Higher Fractional Exhaled Nitric Oxide Research Articles

The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol.

Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.

Lack of association between Inhaled Corticosteroid use based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. We retrospectively analyzed 107 COPD patients without history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion [ppb] were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. The median FeNO value was 32 (Interquartile range [IQR], 19-45) ppb, and 34 (20.0%) patients were classified as high FeNO group (median 74ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥ 300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01-6.91; p = 0.049). High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

Acute exposure to pollen and airway inflammation in adolescents.

Pollen exposure is known to exacerbate allergic asthma and allergic rhinitis symptoms, yet few studies have investigated if exposure to pollen affects lung function or airway inflammation in healthy children. We evaluated the extent to which higher pollen exposure was associated with differences in airway inflammation and lung function among 490 early adolescent participants (mean age of 12.9 years) in Project Viva, a prebirth cohort based in Massachusetts. We obtained regional daily total pollen counts, including tree, grass, and weed pollen, from a Rotorod pollen counter. We evaluated associations of 3- and 7-day moving averages of pollen with fractional exhaled nitric oxide (FeNO) and lung function using linear regression models and evaluated the linearity of associations with penalized splines. We tested if associations of pollen with FeNO and lung function were modified by current asthma diagnosis, history of allergic rhinitis, aeroallergen sensitivity, temperature, precipitation, and air pollution. Three- and 7-day median pollen concentrations were 19.0 grains/m3 (IQR: 73.4) and 20.9 grains/m3 (IQR: 89.7). In main models, higher concentrations of total pollen over the preceding 3 and 7 days were associated with a 4.6% (95% CI:0.1,9.2) and 7.4% (95% CI: 0.9,14.3) higher FeNO per IQR of pollen, respectively. We did not find associations of pollen with lung function in main models. Asthma, allergic rhinitis, precipitation, and air pollution (nitrogen dioxide and ozone) modified associations of pollen with lung function (Pinteraction  < 0.1), while temperature, sex, and aeroallergen sensitization did not. Short-term exposure to pollen was associated with higher FeNO in early adolescents, even in the absence of allergic sensitization and asthma.

Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma

BackgroundAssociations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. MethodsThe retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. ResultsNinety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20–35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. ConclusionsHigher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.

Silent zone detection in asthma and its relation to T2 inflammation

Abstract Objective Study objectives are to detect small airways disease in asthma and to study T2 inflammatory markers (eosinophil count, IgE, phenotyping) in association with small airways disease. Methods and patients The retrospective study at OPC at Al Qassimi Hospital of EHS included 83 patients with confirmed asthma diagnosis. Based on their ACT scores, patients were divided into two groups. An assessment of demographic data, blood eosinophils, fractional exhaled nitric oxide, IgE, PFE25-75, FEV1%, R5-20, X5 and AX was carried out. Analyzing and collecting data. Results In this study, a significant correlation was found between the R5-20, X5, and AX values of the small airway and the asthma control test. Uncontrolled asthmatics had a higher fractional exhaled nitric oxide level and blood eosinophilic count. Conclusion In asthma management, small airways clinical impact should be investigated actively. Impulse oscillometry is an excellent marker for asthma control.

Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled <20, controlled ≥20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade ≥2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed.

Exhaled Nitric Oxide and Olfactory Dysfunction in Patients with Asthma: Association with Chronic Rhinosinusitis.

Objectives: Olfactory dysfunction is a clinical sign that is important to detect with coexistent upper airway comorbidities in patients with asthma. This study aimed to investigate the etiology of olfactory dysfunction in patients with asthma and the relationship between fractional exhaled nitric oxide (FeNO) levels. Materials and Methods: This study included 47 asthma patients who were evaluated for olfactory dysfunction at Hiroshima University Hospital between 2012 and 2020. The etiologies of olfactory dysfunction were evaluated, and they were classified according to the FeNO levels of patients with asthma. Results: Olfactory dysfunction was observed in 30 patients with asthma, with chronic rhinosinusitis (77%) being the most prevalent etiology. Eosinophilic chronic rhinosinusitis (ECRS) was the most prevalent etiology of olfactory dysfunction in asthma patients with high FeNO levels (≥25 ppb), while non-eosinophilic chronic rhinosinusitis (NCRS) was the most prevalent etiology in asthma patients with low FeNO levels (<25 ppb). Additionally, the prevalence of ECRS was significantly higher in asthma patients with olfactory dysfunction and high FeNO levels (74%) than in those with either high FeNO levels or olfactory dysfunction and those with low FeNO levels and no olfactory dysfunction (12% and 9%, respectively). Conclusions: We found that ECRS was the predominant cause of olfactory dysfunction in patients with high FeNO levels, while NCRS was more common in those with low FeNO levels. The present study showed that both ECRS and NCRS are common etiologies of olfactory dysfunction in patients with asthma. Additionally, this study supports the link between upper and lower airway inflammation in patients with asthma complicated with olfactory dysfunction.

Asthma, Airflow Obstruction, and Eosinophilic Airway Inflammation Prevalence in Western Kenya: A Population-Based Cross-Sectional Study.

Objectives: Determine the prevalence of airway disease (e.g., asthma, airflow obstruction, and eosinophilic airway inflammation) in Kenya, as well as related correlates of airway disease and health-related quality of life. Methods: A three-stage, cluster-randomized cross-sectional study in Uasin Gishu County, Kenya was conducted. Individuals 12years and older completed questionnaires (including St. George's Respiratory Questionnaire for COPD, SGRQ-C), spirometry, and fractional exhaled nitric oxide (FeNO) testing. Prevalence ratios with 95% confidence intervals (CIs) were calculated. Multivariable models were used to assess correlates of airflow obstruction and high FeNO. Results: Three hundred ninety-two participants completed questionnaires, 369 completed FeNO testing, and 305 completed spirometry. Mean age was 37.5years; 64% were women. The prevalence of asthma, airflow obstruction on spirometry, and eosinophilic airway inflammation was 21.7%, 12.3% and 15.7% respectively in the population. Women had significantly higher SGRQ-C scores compared to men (15.0 vs. 7.7). Wheezing or whistling in the last year and SGRQ-C scores were strongly associated with FeNO levels >50ppb after adjusting for age, gender, BMI, and tobacco use. Conclusion: Airway disease is a significant health problem in Kenya affecting a young population who lack a significant tobacco use history.

Association of size-fractionated particulate matters and their chemical constituents with airway inflammation and lung function among healthy children: A panel study

BackgroundEvidence is limited regarding size-fractionated particulate matters and their constituents responsible for children's respiratory health. ObjectiveTo investigate the short-term effects of size-fractionated particle number counts (PNCs) and their chemical constituents on airway inflammation and lung function in healthy children. MethodsWe conducted a longitudinal panel study involving 3 repeated surveys among 144 children aged 4–12 years in Guangzhou, China. Lung function and the fractional exhaled nitric oxide (FeNO) were measured during each visit. The real-time multi-size PNCs and their 23 constituent counts were obtained from the environmental monitoring station. We applied linear mixed-effects (LME) models, least absolute shrinkage and selection operator (LASSO) regression, and Bayesian kernel machine regression (BKMR) to evaluate the associations. ResultsEach interquartile range (IQR) increase in PNC0.5 was dose-responsive associated with 10.46% (95% CI: 2.54%, 18.98%) increase in FeNO at lag 0 day and 1.12% (95% CI: -1.90%, −0.33%) decrease in the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) at lag 1 day. But results for PNC1.0 and PNC2.5 were not significant. In LASSO regression models, K+, NH4+, and HSO4− were important predictors for FeNO, while Mg+, NH4+, and Mn+ were significant predictors for FEV1/FVC. Additionally, the overall effects of constituent mixture on higher FeNO or lower FEV1/FVC were robust when the mixture was above the 55th or 65th percentiles in PNC0.5 compared to the median. And a significant association between exposure to NH4+ and FeNO increment was identified, when setting all other constituents at the 25th, 50th and 75th percentiles. ConclusionShort-term exposure to PNC0.5 was dose-responsive related to increased FeNO and decreased FEV1/FVC among healthy children, and NH4+ in PNC0.5 might play a more dominant role in airway inflammation.

Recovery of Breakthrough Asthma Attacks Treated With Oral Steroids While on Monoclonal Antibody Therapy: Protocol for a Prospective Observational Study (BOOST).

Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. DERR1-10.2196/46741.

The Practical Role of FEF25-75 in Young Patients with Allergic Rhinitis.

Allergic rhinitis (AR) is a relevant risk factor asthma as it may frequently precede asthma onset. There is evidence that lung function may be early impaired in AR patients. In this regard, the forced expiratory flow at 25%-75% of vital capacity (FEF25-75) could be a reliable marker of bronchial impairment in AR. Therefore, the present study investigated the practical role of FEF25-75 in young people with AR. The parameters included history, body mass index (BMI), lung function, bronchial hyperresponsiveness (BHR), and fractional exhaled nitric oxide (FeNO). This cross-sectional study included 759 patients (74 females and 685 males, mean age of 29.2 years) suffering from AR. The study demonstrated a significant association between low FEF25-75 values and BMI (OR 0.80), FEV1 (OR 1.29), FEV1/FVC (OR 1.71), and BHR (OR 0.11). Stratifying the patients on the basis of the presence (or absence) of BHR, sensitization to house dust mites (OR 1.81), AR duration (OR 1.08), FEF25-75 (OR 0.94), and FeNO (OR 1.08) were associated with BHR. Stratifying patients based on high FeNO values (>50 ppb), BHR was associated with high FeNO (OR 39). In conclusion, the present study showed that FEF25-75 was associated with low FEV1 and FEV1/FVC and BHR in AR patients. Therefore, spirometry should be considered in the long-term workup of patients with allergic rhinitis as impaired FEF25-75 might suggest an initial progression toward asthma.

Association between lipid-A-producing oral bacteria of different potency and fractional exhaled nitric oxide in a Norwegian population-based adult cohort

BackgroundLipid A is the primary immunostimulatory part of the lipopolysaccharide (LPS) molecule. The inflammatory response of LPS varies and depends upon the number of acyl chains and phosphate groups in lipid A which is specific for a bacterial species or strain. Traditional LPS quantification assays cannot distinguish between the acylation degree of lipid A molecules, and therefore little is known about how bacteria with different inflammation-inducing potencies affect fractional exhaled nitric oxide (FeNO). We aimed to explore the association between pro-inflammatory hexa- and less inflammatory penta-acylated LPS-producing oral bacteria and FeNO as a marker of airway inflammation.MethodsWe used data from a population-based adult cohort from Norway (n = 477), a study center of the RHINESSA multi-center generation study. We applied statistical methods on the bacterial community- (prediction with MiRKAT) and genus-level (differential abundance analysis with ANCOM-BC) to investigate the association between the oral microbiota composition and FeNO.ResultsWe found the overall composition to be significantly associated with increasing FeNO levels independent of covariate adjustment, and abundances of 27 bacterial genera to differ in individuals with high FeNO vs. low FeNO levels. Hexa- and penta-acylated LPS producers made up 2.4% and 40.8% of the oral bacterial genera, respectively. The Bray–Curtis dissimilarity within hexa- and penta-acylated LPS-producing oral bacteria was associated with increasing FeNO levels independent of covariate adjustment. A few single penta-acylated LPS producers were more abundant in individuals with low FeNO vs. high FeNO, while hexa-acylated LPS producers were found not to be enriched.ConclusionsIn a population-based adult cohort, FeNO was observed to be associated with the overall oral bacterial community composition. The effect of hexa- and penta-acylated LPS-producing oral bacteria was overall significant when focusing on Bray–Curtis dissimilarity within each of the two communities and FeNO levels, but only penta-acylated LPS producers appeared to be reduced or absent in individuals with high FeNO. It is likely that the pro-inflammatory effect of hexa-acylated LPS producers is counteracted by the dominance of the more abundant penta-acylated LPS producers in this population-based adult cohort involving mainly healthy individuals.

Fractional exhaled nitric oxide in the assessment of exercise-induced bronchoconstriction: A multicenter retrospective analysis of UK-based athletes.

Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes. Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds-that is, intermediate (≥25 ppb) and high FeNO (≥40 ppb and ≥ 50 ppb)-and were evaluated against objective evidence of EIB (≥10% fall in FEV1 ). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25 ppb, ≥40 ppb, and ≥ 50 ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25 ppb was 55%, which decreased to 37% and 27% at ≥40 ppb and ≥ 50 ppb, respectively. The specificity of FeNO ≥25 ppb, ≥40 ppb, and ≥ 50 ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656. FeNO ≥40 ppb provides good specificity, that is, the ability to rule-in a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes.

The Correlation Between Fractional Exhaled Nitric Oxide (FeNO), Blood Eosinophil Count, Immunoglobulin E Levels, and Spirometric Values in Patients With Asthma.

In patients with asthma, fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic airway inflammation. However, the correlation with the blood eosinophil count, immunoglobulin E (IgE), and spirometric values is not well established. We aimed to investigate the correlation between FeNO, blood eosinophils, IgE, and spirometric values in asthmatic patients. Data were extracted from the electronic medical records of adult asthmatic patients, and included the FeNO, blood eosinophil count, IgE, and spirometric values. The correlation between the markers was investigated using receiver operating characteristics (ROC) and the area under the curve (AUC). A total of 135 adult patients (30% male) were analyzed. The mean FeNO was 36 ppb and almost half (48%) had a FeNO > 25 ppb. The mean blood eosinophil count was 377 cells/mm3, and 42% had a blood eosinophil count > 300 cells/mm3. There was a significant positive correlation between FeNO and the blood eosinophil count (r = 0.42, sensitivity 63%, specificity 77%, AUC 72%, p < 0.0001) as well as with the IgE (r = 0.35, sensitivity 78%, specificity 44%, AUC 68%, p < 0.0007). There was significant negative correlation between FeNO and FEV1% (r = -0.18, sensitivity 35%, specificity 85%, AUC 67%, p = 0.027). The blood eosinophil count, IgE, and spirometric values were correlated with the severity of the eosinophilic airway inflammation (high FeNO). Asthmatic patients with a higher FeNO level had a higher eosinophil count, higher IgE levels, and lower FEV1 values.

The Long-Term Impact of Early-Life Tuberculosis Disease on Child Health: A Prospective Birth Cohort Study.

There is growing concern that post-tuberculosis disease (TB) sequelae and morbidity are substantial but no studies have controlled for pre-existing factors prior to disease. Whether children have post-TB morbidity is not well characterized. To assess the effect of a TB diagnosis on wheezing episodes, lung function, and anthropometric measurements among children enrolled in a prospective birth cohort study in South Africa. We prospectively followed children from birth through 5 years for TB using diagnostic tests including chest radiography, and repeated induced sputum sample testing with Xpert MTB/RIF and liquid culture. We longitudinally measured health outcomes including growth, wheezing, and lung function up to 5 years. Mixed-effects linear regression models were used to assess growth and lung function after TB. Poisson regression was used to assess risk of subsequent wheezing. Among 1,068 participants, 96 TB cases occurred (1,228 cases per 100,000 person-years, 95%CI, 1,006-1,500) occurred over 7,815 child-years of follow-up. TB was associated with lower length-for-age (-0.40; 95%CI, -0.68, -0.11), weight-for-age (-0.30; 95%CI, -0.59, -0.01), and BMI z-scores (-0.54; 95%CI, -0.83, -0.25) at 5 years. Children developing TB were consistently more likely to wheeze regardless of the timing of TB. Children diagnosed with TB between 0-1 year old had reduced tPTEF/tE (-2.35%; 95% CI, -4.86, -0.17) and higher fractional exhaled nitric oxide (2.88ppb; 95% CI, 0.57-5.19) at 5 years. Children diagnosed with TB between 1-4 years old had impaired tidal volume (-9.32 mL; 95% CI, -14.89, -3.75) and tPTEF/tE (-2.35%; 95%CI, -4.86, -0.17]) at 5 years. Prevention of TB disease in the first few years of life may have substantial long-term benefits through childhood. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

[LOWER RESPIRATORY TRACT SCREENING USING FRACTIONAL EXHALED NITRIC OXIDE IN PATIENTS WITH EOSINOPHILIC CHRONIC RHINOSINUSITIS].

It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma. We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment. Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation. A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.

Биомаркеры воспаления и контроль бронхиальной астмы у детей

Asthma is the heterogeneous lung disease, caused by a chronic inflammation, characterized by various phenotypes, for the identification of which biomarkers can be used. However, most biomarkers are still experimental and have limitations for clinical practice. Objective. To study the link between the values of T2-inflammatory biomarkers in children with poor asthma control and features of asthma treatment. Patients and methods. The study included 100 patients aged 5 to 17 years (average age 13 years) with an established diagnosis of asthma. The level of asthma control of patient was assessed using asthma control tests and asthma control tests in children (ACT and C-ACT). The following markers were studied: the level of total immunoglobulin E (total IgE), peripheral blood eosinophils, fractional exhaled nitric oxide (FeNO), the number of eosinophils in nasal smears. The significance of the marker was determined by statistical data analysis methods used in medicine. Results. Despite the prescribed basic therapy, most children do not achieve normal asthma control. It was revealed that 43% of patients had one or more elevated markers of T2 inflammation. Children with partially controlled and uncontrolled asthma had high levels of total IgE (≥100 IU/ml), elevated levels of eosinophils in the blood (≥400 cells/ml) and high FeNO values (≥20 parts per billion). The most significant biomarker of poor asthma control in children is the level of total serum IgE ≥100 IU/ml. It has been established that allergic asthma in children is usually combined with the predominance of Th2 lymphocytes and eosinophilic inflammation of the respiratory tract. Conclusion. T2-inflammation biomarkers can be used as indicators of respiratory tract inflammation activity and to assess asthma control in children. Key words: biomarkers, asthma, children, asthma control, T2-inflammation

Prediction of bronchodilation test in adults with chronic cough suspected of cough variant asthma.

Many patients with cough variant asthma (CVA) are underdiagnosed and undertreated due to the atypical symptoms, low diagnostic sensitivity of bronchodilator response (BDR), and limited application of bronchial challenge test. To investigate whether airway reversibility in BDR can predict CVA diagnosis in patients with chronic cough and negative BDR. This open-label, prospective cohort study included patients with chronic cough, nearly normal chest CT scan, and negative BDR results. Inhaled corticosteroids and long-acting β2 agonists were given for 4 weeks. The confirmed diagnosis of CVA was defined as improved symptoms and an increase of forced expiratory volume in 1 s (FEV1) by >12% and >200 mL after 4 weeks of treatment. Of 155 patients recruited, 140 completed the study. Patients in the CVA positive diagnosis group had greater absolute (Δ) and percent (Δ%) improvements in FEV1 and forced expiratory flows (FEFs), and higher fractional exhaled nitric oxide (FENO) than in the CVA negative diagnosis group. The area under the receiver operating characteristic curves (AUCs) of ΔFEV1%, FEF25-75%pred (percentage of predicted forced expiratory flow at 25% to 75%) and FENO for CVA positive diagnosis was 0.825, 0.714, and 0.637, with cutoff values of 5.90%, 61.99% and 41.50 ppb, respectively. A joint model of ΔFEV1% combined with FEF25-75%pred or FENO increased the AUC to 0.848 and 0.847, respectively. ΔFEV1% in BDR can predict a CVA diagnosis and response to anti-asthma treatment in patients with chronic cough and negative BDR. [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2000029065].

Use of fractional exhaled nitric oxide to guide the treatment of asthma and chronic cough

Fractional exhaled nitric oxide (FeNO) is a breath biomarker that is easy to perform at the point of care in individuals 5 years or older. Elevated FeNO levels indicate increased type 2 airway inflammation, specifically increased interleukin 4/13 activity. Recent guidelines have made recommendations on the utility of FeNO measurement in the diagnosis and management of asthma. Measurement of FeNO is recommended as an adjunct to the evaluation process in patients with suspected asthma in whom the diagnosis of asthma is uncertain based on clinical presentation, spirometry, and bronchodilator challenge testing. Elevated FeNO levels are associated with an increased risk of asthma exacerbation, and FeNO suppression test can help differentiate “difficult” from “severe” asthma. High FeNO levels can predict response to anti-inflammatory therapies, including corticosteroids and certain biologics. FeNO measurement also has value in evaluation of chronic cough with increased levels suggesting a corticosteroid responsive condition such as cough-variant asthma or eosinophilic bronchitis.

DOES RACE IMPACT THE RELATIONSHIPS BETWEEN FENO AND CLINICAL CHARACTERISTICS OF ASTHMA AND ALLERGIC DISORDERS?

<h3>Introduction</h3> Fractional exhaled nitric oxide (FeNO) is an adjunctive tool for asthma management. It is also elevated in atopic patients without asthma. We sought to evaluate whether race modifies the association of FeNO with indicators of allergy and asthma. <h3>Methods</h3> Children attending a scheduled 10 year visit as part of the WHEALS (Wayne County Health Environment Allergy and Asthma Longitudinal Study) birth cohort were included, with analysis restricted to participants whose reported race was Black or White. The 10 year visit included determination of allergic rhinitis (AR), atopic dermatitis (AD), asthma, food allergy (FA), spirometry, methacholine challenge, total IgE, eosinophil count, and allergen sensitization. <h3>Results</h3> 459 children (75.4% Black, mean age 10.2 years) had sufficient data for analysis. Children with current asthma, AR, AD, FA, or sensitization to common foods or inhalant allergen had higher FeNO (p <0.001 for each). Black children had higher FeNO levels (p=0.002). Following adjustment for other variables including allergic disorders and atopy, race had no significant association with FeNO (p=0.094). Following adjustment, race was a significant effect modifier only for the association between PC20 and FeNO (p=0.007), where an association of higher FeNO with bronchial hyperresponsiveness was found amongst Black children. <h3>Conclusion</h3> Our data reflects a diverse population with higher levels of FeNO in Black children compared to White children, largely explained by a higher prevalence of allergic disorders and atopy. Although the association between PC20 and FeNO was modified by race, a potential limitation was that we could not conduct a methacholine challenge in all children.