Predicting dupilumab effectiveness with Type-2 biomarkers: A real-world study of severe asthma.

BACKGROUND: The therapeutic effectiveness of dupilumab for severe asthma in real-world settings is yet to be prospectively investigated across multiple institutions, and uncertainties persist regarding predictive factors for its effectiveness. We aimed to assess the effectiveness of dupilumab and identify predictors of its effectiveness in real-world settings using two type-2 biomarkers: FeNO concentration and blood eosinophil count. METHODS: This prospective multicenter study included 103 patients with severe asthma. Exacerbations and respiratory functions were monitored for 24 weeks. Asthma control was evaluated using the Asthma Control Questionnaire-5. Clinical symptoms and their impact on cough and sputum were assessed using the Cough and Sputum Assessment Questionnaire (CASA-Q). Subgroup analyses of type-2 biomarkers were conducted based on FeNO levels and blood eosinophil counts at baseline. RESULTS: Treatment with dupilumab led to a reduction in exacerbations and enhancement in asthma control, FEV1, and CASA-Q scores. FEV1 improvement was correlated with enhancement in the sputum domain of the CASA-Q. Patients exhibiting elevated FeNO levels and blood eosinophil counts demonstrated more significant enhancements in FEV1. CASA-Q sputum domain scores were significantly higher in the group with elevated eosinophil counts. Regression analysis revealed that FeNO levels and blood eosinophil counts are significant predictors of FEV1 improvement, with blood eosinophil counts also predicting sputum improvement in patients treated with dupilumab. CONCLUSIONS: Type-2 biomarkers may act as indicators of improvement in FEV1 and sputum outcomes among patients with severe asthma undergoing dupilumab treatment in real-world settings.

Effect of Air Pollutants Particulate Matter PM2.5, PM10, Carbon Monoxide (CO), Nitrogen Dioxide (NO2), Sulfur Dioxide (SO2), and Ozone (O3) on Fractional Exhaled Nitric Oxide (FeNO).

Objectives: This study aimed to investigate the effect of Environmental Pollutants Particulate Matter PM2.5, PM10, Carbon Monoxide (CO), Nitrogen Dioxide (NO2), Sulfur Dioxide (SO2), and Ozone (O3) on lung airway inflammation by assessing the Fractional Exhaled Nitric Oxide (FeNO) in students studying in schools located in or away from air-polluted areas. Methods: This matched case-control cross-sectional study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia from August 2022 to July 2023. In this study, two schools were selected, one was located near a traffic-polluted area (School #1), and the second was located away from the traffic-polluted area (School #2). A total of 300 students were recruited, 150 (75 male and 75 female) students from the school located in a traffic-polluted area, and 150 students (75 male and 75 female) from the school located away from a traffic-polluted area. Environmental pollutants PM2.5, PM10, CO, NO2, O3, and SO2, were recorded. The Fractional Exhaled Nitric Oxide (FeNO) was measured using a Niox Mino. Results: The mean concentration of PM2.5, PM10, CO, NO2, O3, and SO2 were 35.00±0.65 significantly higher in a school located in motor vehicle polluted area compared to a school located away from a motor vehicle-polluted area (29.95±0.32) (p=0.001). The mean values for FeNO were significantly higher (18.75±0.90) among students studying in a school located in the motor vehicle-polluted area compared to students studying in a school located away from the motor vehicle-polluted area (11.26±0.56) (p=0.001). Conclusions: Environmental pollution can cause lung inflammation among students in schools located in traffic-polluted areas.

Role of fractional exhaled nitric oxide in patients with sickle cell disease.

INTRODUCTION: Patients with sickle cell disease exhibit different patterns in pulmonary function tests. In particular, there is little evidence on the fractional exhaled nitric oxide (FeNO) test, and its value ranges and its interpretation in these patients have been under debate in recent years. METHODS: We conduced a cross-sectional, observational and descriptive study between November 2021 and January 2023 including patients aged 6-18 years with sickle cell disease able to perform the FeNO test. We applied the GLI-2012 reference values and the ERS/ATS standards. We defined statistical significance as P < 0.05. RESULTS: The sample included 43 patients with a median age of 12 years (IQR, 10-15). We did not find an association between significantly elevated FeNO (≥25 ppb) and the diagnosis of asthma (P = 0.37), an obstructive pattern in spirometry (P = 0.67), a positive bronchodilator test (P = 0.53), clinical bronchial hyperreactivity in the context of cold or flu-like symptoms (P = 0.48), cough with exercise (P = 0.42) or nocturnal cough (P = 1.0), but found an association with peripheral eosinophilia (P < 0.01). CONCLUSIONS: We found no association between FeNO values and the classic features of asthma (clinical or spirometric) in patients with sickle cell disease. Therefore, airway inflammation mechanisms are probably different in these patients.

Utility of exhaled nitric oxide to guide mild asthma treatment in atopic patients and its correlation with asthma control test score: a randomized controlled trial.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is used for the diagnosis and monitoring of asthma, although its utility to guide treatment and its correlation with other tools is still under discussion. We study the possibility to withdraw inhaled corticosteroid treatment in atopic patients with mild asthma based on the FeNO level, as well as to study its correlation with other clinical control tools. METHODS: Prospective and randomized study including atopic patients aged 18 to 65 with mild asthma, stable, on low-dose inhaled corticosteroid (ICS) treatment, who had their treatment withdrawn based on a FeNO level of 40 ppb. Patients were randomized into two groups: control group (treatment with ICS was withdrawn regardless of FeNO level) and experimental group (according to the FeNO levels, patients were assigned to one of two groups: FeNO > 40 ppb on treatment with budesonide 200 mcg every 12 h and SABA on demand; FeNO ≤ 40 ppb only with SABA on demand). Follow-up was conducted for one year, during which medical assessment was performed with FeNO measurements, asthma control test (ACT), lung function tests (FEV1, FEV1/FVC, PEF, and RV/TLC), and recording of the number of exacerbations. RESULTS: Ninety-two patients were included, with a mean age of 39.92 years (SD 13.99); 46 patients were assigned to the control group, and 46 patients to the experimental group. The number of exacerbations was similar between the groups (p = 0.301), while the time to the first exacerbation was significantly shorter in the control group (30.86 vs. 99.00 days), p < 0.001, 95% CI (43.332-92.954). Lung function tests (FEV1, FEV1/FVC, PEF, and RV/TLC) showed no differences between the groups (p > 0.05). Both FeNO and ACT showed significant changes in the groups in which ICS was withdrawn (p < 0.05 for both parameters). A significant negative correlation was observed between FeNO and ACT (r = -0.139, p = 0.008). CONCLUSIONS: In atopic patients with mild asthma, withdrawal of ICS based on an FeNO of 40 ppb led to worsened symptoms but without changes in lung function tests or an increase in exacerbations. There was a negative correlation between FeNO values and symptomatic control measured by the ACT. TRIAL REGISTRATION: Clinical Trial Number: 2012-000372-42. Start Date: 2012-07-23. Trial registered prospectively ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-000372-42 ). This study adheres to CONSORT guidelines of randomised control trials.

Acute Effects of Exercise at Different Temperatures on Clinical Symptoms and Nasal Blood Flow in Patient with Allergic Rhinitis: A Randomized Crossover Trial.

Allergic rhinitis (AR) affects the nose and is triggered by allergens. However, no research studies have analyzed the acute effect of aerobic exercise at different temperatures in AR patients. This study was to determine the acute effect of aerobic exercise at different temperatures on rhinitis symptoms and nasal blood flow (NBF) in AR patients. Fifteen AR patients aged 18-24 years were randomized in a crossover fashion into two protocols: 60 minutes of aerobic exercise at temperatures of 25 °C and 34 °C. The NBF, rhinitis symptoms, peak nasal inspiratory flow (PNIF), fractional exhaled nitric oxide (FeNO) and oxygen saturation (SpO2) variables were measured. During exercise at 25°C, a notable reduction was observed in NBF, nasal congestion, and sneezing in comparison to exercising at 34°C (p < 0.05). The SpO2 demonstrated significant decreases at 34°C compared to exercise at 25°C after 30 minutes post exercise. The rhinitis symptom scores and NBF in both exercise at 25°C and 34°C significantly decreased and PNIF increased during and after exercise compared to before exercise (p < 0.05). In conclusion, both exercising at 25°C and 34°C can contribute to the alleviation of allergic rhinitis symptoms by decreasing rhinitis symptom and NBF. However, exercising in a room at 25°C exhibits a more significant reduction in nasal blood flow, nasal congestion, and sneezing compared to the 34°C setting.

Fractional exhaled nitric oxide (FeNO) among school children in Java and Sumatra, Indonesia: associations with respiratory symptoms, house dust mite sensitization and the home environment.

OBJECTIVE: To study associations between fractional exhaled nitric oxide (FeNO) and asthma, airway symptoms, sensitization to common allergens, outdoor pollution and home environment among 380 students in eight junior high schools in two areas in Indonesia. METHODS: Data on health and home were collected by a face-to face interview before measuring FeNO and performing skin prick test against common allergens. Exploratory linear mixed and logistic regression models were employed. RESULTS: Geometric mean of FeNO was 17.8 ppb (GSD 2.09) and 139 students (36.6%) had elevated FeNO (>20 ppb). In total, 107 students (28.2%) were sensitized to house dust mite (HDM) (Der p1 or Der f1), 4 (1.1%) to cat and 3 (0.8%) to mold (Cladosporium or Alternaria). Moreover, 20 students (5.3%) had diagnosed asthma, 38 (10.0%) had current wheeze, and 107 (28.2%) had current rhinitis. HDM sensitization, diagnosed asthma, current wheeze, and current rhinitis were associated with FeNO. In total, 281 students (73.9%) had mold or dampness, 232 (61.1%) had environmental tobacco smoke (ETS) and 43 (11.3%) had other odor at home. Indoor mold or dampness and other odor at home were associated with FeNO. ETS was negatively associated with FeNO. CONCLUSION: HDM sensitization and elevated FeNO can be common among children in this part of Indonesia. The high prevalence of elevated FeNO indicate that undiagnosed childhood asthma is common. Dampness, mold and odor at home can be associated with increased FeNO while ETS can be associated with decreased FeNO.

Allergy in Young Adults Associates with Elevated Fractional Exhaled Nitric Oxide Levels and IgE-Verified Parental Allergy but Is Confounded by Self-Reported Symptoms.

INTRODUCTION: Knowledge of IgE-verified allergy in young adults is limited as most studies are based on self-reported data. Allergic heredity is important in allergy development in early life, but less is known about the hereditary component later in life. The aim was to investigate IgE-verified and self-reported allergy and asthma at 20 years of age in association to parental allergy and environmental factors. METHODS: In total, 281 individuals born into the cohort of well-characterized parents regarding allergic disease were followed to 20 years of age. The participants were categorized by parental allergy and examined regarding allergic diseases (IgE sensitization and allergic symptoms) at 2, 5, 10, and 20 years of age. FeNO was measured at 10 and 20 years. RESULTS: In total, 45% of the study participants were allergic, with twice as many self-reported cases at age 20. Rhinitis was key to distinguishing confirmed allergy from self-reported. Having two allergic parents and increased FeNO were associated with an increased prevalence of allergic disease at 20 years. From a longitudinal perspective, rhinitis increased from childhood to young adulthood, in all heredity groups. CONCLUSION: In this longitudinal study, we have shown that two allergic parents as well as increased FeNO levels seem to be of importance for being allergic at 20 years old. Self-reported allergy was overreported - a result that should be considered in future survey-based reports on allergic diseases.

Impact of Long COVID on Lung Function in Children.

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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

PURPOSE: Bronchiectasis 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. METHODS: In 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. RESULTS: Among 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. CONCLUSIONS: Our 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.

Asthma control associated with anxiety and depression in asthmatic children following post-acute COVID-19.

BACKGROUND: Poor asthma control may adversely affect mental health. Our study investigates the correlation between inadequate asthma control, exhaled nitric oxide (FENO) levels, and anxiety and depression among pediatric asthma patients with COVID-19. METHODS: This prospective case-control study enrolled 520 asthmatic children (8-15 years), including 336 patients diagnosed with COVID-19 after rapid antigen testing at home and 184 age-matched asthmatic patients without COVID-19 infection. FENO and spirometry were performed 1 month after COVID-19 infection. Scores for Child Anxiety-Related Disorders (SCARED) and depression screen derived from Patient Health Questionnaire-9 (PHQ-9) to assess their mental health status. Childhood asthma control test (C-ACT), FENO levels, and spirometry were correlated with the SCARED and PHQ-9 questionnaires. RESULTS: SCARED subscales, including generalized anxiety disorder, social anxiety disorder, school avoidance, and depression scores from PHQ-9, exhibited a significant increase in asthmatic patients diagnosed with COVID-19 (p < .05). Among asthmatic children with SARS-CoV-2 infection, the poor asthma control group exhibited the highest SCARED and PHQ-9 measurements (p < .01). Multiple linear regression analysis indicated that reduced C-ACT scores and elevated FENO levels in asthmatic children with COVID-19 were significant risk factors for both anxiety and depression scores (p < .05). Lower C-ACT scales were associated with high scores of SCARED (r = -0.471) and PHQ-9 (r = -0.329) in asthmatic children (p < .001). CONCLUSIONS: The current study emphasizes the need for healthcare professionals to closely monitor asthma control in asthmatic children to prevent heightened risks of depression and anxiety during the ongoing COVID-19 pandemic.

Cough Response to High-Dose Inhaled Corticosteroids in Patients with Chronic Cough and Fractional Exhaled Nitric Oxide Levels ≥ 25 ppb: A Prospective Study.

This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.

Association between exposure to airborne trichloramine and health effects in indoor swimming pool workers.

OBJECTIVE: The main objective of this study was to comprehensively investigate the association between trichloramine (TCA) exposure and respiratory health effects in swimming pool workers. METHODOLOGY: In this study, air sampling was performed for TCA concentrations at fixed locations (static measurements) and on individual workers (personal measurements) in six indoor public swimming pools during periods of high swimmer attendance over the winter school break. Health effects were evaluated using questionnaires and fractional exhaled nitric oxide (FENO) tests performed before and after the working day. RESULTS: In these swimming pools, the environmental TCA concentration ranged from 0.11 to 0.88 mg/m³. Worker exposure ranged from 0.05 to 0.72 mg/m³ for personal measurements. Furthermore, in each swimming pool, the average worker exposure to TCA exceeded the recommended occupational exposure limit of 0.35 mg/m³. Personal TCA measurements were consistently lower than static measurements performed around the pool, with a reduction ranging from 21% to 49%. This can be explained by the time that the workers spend in the pool area, office, and break room. The most common respiratory health effects self-reported by the workers were coughing, shortness of breath, and sneezing with prevalence rates of 38%, 37%, and 35%, respectively. This study demonstrated an association between TCA exposure and eye irritation. Analysis of the FENO tests revealed that individuals with preexisting asthma or allergies exhibited sustained FENO elevation. CONCLUSION: The findings suggest that occupational exposure to TCA in indoor swimming pools is a matter of concern. Implementing and improving workplace safety measures is crucial for safeguarding the respiratory health of swimming pool workers.

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

BACKGROUND: Fractional 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. METHODS: A 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. RESULTS: A 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. CONCLUSION: In 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.

Sources, trigger points, and effect size of associations between PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and fractional exhaled nitric oxide (FeNO): A panel study with 16 follow-up visits over 4 years.

Exposure to fine particulate matter (PM2.5) is a significant concern for respiratory health. However, the sources, trigger points, and effect size of specific associations between PM2.5 components, particularly polycyclic aromatic hydrocarbons (PAHs) and the airway inflammatory marker fractional exhaled nitric oxide (FeNO) have not been fully explored. In this study, 69 healthy college students were enrolled and followed up 16 times from 2014 to 2018. Individual FeNO was measured and ambient air PM2.5 samples were collected for 7 consecutive days before each follow-up. PAHs were quantified using Gas Chromatography-Mass Spectrometry. Linear mixed-effect regression models were employed to evaluate the associations between PM2.5-bound PAHs and FeNO. Additionally, PMF (Positive Matrix Factorization) was utilized to identify sources of PM2.5-bound PAHs and assess their impact on FeNO. Throughout the study, the average (SD) of ΣPAHs concentrations was 78.50 (128.9) ng/m3. PM2.5 and PM2.5-bound PAHs were significantly associated with FeNO at various lag days. Single-day lag analyses revealed maximum effects of PM2.5 on FeNO, with an increase of 7.71% (95% CI: 4.67%, 10.83%) per interquartile range (IQR) (48.10 µg/m3) increase of PM2.5 at lag2, and ΣPAHs showed a maximum elevation in FeNO of 6.40% (95% CI: 2.33%, 10.63%) at lag4 per IQR (57.39 ng/m3) increase. Individual PAHs exhibited diversity peak effects on FeNO at lag3 (6 of 17), lag4 (9 of 17) in the single-day model, and lag0-5 (8 of 17) (from lag0-1 to lag0-6) in the cumulative model. Source apportionment indicated coal combustion as the primary contributor (accounting for 30.7%). However, a maximum effect on FeNO (an increase of 21.57% (95% CI: 13.58%, 30.13%) per IQR increase) was observed with traffic emissions at lag4. The findings imply that strategic regulation of particular sources of PAHs, like traffic emissions, during specific periods could significantly contribute to safeguarding public health.

Correlation analysis between serum total IgE and FeNO and idiosyncratic reaction in bronchiolitis.

OBJECTIVE: This article focused on the correlation between the changes of serum total Immunoglobulin E (IgE) and Fractional exhaled Nitric Oxide (FeNO) and idiosyncratic reactions in children with bronchiolitis. METHODS: One hundred children with bronchiolitis and fifty healthy children were enrolled. Serum total IgE and FeNO were assessed, and the diagnostic value for bronchiolitis and the correlation with the severity of bronchiolitis were analyzed. Bronchiolitis children were divided into idiosyncratic + bronchiolitis and non-idiosyncratic + bronchiolitis groups, the relationship between serum total IgE and FeNO and idiosyncratic reaction was determined, and the diagnostic value of serum total IgE and FeNO for idiosyncratic bronchiolitis was examined. RESULTS: FeNO in bronchiolitis children was lower than that in healthy children but there was no significant difference in serum total IgE levels between the two populations. Serum total IgE increased while FeNO decreased with the aggravation of bronchiolitis in bronchiolitis children. The serum total IgE was positively correlated while FeNO was negatively correlated with the severity of bronchiolitis. Serum total IgE was higher in children with idiosyncratic bronchiolitis, but serum total IgE and FeNO were not the risk factors for idiosyncratic bronchiolitis; Area Under the Curve (AUC) of serum total IgE and FeNO for the diagnosis of idiosyncratic bronchiolitis was less than 0.7. CONCLUSION: Serum total IgE and FeNO in children with bronchiolitis are related to disease severity and idiosyncratic reaction. FeNO has a diagnostic value for bronchiolitis, but not for idiosyncratic bronchiolitis.

Fractional exhaled nitric oxide distribution and its relevant factors in the general adult population and its healthy subpopulation.

Background: Measurement of fractional exhaled nitric oxide (Feno) has been used in the diagnosis and management of asthma. Understanding the distribution of Feno in a larger resident population and its "healthy" subpopulation would contribute to the interpretation of Feno in clinical practice. Objective: This study aimed to investigate the distribution and its associated factors in the adult population and its healthy subpopulations. Methods: We conducted a cross-sectional study of 8,638 men and 17,288 women aged 20 years or older living in Miyagi prefecture, Japan. We investigated the distribution of Feno and its associated factors in all subjects, a subpopulation with no history of upper and lower airway diseases (healthy subpopulation 1), and a subpopulation with no history of upper and lower airway diseases, normal lung function, and no positivity for other biomarkers of type 2 inflammation (healthy subpopulation 2). Results: The distribution of Feno in healthy subpopulations, especially in healthy subpopulation 2 (median [interquartile range], 17 [12-23] with 95th percentile of 36 ppb) was lower than in all subjects (19 [13-26] ppb with 95th percentile of 47 ppb). In healthy subpopulation 1, 10.3% had elevated Feno (≥35 ppb), and elevated Feno was positively associated with factors including obstructive ventilatory defect, blood eosinophilia, house dust mite-specific IgE positivity, and history of hypertension. Male sex was associated with elevated Feno in all subjects and healthy subpopulations. Conclusion: The distribution of Feno in the healthy subpopulation supports the validity of the criteria (≥35 ppb) currently used in Japan for the diagnosis of asthma.

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 65 years 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 ± 5.40 years 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.

Prediction of Clinical Response to Dupilumab in Patients with Severe Asthma Using Fractional Exhaled Nitric Oxide Combined with Pulmonary Function Testing.

INTRODUCTION: This study aimed to assess the effectiveness of fractional exhaled nitric oxide (FeNO) combined with pulmonary function testing (PFT) for predicting the treatment outcome of patients with severe asthma receiving dupilumab. METHODS: A total of 31 patients with severe asthma visiting our hospital from January 2022 to June 2023 were included in this study, with 28 patients completing a 16-week course of dupilumab treatment. Baseline clinical data, including demographic information, blood eosinophil counts, serum IgE levels, FeNO, asthma control test (ACT), asthma control questionnaire (ACQ), and other parameters, were collected. A predictive model using a generalized linear model was established. RESULTS: Following the 16-week course of dupilumab treatment, 22 patients showed effective response based on GETE scores, while 6 patients were nonresponders. Notably, significant improvements were observed in clinical parameters such as blood eosinophil counts, serum IgE levels, FeNO, FEV1, FEV1%, ACT, and ACQ in both response groups (p < 0.05). FeNO and pulmonary function tests demonstrated AUC values of 0.530, 0.561, and 0.765, respectively, in predicting the clinical efficacy of dupilumab, which were lower than when FeNO was combined with FEV1%. The combination of FeNO and FEV1% had a sensitivity of 1.000 and specificity of 0.591 in predicting treatment response. CONCLUSION: The combined assessment of FeNO and FEV1% provides improved accuracy for predicting the clinical efficacy of dupilumab in managing severe asthma. However, further larger scale clinical studies with comprehensive follow-up data are needed to validate the therapeutic efficacy and applicability across diverse patient populations.