudo mostrou que o tratamento com corticosteroide inalatório melhorou a classificação do nível de controle da asma e que apesar da grande dispersão dos níveis da FeNO, ela correlacionou-se inversamente com a relação VEF 1 /CVF nas três avaliações.…”

“…Além disso, existe uma grande variação nos níveis da FeNO entre os indivíduos, que pode refletir a heterogeneidade da atividade enzima óxido nítrico sintase (NOS) no epitélio e/ou a contribuição de outros factores não eosinofílicos epiteliais da atividade da NOS. 8 O objetivo do manejo da asma é o controle da doença, que refere-se à extensão com a qual as manifestações da asma são atenuadas ou suprimidas pelo tratamento, e compreende Introdução A asma é uma doença heterogênea, caracterizada por inflamação crônica das vias aéreas, definida pela história de sintomas respiratórios de sibilos, dispneia, aperto no peito, tosse e limitação crônica do fluxo aéreo. 1 A asma apresenta diferentes fenótipos que podem estar relacionados com a história natural da doença, com as características imunológicas, inflamatórias, estruturais das vias aéreas e o controle clínico.…”

Exhaled nitric oxide can't replace the methacholine challenge in suspected pediatric asthma

“…[8]). Apart from this, the power of F E NO as a tool for the diagnosis of asthma and as a substitute for bronchial provocation is under discussion [5,6,9,10]. Despite differences in the cut-off values used for discrimination between patients without and with asthma, these meta-analyses revealed that the overall specificity of F E NO was higher than sensitivity, especially in adults.…”