FeNO Levels Research Articles

Circulating miRNA expression in asthmatics is age-related and associated with clinical asthma parameters, respiratory function and systemic inflammation

BackgroundThe course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA.MethodsControl and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry.ResultsNo difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs.ConclusionSerum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

Mediterranean diet and lung function, sensitization, and asthma at school age: The PARIS cohort

The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age. Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8years, as well as higher FEV1 and FVC. This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children.

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status

BackgroundFractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. ObjectivesTo study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. MethodsLongitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. ResultsAmong asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. ConclusionsWe found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.

Inhibition of GATA3 and Th2 cytokines expression in type 2 high asthmatics by a small molecule targeting RNA-binding protein HuR

Abstract RNA-binding protein human antigen R (HuR) is a master regulator of gene expression in human pathophysiology. Our animal studies in the past showed multiple critical roles for HuR in regulating proinflammatory markers in CD4+ T cells. We hypothesized HuR plays an important role in expression of GATA3 and Th2 cytokines in type 2 high asthma and its inhibition impairs these Th2 inflammatory responses. Peripheral CD4+ T cells were isolated from 26 healthy controls and 32 type 2 high asthmatics (blood eosinophil ≥300 cells/μl or FeNO levels ≥25ppb) and stimulated with anti-CD3/CD28 for 4 days, followed by determination of GATA3 and cytokines expression by flow cytometry and LEGENDplex. HuR levels were quantitated by Western blot, flow cytometry, and qPCR. Inhibition of inflammatory responses was evaluated using a cumarin-derived small molecule named CMLD-2 (a HuR-specific inhibitor). Actinomycin D treatment was used to measure mRNA decay rates of targeted HuR mRNAs. HuR protein levels in CD4+ T cells was significantly higher in type 2 high asthmatics compared to healthy controls. The expression and secretion of Th2 cytokines were significantly higher in asthmatics compared to controls. Our further mRNA and protein studies in type 2 high asthmatics showed reduced expression of GATA3 and Th2 cytokines after CMLD-2 treatment. There was also a significant reduction in gata3 mRNA stability with CMLD-2 treatment, compared with vehicle in the asthmatics. Our study is the first to demonstrate the role of RNA-binding protein HuR in type 2 high asthmatics and that interfering with HuR action using CMLD-2 ameliorates GATA3 and Th2 cytokines production. This data suggests HuR may serve as a novel and powerful therapeutic target to treat type 2 high asthmatics.

High-Sensitivity C - reactive protein Assessment in Bronchial Asthma: Impact of Exhaled Nitric Oxide and Body Mass Index

Background: Bronchial asthma (BA), is a chronic airway inflammatory illness affecting over 315 million individuals globally, initiating a major cause for illness and significant burden on communities. C-reactive protein (CRP) is a finely delicate, nonspecific biomarker of acute phase inflammation and injured cells. This protein is raised up during early stages of inflammation in bronchial asthma. The fraction exhaled nitric oxide test is feasible and non-invasive test, also it delivers an immediate result, besides it is reproducible marker of airways inflammation This study designed to illuminate the relationship between Hs/CRP levels, and FeNo index in patients with asthma. Patients and methods: the study was performed in Merjan Medical City and spiro private clinic, it included 80 asthmatic patients with 60 healthy subjects as control group. The age ranged from 10 to 66 years old, male was dominant. The asthma was assessed using fractional exhaled nitric oxide (FeNo) test (medisoft® company, Belgium) Results: Mean age of all study participants was 33.3±13.0, the asthmatic patients were on treatment for mean duration of 8.02 years. The mean obesity indices being significantly higher in BA group (p-0.041). Both FeNo and Hs/CRP levels were expressively high in individuals with mean of 28.6±28.2 ppb (p-0.001) and (p-0.028) sequentially. Meanwhile, there was no significant correlation of Hs/CRP with W/H, BMI, and duration of the asthma in BA patients. There was no effect of history of asthma treatment on the blood levels of Hs/CRP (p-0.34). Nevertheless, those on regular asthma therapy correlated with decreased levels of FeNo test (p-0.001). More than 50% of obese patients had higher levels of Hs/CRP. This is not the case for relation of obesity with the two FeNo categories which was not significant. In the meantime, the FeNo levels were significantly increased with the increment of Hs/CRP classes. ROC curve analysis of FeNo test in BA patients, showed significant (p-0.000) high accuracy, AUC, sensitivity and specificity. However, ROC curve analysis of Hs/CRP in BA patients revealed significant (p-0.006), but, lower accuracy, AUC, sensitivity and specificity. Conclusion: In this study, there was strong correlation between degree of systemic inflammation as assessed by hs-CRP and asthma inflammation as assessed by measuring exhaled nitric oxide (FeNo concentration). In addition, there was high correlation between increased body weight with asthmatic airways inflammation

Nasal polyp eosinophilia and FeNO may predict asthma symptoms development after endoscopic sinus surgery in CRS patients without asthma

Background Asthma is a significant comorbidity of eosinophilic chronic rhinosinusitis (CRS). Type2-driven biomarkers such as sinus tissue eosinophilia and fractional nitric oxide (FeNO) may be utilized to detect high risk patients who develop asthma symptoms after endoscopic sinus surgery (ESS) in CRS patients. Methods Thirty-six CRS patients without asthma who agreed to undergo ESS between October 2015 and December 2017 were prospectively observed for 12 months following ESS. They were monitored for the development of typical asthma symptoms including dyspnea, wheezes, and cough which responded to anti-asthma medication. Biomarkers were compared between patients who developed asthma symptoms after ESS (asthma symptoms group) and those who did not (non-asthma group). Biomarker changes following ESS intervention were also evaluated. Results Six patients were lost to follow after ESS. Thus, 30 CRS patients [16 with nasal polyps (NPs) proved by surgery] were followed. Seven (23%) newly complained of asthma symptoms during follow-up. Levels of FeNO and the prevalence of eosinophilic NPs (eosinophils ≥ 70/high power fields) were significantly higher in the asthma symptom group than in non-asthma group [50.7 ppb vs 22.4 ppb for FeNO levels, and 100% (n = 3) vs 23% (n = 3) for eosinophilic NP prevalence, both p < 0.05]. Levels of sputum periostin decreased significantly by ESS in the non-asthma group. However, changes of biomarkers after ESS were comparable between the two groups. Conclusions Eosinophils in NPs (≥70/high power fields) and preoperative FeNO may be significant biomarkers for predicting the development of asthma symptoms after ESS.

Measurement of Fractional Exhaled Nitric Oxide in Adults: Comparison of Two Different Analyzers (NIOX VERO and NObreath).

BackgroundFractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and a good predictor of response to corticosteroids. There is a need for a reliable and accurate measurement method, as FeNO measurements have been widely used in clinical practice. Our study aimed to compare two FeNO analyzers and derive a conversion equation for FeNO measurements in adults.MethodsWe included 99 participants who had chief complaints of chronic cough and difficulty in breathing. The participants underwent concurrent FeNO measurement using NIOX VERO (Circassia AB) and NObreath (Bedfont). We compared the values of the two devices and analyzed their correlation and agreement. We then formulated an equation to convert FeNO values measured by NObreath into those obtained by NIOX VERO.ResultsThe mean age of the participants was 51.2±17.1 years, with a female predominance (58.6%). Approximately 60% of the participants had asthma. The FeNO level measured by NIOX VERO (median, 27; interquartile range [IQR], 15–45) was significantly lower than that measured by NObreath (median, 38; IQR, 22–58; p<0.001). There was a strong positive correlation between the two devices (r=0.779, p<0.001). Additionally, Bland-Altman plots and intraclass correlation coefficient demonstrated a good agreement. Using linear regression, we derived the following conversion equation: natural log (Ln) (NObreath)=0.728×Ln (NIOX VERO)+1.244.ConclusionThe FeNO values of NIOX VERO and NObreath were in good agreement and had positive correlations. Our proposed conversion equation could help assess the accuracy of the two analyzers.

Exposure to traffic-related air pollution and changes in exhaled nitric oxide and DNA methylation in arginase and nitric oxide synthase in children with asthma

BackgroundTraffic-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.MethodsWe 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.ResultsExposure 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.ConclusionsExposure 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.

Application of exhaled nitric oxide (FeNO) in pediatric asthma.

Fractional concentration of Nitric Oxide in the exhaled air (FeNO) is a moderately good biomarker of type-2 airway inflammation, and its measurement is feasible also in children. The available evidence is still not enough to support the routine use of FeNO to diagnose or manage asthma in every patient in clinical practice. However, its role in identifying asthma with eosinophilic inflammation is of particular interest in the management of severe asthma. In healthy subjects, FeNO levels increase with age and height, particularly in males, and are also influenced by ethnicity. FeNO measurement can support asthma diagnosis and help in predicting asthma development later in life in young children with recurrent wheezing. FeNO-guided asthma management is effective in reducing asthma exacerbations but may result in a higher daily dose of inhaled corticosteroids. FeNO can also be used as a marker to evaluate adherence to asthma treatment and predict response to different biologicals, especially Omalizumab and Dupilumab. This review outlines recent data on the application of FeNO in childhood-onset asthma diagnosis and management, as well as in phenotyping subjects with severe asthma who may benefit from monoclonal antibodies administration.

Comparison of fractional exhaled nitric oxide in asthmatics with and without allergic rhinitis

Purpose of the study The aim of this study was to measure the concentration of FeNO in asthmatics with and without allergic rhinitis (AR) and to determine usefulness of the test in the assessment of asthma control in the Polish population. The next objective of this study was to estimate the cut-off point of FeNO which might be a good indicator of uncontrolled asthma. Materials and methods The measurements were taken using the Hyp’Air FeNO in 303 adult patients with asthma, AR, comorbid AR and asthma, and non-diseased volunteers. Results FeNO level in healthy adults was similar to the FeNO concentration in AR as well as controlled asthmatic patients without and with AR. Patients with partly controlled and uncontrolled asthma with and without AR had higher FeNO (>60 ppb) levels when compared to adults with controlled disease. The optimal cut-off point of FeNO > 46 ppb and FeNO > 33 ppb was estimated for identification of uncontrolled asthmatics without and with AR, respectively. Conclusion In conclusion, we found a significant correlation between the FeNO concentration and the level of asthma symptom control in asthmatic patients with and without AR.

Exhaled Nitric Oxide (FeNO) in Patients Hospitalized for an Exacerbation of Bronchiectasis and/or COPD : FeNO Levels in COPD and Bronchiectasis.

Exhaled nitric oxide (FeNO) represents an important marker of airway inflammation, yet its role in chronic obstructive pulmonary disease (COPD) and/or bronchiectasis is not well studied. We aimed to measure FeNO in patients with COPD, bronchiectasis, and combination of COPD/bronchiectasis during an acute exacerbation (AE) of the underlying disease as well as to describe the characteristics of patients with COPD/bronchiectasis overlap in patients hospitalized for an acute exacerbation (AE). Seventy-nine patients were enrolled in the study as follows: COPD n=45, bronchiectasis n=18, and COPD and bronchiectasis n=16. FeNO was measured with a commercially available analyzer within 24hours of admission and at discharge. FeNO differed significantly on admission when compared at discharge in the whole group (16.91±16.14 vs 12.48±10.67, p=0.008, respectively). On admission, FeNO was 17.80±18.77ppb in COPD patients, 17.12±6.59 in bronchiectasis patients, and 11.55±2.42 in patients with COPD/bronchiectasis overlap. At discharge, FeNO was 12.40±12.11ppb in COPD patients, 15.50±6.39 in bronchiectasis patients, and 9.00±3.22 in patients with combination. FeNO differed significantly in bronchiectasis patients versus patients with COPD/bronchiectasis overlap at admission (p=0.043) and at discharge (p=0.020) and versus COPD patients at discharge (p=0.043). FeNO decreased significantly during the AE in all groups (p=0.001 for COPD, p=0.021 for bronchiectasis, and p=0.026 for combination). FeNO levels in patients with COPD and/or bronchiectasis exacerbation are possibly increased at admission and decrease at discharge. The differences in FeNO levels between groups may reflect different underlying inflammatory mechanisms.

Eucapnic voluntary hyperventilation test decreases exhaled nitric oxide level in children.

Exhaled nitric oxide (FeNO) measurements and eucapnic voluntary hyperventilation (EVH) tests have been used as diagnostic tools for asthma. Data on the impact of hyperventilation on the level of FeNO are limited. We aimed to evaluate whether EVH tests affect the level of FeNO in children aged 10-16years. A total of 234 children aged 10-16years had a 6-min EVH test performed. In total, FeNO values for 153 of 234 children were measured before the test and within 15min after the test. According to a baseline FeNO level of 20ppb, children were divided into two groups: those with low values (FeNO<20ppb) and those with high values (FeNO≥20ppb). The median age of the children was 13.4years (interquartile range 12.3-15.3years); 58% were boys and 42% were girls. Of these children, 51% were sensitized to aeroallergens. In 101 of 153 children (66%), the FeNO values decreased after the EVH test. In children with low and high baseline levels, the median level of FeNO decreased after the EVH test: 10.5ppb before versus 9.5ppb after (p<.011), and 31.0ppb before versus 28.0ppb after (p<.011), respectively. The decrease in FeNO after EVH test was not associated with induced bronchoconstriction expressed as a change in FEV1 (Rs =.19). The EVH test decreases FeNO levels. Therefore, FeNO should be measured before an EVH test is performed.

Effects of Sublingual Duster Mite Drops on Lung Function and Exhaled Nitric Oxide in Children with Multiple and Single Allergic Respiratory Diseases.

Objective To evaluate the efficiency of sublingual immunotherapy with Dermatophagoides Farinae Drops in children with single and multiple respiratory allergic diseases. Methods Seventy-one children with allergic respiratory diseases who had been treated with Dermatophagoides Farinae Drops for one year or more were divided into a single allergic group (12 cases) and multiple allergic group (59 cases). The rhinitis score, daytime and night symptom score of asthma, VAS score, drug score, pulmonary function, and FeNO level before and after treatment were evaluated and compared between the two groups. Results The rhinitis score, night symptom score, VAS score, and drug score in the single allergic group after treatment were significantly lower than those before treatment (p < 0.05), but there was no significant difference in the daytime symptom score before and after treatment (p > 0.05). The rhinitis score, VAS score, and drug score in the multiple allergic group after treatment were significantly lower than those before treatment (p < 0.05), but there was no significant difference in the scores of daytime symptoms and nighttime symptoms before and after treatment (p > 0.05). In both the single allergic group and multiple allergic group, the pulmonary function indexes of the patients were significantly improved after treatment, and the FeNO after treatment was significantly lower than that before treatment (p < 0.05). There was no significant difference in scores, pulmonary function, and FeNO between the two groups (p > 0.05). Conclusion Sublingual specific immunotherapy is effective in treating multiple and single allergic respiratory diseases in children.

Hyperreactivity of the bronchi in children, whooping cough convalescents

Objective:to assess the presence and degree of bronchial hyperreactivity in convalescents of whooping cough based on the results of bronchial provocation tests.Materials and methods. Using bronchial provocative samples with a 0,02/0,33% histamine solution and 0,33% methacholine solution on a PROVOTEST-2 apparatus from PARI, bronchial hyperreactivity was studied in 12 pertussis convalescents aged 7 to 17 years. The level of endogenous nitrogen monoxide in exhaled air (FeNO) was measured using a portable NObreath electrochemical analyzer (from Bedfont Scientific Ltd.).The results.According to the results of BPP, 6 of 12 convalescents of whooping cough were found to have bronchial hyperreactivity of varying degrees. When conducting a breath test with a histamine solution, bronchial hyperreactivity was recorded in three children, in a sample with methacholine, in five. In 3 out of 6 children with revealed signs of bronchial hyperreactivity, the history of atopy was not burdened, which suggests a connection between the pertussis and the development of bronchial hyperreactivity. A significant increase in the level of endogenous nitric monoxide (above 16 ppb) was observed in 2 out of 10 patients. Follow-up observation showed that the duration of cough with whooping cough ranged from 3 to 6 months, and in patients with positive results of several tests it was maximum. Two out of three children with bronchial asthma showed elevated levels of FeNO and samples with methacholine. Follow-up observation showed that whooping cough aggravated bronchial asthma and demanded correction therapy.Conclusion. A pilot study on the evaluation of bronchial provocative tests suggests that the formation of bronchial hyperreactivity in convalescents of whooping cough is probable, including without a history of atopy, which increases the risk of developing bronchial asthma, however, additional studies are required for a final conclusion.

THE CORRELATION OF FRACTIONAL EXHALED NITRIC OXIDE LEVEL WITH THE ABSOLUTE EOSINOPHIL COUNT AND LEVEL OF BRONCHIAL ASTHMA CONTROL

SESSION TITLE: Asthma: Mechanisms and Management SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: The authors aimed to determine the correlation between the fractional exhaled Nitric Oxide levels, absolute blood eosinophil count with levels of asthma control. METHODS: This was a prospective cross sectional study, from August 2019 to December 2019. Participants aged > 19 years old diagnosed with Bronchial asthma as defined by GINA, were included. The participants were grouped according to the level of asthma control. Spirometry was done for participants who were diagnosed with asthma based on symptoms only. FeNO analysis was performed on the same visit. Eosinophil count were collected and recorded. Correlation between Asthma severity and FeNO levels was determined and tested using Spearman correlation analysis, and graphically presented using box and whiskers. The level of significance was set at 0.05. RESULTS: Our study revealed that older age groups (mean age 60 + 14) had the tendency to develop uncontrolled asthma, and higher FeNO levels, although baseline demographics and clinical characteristics were not statistically significant. The lowest mean FeNO seen among patients with controlled asthma was 25.55 + 4.70 with a significant increase in the concentration of FeNO (53.86 + 25.89) as Asthma becomes uncontrolled, p=0.001. Higher FeNO levels were strongly correlated with uncontrolled asthma, r=0.78. A cut off value of >41 ppb had a sensitivity of 71.43% and specificity of 76.47% in predicting uncontrolled Bronchial Asthma On the other hand, the difference in the absolute eosinophil count among the groups was not statistically significant, p=0.90, but still revealed a weak positive correlation, r=0.33. A cut off value >0.4 ×109/L was noted to have a sensitivity of 71.43% and specificity of 58.82% in predicting uncontrolled Asthma. CONCLUSIONS: This study was able to ascertain that FeNO levels equal or above 41 ppb is associated with uncontrolled Asthma. Although absolute eosinophil count above or equal to 0.4 ×109/L is sensitive in predicting uncontrolled asthma, this parameter was not specific. Hence, an elevated FeNO measurement is more sensitive in accurately predicting uncontrolled asthma as compared to absolute eosinophil counts. CLINICAL IMPLICATIONS: Fractional exhaled nitric oxide levels may have a role in the monitoring of asthma control and confirm adherence to therapy. DISCLOSURES: No relevant relationships by Jamaica Ross David, source=Web Response

Effects of sublingual-specific immunotherapy on pulmonary function and exhaled nitric oxide levels in asthmatic children with and without allergic rhinitis.

BackgroundAllergic asthma and allergic rhinitis are common chronic respiratory diseases in children. The prevalence rate of disease is increasing year by year. And avoid allergens, drug treatments and special immunotherapy (SIT) is the fundamental treatment for respiratory allergies diseases. But there are few comprehensive studies on the control level of asthma, improvement of lung function, and changes of exhaled nitric oxide (FeNO) after SLIT treatment in children with allergic asthma and rhinitis.MethodsIn all, 71 child asthma patients who received sublingual-specific immune therapy for 1 year or more were divided into an asthmatic rhinitis group (31 cases) and an asthma-alone group (40 cases). The two groups of patients were compared before and after treatment in terms of rhinitis symptom scores, daytime and nighttime asthma symptom scores, visual analog scale (VAS) score, drug score, pulmonary function, and exhaled nitric oxide level (FeNO).ResultsAfter treatment, daytime symptom scores, VAS scores, drug scores, and FeNO levels of the asthma-alone group were all lower than before treatment, and the lung function was significantly improved (P<0.05), while the difference in night symptom scores before and after treatment was not statistically significant (P>0.05). The lung function and FeNO level of children in the asthmatic rhinitis group were lower after treatment than before treatment, with statistically significant differences (P<0.05). The scores of rhinitis and VAS in the asthmatic rhinitis group were higher than those in the asthma-alone group, and the differences were statistically significant. There was no significant difference in other scores between the two groups. There was no significant difference in lung function and FeNO level between the two groups.ConclusionsSLIT for children with or without allergic asthma or with or without rhinitis has a significant effect, but its effect on children with asthma combined with rhinitis is not superior to that of children with asthma alone.

Parallel gradients in FENO and in the prevalences of asthma and atopy in adult general populations of Sweden, Finland and Estonia — A Nordic EpiLung study

The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases.We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and Örebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997–2003.The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO ≥25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29–6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02–5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04–6.02), Narva OR 2.45 (1.05–6.19), Örebro OR 3.38 (1.59–8.09), and Stockholm OR 5.54 (2.18–14.79).There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FENO level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.

The Value of FENO Measurement for Predicting Treatment Response in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BackgroundFractional exhaled nitric oxide (FENO) has been shown to be a marker of airway inflammation in various pulmonary diseases, including chronic obstructive pulmonary disease (COPD). In this study, we assessed the FENO level in patients with acute exacerbations of COPD (AECOPD) and analyzed the predictive value of the FENO level for treatment response.MethodsDemographic data were collected at admission. FENO, lung function, blood gases, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) scores were measured at admission and on day 7. At the second visit, the patients were asked to report their health status; scores ranged from 1 to 5, representing “much better”, “slightly better”, “no change”, “slightly worse”, and “much worse”, respectively. The treatment response was evaluated based on the patient’s reported health status (responders were those who reported much better and slightly better) and lung function (responders were those who presented an increase in FEV1 over 200 mL).ResultsA total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV1 and FEV1% (r = 0.291, p < 0.001 and r = 0.205, p = 0.005, respectively), but negatively correlated with a decrease in the COPD Assessment Test (CAT) score (r = −0.197, p = 0.008) and patient-reported health status (rho = −0.408, p<0.001). An inverse correlation was observed between FENO concentrations at admission and the length of hospital stay. The cut-off point for differentiating responders, identified by health status, was 18 ppb, with the sensitivity being 89.7% and specificity 88.9%.ConclusionFENO levels, determined at hospital admission, are potential to predict the overall treatment response in AECOPD patients, including remission in subjective patient-reported health statuses and, also, improvements in lung function.Registry NumberChiCTR-ROC-16,009,087 (http://www.chictr.org.cn/).

Increased Serum Periostin Levels and Eosinophils in Nasal Polyps Are Associated with the Preventive Effect of Endoscopic Sinus Surgery for Asthma Exacerbations in Chronic Rhinosinusitis Patients

Background: Eosinophilic nasal polyps (NPs) are associated with the presence of asthma in chronic rhinosinusitis (CRS) patients. Serum periostin has been considered a relevant biomarker for unified airway diseases. Objective: To determine the utility of biomarkers including serum periostin that reflects reduction of exacerbations of comorbid asthma in CRS patients. Methods: We prospectively recruited 56 CRS patients who were subjected to undergo endoscopic sinus surgery (ESS) (20 with asthma) between October 2015 and December 2017 and followed them for 1 year after ESS. Blood eosinophil count, serum periostin, and fractional nitric oxide (FeNO) were measured at enrollment. How these type 2-driven biomarkers reflect comorbid asthma was determined using receiver operating characteristic (ROC) analysis. The frequency of asthma exacerbations during 1 year was counted both before and after ESS. Associations between preoperative biomarkers including eosinophils in NPs and asthma exacerbations were evaluated. Results: Blood eosinophil count, FeNO, and serum periostin levels were significantly higher in CRS patients with asthma than in those without (p < 0.01 for all) and discriminated comorbid asthma among CRS patients (p < 0.05; AUC > 0.80 for all). The increased preoperative serum periostin correlated with lower absolute number of postoperative exacerbations (ρ = −0.49, p = 0.03) and its relative reduction after ESS (ρ = 0.53, p = 0.03) in asthmatic patients. Increased eosinophils in NPs were also associated with reduced asthma exacerbations. Conclusion: Preoperative increased serum periostin and eosinophils in NPs are associated with the preventive effect of ESS for asthma exacerbations in CRS patients comorbid with asthma.

Biomarkers of Type 2 Airway Inflammation as Predictors of Loss of Asthma Control During Step-Down Therapy for Well-Controlled Disease: The Long-Acting Beta-Agonist Step-Down Study (LASST)

Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking. To evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (Feno) predict loss of asthma control as therapy is stepped down. In subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial Feno measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator). Four hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of Feno were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P= .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, Feno levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers. In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of Feno are strong predictors of treatment failure.