Fractional Exhaled Nitric Oxide Values Research Articles

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

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 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 (Interquartile range [IQR], 19-45) ppb, and 34 (20.0%) patients were classified as high FeNO group (median 74ppb). 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, 1.01-6.91; 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.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study

BackgroundThere is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma–COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result.MethodsThree standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study.ResultsThe rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83–0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72–0.83).ConclusionThe simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Lung Involvement in Patients with Ulcerative Colitis: Relationship between Exhaled Nitric Oxide and Lung Function.

Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airway involvement. A reduction in CO diffusing capacity and functional alterations in small airways have been described. An extended analysis of fractional exhaled nitric oxide (FeNO) may distinguish the sites of production, and the presence of small airway inflammation may be a useful, non-invasive marker for patient follow-up. The aim of our study was to compare the PFTs as well as FeNO and CANO values of UC patients with different clinical disease activities and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. We enrolled 42 adult outpatients at different clinical activity stages of UC (39 ± 13 years) and a healthy control group of 41 subjects (29 ± 3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100, and 200 mL/s) were collected. All patients performed pulmonary function tests (PFTs) with static volumes and diffusing capacity (DLCO). FeNO and CANO values were significantly increased in UC patients when compared with controls (p = 0.0008 and p < 0.0001, respectively) and were proportional to disease activity (FeNO class 3: 28.1 ppb vs. classes 1-2: 7.7 ppb; CANO values class 3: 8.6 ppb vs. classes 1-2: 2.7 ppb (p < 0.0001)). TLC and DLCO were significantly reduced in severe (Mayo 3) UC patients (p = 0.010 and p = 0.003, respectively). The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with disease activity, suggesting the need for an integrated approach in routine assessment.

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.

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

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

Association between fractional exhaled nitric oxide and therapeutic adherence to controller management in pediatric asthma patients.

Guidelines for asthma management recommend, before establishing additional therapeutic behaviors, to confirm correct use and adequate therapeutic adherence to treatment. Evidence exists on the use of fractional exhaled nitric oxide (FeNO) values for monitoring therapeutic adherence in adults. It is important to establish whether there is a correlation between FeNO and therapeutic adherence in children. This study aims to provide new knowledge about the relationship between FeNO and therapeutic adherence in asthmatic children. Analytical cross-sectional study including asthma patients 5-18 years of age, attending follow-up at Hospital Militar Central (HMC) between May and November 2022 in Colombia. A sociodemographic survey was carried out, followed by the Pediatric Inhaler Adherence Questionnaire (PIAQ), and asthma control test (ACT) or childhood asthma control test (cACT). We defined adequate therapeutic adherence as not missing a single application of inhaled steroids in the last 15 days according to PIAQ. A poisson regression model was carried out including relevant predictors for therapeutic adherence such as FeNO values, age, tobacco exposure at home, atopy, and time since initiation of use of inhaled controller. Eighty-two children with a median age of 10 years (interquartile range: 7-12 years) were included. Adequate therapeutic adherence was reported by 68.3%. After adjusting for age, sex, exposure to cigarette smoke, duration of controller therapy, and atopy, FeNO < 20 ppb was independently associated with adequate therapeutic adherence (RR = 1.5, p = .04, 95% confidence interval: 1.03-2.19). FeNO values seem to be useful to identify pediatric patients with asthma who have adequate adherence to inhaled steroids in a MIC.

Validity of fractional exhaled nitric oxide and small airway lung function measured by IOS in the diagnosis of cough variant asthma in preschool children with chronic cough

BackgroundTo investigate the role of combined impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) in the diagnosis of cough variant asthma (CVA) in preschool children.MethodsA total of 197 preschool-aged children with chronic cough were selected from the paediatric outpatient clinic. Allergy histories were collected for all children along with IOS and FeNO. Paediatric respiratory specialists divided the children into a CVA group (n = 90) and a noncough variant asthma (nCVA) group (n = 107) according to the diagnostic criteria for CVA After diagnostic treatment, the correlation between the FeNO and IOS values and the diagnosis in the two groups was analysed, and the area under the curve (AUC) of each index was calculated.Results(1) X5 was significantly different between the CVA group and the nCVA group (− 4.22 vs. − 3.64, p < 0.001), as was the FeNO value (29.07 vs. 16.64, p < 0.001). (2) Receiver operating characteristic (ROC) analysis showed that the AUCs of FeNO alone and X5 alone were 0.779 and 0.657, respectively, while the AUC of FeNO (cut-off value of 18 ppb) plus X5 (cut-off value of -4.15 cmH2O/(l/s)) reached 0.809.ConclusionsChildren with CVA may have small airway dysfunction at an early stage. For preschool children with chronic cough, the combination of FeNO and X5 can better identify those with CVA.Trial registration number: This trial was registered with and approved by the Chinese Clinical Trial Registry, with registration number ChiCTRcRRC-17011738, and was reviewed and approved by the Ethics Committee of Southwest Hospital.

Use of fractional exhaled nitric oxide as a potential predictor of bronchodilator response.

Nitric oxide (NO) is an important product of eosinophilic metabolism, and its increase is associated with bronchial remodeling and airway hyperresponsiveness. Fractional exhaled NO (FENO) in the expired air of patients with suspected or diagnosed asthma has been used as a marker for eosinophilic inflammation. This cohort study included asthmatic patients classified under steps 3, 4, or 5 of the global strategy for asthma management and prevention. In the morning of the same day, all patients underwent blood collection for eosinophil counts, followed by FENO measurement and spirometry. We considered 2 groups based on the bronchodilation (BD) response on spirometry (>10% of FVC or FEV1): positive (BD+) and negative (BD-). Differences between the 2 groups were analyzed for demographic features, FENO values, and predictive correlations between FENO and BD. Both groups of patients showed an increase in the eosinophil count (BD+, P = .03; BD-, P = .04) and FENO values (P = .015 for both) with an increase in the asthma severity from step 3 to step 5 of the global strategy for asthma management and prevention. The correlations of FENO and eosinophils as well as FENO values and BD + were 0.127 (95% confidence interval,-0.269 to -0.486) and 0.696 (95% confidence interval, 0.246-0.899; P = .007), respectively. Measuring FENO levels may be useful for identifying patients with BD+.

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

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

Effectiveness of FeNO-guided treatment in adult asthma patients: A systematic review and meta-analysis.

Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta-analysis to obtain summary estimates of the effectiveness of FeNO-guided asthma treatment. We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse-variance random-effects meta-analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. The Cochrane Airways Group Trials Register was searched on 9 May 2023. We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO-guided treatment versus usual (symptom-guided) treatment in adult asthma patients. We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO-guided treatment probably reduces the number of patients having ≥1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = -0.10; 95%CI -0.18 to -0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. FeNO-guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes.

Biomarkers for predicting type 2-high and uncontrolled asthma in real-world practice

BackgroundBlood eosinophil count (BEC), immunoglobulin (Ig) E, and fractional exhaled nitric oxide (FeNO) are key clinical indicators for identifying type 2 (T2) asthma. ObjectiveTo provide optimal cutoff points of T2 markers for assessing T2-high or uncontrolled asthma in real-world practice. MethodsVarious clinical and laboratory parameters were analyzed according to the result of T2 markers (BEC, serum-free IgE, and FeNO) in adults with asthma who had maintained antiasthmatic medications. The cutoff levels for representing uncontrolled asthma were determined using receiver operating characteristic analysis. Blood levels of periostin and eosinophil-derived neurotoxin were measured by enzyme-linked immunosorbent assay. Activation markers of circulating eosinophils (Siglec8+) and neutrophils (CD66+) were analyzed by flow cytometry. ResultsOf 133 patients with asthma, 23 (17.3%) had 3 T2 markers (BEC ≥ 300 cells/μL, serum-free IgE ≥ 120 ng/mL, and FeNO ≥ 25 parts per billion) and significantly higher levels of sputum eosinophils, blood eosinophil-derived neurotoxin, and Siglec8+ eosinophils but lower 1-second forced expiratory volume percentage, in addition to a higher rate of uncontrolled status (P < .05 for all). Furthermore, patients with uncontrolled asthma had significantly higher levels of FeNO and BEC with lower 1-second forced expiratory volume percentage (P < .05 for all). The optimal cutoff values for predicting uncontrolled asthma were found to be 22 parts per billion of FeNO levels, 161.4 cells/L of BECs, and 85.9 ng/mL of serum-free IgE levels. ConclusionWe suggest the optimal cutoff values of BEC, IgE, and FeNO for classifying T2-high or uncontrolled asthma, which could be applied as candidate biomarkers for targeting patients with asthma who require T2 biologics.

The Role of Fractional Exhaled Nitric Oxide in Diagnosing Asthmatic Type 2 Chronic Rhinosinusitis With Nasal Polyps.

Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund-Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P < .05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P < .001) and FEV1/FVC (r = -0.324, P = .001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment.

Fractional exhaled nitric oxide in the assessment of exercise-induced bronchoconstriction: A multicenter retrospective analysis of UK-based athletes.

Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes. Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds-that is, intermediate (≥25 ppb) and high FeNO (≥40 ppb and ≥ 50 ppb)-and were evaluated against objective evidence of EIB (≥10% fall in FEV1 ). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25 ppb, ≥40 ppb, and ≥ 50 ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25 ppb was 55%, which decreased to 37% and 27% at ≥40 ppb and ≥ 50 ppb, respectively. The specificity of FeNO ≥25 ppb, ≥40 ppb, and ≥ 50 ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656. FeNO ≥40 ppb provides good specificity, that is, the ability to rule-in a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes.

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps.

The efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation. To assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence. Clinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP. Among the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p < 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p < 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p < 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p < 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p < 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p < 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p < 0.01). Our results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation.

The Correlation Between Fractional Exhaled Nitric Oxide (FeNO), Blood Eosinophil Count, Immunoglobulin E Levels, and Spirometric Values in Patients With Asthma.

In patients with asthma, fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic airway inflammation. However, the correlation with the blood eosinophil count, immunoglobulin E (IgE), and spirometric values is not well established. We aimed to investigate the correlation between FeNO, blood eosinophils, IgE, and spirometric values in asthmatic patients. Data were extracted from the electronic medical records of adult asthmatic patients, and included the FeNO, blood eosinophil count, IgE, and spirometric values. The correlation between the markers was investigated using receiver operating characteristics (ROC) and the area under the curve (AUC). A total of 135 adult patients (30% male) were analyzed. The mean FeNO was 36 ppb and almost half (48%) had a FeNO > 25 ppb. The mean blood eosinophil count was 377 cells/mm3, and 42% had a blood eosinophil count > 300 cells/mm3. There was a significant positive correlation between FeNO and the blood eosinophil count (r = 0.42, sensitivity 63%, specificity 77%, AUC 72%, p < 0.0001) as well as with the IgE (r = 0.35, sensitivity 78%, specificity 44%, AUC 68%, p < 0.0007). There was significant negative correlation between FeNO and FEV1% (r = -0.18, sensitivity 35%, specificity 85%, AUC 67%, p = 0.027). The blood eosinophil count, IgE, and spirometric values were correlated with the severity of the eosinophilic airway inflammation (high FeNO). Asthmatic patients with a higher FeNO level had a higher eosinophil count, higher IgE levels, and lower FEV1 values.

Exploring the Interaction between Fractional Exhaled Nitric Oxide and Biologic Treatment in Severe Asthma: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored. The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics. The systematic search was conducted on the Medline database through the Pubmed search engine, including all studies from 2009 to the present. Higher baseline values of FeNO are associated with better clinical control in patients treated with omalizumab, dupilumab, and tezepelumab. FeNO dynamics during biologic treatment highlights a clear reduction in FeNO values in patients treated with anti-IL4/13 and anti-IL13, as well as in patients treated with tezepelumab. During the treatment, FeNO may help to predict clinical worsening and to differentiate eosinophilic from non-eosinophilic exacerbations. Higher baseline FeNO levels appear to be associated with a greater benefit in terms of clinical control and reduction of exacerbation rate, while FeNO dynamics during biologic treatment remains a largely unexplored issue since few studies have investigated it as a primary outcome. FeNO remains detectable during biologic treatment, but its potential utility as a biomarker of clinical control is still unclear and represents an interesting research area to be developed.

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia.

The objectives of this study were, for patients attending a specialist asthma clinic at a tertiary care hospital, to determine, from sputum induction (SI), proportions of bronchial inflammatory phenotypes, demographic, clinical and functional characteristics of each phenotype, and the most accessible non-invasive inflammatory marker that best discriminates between phenotypes. Included were 96 patients with asthma, attending a specialist asthma clinic at a tertiary care hospital, who underwent testing as follows: SI, spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophilia, total immunoglobulin E (IgE), and a skin prick test. SI phenotypes were 46.9% eosinophilic, 33.3% paucigranulocytic, 15.6% neutrophilic, and 4.2% mixed. No significantly different clinical or functional characteristics were observed between the phenotypes. A positive correlation was observed between SI eosinophilia and both emergency visits in the last 12 months (p = 0.041; r = 0.214) and FeNO values (p = 0.000; r = 0.368). Blood eosinophilia correlated with SI eosinophilia (p = 0.001; r = 0.362) and was the best predictor of bronchial eosinophilia, followed by FeNO, and total blood IgE (area under the receiver operating characteristic curve (AUC-ROC) 72%, 65%, and 53%, respectively), although precision was only fair. In consultations for severe asthma, the most frequent phenotype was eosinophilic. Peripheral blood eosinophilia is a reliable marker for discriminating between different bronchial inflammatory phenotypes, is useful in enabling doctors to select a suitable biologic treatment and so prevent asthma exacerbation, and is a better predictor of bronchial eosinophilia than FeNO and IgE values.

LOWER RESPIRATORY TRACT SCREENING USING FRACTIONAL EXHALED NITRIC OXIDE IN PATIENTS WITH EOSINOPHILIC CHRONIC RHINOSINUSITIS

It is known that eosinophilic chronic rhinosinusitis is often associated with adult-onset bronchial asthma, and undiagnosed bronchial asthma is also known to be included. The purpose of this study is to screen patients with eosinophilic chronic rhinosinusitis using fractional exhaled nitric oxide, and to examine its usefulness in detecting undiagnosed bronchial asthma. We retrospectively examined the data of patients with eosinophilic chrnoic rhinosinusitis who underwent surgical treatment at Kagawa University from April 2015 to July 2022. Patients were included if they received examinations of fractional exhaled nitric oxide and spirometry before surgical treatment. Of the 127 subjects, 52 had no history of treatment or diagnosis of bronchial asthma at the initial consultation. Among them, 15 patients who had high fractional exhaled nitric oxide value were diagnosed with bronchial asthma by the respiratory medicine department. Comorbid of bronchial asthma was eventually increased to 70.9% even though it was 59.1% at initial consultation. A certain number of patients with eosinophilic chronic rhinosinusitis have undiagnosed bronchial asthma, which can be difficult to detect with basic examination alone therefore fractional exhaled nitric oxide is useful as an additional screening examination.