Exhaled Nitric Oxide Research Articles

Correlation of Fractional Exhaled Nitric Oxide [Feno], Spirometry, and Symptom Control in Childhood Asthma, A Cross-Sectional Study

Correlation of Fractional Exhaled Nitric Oxide [Feno], Spirometry, and Symptom Control in Childhood Asthma, A Cross-Sectional Study

Pharmacologic Treatment of Type 2-High Severe Asthma

Asthma is a common and heterogeneous disease whose treatment has considerably changed over the last decades. While inhaled therapies based on inhaled corticosteroids and long acting β2 agonists are effective in controlling asthma in the majority of patients, about 5% of asthmatics poorly respond to inhaled steroids or inhaled steroids/long acting β2 agonists combinations. These patients are affected by “severe asthma”, which is associated with need of oral corticosteroids, progression of the disease, increased use of healthcare services, deterioration of quality of life, and a significant economic burden on society. Asthma is no longer considered a single disease, but a respiratory syndrome with complex biological network of distinct and interrelating inflammatory and remodeling pathways (endotypes) that are associated with different clinical manifestations (phenotypes) both in the lungs (asthma) and other organs (e.g. nose and skin). Severe asthma endotypes may be broadly regarded as Type 2-high and Type 2-low, a model that has become central to asthma management with the development of novel treatments for the Type 2-high endotypes. The hallmark feature of Type 2-high asthma is eosinophilic inflammation, often associated with increased serum IgE, increased exhaled nitric oxide (FeNO) and blood eosinophilia. The discovery of the main key drivers of Type 2-high inflammation (IgE, cytokines such as interleukin IL-5, -4 and -13) enabled the development of new biological agents directed towards specific molecular targets. These advances have shifted the existing paradigm “one drug fits all” to “patient-tailored” novel therapies. The monoclonal antibodies direct to IgE (omalizumab), IL-5 and IL-5 receptor (mepolizumab, benralizumab, reslizumab), and to the α chain of the IL-4 and IL-13 combined receptor (dupilumab), and more recently, to the thymic stromal lymphopoietin (tezepelumab) have been shown in both clinical trials and real-life studies to control symptoms, reduce asthma exacerbations and improve lung function in severe asthmatics not controlled by full inhalation therapies. More recently, the Single Inhaler Triple Therapy (SITT) containing inhaled steroids, long acting β2 agonists and muscarinic antagonists has been developed, slightly improving the effectiveness/safety of the inhalation therapy. This report aims to review available therapeutic opportunities for patients with severe asthma focusing on patients with Type 2-high severe asthma and how to position these new therapeutic alternatives in clinical practice.

Research Progress on the Correlation between Exhaled Nitric Oxide Detection and Chronic Obstructive Pulmonary Disease

Research Progress on the Correlation between Exhaled Nitric Oxide Detection and Chronic Obstructive Pulmonary Disease

Exploration on the use of abbreviations in Chinese medical journals as units of measurement: A case study of “ppb”

In the editorial work, abbreviations of English names are often encountered as symbols of measurement units, which are not in line with editorial norms. This study investigated the implementation of standardization in Chinese medical journals by taking “part per billion (ppb)” as an example, analyzed the reasons for its difficulty in implementation, and provided corresponding countermeasures, in order to provide reasonable suggestions for promoting the implementation of national standardization. During the editorial work, it was found that “ppb” was mostly used as a symbol of measurement units for fractional exhaled nitric oxide (FeNO) in exhaled breath. Therefore, “FeNO” and “fractional exhaled nitric oxide” were used as keywords to retrieve relevant literature on China National Knowledge Infrastructure (CNKI, https://www.cnki.net/) from January 2021 to July 2023. A total of 116 articles were retrieved, 8 of which were removed as reviews, or meta-analyses, and other articles without symbols of measurement units. A total of 108 articles were retrieved. Among the 108 articles, only 2 (1.85%) complied with editorial norms, 78 (72.22%) still used “ppb” as a symbol of measurement units, and 28 (25.93%) had different errors. Medical sci-technology journals have a long way to go in implementing the standardization of measurement unit symbols. It requires international and domestic standards and guidelines to be revised from top to bottom, further cooperation and adjustment from instrument manufacturers, and gradual adaptation of clinicians to new standards and norms, in order to fulfill their respective responsibilities in promoting the national standardization process.

Dietary nitrate supplementation to enhance exercise capacity in patients with COPD: Evidence from a meta-analysis of randomized controlled trials and a network pharmacological analysis

ObjectiveThe potential effects of nitrate in patients with chronic obstructive pulmonary disease (COPD) have attracted increased research interest. However, previous clinical trials have reported inconsistent results, and consecutive meta-analyses have failed to reach a consensus. Since some randomized controlled trials have recently been conducted that can provide more evidence, we performed an updated meta-analysis. MethodsA comprehensive literature search was conducted using PubMed, the Cochrane Library, Embase, and Web of Science databases to identify trials that assessed the efficacy and safety of nitrate in patients with COPD. The Revman 5.3 software was used for data analysis. Mean difference (MD) or standardized mean difference (SMD) with 95 % confidence interval (CI) was used as the effect measure, and forest plots were used to display individual and pooled results. Network pharmacology analysis was conducted to investigate the potential mechanisms of nitrate action in COPD. ResultsEleven studies involving 287 patients were included in this meta-analysis. The results indicated that dietary nitrate supplementation increased plasma nitrate and nitrite concentrations and fractional exhaled nitric oxide in patients with COPD. Nitrate improved exercise capacity [SMD = 0.38, 95 % CI = 0.04–0.72] and endothelial function [MD = 9.41, 95 % CI = 5.30–13.52], and relieved dyspnea in patients with COPD. Network pharmacology identified AKT1, IL1B, MAPK3, and CASP3 as key treatment targets. ConclusionDietary nitrate supplementation could be used as a potential treatment for patients with COPD, especially to increase their exercise capacity. The underlying mechanisms may be related to AKT1, IL1B, MAPK3, and CASP3.

Pretreatment asthma control test score as a predictive score for clinical remission after bronchial thermoplasty in younger patients with severe asthma and preserved lung function

Objective Bronchial thermoplasty (BT) decreases the incidence of asthma exacerbations, emergency room visits, and hospitalizations among patients with severe asthma. Predictors of BT effectiveness remain unclear as its mechanism of action and invasiveness remain obscure. This study aimed to identify factors that could predict BT outcomes. Methods Two respiratory physicians treated 20 consecutive patients with severe asthma using BT. The patients were assigned to groups based on clinical remission following an expert consensus proposed in 2020. Predictors of clinical remission were analyzed using asthma control test (ACT) score, pulmonary function and blood tests, and fractional exhaled nitric oxide. Results At baseline, the median age was 44 years (interquartile range [IQR], 31.0–52.8), and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in one second (%FEV1) was 85.9% (IQR, 74.8–100.5). Six (30%) patients achieved clinical remission. Among the patients treated with biologics, 20% had clinical remission, and 20% discontinued biologic therapy. The pre-BT ACT score was significantly lower in the group with than without remission (11.0 [IQR, 8.0–14.5] vs. 15.0 [IQR, 11.0–17.3], p = .016). Adverse events did not significantly differ between the groups. Conclusions To the best of our knowledge, this is the first study to use clinical remission as a criterion for evaluating BT efficacy. The pre-BT ACT score might a the predict response to BT in younger adult patients with severe asthma and pre-BD %FEV1 ≥ 70%.

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

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

Acute bronchitis - modern possibilities of mucactive therapy

Analysis of the clinical effectiveness and safety of erdosteine use in comparison with standard (real practice) mucoactive therapy in patients with acute bronchitis (АВ) in adults. The observational program included 100 adult patients with АВ, 50 of them (group 1) received erdosteine, the group 2 also included 50 patients who received acetylcysteine, bromhexine and other mucolytics (real clinical practice). The following were assessed: cough severity, average time for resolution of night and daytime cough, satisfaction with treatment, NO concentration in exhaled air, levels of C-reactive protein (CRP) and interleukin-6 (IL-6). The average duration of relief of severe daytime cough requiring continued therapy was: in group 1 - 3.7±0.46 days, night cough - 1.14±0.94 days. In the second group, daytime cough was relieved in 3.8±0.4 days, night cough - 1.08±0.7 days. The duration of mucoactive therapy in group 1 was 5.32±0.82 days, in group 2 this figure was 8.5±1.4 days (p<0.05). The number of АВ patients with a significant reduction in the severity of productive cough (1 point on cough severity scale) on the 6th day from the beginning of treatment in group 1 (erdosteine) amounted to 32 (64%), in group 2 - 27 (54%). Satisfaction with the treatment was higher in the group receiving erdosteine: according to the indicators "very satisfied" and "extremely satisfied" the patients of the group 1 - 42 - were the leaders in comparison with the group 2, where these positions were marked by 28 patients. The level of CRP in patients with АВ in group 1 was 24.7±21.24 mg/l, in group 2 - 16.37±16.5 mg/l, which indicates the viral etiology of the process and no need in the prescription of antimicrobial drugs. For the first time in Russian practice, the following were determined: the level of IL-6, which in the group 1 was 10.3±6.7 pc/ml; in the group 2 - 10.03±3.94 pc/ml; the level of exhaled NO in group 1 was 16.5±5.1 ppb, in group 2 - 14.9±4.6 ppb (the norm is up to 25 ppb). These indicators, against the background of mucoactive therapy, decreased to normal values by 6th day. The findings expand our understanding of АВ in adults. New results have been obtained on the role of CRP, IL-6 and NO in exhaled air during АВ. The use of erdosteine was accompanied by a significant mucoactive effect in the form of a pronounced regression of cough in patients with АВ compared to the comparison group in shorter term.

Bacterial colonisation of the airway in neonates and risk of asthma and allergy until age 18 years.

We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5 years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18 years. We investigated the association between airway colonisation with Streptococcus pneumoniae, Moraxella catarrhalis and/or Haemophilus influenzae in 1-month-old neonates from the COPSAC2000 mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18 years using generalised estimating equations. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Neonatal airway colonisation was present in 66 (21%) out of 319 children and was associated with a 4-fold increased risk of persistent wheeze/asthma (adjusted OR 4.01 (95% CI 1.76-9.12); p<0.001) until age 7 years, but not from age 7 to 18 years. Replication in the COPSAC2010 cohort showed similar results using 16S data. Colonisation was associated with an increased number of exacerbations (adjusted incidence rate ratio 3.20 (95% CI 1.38-7.44); p<0.01) until age 7 years, but not from age 7 to 18 years. Colonisation was associated with increased levels of blood eosinophils (adjusted geometric mean ratio 1.24 (95% CI 1.06-1.44); p<0.01) and tumour necrosis factor (TNF)-α (adjusted geometric mean ratio 1.09 (95% CI 1.02-1.16); p=0.01) until age 12 years. There were no associations with lung function, bronchial reactivity, fractional exhaled nitric oxide, allergic sensitisation, total IgE or atopic dermatitis up to age 18 years. Neonatal airway colonisation was associated with early-onset persistent wheeze/asthma, exacerbations, elevated blood eosinophils and elevated TNF-α in blood, most prominent in early childhood, thereafter diminishing and no longer evident by age 18 years.

Doxofylline as a steroid-sparing treatment in Mexican children with asthma

Objective The aim of this pilot study was to assess the efficacy of doxofylline as an ICS-sparing agent in the treatment of Mexican children with asthma. Methods 10-week, open-label, crossover, pilot study, we examined the steroid-sparing effect of doxofylline in Mexican children with asthma. Patients aged 6–16 years treated with inhaled corticosteroids (ICS) for at least 8 wk before enrollment were divided randomly into two groups at the baseline visit. Group A (n = 31) received doxofylline (18 mg/kg/day) plus standard-dose budesonide (D + SDB) for the first 4-week period followed by doxofylline plus reduced-dose budesonide (D + RDB) for the second 4-week period. Group B (n = 30) received D + RDB followed by D + SDB. Clinical outcomes assessed included lung function (forced expiratory volume; in 1 s, FEV1), fractional exhaled nitric oxide (FeNO), asthma control, number of exacerbations and use of rescue medication (salbutamol). Results It was shown that combined use of doxofylline and ICS may allow children with asthma to reduce their daily dose of ICS while maintaining lung function and improving asthma control (p = 0.008). There were few asthma exacerbations and only one patient required treatment with systemic corticosteroids. Rescue medication use decreased significantly in patients receiving D + SDB during the first 4-week period. Conclusions Our results suggest that doxofylline may be a steroid-sparing treatment in asthma, but longer-term, controlled studies are needed to confirm these observations.

Association of Sputum Eosinophilia With Easily Measured Type-2 Inflammatory Biomarkers in Untreated Mild Persistent Asthma

A multicenter clinical trial in patients with mild persistent asthma indicated that response to inhaled corticosteroids (ICS) is limited to those with sputum eosinophilia. However, testing for sputum eosinophilia is impractical in most clinical settings. We examined associations between sputum eosinophilia and type 2 inflammatory biomarkers in untreated mild persistent asthma. Induced sputum, blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and serum periostin were obtained twice during the 6-week run-in period in a clinical trial that enrolled patients 12 years and older with symptomatic, mild persistent asthma without controller therapy. The optimal threshold for each biomarker was based on achieving 80% or greater sensitivity. Performance of biomarkers (area under the receiver operating characteristics curve [AUC], range 0.0-1.0) in predicting sputum eosinophilia 2% or greater was determined; AUCs of 0.8 to 0.9 and more than 0.9 define excellent and outstanding discrimination, respectively. Of 564 participants, 27% were sputum eosinophilic, 83% were atopic, 70% had BEC of 200/uL or higher or FeNO of 25 ppb or greater; 64% of participants without sputum eosinophilia had elevated BEC or FeNO. The AUCs for BEC, FeNO, and both together in predicting sputum eosinophilia were all below the threshold for excellent discrimination (AUC 0.75, 0.78, and 0.79, respectively). Periostin (in adults) had poor discrimination (AUC 0.59; P= .02). In untreated mild persistent asthma, there is substantial discordance between sputum eosinophilia, BEC, and FeNO. Until prospective trials test the ability of alternative biomarkers to predict ICS response, BEC or FeNO phenotyping may be an option to consider ICS through a shared decision-making process with consideration of other clinical features.

Real-World Characteristics of Patients with Severe Asthma prior to Starting Dupilumab: The ProVENT Study

Introduction: Dupilumab is approved for the treatment of severe type 2 (T2) asthma; however, the characteristics of patients receiving dupilumab in routine clinical practice are incompletely understood. This study describes the characteristics of patients with severe asthma before dupilumab treatment in a real-world setting. Methods: This interim analysis of an ongoing real-life study of dupilumab assessed baseline characteristics of the first patient cohort enrolled in the ProVENT study. Results: A total of 99 patients (59% females) were analyzed (17% received another biologic before dupilumab treatment and 15% were on maintenance oral corticosteroid treatment). Adult-onset asthma (>18 years) and an allergic phenotype were documented in 58% and 48% of patients, respectively. Median (interquartile range) age was 54 (40–61) years; the median number of exacerbations in the last 24 months was 1 (0–3); median fractional exhaled nitric oxide (FeNO) value was 38 (23–64) ppb; and median blood eosinophils (bEOS) count was 184 (8–505) cells/µL. According to the United Kingdom Severe Asthma Registry classification, 53% of patients had T2 intermediate asthma (bEOS ≥150 cells/µL or FeNO ≥25 ppb), 17% had T2 high asthma (bEOS ≥150 cells/µL and FeNO ≥25 ppb), and 4% had T2 low asthma (bEOS <150 cells/µL and FeNO <25 ppb). At least one GINA criterion for T2 airway inflammation was documented in 70% of patients. T2 comorbidities were observed in 64% of patients. Conclusions: This analysis suggests that patients eligible for dupilumab treatment display various clinical and biochemical characteristics rather than one clear-cut phenotype.

Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE Study

Uncontrolled asthma in growing children can impair lung growth that may lead to adverse complications in later life. Dupilumab, a human monoclonal antibody, blocks the shared receptor for IL-4 and IL-13, key drivers of type 2 inflammation. To extensively evaluate the effect of dupilumab on lung function in children (6-11 years) with moderate-to-severe asthma enrolled in phase 3 LIBERTY ASTHMA VOYAGE (NCT02948959). Children with asthma were randomized 2:1 to add-on dupilumab 100/200 mg by bodyweight or placebo every 2 weeks, for 52 weeks. We analyzed spirometry parameters in children with type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥20 parts per billion [ppb] at baseline) and within subgroups defined by baseline blood eosinophils or FeNO values. A total of 116 (49%) dupilumab-treated children and 59 (52%) on placebo had impaired lung function (prebronchodilator percent-predicted forced expiratory volume in 1 second [ppFEV1] <80%) at baseline. Dupilumab improved pre- and postbronchodilator ppFEV1 as early as week 2, sustained for up to 52 weeks (least-squares mean difference vs placebo at week 52: 7.79 percentage points; 95% confidence interval [CI]: 4.36-11.22; P < .001 and 4.37 points; 95% CI: 0.95-7.78; P= .01, respectively). Sustained improvements were also observed in other lung function parameters, including pre- and postbronchodilator forced vital capacity (FVC), prebronchodilator forced expiratory flow, and FEV1/FVC ratio across all populations. Dupilumab led to significant, sustained lung function improvements across a range of lung function measures in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma.

Simultaneous real-time detection of fractional exhaled nitric oxide and end-tidal carbon dioxide by quantum cascade laser absorption spectroscopy

The simultaneous detection of fractional exhaled nitric oxide (FeNO) and end-tidal carbon dioxide (ETCO2) is of great importance for the distinguishing and diagnosis of asthma and chronic obstructive pulmonary disease (COPD), providing more comprehensive information on respiratory disorders. This work demonstrates a simultaneous ETCO2 and FeNO detection system based on quantum cascade laser absorption spectroscopy (QCLAS) technology was presented. The system employs wavelength modulation spectroscopy (WMS) technology and the Herriott multi-pass cell, achieving a detection limit of 2.82 ppb for nitric oxide (NO) and 0.05 % for carbon dioxide (CO2). Real-time exhalation measurements were performed on volunteers with varying ETCO2 and FeNO levels, and the results of the test can accurately distinguish whether the corresponding volunteer was healthy, had asthma or COPD. The effect of exhalation flow rate on the concentration of the two gases was explored. A range of expiratory flow rates were tested in the flow rate interval from 1 to 4 L/min, and there was always an inverse relationship between expiratory flow rate and FeNO concentration, but flow rate changes did not affect ETCO2 concentration. The results indicate that this detection system can simultaneously and effectively measure ETCO2 and FeNO concentrations in real-time.

Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation

BackgroundThymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a Type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR) and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of Type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes only has been described sparsely. ObjectiveTo investigate the association between AHR and levels of TSLP in serum, sputum and BAL in patients with asthma with and without Type-2 inflammation. MethodsA novel ultra-sensitive MSD S-plex assay was used to measure levels of TSLP in patients with asthma (serum n=182, sputum n=81, BAL n=85) and healthy controls (serum n=47). The distribution and association between airway and systemic TSLP, measures of AHR, Type-2 inflammation and severity of disease were assessed. ResultsTSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide, ρ=0.49, p=0.005. Serum TSLP (geo.mean (95% CI)) was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: 1600 fg/ml (1468-1744) and 1294 fg/ml (1167-1435) vs. 846 fg/ml (661-1082), but did not correlate with the level of AHR. Increasing age, male sex and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, ICS dose and symptom score were not. ConclusionThe association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation.

Lung function in young adulthood in relation to moderate-to-late preterm birth.

Moderate-to-late preterm birth (32 to <37 weeks of gestation) has been associated with impaired lung function in adolescence, but data in adulthood and physiological phenotyping beyond spirometry are scarce. We aimed to investigate lung function development from adolescence into young adulthood and to provide physiological phenotyping in individuals born moderate-to-late preterm. Lung function data from individuals born moderate-to-late preterm (n=110) and term (37 to <42 weeks of gestation, n=1895) in the Swedish birth cohort BAMSE were used for analysis and included dynamic spirometry, fractional exhaled nitric oxide and multiple breath nitrogen wash-out. Data from 16- and 24-year follow-ups were analysed using regression models stratified on sex and adjusted for smoking. Data-driven latent class analysis was used to phenotype moderate-to-late preterm individuals at 24 years, and groups were related to background factors. Males born moderate-to-late preterm had lower forced expiratory volume in 1 s (FEV1) at 24 years of age (-0.28 z-score, p=0.045), compared to males born term. In females, no difference was seen at 24 years, partly explained by a significant catch up in FEV1 between 16 and 24 years (0.18 z-score, p=0.01). Lung function phenotypes described as "asthma-like", "dysanapsis-like" and "preterm reference" were identified within the preterm group. Maternal overweight in early pregnancy was associated with "asthma-like" group membership (OR 3.59, p=0.02). Our results show impaired FEV1 at peak lung function in males born moderate-to-late preterm, while females born moderate-to-late preterm had significant catch up between the ages of 16 and 24 years. Several phenotypes of lung function impairment exist in individuals born moderate-to-late preterm.

Exploring the Autoimmune Pathogenesis in Severe Asthma

Introduction: Severe asthma has a poor response to hormone therapy and a poor level of control, so the discovery of new pathogenetic mechanisms is important for diagnosing and treating severe asthma. IL-35 may play a protective role in autoimmune diseases by directly or indirectly inhibiting the secretion of IL-17, which is an important proinflammatory factor involved in the occurrence and development of autoimmune diseases. The autologous serum skin test (ASST) is a good sensitivity and specificity screening test for autoimmune functional autoantibodies. We compared the levels of IL-35 and IL-17 in serum samples, the positive rate of ASST, the level of exhaled nitric oxide (FeNO), and the atopic constitution in patients with severe asthma to those with mild-to-moderate asthma so as to explore the possible autoimmune pathogenesis of severe asthma. Methods: Patients with mild-to-moderate and severe asthma were enrolled. Their age, gender, smoking history, family history of asthma, history of allergic rhinitis, positive allergen results, serum total IgE (TlgE), allergen-specific IgE (slgE), routine blood, ASST results, and FeNO test results were compared and analyzed. The IL-35 and IL-17 levels in serum samples from both groups were measured by enzyme-linked immunosorbent assay for comparison and analysis. The SPSS 22.0 software package was used for statistical analysis. Results: A total of 50 patients with mild-to-moderate asthma and 31 patients with severe asthma were included in this study. The proportion of patients with a history of smoking and a family history of asthma was significantly higher in the severe asthma group compared to the mild-to-moderate asthma group (all p < 0.05); the number of positive allergen tests was significantly lower in patients with severe asthma compared to those with mild-to-moderate asthma (p < 0.001). The rate of positive ASST was significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05). Serum IL-17 levels were significantly higher in patients with severe asthma than in patients with mild-to-moderate asthma (p < 0.05), but serum IL-35 level between the two group was not significantly different (p = 0.113). ASST-positive patients had a statistically significant increase in the risk of developing severe asthma, while patients with allergen positive were less likely to develop severe asthma (positive ASST: OR = 5.277, p = 0.024; allergen positivity: OR = 0.123, p = 0.001). Conclusions: IL-35 has a weaker inhibitory effect on high IL-17 expression in patients with severe asthma, and the rate of positive ASST was significantly higher in patients with severe asthma, which all suggested the possibility of autoimmune pathogenesis in patients with severe asthma.

The association of exhaled nitric oxide with air pollutants in young infants of asthmatic mothers

BackgroundExhaled nitric oxide is a marker of airway inflammation. Air pollution induces airway inflammation and oxidative stress. Little is known about the impact of air pollution on exhaled nitric oxide in young infants.MethodsThe Breathing for Life Trial recruited pregnant women with asthma into a randomised controlled trial comparing usual clinical care versus inflammometry-guided asthma management in pregnancy. Four hundred fifty-seven infants from the Breathing for Life Trial birth cohort were assessed at six weeks of age. Exhaled nitric oxide was measured in unsedated, sleeping infants. Its association with local mean 24-h and mean seven-day concentrations of ozone, nitric oxide, nitrogen dioxide, carbon monoxide, sulfur dioxide, ammonia, particulate matter less than 10 μm (PM10) and less than 2.5 μm (PM2.5) in diameter was investigated. The air pollutant data were sourced from local monitoring sites of the New South Wales Air Quality Monitoring Network. The association was assessed using a ‘least absolute shrinkage and selection operator’ (LASSO) approach, multivariable regression and Spearman’s rank correlation.ResultsA seasonal variation was evident with higher median exhaled nitric oxide levels (13.6 ppb) in warmer months and lower median exhaled nitric oxide levels (11.0 ppb) in cooler months, P = 0.008. LASSO identified positive associations for exhaled nitric oxide with 24-h mean ammonia, seven-day mean ammonia, seven-day mean PM10, seven-day mean PM2.5, and seven-day mean ozone; and negative associations for eNO with seven-day mean carbon monoxide, 24-h mean nitric oxide and 24-h mean sulfur dioxide, with an R-square of 0.25 for the penalized coefficients. These coefficients selected by LASSO (and confounders) were entered in multivariable regression. The achieved R-square was 0.27.ConclusionIn this cohort of young infants of asthmatic mothers, exhaled nitric oxide showed seasonal variation and an association with local air pollution concentrations.

Study of Fractional Exhaled Nitric Oxide among Chronic Obstructive Pulmonary Disease Patients in Acute Exacerbation

Study of Fractional Exhaled Nitric Oxide among Chronic Obstructive Pulmonary Disease Patients in Acute Exacerbation

The Relationship of Fractional Exhaled Nitric Oxide in Patients with AECOPD.

To identify the relationship between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their fractional-exhaled nitric oxide (FeNO) levels. Patients diagnosed with AECOPD in the respiratory department of Beijing Chaoyang Hospital from June 2017 to August 2019 were recorded. The demographic data, FeNO value, peripheral blood eosinophil count, number of acute exacerbations in the past year, pulmonary function test, use of inhaled glucocorticoids (ICS) and other data were collected and analyzed. FeNO was measured again three months after discharge, the participants were assessed to determine if the stable period criteria were met. A total of 214 patients met the requirements of this study. 25ppb for FeNO was used as the cutoff for further analysis. The proportion of males, number of acute exacerbations in the past year, number of ICS users, leukocyte count and eosinophil count in the high FeNO-level group was significantly higher than that in the low-level group (P < 0.05). The results showed that the number of acute exacerbations in the past year, number of ICS users, and eosinophil count were statistically significant in the model (P < 0.05). The study also showed that the level of FeNO in the acute exacerbation phase was significantly higher than that in the stable phase. The ROC curve that the area under the curve used by FeNO to predict ICS used is 0.631 (95% CI: 0.526-0.736), and the corresponding P value is 0.022. FeNO is closely related to activated T2 inflammation and eosinophil count in COPD patients. The FeNO levels can be used as an index to evaluate the severity of COPD and predict the recovery of activity after ICS treatment. FeNO can predict the use of ICS and is a beneficial supplement to eosinophils.