Fractional Exhaled Nitric Oxide Measurements Research Articles

Protocol for the INFORM ASTHMA Trial: Budesonide-formoterol reliever in adults with asthma on maintenance inhaled corticosteroid

BackgroundInternational asthma guidelines recommend inhaled corticosteroid (ICS)/formoterol in preference to short-acting beta2-agonist (SABA) reliever-based regimens as reliever therapy in adults and adolescents of all asthma severities. A major limitation to this recommendation is the absence of randomised controlled trial (RCT) efficacy and safety data for this approach in patients who continue to use maintenance ICS. The anti-inflammatory effect of ICS/formoterol reliever therapy on airway inflammation is also not well characterised.ObjectiveTo determine the anti-inflammatory effect, efficacy and safety of budesonide-formoterol reliever therapyversusterbutaline reliever therapy in adults with asthma on maintenance ICS therapy. Fractional exhaled nitric oxide (FeNO) will specifically be examined to determine the time-course and magnitude of anti-inflammatory effect.MethodsA 26-week, open-label, parallel-group, 2-arm, phase IV, two-sided superiority RCT will recruit 180 adults aged 16–75 with a clinical diagnosis of asthma using reliever only therapy, or SABA reliever therapy with maintenance ICS at baseline, and with baseline FeNO at screening ≥25 ppb. Enrolled participants will be allocated to maintenance budesonide with the dose based on their baseline treatment step and randomised 1:1 to either budesonide-formoterol or terbutaline reliever therapy. All participants will perform at home FeNO measurements at regular intervals for the first 12 weeks of the study. The primary outcome is FeNO at 26 weeks. Key secondary outcomes include FeNO time-course, asthma exacerbations, asthma control and spirometry.ConclusionThis will be the first RCT comparing ICS-formoterolversusSABA reliever therapy in patients who use maintenance ICS therapy.

Role of Fractional Exhaled Nitric Oxide for Monitoring Bronchial Asthma

Background: Monitoring during treatment of asthma is usually done by various clinical tools, spirometry, sputum eosinophils and fractional exhaled nitric oxide. Fractional exhaled nitric oxide is a simple and noninvasive tool and has a good agreement with asthma control test score. This study aims to correlate fractional exhaled nitric oxide with asthma control test score. Methods: This cross-sectional study was conducted at National Academy of Medical Sciences, Bir hospital, Chest unit, Department of Medicine, over a duration of six months. Patients aged more than 18 years with bronchial asthma diagnosed at least three months prior were included into the study. Those with recent severe exacerbations, known other chronic respiratory disease and smokers were excluded. Asthma control test score was obtained at baseline. All included patients underwent fractional exhaled nitric oxide measurement followed by measurement of Forced vital capacity(FVC) Forced expiratory volume in one second (FEV1) and FEV1/FVC ratio. Results: Forty patients with a mean age of 40.5±11.1 years were included in the study. Majority were females (65%) and the median duration of symptoms was 24 months (Interquartile range= 18-60). Mean fractional exhaled nitric oxide level was 27.8 (±16.0) parts per billion (ppb) and asthma control test score was 19.3 (±4.7). Mean fractional exhaled nitric oxide levels were significantly different across different severity (well controlled, partially controlled and poorly controlled) of asthma (p=0.013). The mean fractional exhaled nitric oxide values and total asthma control test score shows statistically significant negative correlation (Pearson correlation coefficient (r) = -0.462, p=0.003). Asthma control test and FeNO values guided the change of inhaled steroid dose in 17 of the 40 patients. Conclusion: Fractional exhaled nitric oxide can be used when available, along with asthma control test for monitoring control and adjusting the inhaled steroid dose in asthma. Keywords: Asthma control test (ACT); bronchial asthma; Fractional exhaled nitric oxide (FeNO).

Evaluating serum periostin and YKL-40 as biomarkers for airway remodeling and hyperresponsiveness in pediatric asthma

BackgroundPeriostin and human chitinase-3-like protein 1 (YKL-40) have been suggested to be involved in the development of airway fibrosis and remodeling. This study aimed to investigate the relationship between serum periostin levels and airway hyperresponsiveness (AHR) and between serum YKL-40 levels and AHR in children with asthma, comparing periostin as a marker for Th2 inflammation and atopy with YKL-40. MethodsThe study involved children aged 6–15 years, comprising 75 with asthma and 29 healthy controls. We measured serum periostin and YKL-40 levels and performed exercise bronchial provocation tests, methacholine challenge tests, spirometry, and FeNO measurements. ResultsCompared to the healthy controls, asthmatic children exhibited significantly elevated levels of periostin (86.7 [71.0–104.0] vs 68.3 [56.0–82.0] ng/mL; P = 0.006) and YKL-40 (29.0 [15.0–39.5] vs 27.7 [14.0–34.1] ng/mL; P = 0.034). The subgroup analysis revealed that periostin levels were significantly higher in the atopic asthma group than in the healthy controls (P = 0.003), but not in the non-atopic asthma group. YKL-40 levels were elevated in both the atopic and non-atopic asthma groups compared to healthy controls (P = 0.012 and P = 0.001, respectively). Serum periostin levels were significantly correlated with the postexerceise maximum percentage decrease in forced expiratory volume (FEV1), as well as with fractional exhaled nitric oxide (FeNO) and blood eosinophil counts, but showed no significant correlation with overall lung function. Conversely, serum YKL-40 levels were significantly linked to the Z score of FEV1 and AHR to methacholine but not with AHR to exercise or FeNO or blood eosinophil count. ConclusionsPeriostin is linked to atopic asthma and correlates with exercise-induced bronchoconstriction, FeNO, and eosinophil counts, highlighting its role in Th2 inflammation. YKL-40 is a general asthma marker, indicating airway remodeling. These findings suggest that targeting these markers can improve personalized treatment strategies for pediatric asthma.

Fractional Exhaled Nitric Oxide (FeNO) in Biomass Smoke-Associated Chronic Obstructive Pulmonary Disease.

To measure FeNO levels in patients with COPD-BS and to compare these with those of patients with stable COPD-TS and in healthy controls. Transversal, observational, descriptive, comparative, and analytical study. A total of 57 patients, including 23 with COPD-BS, 17 with COPD-TS, and 17 healthy control subjects. The measurement of FeNO was carried out on all of these by means of the on-line chemiluminescence technique; the values were expressed in parts per billion (ppb) for their analysis. It was observed that the FeNO values were similar between COPD-BS and COPD-TS and were significantly different between the healthy and stable COPD (both groups). No correlation was found between pulmonary function and symptoms with FeNO in any of the groups. The level of FeNO in stable COPD is found to be increased in a similar manner in COPD-BS and COPD-TS, with a significant difference on comparing it with that of the healthy subjects.

Identifying the predictive value of fractional exhaled nitric oxide (FeNO) for uncontrolled asthma in 3-7-year-old Thai children.

Fractional exhaled nitric oxide (FeNO) is the method for monitoring airway inflammation. However, a singular FeNO value cutoff may not adequately represent the control status across different ages and demographics. This study aimed to evaluate the correlation between FeNO values and asthma control levels, identifying an optimal cutoff point for children aged 3 to 7 years. This cross-sectional study was conducted at Naresuan University Hospital from April 1, 2023 to July 31, 2023. Inclusion criteria were asthmatic patients aged 3 to 7 years who were capable of following commands. Exclusion criteria included children who had a coronavirus disease 2019 (COVID-19) infection, those experiencing difficulty breathing, or unable to perform the FeNO measurement. Eligible patients were classified according to their level of asthma control and underwent FeNO testing. Out of 108 participants who successfully completed FeNO measurements, a significant difference in FeNO values was observed across controlled, partially controlled, and uncontrolled asthma groups, with uncontrolled asthma presenting significantly higher values. The optimal FeNO cutoff point for predicting uncontrolled asthma was identified as ≥15 ppb with a sensitivity 46.7%, specificity 86.0%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 90.9%. This study established a significant correlation between FeNO levels and uncontrolled asthma, FeNO cutoff point ≥15 ppb as the optimal value in predicting uncontrolled asthma in Thai children aged 3-7 years. Factors such as uncontrolled allergic rhinitis, symptoms at onset, smoking exposure, treatment compliance, and inhaled corticosteroid (ICS) usage were associated with FeNO values. The application of FeNO measurement should be integrated with clinical assessments and consideration of these associated factors.

Relationship between fraction of exhaled nitric oxide and peripheral eosinophilia in asthma

Background Achieving disease control is the goal of asthma management. Serum or sputum eosinophil counts have been known traditional means of assessing eosinophilic airway inflammation in asthma, which is vital in predicting response to corticosteroid therapy which ultimately promotes control of the disease. Evidence suggests that fraction of exhaled nitric oxide (FeNO) may be a more useful non-invasive surrogate biomarker for the assessment of eosinophilic airway inflammation and could help with the timely adjustment of inhaled corticosteroid therapy in the uncontrolled asthma patient. The relationship between FeNO and other markers of airway inflammation has been variable in literature, with limited data in sub-Saharan Africa where FeNO testing is very sparse. We sought to define the relationship between FeNO levels, serum eosinophil counts, spirometry measures and symptom control among asthma patients. Materials and methods The study was conducted at the Asthma Clinic of a large tertiary hospital. This study included 82 patients with physician-diagnosed asthma being regularly managed at the clinic. All participants were taken through the asthma control test (ACT), had FeNO and spirometry measurements taken according to the American Thoracic Society (ATS) guidelines. Blood samples were obtained from all participants for serum eosinophil counts. Correlation coefficient was used to ascertain the relationship between FeNO levels and serum eosinophil counts, ACT scores, and spirometry measurements. Logistic regression was used to examine the association between high FeNO and abnormal FEV1 percentage predicted (<80%) with adjustments for age, sex, and BMI. Results A total of 82 patients with asthma were included in the study, with higher prevalence of females (72%). Majority (40.2%) of the patients were found in the 60 and above age category. The median FeNO level and ACT score was 42.00 (26.00–52.50) parts per billion (ppb) and 20.0 (18–23) respectively. The median serum eosinophil counts was 0.25(0.90–0.38) × 109/L. The median FeNO levels were significantly higher in patients with partly and very poorly controlled asthma than in the well-controlled group (p < 0.001). A total of 47(57%) of the patients were classified as having well controlled asthma and 35 (42%) uncontrolled. FeNO correlated with serum eosinophil counts (r = 0.450, p < 0.001), ACT (r = −0.648, p < 0.001), and FEV1 percentage predicted (r = −0.353, p = 0.001). High FeNO (>50 ppb) was associated with an over fivefold increased risk of having an abnormal FEV1 percentage predicted. Conclusion FeNO levels significantly correlated with the ACT scores, serum eosinophil counts and FEV1% predicted among the asthma patients who were on inhaled corticosteroid therapy. High FeNO was significantly associated with abnormal FEV1 percentage predicted. We suggest that the point of care assessment of FeNO is a reliable marker of eosinophilic inflammation in our cohort of patients and together with ‘ACT scores’ in our asthma clinics could increase asthma control rates.

Impact of Long COVID on Lung Function in Children.

While the coronavirus disease-2019 (COVID-19) pandemic has generally resulted in milder illness among children than adults, persistent respiratory symptoms have been increasingly reported in this population. We conducted a prospective, single-center cohort study focusing on children experiencing prolonged respiratory symptoms after contracting COVID-19. Spirometry, 6- minute walk tests (6MWTs), and tests of lung volume, the diffusing capacity of the lungs for carbon monoxide (DLCO), and fractional exhaled nitric oxide (FeNO) were performed on COVID-19 survivors at least 4 weeks after infection and a group of healthy control subjects. Fifty-five children with long-term COVID and 55 healthy control subjects were recruited. The weight, height, and body mass index Z-scores were similar in the groups. Within a median duration of 85 days (minimummaximum: 35-194) following COVID-19 infection, a restrictive pattern was observed to be more common in the study group (p=0.021). In children with long COVID, 6MWT distances, DLCO Z-scores, and the predicted values of spirometry and lung volume tests were found to be significantly lower but in the normal range. The average predicted values for DLCO, FeNO, and 6MWT were similar in the two groups. Prolonged respiratory symptoms often persist long after COVID-19 infection, necessitating comprehensive evaluation of affected children. Close monitoring, including spirometry and lung volume assessments, is crucial for children with abnormalities in lung imaging. However, FeNO measurements were found to be ineffective in monitoring long COVID.

Role of FeNO in predicting the responsiveness of inhaled corticosteroids in COPD: a systematic review.

Fractional exhaled nitric oxide (FeNO) as a predictor of inhaled corticosteroid (ICS) response in asthma has been established. However, the same has not been established in chronic obstructive pulmonary disease (COPD). An optimal value of FeNO for prescribing and monitoring ICS response has not been quantified. To examine the evidence for this association. A systematic review was conducted of randomised controlled trials and observational studies examining the association between FeNO level and response to ICS in COPD patients. All studies examining this association were included. Five databases were searched thoroughly. Systematic screening, full-text reviews, and data extraction were carried out based on eligibility criteria. A total of 8690 studies were identified, 342 texts were screened fully, and six studies were included for the final review. One was a randomised controlled trial and the other five were non-randomised interventional trials. One study was conducted in asthma-COPD overlap (ACO patients). After ICS use, three studies found statistically significant correlations between FeNO and lung function improvement (FEV1), and three studies also found significant correlations between FeNO and COPD quality-of-life scores. Measurement of FeNO is non-invasive and standardised, with results available at the point of testing. Because of the small sample size and short duration of studies, exacerbation frequencies were not measured. Despite this, the review suggests that FeNO may be a potential biomarker for assessing ICS response in COPD. Further research that stratifies patients by FeNO levels and assesses the impact on acute exacerbations is needed to understand its potential value in routine clinical practice.

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.

Elevated Saliva Pepsin Concentration as a Risk Factor for Asthma in Children with Allergic Rhinitis: A Preliminary Study.

This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.

Diagnosis and therapy of patients with asthma in Germany. Results of the care study RELEVANT

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

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.

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

The follow-up included 128 (out of 447) children, 70 girls and 58 boys. The FeNO was measured at baseline only. The prevalence of asthma-like symptoms was measured with the adopted version of the ISAAC questionnaire. After 8 years of FeNO measurement, 5 new cases of asthma, 2 cases of attacks of dyspnoea, 1 case of wheezy in the chest, and 18 cases of allergic rhinitis occurred. The FeNO values, measured at the baseline of the study, for new cases of the above diseases were 53.4 ± 75.9 ppb, 11 ± 1.5 ppb, 12.0 ppb, and 16.3 ± 12.4 ppb, respectively. The best diagnostic accuracy parameters were found in the new cases of asthma, where the sensitivity was 40.0%, the specificity was 98.6%, and the AUC was 66.6%. The diagnostic odds ratio was 46.9 when considering the FeNO cut-off >35 ppb. The FeNO measurement is a fair method for asthma prognosis in early school-aged children with asthma-like symptoms measured on the population level but requires further confirmation at the clinical level with more accurate diagnostic tools.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Traffic-related air pollution, chronic stress, and changes in exhaled nitric oxide and lung function among a panel of children with asthma living in an underresourced community

We examined associations between short-term exposure to traffic-related air pollutants (TRAP) and airway inflammation and lung function in children with asthma, and whether these associations are modified by chronic psychological stress. Residents of underresourced port-adjacent communities in New Jersey were concerned about the cumulative impacts of exposure to TRAP, particularly diesel-engine truck emissions, and stress on exacerbation of asthma among children. Children with asthma aged 9–14 (n = 35) were recruited from non-smoking households. We measured each participant's (1) continuous personal exposure to black carbon (BC, a surrogate of TRAP) at 1-min intervals, (2) 24-h integrated personal exposure to nitrogen dioxide (NO2), (3) daily fractional exhaled nitric oxide (FeNO), and (4) lung function for up to 30 consecutive days. Personal BC was recorded by micro-aethalometers. We measured daily FeNO using the NIOX MINO, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) using Easy One Frontline spirometers. Chronic stress was measured with the UCLA Life Stress Interview for Children. The association was examined using linear mixed-effect models. In the fully adjusted model, an interquartile range (IQR) increase in BC at lag 0–6 h before the FeNO measurement was associated with 8 % (95 % CI: 3 % - 12 %) increase in FeNO, whereas an IQR increase in BC at lag 7–12 h and lag 0–24 h were associated with 6 % (95 % CI: 2 % - 11 %) and 7 % (2 % - 12 %) FeNO increases, respectively. There were no significant lung function changes per IQR increase in BC. No interactions were observed between chronic stress and BC on FeNO. Chronic stress was negatively associated with individual average FeNO levels. Our findings suggest that higher levels of BC exposure within the prior 24 h increased airway inflammation levels in children with asthma, with the strongest effect observed within the first 6 h.

Association of inflammatory cytokines with obesity and pulmonary function testing.

The World Health Organization (WHO) reported that the prevalence of obesity in the Kingdom of Saudi Arabia (KSA) is 33.7% (women 39.5% and men 29.5%), respectively. The effects of obesity on airway inflammation and respiratory mechanics as well as the function of adipose tissue has a key role in the development of various lung diseases. Therefore, this study aimed to compare the level of cytokines between obese (BMI ≥ 30) and non-obese participants and to assess their association with BMI, airways inflammation and pulmonary function. One-hundred and seven non-smoking students (18-25 years of age) were recruited using convenience sampling technique for comparative cross-sectional study. Of them, 80 students were eligible and included in the analysis; 54 were non-obese (BMI<30) and 26 were obese (BMI ≥ 30). All the participants underwent anthropometric measurements, fractional exhaled nitric oxide (FeNO) measurement, spirometry and cytokines measurement (IL-6, IL-1β, GM-CSF, IL-7, IL-8 and IL-10). Measurements were compared between obese and non-obese groups. Then a correlation test was made between pro- and anti-inflammatory cytokines with BMI, pulmonary function test finding and FeNO. The prevalence of obesity was 32.5% in the study population. Levels of pro-inflammatory cytokine IL-6 levels was significantly higher in obese than non-obese participants (p = 0.044). The level of FeNO log was significantly higher in obese participants than non-obese (p = 0.002). The pro-inflammatory cytokine IL-6 showed positive correlation with BMI while GMCSF showed negative correlation with FVC (p<0.05). The levels of pro-inflammatory cytokine IL-6 was found to be significantly higher in obese participants than non-obese participants. Furthermore, it showed positive correlation with BMI whereas pro-inflammatory cytokine GMCSF showed negative correlation with FVC.

Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers.

Airway inflammation in patients with obstructive sleep apnea (OSA) has been described and can be assessed by measuring the biomarker fractional exhaled nitric oxide (FeNO). In this pilot study, we investigated FeNO measurements in identification of OSA among persons with snoring. In this study we aimed to investigate (1) if FeNO could be used in screening for OSA, (2) if daytime sleepiness correlated to FeNO levels, and (3) whether asthma affected FeNO levels. Persons with snoring were prospectively included in three primary care ear, nose, and throat clinics. Patients underwent spirometry, FeNO tests, and partial polygraphy. They filled out questionnaires on sinonasal and asthma symptoms, daytime sleepiness, and quality of life. Current smokers, patients with upper airway inflammatory conditions, and patients treated with steroids were excluded. Forty-nine individuals were included. Median apnea-hypopnea index was 11.4, mean age was 50.9 years, and 29% were females. OSA was diagnosed in 73% of the patients of whom 53% had moderate-severe disease. Patients with moderate-severe OSA had significantly higher FeNO counts than patients with no or mild OSA (P = .024). Patients younger than 50 years with a FeNO below 15 had the lowest prevalence of moderate-severe OSA. No correlation was found between FeNO measurements and daytime sleepiness, and asthma did not affect FeNO levels. We found a low prevalence of moderate-severe OSA in persons with snoring when FeNO and age were low. This might be considered in a future screening model, though further studies testing the FeNO cutoff level and the diagnostic accuracy are warranted. Registry: ClinicalTrials.gov; Name: NO Measurements in Screening for Asthma and OSA, in Patients With Severe Snoring; URL: https://clinicaltrials.gov/study/NCT03964324; Identifier: NCT03964324. Kiaer E, Ravn A, Jennum P, etal. Fractional exhaled nitric oxide-a possible biomarker for risk of obstructive sleep apnea in snorers. J Clin Sleep Med. 2024;20(1):85-92.

Diagnostic accuracy of blood eosinophils in comparison to other common biomarkers for identifying sputum eosinophilia in patients with chronic cough

BackgroundSputum eosinophilia is a treatable trait for chronic cough. It is currently not clear whether the blood eosinophil counts could be used to identify sputum eosinophilia in patients with chronic cough. This study aimed to evaluate the diagnostic accuracy of blood eosinophils in comparison to other common type 2 biomarkers for identifying sputum eosinophilia in patients with chronic cough. MethodsIn this prospective study, a total of 658 patients with chronic cough were enrolled. Induced-sputum test, routine blood test, total immunoglobulin E (TIgE), and fractional exhaled nitric oxide (FeNO) level were measured. The percentage of sputum eosinophils (Eos%) ≥ 2.5% was defined as sputum eosinophilia. The area under the curve (AUC) of blood eosinophil counts, TIgE, and FeNO alone or in combination for predicting sputum eosinophilia were analyzed. ResultsThe AUC of blood eosinophil counts for predicting sputum eosinophilia in chronic cough patients was moderate [0.826 (0.767–0.885)], as compared to that of FeNO [0.784 (0.720–0.849), P = 0.280] and TIgE [0.686 (0.613–0.760), P = 0.001]. When combining blood eosinophil counts and FeNO for detecting sputum eosinophilia, a significantly larger AUC [0.868 (0.814–0.923), with a sensitivity of 84.2% and a specificity of 82.8%] was yielded, as compared to each single marker alone (all P < 0.05). ConclusionsBlood eosinophil counts have a moderate diagnostic value for identifying sputum eosinophilia in patients with chronic cough, while a combination of blood eosinophil counts and FeNO measurement can provide additional predictive value.

A miniaturized photodiode-based chemiluminescence sensor for measurement of fractional exhaled nitric oxide

Fractional exhaled nitric oxide (FENO) measurement is a valuable tool in diagnosing and monitoring certain respiratory diseases, low cost and miniaturized NO sensor is highly demanded for FENO home healthcare self-monitoring. In this work, a miniature photodiode-based chemiluminescence sensor is presented for the sensitive measurement of NO concentration. Effects of various reflective film materials including stainless-steel, aluminum and silver for coating the inner surface of the optical cell were investigated for higher photon collection efficiency, and the silver reflective film displayed the best sensitivity. As the oxidation and pollution of silver film led to dramatical decay of signal, a quartz inner chamber with reflectance film layer coated on its outer surface was developed to achieve high stability and sensitivity simultaneously. The limit of detection for FENO was 6.6 ppb, the linear range of 10–100 ppb with a response time of 6.8 s was reached, which was satisfied the requirements for FENO measurement. The weight of the sensor is 96 g with a size of only 6.5 × 3 × 2 cm3, and the cost is estimated less than $1 K, which is suit for on-site monitoring of FENO. FENO50 was obtained the response difference of room air and breath air measured successively with a switching valve, the beath air was sampled into a bag at flow rate of 50 ml/s by offline sampling device, and multiple measurements were executed for better accuracy. The potential usage of the sensor was further illustrated by studying the FENO50 levels of individuals before and after consuming nitrate-rich sports drinks.