Higher Fractional Exhaled Nitric Oxide Research Articles

Long-Term Exposure to Nitrogen Dioxide and Ozone and Respiratory Health in Children.

Further evaluation of the impact of long-term exposure to the gaseous air pollutants nitrogen dioxide (NO2) and ozone (O3) on child lung function, and of NO2 or O3 on eosinophilic airway inflammation, is needed. To determine whether NO2 and O3 are associated with lung function and FeNO in children. We measured lung function (FEV1 and FVC) at mid-childhood (mean age 7.9 years, n=703), early teens (13.2 years, n=976), and mid-teen (17.6 years, n=624) study visits, and fractional exhaled nitric oxide (FeNO) at the early and mid-teen study visits in Project Viva, a cohort of mother-child pairs in the Boston, MA area. Long-term exposure to NO2 and O3 was estimated at home address using geospatial models. We examined associations of home address NO2 and O3 exposure and proximity to roadway with lung function and FeNO using linear regression models, adjusting for age, sex, height, weight, season, relative humidity, temperature, parental smoking, and measures of socioeconomic status. We examined for effect modification of the mid-teen associations by blood eosinophil level, physical activity, aeroallergen sensitization, and parental atopy. Median exposure to NO2 was 33.1 ppb (interquartile range [IQR] 10.4 ppb) and to O3 was 35.3 ppb (IQR 3.4) in the first year of life. Exposure to NO2 was associated with lower FEV1 and FVC across all age groups and exposure time intervals: e.g. an IQR increment of NO2 exposure from birth through the early teen visit was associated with 189.9 mL lower FEV1 (95% CI -273.3, -106.5) at the mid-teen visit. Lifetime NO2 exposure at was associated with higher FeNO at the early teen visit: e.g. 16.2% higher FeNO [95% CI 7.1-26.4%) per IQR of lifetime NO2 through the early teen visit. O3 exposure was not associated with lung function or FeNO. Aeroallergen sensitization (measured in a subset of participants) modified associations of NO2 and O3 with FeNO. Exposure to NO2 was associated with lower lung function and higher FeNO among generally healthy children and teenagers. As NO2 exposure levels were within the annual EPA standard, these findings suggest a need to reduce exposure to this pollutant to optimize child respiratory health.

Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study

IntroductionAsthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive...

Role of Exhaled Nitric Oxide in Management of Asthma in Pediatric Patients: A Systematic Review

Background: Fractional exhaled nitric oxide (FeNO) has emerged as a potential tool for managing asthma in children, but its precise role remains under investigation. Objectives: This systematic review aims to comprehensively evaluate the current research on FeNO's utility in managing pediatric asthma. Methods: We conducted a systematic search of electronic databases like PubMed, MEDLINE, Science Direct, and Scopus. Two independent reviewers screened and extracted data from eligible studies. Results: Sixteen studies including 4612 participants in total and more than half of them 2558 (55.5%) were males—were included in our data. Intermediate FeNO levels had a higher yearly hospitalization rate than those with low or high FeNO levels. FeNO can be a predictive marker as one study found that FeNO levels of more than 35 ppb have the highest risk of developing respiratory disease in the future. Regarding the benefits of FeNO-guided therapy, the use of FENO in conjunction with GINA guidelines for ICS titration can help reduce daily ICS doses and treatment costs. FeNO was found reliable as an asthma biomarker only in children with concomitant aeroallergen sensitivity. Conclusion: The evidence for the effectiveness of FeNO-guided asthma care in children is critical. The effect of FeNO-guided treatment on pharmaceutical use is unclear. Any benefits in illness control must be balanced against the risk of increased drug use, particularly ICS, as higher rates were frequently observed in children with FeNO-guided monitoring. There is an obvious need for larger, longer-term research to address these problems before making firm recommendations for routine therapeutic use.

Characteristics of Adults With Severe Asthma in Childhood: A 60-Year Follow-Up Study

BackgroundChildhood asthma is a prevalent condition with potential impact on adult life. Research QuestionIn a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood? Study Design and MethodsDanish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was done through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months with the remaining participants being classified as having current asthma. ResultsAmong 1394 eligible participants, 232 completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared to participants in remission, participants with persistent asthma had higher total immunoglobulin E (p=0.03), and both lower FEV1%pred (p=0.03), and FEV1/FVC ratio (p<0.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count. InterpretationOur 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine out of ten still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared to those with asthma remission.

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study

PurposeBronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients.MethodsIn a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO.ResultsAmong 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence.ConclusionsOur study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

An observational analysis on the influence of parental allergic rhinitis, asthma and smoking on exhaled nitric oxide in offspring

BackgroundParental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring. MethodsWe studied 609 offspring aged 16–47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors. ResultsParental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0–37.7], p = 0.008, and 13.8 % [0.4–28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9–33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors. ConclusionsParental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.

Correlation of fractional exhaled nitric oxide (FeNO) and clinical outcomes in patients with chronic obstructive pulmonary disease: A prospective cohort study

BackgroundFractional exhaled nitric oxide (FeNO) is an acceptable and noninvasive marker for defining eosinophilic airway inflammation. Further study is necessary to clarify the role of FeNO in patients with chronic obstructive pulmonary disease (COPD). This study aimed to determine the association between FeNO levels and clinical outcomes. MethodsA prospective observational study was conducted at Songklanagarind Hospital from October 2020 to November 2022. FeNO testing and spirometry were performed at the initial visit and 12-month follow-up. Exacerbation, hospitalization, lung function decline, and all-cause mortality were analyzed to determine the association between FeNO levels and clinical outcomes. ResultsA total of 60 patients with COPD were enrolled, 88.3 % of whom were male, with a mean age of 71.3 ± 9.5 years. There were 18 patients (30 %) in the high FeNO group (≥25 ppb) and 42 patients (70 %) in the low (<25 ppb) FeNO group. The mean blood eosinophil count (BEC) was significantly higher in the high FeNO group (p < 0.001). After a 12-month follow-up period, high FeNO group had higher exacerbation events (HR of 1.26, 95 % confidence interval (CI), 1.10–1.97, p= 0.025). Hospitalization and mortality rates were significantly higher in the high FeNO group. Regardless of the inhaled corticosteroids used, patients with high BEC and FeNO levels tended to have a greater risk of exacerbation. ConclusionIn patients with COPD, FeNO levels are strongly correlated with BEC. Poor clinical outcomes were reported in patients with high FeNO levels. FeNO may be a useful biomarker for predicting clinical outcomes in patients with COPD.

Fractional exhaled nitric oxide, a potential biomarker for evaluating glucocorticoids treatment and prognosis in allergic bronchopulmonary aspergillosis

BackgroundAllergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. ObjectiveTo investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. MethodsThis study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. ResultsDifferent prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. ConclusionOur findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.

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

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

Lack of Association between Inhaled Corticosteroid Use Based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

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

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

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

Acute exposure to pollen and airway inflammation in adolescents.

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

Silent zone detection in asthma and its relation to T2 inflammation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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