FeNO Levels Research Articles

Type-2 Inflammation in Health and Disease: Prevalence, Risk Factors and Multimorbidity

Background: In patients with airflow obstruction, the levels of biomarkers of Type-2 (T2) inflammation serve to predict the effectiveness of inhaled corticosteroid and biological therapies. Elevated biomarkers of T2 inflammation, including fractional exhaled nitric oxide (FeNO, ≥20 ppb) and blood eosinophil counts (BEC, ≥300 cells/µL), were investigated in a population-based cohort of the Austrian LEAD study. Methods: A total of 4976 individuals (aged 18–82 years) were categorised into four groups based on their FeNO and BEC levels: normal with FeNO < 20 ppb and BEC < 300 cells/µL (n = 2634); FeNO ≥ 20 ppb only (n = 1623); BEC ≥ 300 cells/µL only (n = 340); and FeNO ≥ 20 ppb and BEC ≥ 300 cells/µL (n = 379). Results: In age- and sex-adjusted regression models, individuals with elevated BEC only were most associated with chronic cough and sputum production (odds ratios [95% CI]: 1.22 [0.78, 1.84] and 1.37 [1.13, 2.62], respectively), whilst individuals with both elevated T2 biomarkers were most associated with wheezing, dyspnoea and asthma (odds ratios [95% CI]: 2.27 [1.56, 3.26], 1.32 [0.64, 2.50] and 3.63 [2.69, 4.88] respectively). Elevated levels of both FeNO and BEC presented an additive effect in extrapulmonary conditions, particularly in allergy, eczema and rhino conjunctivitis (odds ratios [95% CI]: 2.30 [1.84, 2.88], 1.37 [1.03, 1.81] and 2.95 [2.34, 3.70], respectively). Conclusions: T2 inflammation marked by elevated levels of FeNO and/or BEC is not only associated with respiratory conditions but also extends to extrapulmonary characteristics, with an additive effect.

Four-month real-life response to Tezepelumab in patients with multi-failure to other biologics

To evaluate the response to Tezepelumab in real clinical practice, we performed an analysis of the clinical, functional, and inflammatory characteristics of 13 patients with severe asthma after completing four doses of Tezepelumab was performed. When comparing clinical parameters such as asthma control test (ACT), FENO value, exacerbations in the last 4 months, blood eosinophils and FEV1%, before receiving Tezepelumab and after four doses of Tezepelumab, statistically significant differences were found in ACT levels (p=0.0072), exacerbations (p=0.018) and FEV1% (p=0.012) before and after four doses of Tezepelumab.No statistically significant differences were found in blood eosinophils or FeNO levels, however, a mean reduction of 102.5±231 cells/mm3 and 14.67±30 ppb, respectively, was observed. Patients with a high T2 profile had significantly higher baseline FeNO (p<0.05), but no significant improvement in lung function or asthma control was observed in this group. Patients with Aspirin-exacerbated respiratory disease (AERD) were evaluated separately. There was no difference in ACT, FeNO, or lung function changes after tezepelumab use compared to patients without AERD (all p>0.05). We demonstrated, in a multicenter study, the clinicalimprovement associated with tezepelumab treatment in severe uncontrolled asthma, independent of inflammatory biomarkers, eosinophilic profile, or previous biological failure.

Association between acute tobacco exposure and fractional exhaled nitric oxide in patients with chronic obstructive pulmonary disease: National health and Nutrition Examination Survey (NHANES) 2007–2012

BackgroundFractional exhaled nitric oxide (FeNO) is a marker of type 2 airway inflammation. Tobacco exposure can lower FeNO levels. However, the effect of acute tobacco exposure on FeNO in patients with chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate the relationship of acute tobacco exposure with FeNO and eosinophils in COPD patients. MethodsThis retrospective cohort study included 445 patients with COPD based on the 2007–2012 National Health and Nutrition Examination Survey. Serum cotinine levels were examined to assess environmental tobacco smoke exposure. The patients were divided into five groups based on cotinine levels: Q1 (first quintile), Q2 (second quintile), Q3 (third quintile), Q4 (fourth quintile) and Q5 (fifth quintile). Logistic regression models and linear logistic regression models were used to evaluate the relationship between serum cotinine and FeNO and EOS levels. ResultsApproximately 16.5 % (75/445) of the participants had elevated FeNO (>25 bbp). In the unadjusted model, COPD patients with the lowest quintile of serum cotinine levels (0.011–0.0185 ng/mL) had higher FeNO levels compared to those with the highest quintile (≥309 ng/mL) (odds ratios (OR), 5.86 [2.11–16.20]). These findings remained consistent even after adjusting for covariates of demographics, lifestyle, diabetes, coronary heart disease, tumours, hypertension, using oral or inhaled steroids within 2 days, asthma and respiratory symptoms within 7 days. Furthermore, a standard deviation increase of ln-transformed cotinine levels was associated with decreased FeNO levels (OR, 0.45 [0.33, 0.60]). No significant correlation was observed betweenserum cotinine and blood eosinophils. After high extents of tobacco exposure, no correlation was found between FeNO and eosinophils.Our findings indicate that high cotinine levels are associated with decreased FeNO in COPD patients but not with blood eosinophils. This reveals that smoking may affect FeNO levels in patients with COPD, whereas it does not appear to influence blood eosinophil levels.

Clinical characteristics analysis of persistent airflow limitation in asthmatic children

Objective: To analyze the clinical characteristics of asthmatic children with persistent airflow limitation (PAL) in order to improve understanding of PAL and improve asthma management. Methods: The clinic data of asthmatic children aged 6 to 18 years with and without PAL, who visited the Department of Allergy at Children's Hospital of the Capital Institute of Pediatrics between January 2021 and June 2023, were analyzed retrospectively. The study included a total of 197 patients (153 males and 44 females), with a median age of 9.0 (7.0, 12.0) years. The analysis encompassed demographic features, disease-related factors, laboratory tests, and spirometry parameters. Quantitative data differences between the two groups were assessed using the Student's t-test or the Mann-Whitney U test. Qualitative data comparisons were made using the Chi-square test or Fisher's exact test. Results: This study included 100 non-PAL and 97 PAL patients. The female-to-male ratio in the two groups was 27/73 and 17/80, respectively. Age and BMI were 11.0 (10.0, 13.0) years and 20.3 (17.7, 24.1) kg/m2 in the PAL group, which was significantly higher than in the non-PAL group (P<0.001). Among the PAL group, 49.5% fell within the 9-12 age group. The PAL group had a higher percentage of patients with an asthma duration of more than 3 years (89.7% vs. 62.0%, P<0.001) and a history of pneumonia (13.4% vs. 4.0%, P=0.036) compared to the non-PAL group. Regarding laboratory tests, a higher percentage of patients in the PAL group had an elevated FeNO level (60.9% vs. 37.6%, P=0.002) and animal sensitization (50.7% vs. 30.7%, P=0.022) compared to the non-PAL group. Of the 69 patients who underwent spirometry before and after PAL development, FEV1%pred, FEV1/FVC, and MMEF%pred values gradually decreased, with a significant decline in the year preceding PAL development. Conclusions: Asthmatic children with PAL had characteristics such as relatively older age, higher BMI, longer duration of asthma, eosinophilic inflammation, and atopy. Lung function decline occurred several years before PAL development. Long-term follow-up should focus on the evolving trend of spirometry parameters.

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

BackgroundFractional 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.MethodsProspective 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.ResultsNinety-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).ConclusionsIn 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 registrationClinical 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.

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.

Analysis of clinical characteristics and risk factors of chest tightness variant asthma in children

Objective: To analyze the clinical features and risk factors of chest tightness variant asthma (CTVA) in children, so as to provide basis for the prevention and management of the disease. Methods: A cross-sectional study was conducted to analyze 178 children aged 6-17 years old who were admitted to the Department of Allergy, Capital Institute of Pediatrics Affiliated Children's Hospital from January 2021 to January 2023 due to chest tightness. The age was 8.83(7.50, 11.58) years old, with 89 males (50%) and 89 females (50%). According to the diagnosis of CTVA, 130 cases were divided into CTVA group and 48 non-CTVA cases were divided into control group. Demographic data, personal history, family history, clinical features, auxiliary examination results and other data were collected. The clinical characteristics, allergens, FeNO level and pulmonary function parameters of the two groups were analyzed. Logistic regression analysis was used to explore the risk factors of the disease. Results: The proportion of school-age children (6-11 years old) in CTVA group was higher than that of adolescent children (≥12 years old) [(113/130,86.9%) vs (26/48,54.2%),Z=21.985,P<0.01]. The proportion of CTVA combined with eczema [(74/130,56.9%) vs (19/48,39.6%), χ2=4.225,P<0.05] and rhinitis symptoms [(98/130,75.4%) vs (27/48,56.2%), χ2=6.138,P<0.05] was higher. The positive rates of mold sensitization [(52/130,40.0%) vs (11/48,22.9%), χ2=4.474,P<0.05] and multiple sensitization [(71/130,54.6%) vs (18/48,37.5%), χ2=4.108,P<0.05] in inhaled allergens were significantly higher than those of control group. The proportion of elevated FeNO (>20 ppb) in CTVA children was 20.8% (27/130), which was significantly higher than that in control group 4.2%(2/48)(χ2=7.086,P<0.01). There were no statistical differences in spirometry parameters FEV1 and FVC between CTVA group and control group (P both>0.05). FEV1/FVC, PEF, FEF25, FEF50, FEF75 and MMEF were significantly lower than those in control group (P all<0.05). Logistic regression analysis showed that rhinitis symptoms (OR=2.351, 95%CI 1.105-5.002, P=0.026), multiple sensitizations (OR=2.184, 95%CI 1.046-4.557, P=0.038), tIgE>60 kU/L(OR=3.080, 95%CI 1.239-7.654, P=0.015), FeNO>20 ppb (OR=6.734, 95%CI 1.473-30.796, P=0.014) and small airway dysfunction (OR=3.164, 95%CI 1.089-9.194, P=0.034) were risk factors for chest tightness variant asthma. FeNO combined with FEF50 has the largest area under the curve (Z=2.744, P<0.01) in diagnosing CTVA. Conclusion: CTVA is more common in school-age children than in adolescent children. Rhinitis symptoms, multiple sensitization, tIgE>60 kU/L, FeNO>20 ppb and small airway dysfunction are risk factors for chest tightness variant asthma. FeNO combined with small airway indexes can improve the diagnostic value of CTVA.

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

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. 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. 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). 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.

Exhaled Nitric Oxide fraction in asthma and obstructive sleep apnea among children at high altitudes. A cross-sectional study

IntroductionExhaled nitric oxide fraction (FeNO) is employed for the diagnosis and phenotyping of asthma as an inflammatory biomarker of the airway. Limited evidence exists regarding its behavior in the presence of asthma and obstructive sleep apnea (OSA). Our objective was to determine whether FeNO levels are associated with the severity of OSA or the coexistence of asthma and OSA in residents at high altitudes. Materials and methodsObservational, analytical, cross-sectional study in children aged 5–16 years residing at 2600 m above sea level treated at a Sleep Study Center between 2019 and 2021. We conducted a medical history, polysomnogram, and measurement of FeNO levels. The children were categorized into four groups: OSA, asthma, asthma with OSA, and controls (without asthma or OSA). FeNO levels among the groups were compared using the Kruskal-Wallis test, and correlations were explored using the Spearman correlation coefficient. Analyses considered statistical significance at a two-tailed p-value <0.05. ResultsAmong the 261 included children, 68 (26.1 %) had OSA, 42 (16.1 %) were diagnosed with asthma, 109 (41.8 %) had both asthma and OSA, and 42 (16.1 %) were controls. Their FeNO medians were 10 ppb, 18.5 ppb, 15 ppb, and 14 ppb, respectively, with no significant differences between the evaluated groups (p = 0.263). We found no correlation between FeNO and apnea-hypopnea index and obstructive apnea index even for the groups of patients with FeNO >20 ppb and FeNO >35 ppb (>75th percentile). In the adjusted model, a significant association was observed between asthma and FeNO levels. ConclusionsOur findings suggest that FeNO measurements in children would not allow establishing this biomarker as part of the diagnosis of OSA. However, these findings may be related to high altitude.

The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.

Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab.

In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. According to the criteria, 39-52% of patients experienced complete remission in the first year, increasing to 51-73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension

BackgroundFractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function.MethodsWe collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient.Results(1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test.ConclusionFeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma

Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation. To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded. Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n= 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P= .03). Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

HIIT as a Safe and Effective Exercise Modality for Improving Pulmonary Function and Exercise Tolerance in Individuals with Asthma

Background – Asthma is a chronic inflammatory disorder affecting millionsglobally, with symptoms including wheezing, chest tightness, and shortnessof breath. Regular physical activity can mitigate these symptoms; however,the effectiveness and safety of HIIT for asthmatics remain underexplored.This study addresses this gap by examining HIIT's impact on asthmaticindividuals, focusing on pulmonary function, FeNO levels (an inflammationmarker), and exercise tolerance.Materials and MethodsFourteen adult males, divided into asthmatic (n=7) and healthy control (n=7)groups, underwent a two-week HIIT protocol. Pulmonary function wasassessed using peak expiratory flow (PEF), forced vital capacity (FVC), andforced expiratory volume in one second (FEV1/FVC ratio). FeNO wasmeasured with a portable device, and exercise tolerance was evaluatedthrough a progressive exercise test on a cycle ergometer to determine peakoxygen uptake (VO2peak), carbon dioxide output (VCO2peak), ventilation(VE), and time to exhaustion (TTE). Statistical analysis was performed usingANOVA with repeated measures.ResultsThe results indicated significant differences between groups in FeNO, VO2peak, TTE, and peak work rate (WR), with no significant changes inpulmonary function measures. Asthmatics showed a marked improvement inTTE and peak WR post-HIIT, with mean FeNO levels and pulmonaryfunction measures remaining unchanged from baseline. Specifically, postHIIT, asthmatics achieved higher VE, VCO2, TTE, and peak WR,demonstrating improved exercise tolerance and ventilation withoutexacerbating lung inflammation.ConclusionHIIT was well-tolerated by individuals with asthma, leading to significantimprovements in exercise tolerance and ventilation without negativelyimpacting pulmonary function or increasing lung inflammation. Thesefindings suggest HIIT as a safe and effective exercise modality for asthmatics,potentially aiding in better asthma management through enhanced physicalfitness and exercise capacity.

Exhaled and Systemic Biomarkers to Aid the Diagnosis of Bronchial Asthma in Elite Water Sports Athletes.

Our aim was to evaluate the accuracy of a combined airway inflammatory biomarker assessment in diagnosing asthma in elite water sports athletes. Members of the Hungarian Olympic and Junior Swim Team and elite athletes from other aquatic disciplines were assessed for asthma by objective lung function measurements, and blood eosinophil count (BEC), serum total immunoglobulin E (IgE), fractional exhaled nitric oxide (F ENO ) measurements, and skin prick testing were performed. A scoring system from BEC, F ENO , serum IgE, and skin test positivity was constructed by dichotomizing the variables and assigning a score of 1 if the variable is elevated. These scores were summed to produce a final composite score ranging from 0 to 4. A total of 48 participants were enrolled (age 21 ± 4 yr, 42% male), of which 22 were diagnosed with asthma. Serum total IgE and F ENO levels were higher in asthmatic individuals (68 [27-176] vs 24 [1-43], P = 0.01; 20 [17-26] vs 15 [11-22], P = 0.02), and positive prick test was also more frequent (55% vs 8%, P < 0.01). Asthmatic participants had higher composite variable scores (2 [1-3] vs 1 [0-1], P = 0.02). Receiver operating characteristic analysis showed that total IgE, F ENO , and composite variable were suitablefor identifying asthmatic participants (area under the curve = 0.72, P = 0.01; 0.70, P = 0.02, and 0.69, P = 0.03). A composite score of >2 reached a specificity of 96.2%, a sensitivity of 36.4%, and a likelihood ratio of 9.5. Logistic regression model revealed a strong association between the composite variable and the asthma diagnosis (OR = 2.71, 95% confidence interval = 1.17-6.23, P = 0.02). Our data highlight the diagnostic value of combined assessment of Th2-type inflammation in elite water sports athletes. The proposed scoring system may be helpful in ruling in asthma in this population upon clinical suspicion.

Impact of biologics on lung hyperinflation in patients with severe asthma

BackgroundIn asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea. MethodsThis is a retrospective observational study evaluating the effect of three months of treatment with different biologic drugs (benralizumab, dupilumab and omalizumab) on pulmonary hyperinflation in a cohort of patients with severe asthma already receiving regular triple inhaled therapy. Changes in RV, RV/TLC ratio, FRC and FRC/TLC ratio were the primary efficacy measures. Secondary outcomes included FEV1, FVC, FEV1/FVC ratio, IC, IC/TLC ratio, asthma control test, the percentage of eosinophils in the blood and fractional FENO. ResultsBenralizumab led to significant changes (p < 0.001) in RV, RV/TLC, FRC, and FRC/TLC. Dupilumab demonstrated a notable reduction in RV (p = 0.017) and RV/TLC (p = 0.002), but the decreases in FRC and FRC/TLC were merely numerical and not as pronounced as those induced by benralizumab. Omalizumab's positive impact on RV (p = 0.057) and RV/TLC (p = 0.085), as well as FRC (p = 0.202) and FRC/TLC (p = 0.096), was also predominantly numerical, with a tendency towards efficacy, albeit excluding the effect on FRC. Treatment with biologics resulted in improvements in all other lung function parameters assessed and a decrease in FENO levels. ConclusionThis study, although limited by small sample size, lack of a placebo control, and unbalanced group sizes, suggests that biological agents are effective in reducing lung hyperinflation even after a relatively short treatment.

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 μg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 μg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Impact of Exacerbation History on Dupilumab Efficacy in Children with Uncontrolled Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE Study.

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥20 ppb) and a history of 1, 2, or ≥3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated. Patients were stratified by the number of exacerbations in the prior year (1, 2, or ≥3) and level of FeNO or blood eosinophil count at baseline. Endpoints included rate of severe exacerbations, percentage of non-exacerbators, and change from baseline in both lung function parameters (pre- and post-bronchodilator [BD] percent predicted forced expiratory volume in 1 s (ppFEV1) and ppFEV1/forced vital capacity [FVC] ratio) and Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) score. A total of 350 patients were included in this analysis. Across patients with 1, 2, or ≥3 prior exacerbations and different levels of type 2 biomarkers, dupilumab reduced the risk of severe asthma exacerbations vs placebo by 53.0-96.0% and improved both pre-BD ppFEV1 and pre-BD FEV1/FVC ratio at Week 52. Dupilumab led to significant reductions in ACQ-7-IA scores in all groups of patients by Week 52. In children with uncontrolled, moderate-to-severe asthma with a type 2 phenotype, dupilumab consistently reduced the risk of asthma exacerbations, improved lung function, and reduced ACQ-7-IA scores, regardless of exacerbation history.

Markers of eosinophilic airway inflammation in patients with asthma and allergic rhinitis.

Background: Measurement of airway inflammation is an important step to determine phenotype of asthma and allergic rhinitis (AR). Objective: To assess the level of nitric oxide in exhaled air (FeNO), nasal fraction of nitric oxide (nasal NO), their relationship with clinical control and blood eosinophils in patients with steroid-naive mild and moderate asthma and AR. Methods: One hundred forty-seven patients (65 men), ages 26-49.5 years (mean age, 32 years) with AR (n = 81) or AR and concomitant asthma (n = 46) and 20 healthy subjects were included in a single-center cohort study. All the patients underwent spirometry with reversibility test. Control of asthma and AR was assessed by using the Asthma Control Questionnaire and the visual analog scale, respectively. Levels of FeNO and nasal NO were measured by chemiluminescent analyzer, peripheral blood eosinophils were counted by automatic analyzer. Results: The FeNO level was significantly elevated in the patients with asthma and concomitant AR compared with the healthy subjects and was associated with control of both asthma and AR. There was no correlation between nasal NO and control of AR. Receiver operating characteristic analysis revealed that the level of eosinophils of 150 cells/μL may be a cutoff for lower airway eosinophilic inflammation. Blood eosinophils count was unable to distinguish eosinophilic and non-eosinophilic upper airway inflammation. Conclusion: We confirm that FeNO but not nasal NO is a marker of eosinophilic airway inflammation in patients with mild-moderate steroid-naive AR and concomitant asthma. A blood eosinophil level of ≥150 cells/µL may be a simple marker of eosinophilic airway inflammation in patients with asthma. However, its low specificity requires repeated measurements and use in combination with other biomarkers.

Pulmonary function characteristics in children with suspected asthma: implications for asthma diagnosis.

In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. However, there is no single gold standard test for diagnosing asthma. This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). We utilized two separate real-world retrospective observational cohorts of children who underwent both spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2019 and December 2019. Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. This group showed a significantly higher FeNO level and prevalence of allergic sensitization. Baseline forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75), and FEF75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients (P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV1/FVC (OR, 2.24 [95%CI, 1.43-3.52])and FEF25-75 (2.05 [1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1(0.05 [0.01-0.19]),FEV1 /FVC (0.27 [0.18-0.41]), FEF25-75 (0.17 [0.11-0.28]), and FEF75 (0.14 [0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR. Repeated pulmonary function tests that closely monitor for subtle lung function impairments and active utilization of additional tests, such as allergic screening and FeNO, should be considered to close the gap in diagnosing asthma.