The relationship of gastroesophageal reflux disease and asthma control.

Purpose: To study whether ACT responses are confounded by gastro-esophageal status (GERD), and if this is in concordance with the variation in Forced Expiratory Volume in 1 second (FEV1%) and Fractional Excretion of Nitric Oxide (FeNO). Materials and Methods: This is a prospective cohort study (n = 307). Patients were surveyed for demographics data, and underwent ACT scoring, FEV1% and FeNO testing. Results: Patients with GERD had mean ACT scores that were 4.1 (p < .001) lower than without-GERD group. Not-well-controlled asthmatics (FEV1% <80, high FeNO) with-GERD had mean ACT scores that were 2.9 (p < .001) for FEV1% <80 and 3.8 (p = .008) for high FeNO lower than without-GERD group respectively. Well-controlled asthmatics (FEV1% ≥80, low FeNO) with-GERD had mean ACT scores that were 5.2 (p < .001) for FEV1% ≥80 and 5.1 (p < .001) for low FeNO lower than without-GERD group respectively. Conclusion: Our study demonstrates that symptoms of GERD can lead to an inaccurate perception of asthma control and ACT as compared to objective measures, such as FEV1% and FeNO. Hence, this can lead to mismanagement of asthma, especially when objective measures are not conducted along with ACT.

Domiciliary monitoring of exhaled nitric oxide in the management of asthma: a pilot study.

BACKGROUND: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. METHODS: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. RESULTS: In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). CONCLUSIONS: The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Association between exposure to airborne trichloramine and health effects in indoor swimming pool workers.

OBJECTIVE: The main objective of this study was to comprehensively investigate the association between trichloramine (TCA) exposure and respiratory health effects in swimming pool workers. METHODOLOGY: In this study, air sampling was performed for TCA concentrations at fixed locations (static measurements) and on individual workers (personal measurements) in six indoor public swimming pools during periods of high swimmer attendance over the winter school break. Health effects were evaluated using questionnaires and fractional exhaled nitric oxide (FENO) tests performed before and after the working day. RESULTS: In these swimming pools, the environmental TCA concentration ranged from 0.11 to 0.88 mg/m³. Worker exposure ranged from 0.05 to 0.72 mg/m³ for personal measurements. Furthermore, in each swimming pool, the average worker exposure to TCA exceeded the recommended occupational exposure limit of 0.35 mg/m³. Personal TCA measurements were consistently lower than static measurements performed around the pool, with a reduction ranging from 21% to 49%. This can be explained by the time that the workers spend in the pool area, office, and break room. The most common respiratory health effects self-reported by the workers were coughing, shortness of breath, and sneezing with prevalence rates of 38%, 37%, and 35%, respectively. This study demonstrated an association between TCA exposure and eye irritation. Analysis of the FENO tests revealed that individuals with preexisting asthma or allergies exhibited sustained FENO elevation. CONCLUSION: The findings suggest that occupational exposure to TCA in indoor swimming pools is a matter of concern. Implementing and improving workplace safety measures is crucial for safeguarding the respiratory health of swimming pool workers.

Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital's coordinated care system.

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

[Diagnosis and therapy of patients with asthma in Germany. Results of the care study RELEVANT]. / Diagnostik und Therapie von Patienten mit Asthma in Deutschland : Ergebnisse der Versorgungsstudie RELEVANT.

BACKGROUND: Diagnostic and therapeutic options for asthma have improved with asthma control and remission being of central importance. The RELEVANT study aimed for a nationwide snapshot of current asthma diagnosis and treatment in general practice and specialty care for identification of further aspects for optimization. METHOD: RELEVANT is a nationwide cross-sectional study using a structured questionnaire. This comprised 14 questions on asthma-related topics covering diagnostics and therapy. Participants were general practitioners/internal medicine specialists and pulmonologists. RESULTS: A total of 1,558 persons took part in the survey. Regarding relevant specific diagnostic procedures for asthma, GPs/internists almost exclusively mentioned pulse oximetry. Among the pulmonologists, fractional exhaled nitric oxide (FeNO) measurement was mentioned, among others. FeNO and blood eosinophils were only mentioned by the pulmonologists as diagnostic and treatment-relevant markers. A total of more than 60% of the GPs/internists surveyed stated that only around 25% or fewer of their patients would voluntarily report restrictions in their everyday lives. Regarding drug treatment, the majority stated that they recognized differences between various ICS/LABA combination therapies. CONCLUSIONS: The results indicate a need for optimization, particularly regarding asthma control. This involves both a better assessment by patients' everyday life restrictions and modern ways of assessing asthma control in cooperation between GPs/internal medicine specialists and pulmonologists. One fifth of respondents do not see any differences between various ICS/LABA combinations in daily practice, although there are pharmacodynamic and pharmacokinetic differences.

[Characterization of asthma phenotypes in children of the tropics]. / Caracterización de fenotipos de asma en niños del trópico.

OBJECTIVE: Determine the main asthma phenotypes in a population of asthmatic children in Cartagena, Colombia. METHODS: 107 children (7 to 17 years old) with a previous diagnosis of asthma were recruited. Biomarkers of T2 inflammation were evaluated by measuring FeNO, eosinophil count in peripheral blood by hemocytometry, and determination of specific IgE to mite allergens by ELISA. The study was approved by the ethics committee of the University of Cartagena (SGR, Grant BPIN2020000100405). RESULTS: The average age of patients was 10,9 years. 19,6% of the children did not show elevation of any of the T2 inflammation biomarkers evaluated (FeNO<20ppb, eos<300/ul, negative specific IgE), so they were considered patients with non-allergic asthma (non-T2). 71,9% of all patients were sensitized to at least one allergen, this phenotype was considered allergic asthma. 30,8% of the patients presented the three elevated biomarkers (FeNO>20ppb + eos >300/ul + positive specific IgE), this phenotype was classified as high T2 allergic asthma. A moderate correlation (Spearman rho=0,44, p<0,0001) was found between FeNO values and eosinophil counts. CONCLUSION: In this study, the following phenotypes were found: allergic asthma, high T2 asthma, and non-allergic asthma. Most patients presented a type 2 inflammatory phenotype with allergic sensitization. In addition to the measurement of specific IgE, the use of FeNO and eosinophil count in peripheral blood help to accurately determine those patients with high T2 asthma phenotypes.

OBJETIVO: Determinar los fenotipos principales de asma en una población de niños asmáticos en Cartagena, Colombia. MÉTODOS: Se reclutaron 107 niños (entre 7 y 17 años), con diagnóstico previo de asma. Se evaluaron biomarcadores de inflamación T2 mediante la medición de FeNO, conteo de eosinófilos en sangre periférica mediante hemocitometría, y la determinación de IgE específica a alergenos de ácaros mediante ELISA. El estudio fue aprobado por el Comité de Ëtica de la Universidad de Cartagena (SGR, Grant BPIN2020000100405). RESULTADOS: La edad media de los pacientes fue de 10,9 años. El 19,6% de los niños no mostró elevación de ninguno de los biomarcadores de inflamación T2 evaluados (FeNO<20 ppb, eos<300/ul, IgE específica negativa), por lo que se consideraron como pacientes con asma no alérgica (no-T2). El 71,9% de todos los pacientes estaban sensibilizados al menos a un alergeno considerándose este fenotipo como asma alérgica. El 30,8% de los pacientes presentaron los tres biomarcadores elevados (FeNO>20 ppb + eos >300/ul + IgE específica positiva), clasificando este fenotipo como asma alérgica T2 alta. Se encontró una correlación moderada (Spearman rho=0,44, p<0,0001) entre los valores de FeNO y los conteos de eosinófilos. CONCLUSIÓN: En este estudio se encontraron los siguientes fenotipos de asma alérgica: asma T2 alta y asma no alérgica. La mayoría de los pacientes presentó un fenotipo inflamatorio tipo 2 con sensibilización alérgica. Además de la medición de la IgE específica, el uso del FeNO y los conteos de eosinófilos en sangre periférica ayudan a determinar con mayor exactitud a aquellos pacientes con fenotipos de asma T2 alto.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Contribution of small airway inflammation to the development of COPD.

BACKGROUND: Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD. METHODS: A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD. RESULTS: Exhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200. CONCLUSION: The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.

Assessing Inhaled Corticosteroid Adherence and Responsiveness in Severe Asthma Using Beclometasone Dipropionate/Formoterol NEXThaler Dose-Counting and Nitric Oxide Monitoring.

BACKGROUND: Sixty-five percent of people with severe asthma and a fractional exhaled nitric oxide (Feno) greater than or equal to 45 parts per billion (ppb) are nonadherent to inhaled corticosteroids (ICSs). Digital devices recording both time of use and inhaler technique identify nonadherence and ICS responsiveness but are not widely available. As the NEXThaler dose counter activates only at an inspiratory flow rate of 35 L/min, this may provide an alternative to identifying ICS responsiveness. OBJECTIVE: To assess ICS adherence and responsiveness in severe asthma using beclometasone/formoterol (200/6 µg) NEXThaler (BFN) dose-counting. METHODS: Patients with severe asthma with a Feno greater than or equal to 45 ppb were invited to use BFN in place of their usual ICS/long-acting ß2-agonist. Feno, 6-item Asthma Control Questionnaire score, lung function, and blood eosinophil count were monitored for 3 months. A log10ΔFeno of greater than or equal to 0.24 was used to define Feno suppression as the primary marker of ICS responsiveness at day 28. RESULTS: Twenty-seven of 48 (56%) patients demonstrated significant Feno suppression at month 1 (median pre-114, post-48 ppb, P < .001). A small but significant reduction occurred in Feno nonsuppressors. The 6-item Asthma Control Questionnaire score fell a median 1.2 units in Feno suppressors (P < .001) and 0.5 units in nonsuppressors (P = .025). These effects were sustained until month 3 in Feno suppressors, with a significant improvement in FEV1 and blood eosinophils. Sixty-seven percent (18 of 27) of those with baseline ICS/long-acting ß2-agonist prescription refills of 80% or more were Feno suppressors, suggesting prior nonadherence despite adequate prescription collection. Seventy-nine percent of Feno suppressors did not require biologics within mean 11.4 months from initial dose counting. CONCLUSIONS: BFN dose-counting identifies ICS responsiveness in severe asthma with the implication that these patients may not need to progress to biological therapies.

Changes in FeNO, d-ROMs, and BH4 by Intravenous L-Arginine in Children and Its Putative Role in Asthma Treatment.

Purpose: Pteridines are metabolites of tetrahydrobiopterin (BH4), being coenzymes for nitric oxide synthase (NOS). No study has clarified the relationship among pteridines and NOS, fractional exhaled nitric oxide (FeNO) generated by pteridines, and reactive oxygen species. In this study, we administered arginine, a precursor of NO, and confirmed changes in the levels of pteridines, FeNO, and reactive oxygen species and their relationship to clarify the pathogenesis of airway inflammation in which oxidative stress is involved, such as bronchial asthma. Patients and Methods: This is a prospective, randomized open-label study. Children, aged 2 to 15 years, who were scheduled for growth hormone stimulation tests and were able to undergo a respiratory function test were recruited. They were randomly divided into two groups: arginine-administered and control groups. In the former, L-arginine hydrochloride was intravenously administered. After administration, the levels of diacron-reactive oxygen metabolites (d-ROMs), serum pteridines, serum amino acids, and fractional exhaled NO (FeNO) were measured. Results: We analyzed 15 children aged 4 to 14 years. In the arginine-administered group, there was an increase in the FeNO level and a decrease in the d-ROMs level, reaching a peak 30 min after administration, compared with the control group. In addition, there was a decrease in the serum biopterin level and an increase in the d-ROMs level, reaching peak 60 min after administration. Conclusion: The administration of L-arginine increased the NO level and decreased the d-ROMs level. Due to this, biopterin may be consumed and decreased, leading to an increase in the d-ROMs level. As a reduction in reactive oxygen species leads to the relief of inflammation, arginine and biopterin may be useful for inhibiting inflammation.

Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007-2012).

BACKGROUND: Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet. METHODS: Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations. RESULTS: This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman's rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (ß = 1.979 ppb and ß = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The ß coefficient for serum Klotho was 0.002 ppb/pg/ml. CONCLUSIONS: Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

Predictive Value of Fractional Exhaled Nitric Oxide (FeNO) in the Diagnosis of Asthma for Epidemiological Purposes-An 8-Year Follow-Up Study.

At the population level, respiratory symptoms in children can be estimated cross-sectionally. However, such methods require additional objective support parameters, such as the measurement of fractional exhaled nitric oxide (FeNO). The aim of the present study was to analyze if the FeNO value measured at baseline can have a predictive value for asthma-like symptoms after 8 years of measurement. METHODS: The follow-up included 128 (out of 447) children, 70 girls and 58 boys. The FeNO was measured at baseline only. The prevalence of asthma-like symptoms was measured with the adopted version of the ISAAC questionnaire. RESULTS: After 8 years of FeNO measurement, 5 new cases of asthma, 2 cases of attacks of dyspnoea, 1 case of wheezy in the chest, and 18 cases of allergic rhinitis occurred. The FeNO values, measured at the baseline of the study, for new cases of the above diseases were 53.4 ± 75.9 ppb, 11 ± 1.5 ppb, 12.0 ppb, and 16.3 ± 12.4 ppb, respectively. The best diagnostic accuracy parameters were found in the new cases of asthma, where the sensitivity was 40.0%, the specificity was 98.6%, and the AUC was 66.6%. The diagnostic odds ratio was 46.9 when considering the FeNO cut-off >35 ppb. CONCLUSIONS: The FeNO measurement is a fair method for asthma prognosis in early school-aged children with asthma-like symptoms measured on the population level but requires further confirmation at the clinical level with more accurate diagnostic tools.

When sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic questions the role of eosinophils in mediating the clinical expression of the disease: a case report.

BACKGROUND: The advent of biologics has resulted in major progress in the treatment of severe T2 high asthmatics. There are currently several classes of biologics approved for severe asthma including anti-immunoglobulin E, anti-interleukin-5/interleukin 5R, anti-interleukin 4/interleukin 13R, and anti-thymic stromal lymphopoietin. CASE PRESENTATIONS: Here we report the case of a 55-year-old Caucasian man with severe eosinophilic atopic asthma, who sequentially benefited from a treatment with mepolizumab, an anti-interleukin-5 monoclonal antibody, followed by treatment with dupilumab, an anti-interleukin-4/interleukin-13R antibody, the switch being justified by a flare-up of dermatitis while on mepolizumab. Overall, the patient has been followed for 72 months, including 42 months on mepolizumab and 30 months on dupilumab. Close monitoring of exacerbations, asthma control, lung function, asthma quality of life, and biomarkers shows that both biologics reduced asthma exacerbation and provided an improvement in asthma control and quality of life, with the patient achieving remission after 30 months on dupilumab. However, the effects of the two biologics on the biomarkers were very different, with mepolizumab controlling eosinophilic inflammation and dupilumab reducing serum immunoglobulin E and fractional exhaled nitric oxide levels. CONCLUSION: The originality of this case resides in the description of clinical status and biomarker evolution after a sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic. It shows that mepolizumab reduces exacerbation and improves asthma control by curbing eosinophilic inflammation whereas dupilumab provides asthma remission without controlling airway eosinophilic inflammation.

Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma.

BACKGROUND: Blood eosinophils and fractional exhaled nitric oxide (Feno) are prognostic biomarkers for exacerbations and predict lung function responses to dupilumab in adolescents and adults with asthma. OBJECTIVE: We evaluated the relationship between baseline blood eosinophils and Feno and response to dupilumab in children with asthma. METHODS: Children aged 6 to 11 years with uncontrolled moderate-to-severe asthma (n = 408) were randomized to receive dupilumab 100/200 mg by body weight or volume-matched placebo every 2 weeks for 52 weeks. Annualized exacerbation rate (AER) reduction and least squares mean change in prebronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) at week 12 were assessed according to cutoff baseline levels for Feno (<20 ppb vs ≥20 ppb) and blood eosinophil count (<150, ≥150 to <300, ≥300 to <500, and ≥500 cells/µL). Quadrant analyses in populations defined by biomarker thresholds and spline models across continuous end points assessed the relationship with Feno and eosinophil count. Interaction testing evaluated the independent roles of Feno and blood eosinophils as predictive markers. RESULTS: Exacerbation risk and magnitude of AER reduction increased in subgroups with higher baseline biomarker levels. Quadrant analyses revealed that disease of patients with either elevated Feno or eosinophil counts demonstrated a clinical response to dupilumab. Interaction testing indicated blood eosinophil counts or Feno independently added value as predictive biomarkers. CONCLUSIONS: In children with uncontrolled moderate-to-severe asthma, blood eosinophil counts and Feno are clinically relevant biomarkers to identify those at risk for asthma exacerbations, as well as those with disease with clinical response to dupilumab. TRIAL REGISTRATION: Liberty Asthma VOYAGE ClinicalTrials.gov NCT02948959.

Incorporating Asthma Evaluation into the Otolaryngic Allergy Practice: Presentation and Diagnosis.

Asthma occurs frequently as a comorbid condition in many patients presenting with common otolaryngology conditions, such as allergic rhinitis and chronic sinusitis with nasal polyps. The classic presentation of asthma includes symptoms of wheezing, shortness of breath, and chest tightness but can include other symptoms such as cough. The diagnosis is made mainly through history, although pulmonary function testing, spirometry, fractional exhaled nitric oxide, and impulse oscillometry may also prove helpful.

Association between fractional exhaled nitric oxide and therapeutic adherence to controller management in pediatric asthma patients.

OBJECTIVES: Guidelines for asthma management recommend, before establishing additional therapeutic behaviors, to confirm correct use and adequate therapeutic adherence to treatment. Evidence exists on the use of fractional exhaled nitric oxide (FeNO) values for monitoring therapeutic adherence in adults. It is important to establish whether there is a correlation between FeNO and therapeutic adherence in children. This study aims to provide new knowledge about the relationship between FeNO and therapeutic adherence in asthmatic children. MATERIALS AND METHODS: Analytical cross-sectional study including asthma patients 5-18 years of age, attending follow-up at Hospital Militar Central (HMC) between May and November 2022 in Colombia. A sociodemographic survey was carried out, followed by the Pediatric Inhaler Adherence Questionnaire (PIAQ), and asthma control test (ACT) or childhood asthma control test (cACT). We defined adequate therapeutic adherence as not missing a single application of inhaled steroids in the last 15 days according to PIAQ. A poisson regression model was carried out including relevant predictors for therapeutic adherence such as FeNO values, age, tobacco exposure at home, atopy, and time since initiation of use of inhaled controller. RESULTS: Eighty-two children with a median age of 10 years (interquartile range: 7-12 years) were included. Adequate therapeutic adherence was reported by 68.3%. After adjusting for age, sex, exposure to cigarette smoke, duration of controller therapy, and atopy, FeNO < 20 ppb was independently associated with adequate therapeutic adherence (RR = 1.5, p = .04, 95% confidence interval: 1.03-2.19). CONCLUSIONS: FeNO values seem to be useful to identify pediatric patients with asthma who have adequate adherence to inhaled steroids in a MIC.

Fractional Exhalation Nitric Oxide (FeNO) changes in cystic fibrosis patients induced by compound honey syrup: a pretest-posttest clinical trial.

OBJECTIVE: To evaluate the effect of Persian medicine Syrup 'compound honey syrup (CHS)' on fractional exhalation nitric oxide (FENO) changes in patients with cystic fibrosis (CF). STUDY DESIGN: We conducted a before-after clinical trial on 70 CF patients. All patients received classical treatments for CF along with CHS (including honey, Ginger, cinnamon, saffron, cardamom and galangal), 5-10 cc (depending on the age and weight of patients) in 100 cc of warm boiled water twice a day, 30 min after meals. In this clinical trial, before and 12 weeks after the start of the CHS, FeNO test was evaluated. RESULTS: From 70 patients were enrolled, 44 patients completed this 12-week course of treatment. At the end of the study, changes in FeNO was significantly different before and after treatment (P-value < 0.05). At the end of the study, no dangerous side effects of CHS was reported. CONCLUSIONS: This study revealed that CHS can be effective as a complementary and safe drug in the medication of CF patients.

Exhaled nitric oxide is only an asthma-relevant biomarker among children with allergic sensitization.

BACKGROUND: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood. METHODS: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5-18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. RESULTS: In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08-1.35), p < .01, and 1.41 (1.21-1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23-1.69), p < .0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65-0.99), p = .05 (p-interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p-interaction <.01). Further, blood eosinophil count, total-IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children. CONCLUSION: Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma-associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO.