The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

Wang, Zhen; Pianosi, Paolo; Keogh, Karina A.; Zaiem, Feras; Alsawas, Mouaz; Alahdab, Fares; Almasri, Jehad; Mohammed, Khaled; Larrea-Mantilla, Laura; Farah, Wigdan; Daraz, Lubna; Barrionuevo, Patricia; Gunjal, Shalak; Prokop, Larry J.; Murad, M Hassan

doi:10.23970/ahrqepccer197

Cited by 40 publications

(55 citation statements)

References 96 publications

(140 reference statements)

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“…35 FeNO is considered as a marker of T helper 2-associated inflammation, but its benefits as a noninvasive biomarker for asthma management are not entirely clear. 36,37 An interesting observation in our study was that allergic 10-year-olds had higher FeNO levels than those who were nonallergic regardless of asthma, also supported by others. 38 Allergic heredity seems to be important for FeNO levels illustrated by the fact that the DH group had higher FeNO levels regardless of being allergic or nonallergic.…”

Section: Discussionsupporting

confidence: 86%

The allergic phenotype during the first 10 years of life in a prospective cohort

Björkander

Hallberg

Persson

et al. 2019

Immunity Inflam & Disease

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Background Heredity and environmental parameters jointly affect allergy development. Here, we used a Swedish prospective cohort to study the influence of heredity and factors usually associated with allergic disease and the development of allergic manifestations in combination with immunoglobulin E (IgE) sensitization at four different time points until 10 years of age. Methods Parents‐to‐be were characterized concerning allergy and their children (n = 281) were divided based on allergic heredity and followed from birth and clinically examined for IgE‐associated allergic symptoms until 10 years of age. The relation between allergy and early‐life parameters was analyzed by logistic regression. Group‐wise comparisons were made by nonparametrical tests. Results Early life eczema and/or asthma in combination with IgE sensitization, was a strong indicator of allergy at a later time point. Further, the early occurrence of multiple allergic symptoms among IgE‐sensitized children predisposed for a more complex allergic phenotype at later ages, independently of allergic heredity. At 10 years of age, allergic children had higher fractional exhaled nitrogen oxide (FeNO) levels, regardless of asthma, and FeNO levels were also influenced by heredity. Birth season was strongly associated with allergy development, but only in children with two allergic parents. Conclusion Allergic eczema/asthma in early life, being born during the autumn/winter, having multiple allergic symptoms and two allergic parents were all strong predictors for having allergic diseases at 5 and 10 years of age. However, the allergic march seems to be independent of heredity, as IgE‐mediated allergies follow the same trajectories in children with and without allergic heredity.

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Section: Discussionsupporting

confidence: 86%

The allergic phenotype during the first 10 years of life in a prospective cohort

Björkander

Hallberg

Persson

et al. 2019

Immunity Inflam & Disease

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“…The measurement of exhaled breath NO is recommended to assist in phenotyping, and perhaps diagnosing, patients with asthma (1)(2)(3). NO is a product of l-arginine conversion to l-citrulline via the NOS enzyme isoforms.…”

Section: Introductionmentioning

confidence: 99%

l-Arginine supplementation in severe asthma

Liao¹,

Showalter²,

Linderholm³

et al. 2020

JCI Insight

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“…Although prior studies have demonstrated general associations between FE NO and atopy, 39 and some studies have reported that FE NO is associated with atopy but not with asthma, 40 a recent comprehensive comparative effectiveness review of the utility of FE NO in asthma management that included 43 studies in adults and children found that although FE NO is associated with atopy, FE NO concentrations increased the odds of correctly diagnosing asthma between 5.9 and 17-fold, demonstrating that elevated FENO levels are also associated with asthma. 13 We observed that enrollment FE NO was not correlated with total IgE level or positive RAST specific IgE tests in subjects at age 6 years, or with a history of eczema at age 6 years; however, it is possible that with a sufficiently large sample size there might have been an association between FE NO and other atopic features that our study was underpowered to detect. Although an association between FE NO and atopy is well accepted, 13,39 our data support the concept that FE NO is not simply a marker of generalized atopy, but rather a marker of lower airway allergic inflammation that is associated with, and predictive of, atopic asthma in infants and toddlers with recurrent wheezing.…”

Section: Discussionmentioning

confidence: 52%

“…13 We observed that enrollment FE NO was not correlated with total IgE level or positive RAST specific IgE tests in subjects at age 6 years, or with a history of eczema at age 6 years; however, it is possible that with a sufficiently large sample size there might have been an association between FE NO and other atopic features that our study was underpowered to detect. Although an association between FE NO and atopy is well accepted, 13,39 our data support the concept that FE NO is not simply a marker of generalized atopy, but rather a marker of lower airway allergic inflammation that is associated with, and predictive of, atopic asthma in infants and toddlers with recurrent wheezing. There are several additional limitations to this study.…”

Section: Discussionmentioning

confidence: 52%

“…The fractional concentration of exhaled nitric oxide (FE NO ) is a biomarker for which an extensive body of clinical data support its use in adults and school-age children to identify eosinophilic airway inflammation, support the diagnosis of allergic asthma, and to determine the likelihood of steroid responsiveness in patients with chronic respiratory symptoms. 12,13 However, there is limited prospective data assessing FE NO prospectively among wheezy infants/toddlers who were followed into their school-age years to determine associations with persistent asthma, [14][15][16][17][18] and to our knowledge, there are no prospective data assessing associations between FE NO measured in wheezy infants and toddlers with asthma exacerbations or lung function at school age among those children. Because the majority of infants and preschool children with recurrent wheezing who go on to develop persistent childhood asthma can be characterized as having an atopic phenotype of asthma, 19 FE NO may be well suited as a biomarker to separate infants/toddlers with evolving atopic asthma from those with wheezing due to other etiologies.…”

Section: Introductionmentioning

confidence: 99%

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<p>Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age</p>

White¹,

Kolstad²,

Elliott³

et al. 2020

JAA

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Background: There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FE NO) in infants/toddlers with recurrent wheezing for asthma at school age. Objectives: In a cohort of infants/toddlers with recurrent wheezing determine the predictive values of sedated single-breath FE NO (SB-FE NO) and awake tidal-breathing mixed-expired FE NO (tidal-FE NO) for active asthma, severe exacerbations, and lung function at age 6 years. Methods: In 44 infants/toddlers, SB-FE NO was measured under sedation at 50 mL/sec in conjunction with forced expiratory flow and volume measurements, and tidal-FE NO was measured during awake tidal breathing. Clinical outcomes and lung function were assessed at age 6 years in 36 subjects. Results: Enrollment SB-FE NO was significantly higher among subjects with active asthma at age 6 years than among subjects without asthma (36.4 vs. 16.9 ppb, p < 0.0001), and the odds of asthma was 7.6 times greater (OR 7.6; 95% CI 1.8-31.6) for every 10 ppb increase in enrollment SB-FE NO. A ROC analysis demonstrated that an enrollment SB-FE NO > 31.5 ppb predicted active asthma at age 6 years with an area under the curve (AUC) of 0.92 (95% CI: 0.82-1). SB-FE NO was also higher among subjects who experienced severe asthma exacerbations during the year preceding age of 6 years. SB-FE NO at enrollment and lung function measures at age 6 years were modestly correlated (FEV1: r = −0.4; FEF25-75: r = −0.41; FEV1/FVC ratio: r=−0.46), and SB-FE NO was significantly higher among subjects with bronchodilator responsiveness (BDR) at age 6 years. Tidal-FE NO was not predictive of active asthma, exacerbations, or lung function at age 6 years. Conclusion: In wheezy infants/toddlers, SB-FE NO was predictive of school-age asthma and associated with lung function measures at age 6 years.

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The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

Cited by 40 publications

References 96 publications

The allergic phenotype during the first 10 years of life in a prospective cohort

The allergic phenotype during the first 10 years of life in a prospective cohort

l-Arginine supplementation in severe asthma

<p>Exhaled Nitric Oxide in Wheezy Infants Predicts Persistent Atopic Asthma and Exacerbations at School Age</p>

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