Patterns and determinants of exhaled nitric oxide trajectories in schoolchildren over a 7-year period

Garcia, Erika; Zhang, Yue; Rappaport, Edward; Berhane, Kiros; Muchmore, Patrick; Silkoff, Philip E.; Molshatzki, Noa; Gilliland, Frank D.; Eckel, Sandrah P.

doi:10.1183/13993003.00011-2020

“…Indeed, our data suggest that differences in height (>80cm range in both MAAS and SEATON cohorts) markedly influence FeNO, particularly in relation to the higher percentile lines. Consistent with this, Garcia et al used repeated measures within children going through puberty and reported a substantial increase in FeNO between 8-16 years, with tracking of personalised FeNO measurements, and highlighted the limitations of fixed FeNO reference values [13]. Whilst using a fixed single FeNO cutoff may seem easier for clinicians to implement, technology allowing input of demographic data and automatic calculation of % predicted values (as for spirometry), would streamline the utility of a height-adjusted approach in practice.…”

Section: Discussionmentioning

confidence: 80%

“…Of 214 symptomatic and treatment-naïve patients referred to the RADicA study from primary care for possible asthma, 73 (median [IQR] age: 11 [8][9][10][11][12][13][14] years, 47.9% male, 54.8% white) were aged 22 years or younger (age-matching for chart development cohort), had a definitive diagnostic outcome (51 had asthma, 22 did not have asthma), and a measurement of FeNO before treatment was initiated (Table E18). Data from these participants were used to assess sensitivity and s pecificity of FeNO percentile charts for asthma diagnosis.…”

Section: Using Feno Percentile Chart For Asthma Diagnosis In Symptoma...mentioning

confidence: 99%

“…The normal ranges of FeNO are influenced by factors such as sex, age, height, ethnicity and allergic sensitisation [6][7][8][9][10][11][12]. Moreover, the pubertal growth spurts influence FeNO trajectory, potentially further affecting the diagnostic accuracy within this age group when a single fixed cut-off value is used [13]. Currently none of these factors are considered when FeNO levels are interpreted in practice [3,7,14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all

Wang

¹

,

Fowler

²

,

Turner

³

et al. 2022

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BackgroundThe normal range of fractional exhaled nitric oxide (FeNO) is influenced by demographic factors. However, single, fixed cut-off values are used for clinical interpretation in children despite rapid growth. We aimed to define the normal range of FeNO during childhood and evaluate its utility in the diagnostic setting.MethodFeNO percentile charts were developed using data from non-asthmatic children in a population-based birth cohort (MAAS). Children were skin prick tested and FeNO measured at the age of 8, 11, 13–16 and 18 years and clinical information was collected. This chart was externally validated in the SEATON cohort before being prospectively tested in symptomatic, treatment-naïve patients with suspected asthma in a diagnostic setting (RADicA study).ResultsHeight, weight, BMI and age were predictive of FeNO in univariate analysis using 1219 FeNO measurements. Only height remained significant after adjustment in the overall, non-atopic and atopic populations, and was included in the predictive equations for 50th, 75th 90th and 98th percentiles. The proposed percentile lines corresponded to the 57th (95%CI:53–61st), 80th (76–83rd), 90th (87–92nd) and 98th (96–99th) percentiles in the SEATON cohort (660 measurements). When tested in 73 symptomatic treatment-naïve children and young adults (median [IQR] age: 11 [8–14] years), a FeNO >90th percentile gave a 96% specificity and positive predictive value of 97%, identifying 59% of children who were subsequently diagnosed with asthma after extensive testing.ConclusionWe developed a height-based FeNO percentile chart which quantifies the probability of asthma in symptomatic children and merits further validation towards clinical implementation.

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“…In a previous longitudinal analysis, FeNO 50 was found to have a strong positive linear association with height across this age range in children without asthma [30]. To complement the previous analysis relating longitudinally assessed FeNO 50 to height, here we relate longitudinally assessed NO parameters (from the up to 2 repeated assessments of multiple flow FeNO) to standardized height (population-mean centered: 162.7 centimeters and population-SD scaled: 8.75 centimeters).…”

Section: Methodsmentioning

confidence: 94%

“…Our findings add to the limited literature on associations of NO parameters with height/age. A previous analysis using longitudinal FeNO 50 data from the same cohort over a longer follow-up period, from ages 8-16, found that FeNO 50 increased approximately linearly with height and FeNO 50 increased nonlinearly with age [30].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Hierarchical Bayesian models of covariate effects on airway and alveolar nitric oxide

Weng

¹

,

Molshatzki

²

,

Marjoram

³

et al. 2022

Preprint

Self Cite

0

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Biomarkers such as exhaled nitric oxide (FeNO), a marker of airway inflammation, have applications in the study of chronic respiratory disease where longitudinal studies of within-participant changes in the biomarker are particularly relevant. A cutting-edge approach to assessing FeNO, called multiple flow FeNO, repeatedly assesses FeNO across a range of expiratory flow rates at a single visit and combines these data with a deterministic model of lower respiratory tract NO to estimate parameters quantifying airway wall and alveolar NO sources. Previous methodological work for multiple flow FeNO has focused on methods for data from a single participant or from cross-sectional studies. Performance of existing ad hoc two-stage methods for longitudinal multiple flow FeNO in cohort or panel studies has not been evaluated. In this paper, we present a novel longitudinal extension to a unified hierarchical Bayesian (L_U_HB) model relating longitudinally assessed multiple flow FeNO to covariates. In several simulation study scenarios, we compare the L_U_HB method to other unified and two-stage frequentist methods. In general, L_U_HB produced unbiased estimates, had good power, and its performance was not sensitive to the magnitude of the association with a covariate and correlations between NO parameters. In an application relating height to longitudinal multiple flow FeNO in schoolchildren without asthma, unified analysis methods estimated positive, statistically significant associations of height with airway and alveolar NO concentrations and negative associations with airway wall diffusivity while estimates from two-stage methods were smaller in magnitude and sometimes non-significant.

show abstract

Longitudinal hierarchical Bayesian models of covariate effects on airway and alveolar nitric oxide

Weng

¹

,

Molshatzki

²

,

Marjoram

³

et al. 2023

Sci Rep

Self Cite

0

View full text Add to dashboard Cite

Biomarkers such as exhaled nitric oxide (FeNO), a marker of airway inflammation, have applications in the study of chronic respiratory disease where longitudinal studies of within-participant changes in the biomarker are particularly relevant. A cutting-edge approach to assessing FeNO, called multiple flow FeNO, repeatedly assesses FeNO across a range of expiratory flow rates at a single visit and combines these data with a deterministic model of lower respiratory tract NO to estimate parameters quantifying airway wall and alveolar NO sources. Previous methodological work for multiple flow FeNO has focused on methods for data from a single participant or from cross-sectional studies. Performance of existing ad hoc two-stage methods for longitudinal multiple flow FeNO in cohort or panel studies has not been evaluated. In this paper, we present a novel longitudinal extension to a unified hierarchical Bayesian (L_U_HB) model relating longitudinally assessed multiple flow FeNO to covariates. In several simulation study scenarios, we compare the L_U_HB method to other unified and two-stage frequentist methods. In general, L_U_HB produced unbiased estimates, had good power, and its performance was not sensitive to the magnitude of the association with a covariate and correlations between NO parameters. In an application relating height to longitudinal multiple flow FeNO in schoolchildren without asthma, unified analysis methods estimated positive, statistically significant associations of height with airway and alveolar NO concentrations and negative associations with airway wall diffusivity while estimates from two-stage methods were smaller in magnitude and sometimes non-significant.

show abstract

Patterns and determinants of exhaled nitric oxide trajectories in schoolchildren over a 7-year period

Cited by 8 publications

References 36 publications

Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all

Defining the normal range of fractional exhaled nitric oxide in children: one size does not fit all

Longitudinal Hierarchical Bayesian models of covariate effects on airway and alveolar nitric oxide

Longitudinal hierarchical Bayesian models of covariate effects on airway and alveolar nitric oxide

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