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Exhaled nitric oxide fraction (FeNO) is employed for the diagnosis and phenotyping of asthma as an inflammatory biomarker of the airway. Limited evidence exists regarding its behavior in the presence of asthma and obstructive sleep apnea (OSA). Our objective was to determine whether FeNO levels are associated with the severity of OSA or the coexistence of asthma and OSA in residents at high altitudes. Observational, analytical, cross-sectional study in children aged 5–16 years residing at 2600 m above sea level treated at a Sleep Study Center between 2019 and 2021. We conducted a medical history, polysomnogram, and measurement of FeNO levels. The children were categorized into four groups: OSA, asthma, asthma with OSA, and controls (without asthma or OSA). FeNO levels among the groups were compared using the Kruskal-Wallis test, and correlations were explored using the Spearman correlation coefficient. Analyses considered statistical significance at a two-tailed p-value <0.05. Among the 261 included children, 68 (26.1 %) had OSA, 42 (16.1 %) were diagnosed with asthma, 109 (41.8 %) had both asthma and OSA, and 42 (16.1 %) were controls. Their FeNO medians were 10 ppb, 18.5 ppb, 15 ppb, and 14 ppb, respectively, with no significant differences between the evaluated groups (p = 0.263). We found no correlation between FeNO and apnea-hypopnea index and obstructive apnea index even for the groups of patients with FeNO >20 ppb and FeNO >35 ppb (>75th percentile). In the adjusted model, a significant association was observed between asthma and FeNO levels. Our findings suggest that FeNO measurements in children would not allow establishing this biomarker as part of the diagnosis of OSA. However, these findings may be related to high altitude. • This study evaluates FeNO levels in children with OSA and asthma at high altitude. • FeNO levels in children would not allow establishing as part of the diagnosis of OSA. • A significant association was observed between asthma and FeNO levels. [ABSTRACT FROM AUTHOR]

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Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. Methods In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. Results A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen‐dependent (BOLD) brain activation to negative (blood–injection–injury themes) and neutral films in 31 participants (15 with asthma). Regions‐of‐interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top‐down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross‐baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO. Using fMRI and emotion induction by films, this study shows for the first time that individuals with asthma process both affective and neutral stimuli differently at the central nervous system level. Nitric oxide, a vasodilator, measured in exhaled breath, was consistently related to stronger activation across brain areas. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA. [ABSTRACT FROM AUTHOR]

Background: Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. Methods: In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. Results: A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. Conclusions: A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function.MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM2.5， PM10， SO2， NO2， O3 and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer.ResultsThe results of single pollutant model showed that PM2.5， PM10， SO2 and NO2 were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P

Abstract Background Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. Methods Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2’-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. Results DLNO, DLCO, KNO, KCO and VA were reduced (p

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics. [ABSTRACT FROM AUTHOR]

Objectives: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. Methods: Individuals aged 6–19 years with HIV‐associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo‐controlled randomized trial investigating the effect of 48‐week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. Results: In total, 172 participants were included in this sub‐study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow‐up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03–1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)‐3, ‐7, and ‐10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72–1.03, p = 0.103). Conclusion: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV‐associated chronic lung disease needs further investigation. [ABSTRACT FROM AUTHOR]

The Western Diet commonly consists of high-fat meals (HFMs) with saturated fats (SF) and increased omega-6 polyunsaturated fatty acids (O6FA) to omega-3 polyunsaturated fatty acids (O3FA) ratios. Even a single high-fat meal (HFM) may increase airway inflammation assessed via exhaled nitric oxide (eNO). When HFMs are consumed chronically, persistent airway inflammation may lead to deleterious structural changes in the airways, decrease pulmonary function, and increase the risk of respiratory disease development. To examine the effect of varying fatty acid composition in a HFM on eNO, pulmonary function, and airway resistance. Fifteen individuals [6 M/9 F; 21.9 ± 1.5 years old] each completed three HFM conditions {SF, O6FA, and O3FA; 12 kcal/kg body weight, 63% total fat, and 0.72 g/kg sugar smoothies} in random order separated by at least 48 h. Airway inflammation assessed via eNO, pulmonary function measured using the maximum flow volume loop (MFVL) and airway resistance measured using impulse oscillometry (iOS) were taken at baseline, 2h and 4h postprandially. There was no difference in eNO or iOS across time in any condition or between conditions (p > 0.05). There was a significant time by condition effect for FEV1 post-HFM in the SF and O6FA conditions (p < 0.05). Different fatty acid compositions do not increase eNO or iOS in healthy, college-aged participants after consumption of a HFM, though the minimally processed meals with fruit added may contribute to these findings. [ABSTRACT FROM AUTHOR]

Background: Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. Methods: Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2'-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. Results: DLNO, DLCO, KNO, KCO and VA were reduced (p < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DLNO (DLCO) were smaller (p < 0.001) than those of KNO (KCO). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising Gz-forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DLNO and DLCO. Conclusions: The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a common complication of deep vein thrombosis that causes high mortality and morbidity. This study aimed to determine the relationship between clinical risk scoring for early mortality and fractional exhaled nitric oxide (FeNO) in PE patients. Methods: The study included a total of 98 subjects, 68 patients diagnosed with PE in the emergency department, and 30 healthy controls. Patients with PE were grouped according to clinical scoring of early mortality risk as low (n = 20), moderate-low (n = 24), and moderate-high (n = 24) risk. FeNO levels were measured after diagnosis. Results: FeNO levels were significantly higher in patients with moderate-high risk PE compared to the other three groups and in those with moderate-low risk PE compared to the control group (p < 0.001 for all). Moderate to strong positive correlations were observed between FeNO level and mean pulmonary artery pressure (r = 0.818, p = 0.01), troponin-I (r = 0.67, p = 0.01), pro-BNP (r = 0.762, p = 0.01), and D-dimer levels (r = 0.652, p = 0.01). A FeNO cutoff value of 7.5 ppb had 84% sensitivity and 78% specificity in differentiating moderate-high risk PE from moderate-low risk PE. Conclusions: FeNO may be as reliable, noninvasive, and easily accessible as cardiac biomarkers in clinical risk scoring for early mortality in PE patients. [ABSTRACT FROM AUTHOR]

Exhaled nitric oxide （eNO）， as a marker of eosinophilic inflammation in the airway， has been widely utilized in the diagnosis and treatment of asthma. The fractional concentration of exhaled NO （FeNO） mainly reflects the degree of airway inflammation. By establishing a pulmonary dynamic model for extended analysis， nitric oxide parameters can be obtained， which contribute to deepen the understanding of the degree of airway inflammation. In this article， recent studies were reviewed to summarize the clinical value of nitric oxide parameters in asthma， aiming to supplement a novel dimension for the evaluation and management of asthma.

Bronchial asthma is the most frequently diagnosed chronic respiratory disease in children. Treatment approaches should aim to achieve the disease control, reduce limiting symptoms, and improve the quality of life. Routine treatment of patients with asthma relies on assessment of symptoms and spirometry results. These diagnostic and therapeutic strategies do not consider the level of inflammation in the airways as a fundamental pathognomonic feature of the disease. The use of biomarkers is increasing in the context of efforts to better understand individual asthma pathways (asthma endotyping), with the potential for personalized treatment with innovative biologics. Elevated levels of exhaled nitric oxide (FENO) represent an indirect marker of T2 inflammation in airways. FENO is one of the few biomarkers that have been applied in routine clinical practice. High levels predict a good therapeutic response to treatment with corticosteroids and selected biologics (Omalizumab, Dupilumab, Mepolizumab, Tezepelumab), or an increased risk of asthma exacerbation. The aim of this review is to evaluate the advantages, disadvantages, and potential applications of this test in relation to new treatment options using biologics for asthma.

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.

Objective·To determine the levels of nasally exhaled nitric oxide (FnNO) combined with fractional concentration of exhaled nitric oxide (FeNO) in children with asthma (AS) complicated with allergic rhinitis (AR), and analyze the levels of FnNO and FeNO in different clinical stages of AS with different severities of AR, so as to provide basis for guiding clinical diagnosis and treatment.Methods·Children diagnosed with AR with AS in the Department of Respiratory and Otolaryngology of Children's Hospital of Soochow University from April 2021 to November 2021 were included, and healthy children who visited the Department of Pediatrics for normal physical examination during the same period were enrolled as the control group. FeNO and FnNO were measured in all children to assess the severity of the children's diseases. The levels of FeNO and FnNO in children with AR and AS at different clinical stages of AS and their correlation with pulmonary function were compared and analyzed.Results·The proportion of persistent moderate-to-severe rhinitis was higher in the acute exacerbation stage of AS, and the proportion of intermittent mild rhinitis was higher in the clinical remission stage of AS. The FeNO level in the acute exacerbation stage were higher than that in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.022, 0.000), and higher in the chronic persistent stage than that in the clinical remission stage of AS (adjusted P=0.002). The FnNO level in the acute exacerbation stage was higher than that in the clinical remission stage of AS (adjusted P=0.044). In the chronic persistent stage of AS, the FnNO levels in the persistent mild group and persistent moderate-to-severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.000). In the clinical remission stage of AS, the FnNO levels in the persistent mild group and persistent moderate to severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.007). In the intermittent mild group of AR, the FnNO levels in the acute exacerbation stage were higher than those in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.010, 0.019). Part of pulmonary functions in the acute exacerbation stage of AS children were negatively correlated with the FeNO and FnNO levels (all P

Exhaled nitric oxide (eNO), as a marker of eosinophilic inflammation in the airway, has been widely utilized in the diagnosis and treatment of asthma. The fractional concentration of exhaled NO (FeNO) mainly reflects the degree of airway inflammation. By establishing a pulmonary dynamic model for extended analysis, nitric oxide parameters can be obtained, which contribute to deepen the understanding of the degree of airway inflammation. In this article, recent studies were reviewed to summarize the clinical value of nitric oxide parameters in asthma, aiming to supplement a novel dimension for the evaluation and management of asthma. [ABSTRACT FROM AUTHOR]

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb. [ABSTRACT FROM AUTHOR]

Objective ·To determine the levels of nasally exhaled nitric oxide (FnNO) combined with fractional concentration of exhaled nitric oxide (FeNO) in children with asthma (AS) complicated with allergic rhinitis (AR), and analyze the levels of FnNO and FeNO in different clinical stages of AS with different severities of AR, so as to provide basis for guiding clinical diagnosis and treatment. Methods ·Children diagnosed with AR with AS in the Department of Respiratory and Otolaryngology of Children's Hospital of Soochow University from April 2021 to November 2021 were included, and healthy children who visited the Department of Pediatrics for normal physical examination during the same period were enrolled as the control group. FeNO and FnNO were measured in all children to assess the severity of the children's diseases. The levels of FeNO and FnNO in children with AR and AS at different clinical stages of AS and their correlation with pulmonary function were compared and analyzed. Results ·The proportion of persistent moderate-to-severe rhinitis was higher in the acute exacerbation stage of AS, and the proportion of intermittent mild rhinitis was higher in the clinical remission stage of AS. The FeNO level in the acute exacerbation stage were higher than that in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.022, 0.000), and higher in the chronic persistent stage than that in the clinical remission stage of AS (adjusted P=0.002). The FnNO level in the acute exacerbation stage was higher than that in the clinical remission stage of AS (adjusted P=0.044). In the chronic persistent stage of AS, the FnNO levels in the persistent mild group and persistent moderate-to-severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.000). In the clinical remission stage of AS, the FnNO levels in the persistent mild group and persistent moderate to severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.007). In the intermittent mild group of AR, the FnNO levels in the acute exacerbation stage were higher than those in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.010, 0.019). Part of pulmonary functions in the acute exacerbation stage of AS children were negatively correlated with the FeNO and FnNO levels (all P<0.05), while FEV1/pred in the chronic persistent stage was negatively correlated with FeNO level (P=0.010). Conclusion ·FeNO and FnNO levels increased in the acute exacerbation stage of AS, and symptom scores of AR also increased. FeNO and FnNO levels were negatively correlated with pulmonary function in AS with AR children. [ABSTRACT FROM AUTHOR]

Background: Lipid 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. Methods: We 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. Results: We 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. Conclusions: In 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. [ABSTRACT FROM AUTHOR]

Objective: The current study aimed to compare and analyze the pulmonary function and eosinophil inflammation parameters between patients with chest tightness variant asthma (CTVA) and those with typical classical (CA) for further recognition about the atypical bronchial asthma with chest tightness as the main manifestation. Methods: A total of 55 patients with CTVA and 94 patients with CA who were diagnosed and treated in the Outpatient Department between October 2019 and October 2021 were retrospectively analyzed (the airway provocation test was positive in both groups, and the medical history and clinical characteristics met the diagnostic criteria of asthma). The pulmonary function test, exhaled nitric oxide, blood eosinophils, specific and total IgE levels were analyzed and compared between the two groups. Results: There was no significant difference in age, sex ratio, allergic history, allergic rhinitis, nasal polyps, eczema and chronic urticarial between the CTVA and CA groups (P > 0.05) . The patients with mild impairment of the small airway function in the CTVA group (CTVA group: CA group=27.27%: 43.62%) were less than those of the CA group (P=0.047). There was no significant in the moderate to severe impairment of small airway function, the percentage of increased airway resistance, and RV/TLC between the two groups (P > 0.05). There was no significant difference in ventilatory function [forced vital capacity (FVC) 、forced expiratory volume in one second/forced vital capacity (FEV1/FVC) 、peak expiratory flow (PEF) ] or pulmonary reserve [maximal voluntary ventilation (MVV) ] between the two groups (P > 0.05). Peripheral blood eosinophils were significantly lower in the CTVA group [absolute: (0.16 ± 0.15) ×109/L, percentage: (2.50 ± 2.25) %] than in the CA group [absolute: (0.27 ± 0.25) ×109/L, percentage (4.0 ± 3.8) %, with a significant difference [P=0.017 (absolute), P=0.031 (percentage) ] . The positive rate of specific IgE in the CTVA group (23.8%) was lower than that in the CA group (48.5%) (P=0.043), and the total IgE level in peripheral blood in the CTVA group [86.7 (24.7, 172.9) kU/L] was significantly lower than that in the CA group [181.2 (97.25, 454.8) kU/L], with a significant difference (P=0.009) . The mean concentration of exhaled nitric oxide in the CTVA group (29 ppb) was significantly lower than that in the CA group (79 ppb), with a significant difference (P=0.027). Conclusion: The rate of mild obstruction of the small airway in CTVA patients was smaller than that in CA patients, the rate of moderate and severe obstruction of the small airway was equal to that in CA patients, and peripheral blood eosinophil levels were lower than in those with CA. [ABSTRACT FROM AUTHOR]

Cancers, chronic diseases and respiratory infections are major causes of mortality and present diagnostic and therapeutic challenges for health care. There is an unmet medical need for non-invasive, easy-to-use biomarkers for the early diagnosis, phenotyping, predicting and monitoring of the therapeutic responses of these disorders. Exhaled breath sampling is an attractive choice that has gained attention in recent years. Exhaled nitric oxide measurement used as a predictive biomarker of the response to anti-eosinophil therapy in severe asthma has paved the way for other exhaled breath biomarkers. Advances in laser and nanosensor technologies and spectrometry together with widespread use of algorithms and artificial intelligence have facilitated research on volatile organic compounds and artificial olfaction systems to develop new exhaled biomarkers. We aim to provide an overview of the recent advances in and challenges of exhaled biomarker measurements with an emphasis on the applicability of their measurement as a non-invasive, point-of-care diagnostic and monitoring tool. [ABSTRACT FROM AUTHOR]

Pulmonary sequelae as assessed by pulmonary function tests (PFTs) are often reported in patients infected by SARS-CoV-2 during the post-COVID-19 period. Little is known, however, about the status of pulmonary inflammation during clinical recovery after patients' discharge from the hospitals. We prospectively measured PFTs coupled with the exhaled nitric oxide (NO) stemming from the proximal airways (FeNO) and the distal lung (CaNO) in 169 consecutive patients with varying degrees of the severity of COVID-19 six weeks to one year after acute infection by SARS-CoV-2. The proportions of patients with abnormal PFTs, defined as the presence of either obstructive/restrictive patterns or impaired lung gas transfer, or both, increased with the severity of the initial lung disease (15, 30, and 52% in patients with mild, moderate, and severe COVID-19). FeNO values remained within normal ranges and did not differ between the three groups of patients. CaNO, however, was significantly higher in patients with severe or critical COVID-19, compared with patients with milder forms of the disease. There was also an inverse relationship between CaNO and DLCO. We conclude that the residual inflammation of the distal lung is still present in the post-COVID-19 follow-up period, in particular, in those patients with an initially severe form of COVID-19. This long-lasting alveolar inflammation might contribute to the long-term development of pulmonary fibrosis and warrants the regular monitoring of exhaled NO together with PFTs in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Introduction The principal goal of bronchial asthma (BA) management is to control and reduce the risk of exacerbations. Poor assessment of asthma control is a major cause of poor asthma management. This study aimed to detect the level of asthma control using spirometry and exhaled nitric oxide (FeNO). Patients and methods This study investigated 210 patients with a diagnosis of BA. Asthma control in included patients was classified according to the Global Initiative for Asthma symptom-based assessment of asthma control, into controlled, partly controlled, or uncontrolled. Spirometry and FeNO results were recorded. Results Most of the studied patients had partly controlled BA (43.3%), while uncontrolled BA was found in 29% of them. There was a significant association between both prebronchodilator forced expiratory volume in 1 s (FEV1) and the presence of reversibility with levels of BA control. There was no significant difference in the FeNO value between the levels of BA control (P=0.5). Combined assessment of BA using low FEV1 with high FeNO showed a significant difference between BA control groups. Conclusion A combination of FeNO and FEV1 provides a better method in detecting the level of BA control. It may be very important for patients with higher airway reversibility to consistently monitor disease control and then to modify therapeutic strategy. [ABSTRACT FROM AUTHOR]

The inflammatory balance is an important factor in the clinical course of COVID-19 (SARS-CoV-2) infection, which has affected over 300 million people globally since its appearance in December 2019. This study aimed to evaluate the correlation between exhaled nitric oxide (FeNO) level and parenchymal involvement in COVID-19. The study included 106 patients with the delta variant of COVID-19 identified by real-time PCR as well as 40 healthy control groups between October 2021 and March 2022. The patients were analyzed in three groups: moderate COVID-19 (group 1), severe COVID-19 without macrophage activation syndrome (MAS) (group 2), and severe COVID-19 with MAS (group 3). FeNO and CT scores were significantly higher in groups 2 and 3 at admission and discharge compared to group 1 (p = 0.001 for all). In addition, CT score at admission and CT score and FeNO level at discharge were higher in group 3 than in group 2 (p = 0.001 for all). It was found that the FeNO levels were higher in Groups 2 and 3 than in the control group (p = 0.001) during the admission. FeNO and CT scores showed strong positive correlation at admission and discharge (r = 0.917, p = 0.001; r = 0.790, p = 0.001). In receiver operating characteristic curve analysis for prediction of MAS, FeNO at a cut-off of 10.5 ppb had 66% sensitivity and 71% specificity. COVID-19 causes more severe lung involvement than other viral lower respiratory tract infections, leading to the frequent use of chest CT in these patients. FeNO assessment is a practical and noninvasive method that may be useful in evaluating for parenchymal infiltration in the diagnosis and follow-up of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Introduction The principal goal of bronchial asthma (BA) management is to control and reduce the risk of exacerbations. Poor assessment of asthma control is a major cause of poor asthma management. This study aimed to detect the level of asthma control using spirometry and exhaled nitric oxide (FeNO). Patients and methods This study investigated 210 patients with a diagnosis of BA. Asthma control in included patients was classified according to the Global Initiative for Asthma symptom-based assessment of asthma control, into controlled, partly controlled, or uncontrolled. Spirometry and FeNO results were recorded. Results Most of the studied patients had partly controlled BA (43.3%), while uncontrolled BA was found in 29% of them. There was a significant association between both prebronchodilator forced expiratory volume in 1 s (FEV1) and the presence of reversibility with levels of BA control. There was no significant difference in the FeNO value between the levels of BA control (P=0.5). Combined assessment of BA using low FEV1 with high FeNO showed a significant difference between BA control groups. Conclusion A combination of FeNO and FEV1 provides a better method in detecting the level of BA control. It may be very important for patients with higher airway reversibility to consistently monitor disease control and then to modify therapeutic strategy.

Introduction. Baker’s asthma is one of the most common causes of occupational asthma worldwide. Beside bread production, all occupations in contact with flour (confectioning, pastry making, milling, farming, cereal handling) can be affected. Objective. To illustrate, through the presentation of a clinical case, an updated interdisciplinary diagnostic approach for the evaluation of suspected occupational asthma, with the aim: to identify the possible causal link between the occupational exposure and the disease, and to formulate a correct judgment for job fitness. Materials and methods. Interdisciplinary (occupational medicine and allergology) specialist evaluation, blood and urine analysis, patch tests, total and specific IgE dosage, eosinophilic cationic protein assay, spirometry, non-specific metacholine bronchostimulation, specific inhalation challenge, with monitoring of airway resistance by FOT (forced oscillation technique), and of nasal and bronchial FeNO (fractional exhaled nitric oxide). Results. Fifty-four year-old man, baker since 1993. In recent months, dyspnoea and dry cough, accompanied by ocular and nasal flogosis, as well as itchy skin rash, mainly during work shifts. High total and specific IgE values. Increased eosinophilic cationic protein. Negative metacholine test. Specific inhalation challenge with buckwheat stopped after 15 minutes due to the onset of rhinitis, conjunctivitis, cough with shortness of breath and wheezing. Post-exposure FEV1 decrease (> 12%) and +76% FOT increase. Progressive and persistent nasal FeNO increase with normalization after 24 hours. These findings indicated bronchial and oculonasal allergic response to buckwheat and other cereals. Conclusion. The diagnostic protocol allowed demonstrating the causal link between occupational exposure and the disease, which was reported to the competent authorities. The patient was advised to refrain from further exposure. The evolution of processing techniques and the new substances used in bread production, require continuous updating of diagnostic and health surveillance protocols.

Background and Aims: Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non‐invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely‐eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset. Materials and Methods: We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity. Results: No correlation was found between both classifications 0.025 (CI = 0.013–0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population. Discussion and Conclusion: In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation. [ABSTRACT FROM AUTHOR]

Background: In asthma, exhaled nitric oxide (FENO) is a clinically established biomarker of airway T2 inflammation and an indicator for anti-inflammatory therapy. Objectives: The aim of the study was to identify, in an observational real-world cross-sectional study, the main characteristics of patients with asthma as classified by their FENO level. Method: We stratified 398 patients with stable mild-to-severe asthma according to FENO level as low (≤25 ppb) versus elevated (>25 ppb), subdividing the latter into two subgroups: moderately elevated (26–50 ppb) versus very high FENO (>50 ppb). Clinical, functional, and blood parameters were extrapolated from patients' chart data and compared with the FENO stratification. Predictors of low and elevated FENO asthma were detected by logistic regression model. Results: Low BMI, higher blood eosinophilia, allergen poly-sensitization, the severest airflow obstruction (FEV1/FVC), and anti-leukotriene use are predictors of elevated FENO values in asthma, as well as persistent rhinitis and chronic rhinosinusitis with or without nasal polyps. Beyond these, younger age, more than 2 asthma exacerbations/year, higher airflow reversibility (post-bronchodilator ∆FEV1), and oral corticosteroid dependence are predictors of very high FENO values. In contrast, obesity, obstructive sleep apnoea syndrome, gastroesophageal reflux disease, arterial hypertension, and myocardial infarction are predictors of low FENO asthma. In our population, FENO correlated with blood eosinophils, airflow obstruction, and reversibility and negatively correlated with age and BMI. Conclusions: Stratifying patients by FENO level can identify specific asthma phenotypes with distinct clinical features and predictors useful in clinical practice to tailor treatment and improve asthmatic patients' outcomes. [ABSTRACT FROM AUTHOR]

Background: Few data are available in Asian children regarding the validity of cord blood immunoglobulin E (IgE) in predicting allergic sensitization and pulmonary function. The relationship between cord blood IgE and fraction of exhaled nitric oxide (FeNO) remains unknown. This study investigated the associations of cord blood IgE with allergic sensitization, FeNO, pulmonary function, and allergic diseases in Asian children. Methods: Five hundred and sixty‐six Asian children with valid cord blood IgE measurements at birth participated a 6‐year follow‐up visit including a questionnaire, serum total and allergen‐specific IgE, FeNO measurement, and spirometry. Regression‐based analyses with covariates adjustment were applied. Results: Cord blood IgE levels were significantly associated with FeNO levels (β = 0.131, p <.001) and serum total IgE levels (β = 0.325, p <.001). Cord blood IgE levels were positively associated with allergic sensitization (adjusted odds ratio [AOR] = 2.22, p <.001), and sensitization to mites (p =.002), animals (p =.023), and foods (p =.048). Subjects with cord blood IgE ≥0.24 kU/L (the optimal cutoff) were significantly associated with an increased risk of allergic sensitization (AOR = 2.63, p <.001) and asthma (AOR = 2.35, p =.024) than those with cord blood IgE <0.24 kU/L. Subjects with cord blood IgE ≥0.24 kU/L had significantly higher FeNO levels than those with cord blood IgE <0.24 kU/L (p =.028). There were no significant associations between cord blood IgE levels and pulmonary function parameters. Conclusion: Cord blood IgE ≥0.24 kU/L predicts allergic sensitization, FeNO elevation, and asthma among Asian schoolchildren, suggesting cord blood IgE would be useful for identifying newborns at risk of subsequent allergic sensitization and allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic cationic protein (ECP) is associated with airway inflammation and asthma. However, the clinical value of measuring ECP in childhood asthma is not fully known. We aimed to study the diagnostic performance of serum ECP and other common asthma biomarkers, individually and in combinations. Methods: In a cross-sectional study, 5–16-year-old children with current asthma (CA) (n = 37), transient asthma (TA) (n = 43), (previous history of wheezing/asthma), and healthy children (HC) (n = 86) were investigated for ECP, blood eosinophil count (B-Eos), fractional exhaled nitric oxide (FeNO), and lung function, i.e., spirometry (forced expiratory volume during the first second [FEV1]/forced vital capacity [FVC] ratio). Results: Both ECP and B-Eos were higher in CA compared to TA (p < 0.01) and HC (p < 0.0001). ECP and B-Eos were also higher in TA compared to HC (p < 0.05 and p < 0.001, respectively). FeNO was higher in CA (p < 0.0001) and TA (p < 0.01) compared to HC but similar between the asthma groups. The FEV1/FVC ratio was lower in CA compared to TA and HC (both p < 0.01) but similar between TA and HC. The best diagnostic performance regarding CA was found for ECP and B-Eos with receiver operating characteristics area under curve (AUC) of 0.801 and 0.810, respectively. The optimal cutoff for ECP (29 μg/L) yielded a sensitivity and specificity of 70.3% and 81.4%. The corresponding AUCs for FeNO and FEV1/FVC were 0.732 and 0.670, respectively. ECP and B-Eos showed the highest AUCs (0.669 and 0.673) for differentiation between CA and TA. Combining ECP with FeNO and FEV1/FVC increased the odds ratio (OR) for having CA from OR 3.97–10.3 for the single biomarkers to OR 20.2 (95% confidence interval: 5.76–68.6). Conclusion: Our results show that serum ECP is a reliable biomarker in the diagnosis of childhood asthma, with additional value in combination with FeNO and FEV1/FVC, and that ECP can be an alternative to B-Eos. [ABSTRACT FROM AUTHOR]

Objectives: To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children., Methods: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3β protein concentrations between the two groups, analyzed the correlation of serum 14-3-3β protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3β protein, FeNO, and conventional ventilatory lung function parameters for asthma in children., Results: The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group ( P <0.001). Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters ( P <0.05). Cross-validation of combined indices showed that the combination of 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy ( P <0.001). The model had the best extrapolation., Conclusions: The combination of serum 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729 .

Abstract Background Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. Methods We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. Results In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017–2019 data as the internal validation dataset. Conclusion FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.

Abstract Background and Aims Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non‐invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely‐eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset. Materials and Methods We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity. Results No correlation was found between both classifications 0.025 (CI = 0.013–0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population. Discussion and Conclusion In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation.

Purpose: Secondary metalworking carries exposure to relatively heavy levels of respirable particulate. We investigated the extent to which metalworking is associated with increased exhaled nitric oxide (FeNO), an established inflammatory biomarker. Methods: We studied 80 metalworking factory employees in Kazakhstan. Informed by industrial hygiene data, we categorized them into three groups: (1) machine operators (41%); (2) welders or assemblers (33%); and (3) all others, including administrative and ancillary staff (26%). Participants completed questionnaires covering occupational history, smoking, home particulate sources, respiratory symptoms, and comorbidities. We measured exhaled carbon monoxide (CO), exhaled fractional nitric oxide (FeNO), and spirometric function. We used mixed-effects modeling to test the associations of occupational group with FeNO, adjusted for covariates. Results: The median age was 51.5 (interquartile range 20.5) years; 7% were women. Occupational group (p < 0.01), daily current cigarette smoking intensity (p < 0.05), and age (p < 0.05), each was statistically associated with FeNO. Welders, or assemblers (Group 2), who had intermediate particulate exposure, manifested significantly higher exhaled FeNO compared to machinists (Group 1, with the highest particulate exposure) and all others (Groups 3, the lowest particulate): adjusted Group 2 mean 44.8 ppb (95% confidence interval (CI) 33.8–55.9) vs. Group 1 24.6 ppb (95% 20.5–28.7) and Group 3, 24.3 ppb (95% CI 17.7–30.9). Secondhand smoking and height were not associated with FeNO. Conclusion: In a metalworking industrial cohort, welders/assemblers manifested significantly higher levels of FeNO. This may reflect respiratory tract inflammation associated with airborne exposures specific to this group. [ABSTRACT FROM AUTHOR]

Khue Dang-Thi-Mai,1 Nhat-Nam Le-Dong,2 Vu Le-Thuong,1 Ngoc Tran-Van,1 Sy Duong-Quy3,4 1Department of Respiratory Diseases, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 2Department of Technology, Sunrise, Namur, Belgium; 3Bio-Medical Research Centre, Lam Dong Medical College, Dalat, Vietnam; 4Penn State Medical College, Hershey Medical Center, Hershey, PA, USACorrespondence: Sy Duong-QuyBio-Medical Research Centre, Lam Dong Medical College, 16 Ngo Quyen, Dalat, VietnamTel +84 918413813Fax +84 2633815000Email sduongquy.jfvp@gmail.comPurpose: Our study aimed to evaluate the relationship between exhaled nitric oxide (eNO) markers and obstructive sleep apnea (OSA) severity and verify the changes in eNO profiles among mild, moderate, and severe OSA subgroups.Methods: This study was a cross-sectional and in-hospital population-based study. We investigated 123 OSA patients (17 mild, 23 moderate and, 83 severe OSA) in the department of respiratory diseases. Studied data included anthropometry, respiratory polygraphy, biological markers, spirometry, and multi-flow eNO measurements. Data analysis implied linear correlation, non-parametric ANOVA, and pair-wise comparison.Results: No significant difference could be found among 3 OSA severity subgroups for FENO at – four sampling flow rates (50– 350 mL/s). The bronchial production rate of NO (J’awNO) was proportionally increased, with median values of 11.2, 33.9, and 36.2 in mild, moderate, and severe OSA, respectively (p=0.010). The alveolar concentration of NO (CANO) changed with a non-linear pattern; it was increased in moderate (6.49) vs mild (7.79) OSA but decreased in severe OSA (5.20, p = 0.015). The only correction that could be established between OSA severity and exhaled nitric oxide markers is through J’AWNO (rho=0.25, p=0.02) and CANO (rho= 0.18, p=0.04). There was no significant correlation between FENO measured at three different flow rates and the OSA severity. We also found a weak but significant correlation between FENO 100 and averaged SpO2 (rho = 0.07, p= 0.03).Conclusion: The present study showed that J’AWNO, which represents eNO derived from the central airway, is proportionally increased in more severe OSA, while eNO from alveolar space, indicated by CANO, was also associated with OSA severity and relatively lower in the most severe OSA patients. In contrast, stand-alone FENO metrics did not show a clear difference among the three severity subgroups.Keywords: exhaled nitric oxide, FENO, J’AWNO, CANO, obstructive sleep apnea

Josep Darbà,1 Meritxell Ascanio,2 Jörgen Syk,3– 5 Kjell Alving4 1Department of Economics, Universitat de Barcelona, Barcelona, Spain; 2BCN Health Economics & Outcomes Research, S.L., Barcelona, Spain; 3Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; 4Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; 5Academic Primary Health Care Centre, Stockholm, SwedenCorrespondence: Josep DarbàDepartment of Economics, Universitat de Barcelona, Diagonal 696, Barcelona, 08034, SpainTel +34 934020110Fax +34 934039082Email darba@ub.eduObjective: To determine the economic impact of the fraction of exhaled nitric oxide (FeNO) in asthma diagnosis and management in primary care in Sweden.Methods: An economic model has been developed to determine the economic impact of the fraction of exhaled nitric oxide (FeNO) in asthma diagnosis and management in primary care in Sweden. The model includes the use and cost of commonly used tests, the associated outcomes and diagnostic accuracy. We compared FeNO with spirometry and reversibility testing, methacholine challenge test, allergy testing, and blood eosinophil count. One-way sensitivity analyses were performed to confirm the robustness of results.Results: Adding FeNO measurement in asthma diagnosis resulted in cost savings of SEK 672 per patient by the fourth year. The use of FeNO testing in asthma management proved to be a dominant strategy when compared with each other test except methacholine challenge test. Sensitivity analyses confirmed the robustness of the results.Conclusion: Introducing FeNO testing in clinical practice for the diagnosis and management of asthma in primary care in Sweden is less costly than standard methods while providing similar health benefits.Keywords: asthma, management, diagnosis, FeNO, exhaled nitric oxide, health economy

Giulia Brindisi,1,* Valentina De Vittori,1,* Rosalba De Nola,2,3 Antonio Di Mauro,4 Giovanna De Castro,1 Maria Elisabetta Baldassarre,4 Ettore Cicinelli,2 Bianca Cinicola,1 Marzia Duse,1 Anna Maria Zicari1 1Pediatrics Department, Umberto I Hospital, Sapienza University, Rome, 00161, Italy; 2Department of Biomedical Science and Human Oncology, Gynecology and Obstetrics Section, “Aldo Moro” University of Bari, Bari, 70124, Italy; 3Department of Tissues and Organs Transplantation and Cellular Therapies, “Aldo Moro” University of Bari, Bari, 70124, Italy; 4Department of Biomedical Sciences and Human Oncology-Neonatology and Neonatal Intensive Care Unit, “Aldo Moro” University of Bari, Bari, 70124, Italy*These authors contributed equally to this workCorrespondence: Giulia BrindisiPediatrics Department, Umberto I Hospital, Sapienza University, Viale Regina Elena 324, Rome, 00161, ItalyTel +39 06 49979333Email giulia.brindisi@gmail.comBackground: Allergic rhinitis (AR) and asthma are two common atopic diseases, often associated with a common ethiopathogenesis characterized by a Th2 inflammatory response with the release of many biomarkers, such as nitric oxide (NO).Purpose: To evaluate and compare inflammatory (nFeNO and eFeNO) and functional (mNF and FEV1) parameters in AR children with or without asthma in comparison to controls. Secondly, we aimed to identify nFeNO cut-off values and verify their reliability to predict the presence of rhinitis or asthma alone or in combination.Patients and Methods: We enrolled 160 children (6– 12 years of age) with AR and/or asthma divided into four groups: controls, AR, asthma, and AR + asthma. All children underwent the following inflammatory and functional measurements: nFeNO, eFeNO, mNF and FEV1.Results: We observed that levels of nFeNO were extremely higher in children with AR and even more in those with AR + asthma in respect to controls. Notably, all the pathological conditions, especially AR + asthma, showed significantly lower values of mNF compared to healthy children. A negative correlation linked mNF and nFeNO. Then, we found eFeNO values significantly higher in all the pathological groups compared to controls, with major values of this marker in patients affected by asthma and AR + asthma, as well as FEV1 values significantly lower in all the disease groups, especially in children with asthma and AR+ asthma. ROC curve analysis showed that nFeNO was a great predictor for rhinitis alone or with asthma, revealing an accurate cut-off of 662 ppb.Conclusion: nFeNO measurement is non-invasive, easy to perform, economic and a valuable test in case of AR alone or in association with asthma. Thus, it should be used in patients with rhinitis, together with anterior active rhinomanometry (AAR) to diagnose and estimate the degree of nasal obstruction but also in children with asthma to assess their nasal involvement and improve the therapeutic management.Keywords: nasal nitric oxide, exhaled nitric oxide, anterior active rhinomanometry, allergic rhinitis, asthma, children

Abstract Background Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma. Methods We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level. Results Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0–6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13–24 h and lag 0–24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed. Conclusions Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

Xiaodong Fan,1,* Nian Zhao,2,3,* Zhen Yu,1 Haoda Yu,1 Bo Yin,1 Lifei Zou,1 Yinying Zhao,1 Xiufen Qian,1 Xiaoyan Sai,1 Chu Qin,1 Congli Fu,1 Caixia Hu,1 Tingting Di,1 Yue Yang,1 Yan Wu,1 Tao Bian1 1Departments of Pulmonary and Critical Care Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 2Departments of Pulmonary and Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, 215300, People’s Republic of China; 3The first medical college of Nanjing Medical University, NanJing, Jiangsu, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Wu; Tao BianDepartment of Pulmonary and Critical Care Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of ChinaEmail wuyanyangting@163.com; biantaophd@126.comPurpose: Exhaled nitric oxide has been used as a marker of airway inflammation. The NO concentration in the central and peripheral airway/alveolar can be measured by a slow and fast exhalation flow rate to evaluate inflammation in different divisions within the respiratory tract. We hypothesized that FeNO200 (exhaled NO at a flow rate of 200mL/s) could be used as an evaluation tool for peripheral airway/alveolar inflammation and corticosteroid therapy in chronic obstructive pulmonary disease (COPD) patients.Methods: We recruited 171 subjects into the study: 73 healthy controls, 59 stable COPD patients, and 39 acute exacerbations of COPD (AECOPD) patients. Exhaled nitric oxide (FeNO50 (exhaled NO at a flow rate of 50mL/s)), FeNO200 and CaNO (peripheral concentration of NO/alveolar NO) and clinical variables including pulmonary function, COPD Assessment Test (CAT), C-reactive protein concentration (CRP) and circulating eosinophil count were measured among the recruited participants. FeNO50, FeNO200 and CaNO were repeatedly evaluated in 39 AECOPD patients after corticosteroid treatment.Results: FeNO200 was significantly higher in stable COPD and AECOPD patients than in healthy controls. Nevertheless, CaNO could not differentiate COPD from healthy controls. No correlation was found between circulating eosinophil counts or FEV1 and exhaled nitric oxide (FeNO50, FeNO200, CaNO) in COPD patients. For AECOPD patients, 64% of patients had eosinophil counts > 100 cells/μL; 59% of patients had FeNO200 > 10 ppb; only 31% of patients had FeNO50 > 25 ppb. Among AECOPD patients, the high FeNO50 and FeNO200 groups’ levels were significantly lower than their baseline levels, and significant improvements in CAT were seen in the two groups after corticosteroid treatment. These implied a good corticosteroid response in AECOPD patients with FeNO200> 10ppb.Conclusion: FeNO200 is a straightforward and feasible method to evaluate the peripheral NO concentration in COPD. FeNO200 can be a type 2 inflammation biomarker and a useful tool for predicting corticosteroid therapy in COPD.Keywords: exhaled nitric oxide, chronic obstruction pulmonary disease, corticosteroid, biomarker