FeNO Values Research Articles

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.

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aged 18 to 65 with mild asthma, stable, on low-dose inhaled corticosteroid (ICS) treatment, who had their treatment withdrawn based on a FeNO level of 40 ppb. Patients were randomized into two groups: control group (treatment with ICS was withdrawn regardless of FeNO level) and experimental group (according to the FeNO levels, patients were assigned to one of two groups: FeNO 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.

Childhood severe asthma: relationship among asthma control scores, FeNO, spirometry and impulse oscillometry

IntroductionThe evaluation of the asthmatic patient is usually based on clinical and functional parameters that do not necessarily evidence the degree of airway inflammation. The aim of this study was to analyze whether clinical scores (CS) correlate with spirometry (S), impulse oscillometry (IO) and FeNO, in severe asthmatic children.Material and methodsA multicentric, prospective, cross-sectional study was conducted over a 12-month period. All SA patients (6–18 years old) followed-up in the Pulmonology Department were recruited. CS, FeNO measurements, IO and S were consecutively performed on the same day. Asthma control was ascertained using ACT and GINAq. A cut-off value of ≥ 25 parts per billion (ppb) was used to define airway inflammation.ResultsEighty-one patients were included. ACT: 75% (n 61) were controlled; GINAq: 44.5% (n 36) were controlled; 39.5% (n 32) were partly controlled, and 16% (n 13) were uncontrolled. FeNO had a median value of 24 ppb (IQR 14–41); FeNO ≥ 25 ppb was observed in 49% of patients (n 39). ROC AUC for FeNO vs. ACT was 0.71 (95%CI 0.57–0.86), PPV 0.47, NPV 0.87, SE 0.61, SP 0.80; FeNO vs. GINAq was ROC AUC 0.69 (95%CI 0.54–0.85), PPV 0.34, NPV 0.91, SE 0.62, SP 0.77; Youden cut-off FeNO > 39 ppb for both CS.ConclusionIn severe asthmatic children, current symptoms control as evidenced by ACT and GINA correlates with low FeNO values. Clinical scores showed good correlation with airway inflammation.

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.

Characterization of asthma phenotypes in children of the tropics

Determine the main asthma phenotypes in a population of asthmatic children in Cartagena, Colombia. 107 children (7 to 17 years old) with a previous diagnosis of asthma were recruited. Biomarkers of T2 inflammation were evaluated by measuring FeNO, eosinophil count in peripheral blood by hemocytometry, and determination of specific IgE to mite allergens by ELISA. The study was approved by the ethics committee of the University of Cartagena (SGR, Grant BPIN2020000100405). The average age of patients was 10,9 years. 19,6% of the children did not show elevation of any of the T2 inflammation biomarkers evaluated (FeNO<20ppb, eos<300/ul, negative specific IgE), so they were considered patients with non-allergic asthma (non-T2). 71,9% of all patients were sensitized to at least one allergen, this phenotype was considered allergic asthma. 30,8% of the patients presented the three elevated biomarkers (FeNO>20ppb + eos >300/ul + positive specific IgE), this phenotype was classified as high T2 allergic asthma. A moderate correlation (Spearman rho=0,44, p<0,0001) was found between FeNO values and eosinophil counts. In this study, the following phenotypes were found: allergic asthma, high T2 asthma, and non-allergic asthma. Most patients presented a type 2 inflammatory phenotype with allergic sensitization. In addition to the measurement of specific IgE, the use of FeNO and eosinophil count in peripheral blood help to accurately determine those patients with high T2 asthma phenotypes.

Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE Study

Uncontrolled asthma in growing children can impair lung growth that may lead to adverse complications in later life. Dupilumab, a human monoclonal antibody, blocks the shared receptor for IL-4 and IL-13, key drivers of type 2 inflammation. To extensively evaluate the effect of dupilumab on lung function in children (6-11 years) with moderate-to-severe asthma enrolled in phase 3 LIBERTY ASTHMA VOYAGE (NCT02948959). Children with asthma were randomized 2:1 to add-on dupilumab 100/200 mg by bodyweight or placebo every 2 weeks, for 52 weeks. We analyzed spirometry parameters in children with type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥20 parts per billion [ppb] at baseline) and within subgroups defined by baseline blood eosinophils or FeNO values. A total of 116 (49%) dupilumab-treated children and 59 (52%) on placebo had impaired lung function (prebronchodilator percent-predicted forced expiratory volume in 1 second [ppFEV1] <80%) at baseline. Dupilumab improved pre- and postbronchodilator ppFEV1 as early as week 2, sustained for up to 52 weeks (least-squares mean difference vs placebo at week 52: 7.79 percentage points; 95% confidence interval [CI]: 4.36-11.22; P < .001 and 4.37 points; 95% CI: 0.95-7.78; P= .01, respectively). Sustained improvements were also observed in other lung function parameters, including pre- and postbronchodilator forced vital capacity (FVC), prebronchodilator forced expiratory flow, and FEV1/FVC ratio across all populations. Dupilumab led to significant, sustained lung function improvements across a range of lung function measures in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma.

Validation of a new portable system containing both FeNO analysis and spirometry measurement.

Pulmonary function tests and FeNO measurements are widely used for the diagnosis and management of respiratory diseases. They are used to evaluate airway limitation and respiratory inflammation. Standard spirometers and nitric oxide (NO) analyzers are widely used in hospitals. However, their high price has made some hospitals in underdeveloped areas unable to afford or purchase these devices. The development of a new portable system (SUNVOU TM2125) combining FeNO measurement and spirometry provides additional possibilities for optimizing the diagnosis and management of respiratory diseases. However, its accuracy needs further validation. The FeNO analysis component of SUNVOU TM2125 was compared with that of a widely used NO analyzer (NIOX VERO). The spirometry component of the TM2125 was compared with a standard spirometer (Jaeger MasterScreen) for pulmonary parameters such as FEV1, FVC, FEV1/FVC, and PEF. Pearson correlation and Bland-Altman plots were used to evaluate the agreement between the devices. FeNO values measured using TM2125 were higher than those measured using VERO, with a mean difference of 1.8 ppb. There was a strong correlation between FeNO values measured using the two devices (r = 0.988, p < 0.001). Bland-Altman plots showed a high degree of agreement between the two devices, with 93.3% of values within the 95% confidence interval range. The spirometric parameters (FEV1, FVC, FEV1/FVC, and PEF) measured using the TM2125 were lower than those measured using the MasterScreen. Good correlations were observed between the values measured using the TM2125 and MasterScreen (r > 0.9). Based on the Bland-Altman plots, there was a high degree of agreement between the devices. The accuracy of FeNO and spirometry measurements using SUNVOU TM2125 was validated. This can help improve the diagnosis and monitoring of chronic respiratory diseases in underdeveloped countries.

The Impact of Airway Obstruction on Feno Values in Asthma Patients

Exhaled nitric oxide (Feno) is used as a marker of type-2 airway inflammation in asthma management. Studies with airway challenges demonstrated that a reduction in airway caliber decreases Feno levels. To evaluate the impact of airway caliber reduction occurring spontaneously in patients with asthma on Feno values in daily clinical practice. In this post hoc analysis, Feno, FEV1, and asthma control questionnaire scores were recorded on each visit for 120 (1073 visits) adult patients with asthma. Blood eosinophils were measured intermittently. The intraindividual relationship between Feno and FEV1 was evaluated via a linear mixed model. The determinants of the individual mean Feno were measured by a stepwise multivariate linear model including individual mean FEV1, inhaled corticosteroid dose, asthma control questionnaire score, and blood eosinophils. Variations in the negative Feno-FEV1 relationship within individuals at different times were significantly determined by the individual's mean FEV1. This relationship did not hold for individuals above the 75th and below the 25th quartiles. The best explanatory variables for individual mean Feno were FEV1 (+4.3 parts per billion/10%pred) and blood eosinophil count (+1 part per billion per 100 cells/mm3). In the presence of variable degrees of heterogeneous patterns of airway inflammation, airway caliber is shown to be an independent and significant determinant of Feno when measured in patients with asthma. We would propose a+4-parts-per-billion correction factor to the measured Feno value for each 10% reduction below 100% predicted FEV1. Doing this should improve the rigor of interpretation of Feno as an indicator of type-2 inflammation in patients with low FEV1.

Omalizumab in Severe Asthma: Effect on Oral Corticosteroid Exposure and Remodeling. A Randomized Open-Label Parallel Study.

Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited. The purpose of the study is to show that in patients with corticosteroid-dependent asthma, omalizumab is a corticosteroid-sparing therapy able to inhibit airway remodeling and to reduce disease burden (lung function impairment, exacerbations). This study is a randomised open-label study evaluating the addition of omalizumab to the standard of care in patients with severe asthma receiving oral corticosteroids. The primary endpoint was represented by the change in OC monthly dose by the end of treatment and secondary endpoints included spirometry changes, airway inflammation (FeNO), number of exacerbations and airways remodelling assessed by bronchial biopsies studied by transmission electron microscopy. As a safety variable, adverse effects were recorded. Efficacy was assessed for 16 patients in the omalizumab group and 13 in the control group. The final cumulative mean monthly OC doses were 34.7mg and 217mg for the omalizumab and control group, respectively; the mean difference between groups adjusted for baseline was -148.1 [95% confidence interval (CI) -243.6, -52.5; p=0.004]. OC withdrawal of 75% versus 7.7% (p=0.001) was observed in the omalizumab and control group, respectively. Omalizumab provided a slowing of forced expiratory volume in one second (FEV1) loss (70 mL versus 260 mL), a significant decrease in FeNO values and a reduction in the annual relative risk of clinically significant exacerbations of 54%. The treatment was well tolerated. The morphological study showed a significant decrease in basement membrane thickness in the omalizumab group (6.7µm versus 4.6µm) compared with controls (6.9µm versus 7µm) [mean difference between groups adjusted for baseline was -2.4 (95% CI -3.7, -1.2; p<0.001], as well as a decrease in intercellular spaces (1.18µm versus 0.62µm and 1.21µm versus 1.20µm, p=0.011, respectively). A qualitative improvement was also observed in the treated group. Omalizumab showed a marked OC-sparing capacity and was associated with an improvement in clinical management that correlated with bronchial epithelial repair. In OC-dependent asthma, reversibility of remodelling is possible; the concepts that basement membrane enlargement is detrimental and that chronic airway obstruction is systematically irreversible are outdated (EudraCT: 2009-010914-31).

Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

IntroductionThe role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response. MethodsObservational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests. ResultsThe study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders. ConclusionsOur study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.

Developing Fractional Exhaled Nitric Oxide Predicted and Upper Limit of Normal Values for a Disadvantaged Population

Fractional exhaled nitric oxide (Feno), used as a biomarker, is influenced by several factors including ethnicity. Normative data are essential for interpretation, and currently single cutoff values are used in children and adults. Accounting for factors that influence Feno, (1) what are appropriate predicted and upper limit of normal (ULN) Feno values in an underserved population (First Nations Australians), (2) how do these values compare with age-based interpretive guidelines, and (3) what factors influence Feno and what is the size of the effect? Feno data of First Nations Australians (age< 16 years, n= 862; age≥ 16 years, n= 348) were obtained. Medical history using participant questionnaires and medical records were used to define healthy participants. Flexible regression using spline functions, as used by the Global Lung Function Initiative, were used to generate predicted and ULN values. Look-up tables for predicted and ULN values using age (4-76 years) and height (100-200cm) were generated and are supplied with a calculator for clinician use. In healthy First Nations children (age< 18 years), ULN values ranged between 25 and 60 parts per billion (ppb) when considering only biologically plausible age and height combinations. For healthy adults, ULN values ranged between 39 and 88 ppb. Neither the current Feno interpretation guidelines, nor the currently recommended cutoff of 50 ppb for First Nations children 16 years of age or younger were appropriate for use in this cohort. Our modelling revealed that predicted and ULN values of healthy participants varied nonlinearly with age and height. Because single pediatric, adult, or all-age Feno cutoff values used by current interpretive guidelines to define abnormality fail to account for factors that modify Feno values, we propose predicted and ULN values for First Nations Australians 4 to 76 years of age. Creating age- and height-adjusted predicted and ULN values could be considered for other ethnicities.

Distal Lung Inflammation Assessed by Alveolar Concentration of Nitric Oxide Is an Individualised Biomarker of Severe COVID-19 Pneumonia.

Pulmonary sequelae as assessed by pulmonary function tests (PFTs) are often reported in patients infected by SARS-CoV-2 during the post-COVID-19 period. Little is known, however, about the status of pulmonary inflammation during clinical recovery after patients’ discharge from the hospitals. We prospectively measured PFTs coupled with the exhaled nitric oxide (NO) stemming from the proximal airways (FeNO) and the distal lung (CaNO) in 169 consecutive patients with varying degrees of the severity of COVID-19 six weeks to one year after acute infection by SARS-CoV-2. The proportions of patients with abnormal PFTs, defined as the presence of either obstructive/restrictive patterns or impaired lung gas transfer, or both, increased with the severity of the initial lung disease (15, 30, and 52% in patients with mild, moderate, and severe COVID-19). FeNO values remained within normal ranges and did not differ between the three groups of patients. CaNO, however, was significantly higher in patients with severe or critical COVID-19, compared with patients with milder forms of the disease. There was also an inverse relationship between CaNO and DLCO. We conclude that the residual inflammation of the distal lung is still present in the post-COVID-19 follow-up period, in particular, in those patients with an initially severe form of COVID-19. This long-lasting alveolar inflammation might contribute to the long-term development of pulmonary fibrosis and warrants the regular monitoring of exhaled NO together with PFTs in patients with COVID-19.

Combined assessment of bronchial asthma control using forced expiratory volume in first second and exhaled nitric oxide

Introduction The principal goal of bronchial asthma (BA) management is to control and reduce the risk of exacerbations. Poor assessment of asthma control is a major cause of poor asthma management. This study aimed to detect the level of asthma control using spirometry and exhaled nitric oxide (FeNO). Patients and methods This study investigated 210 patients with a diagnosis of BA. Asthma control in included patients was classified according to the Global Initiative for Asthma symptom-based assessment of asthma control, into controlled, partly controlled, or uncontrolled. Spirometry and FeNO results were recorded. Results Most of the studied patients had partly controlled BA (43.3%), while uncontrolled BA was found in 29% of them. There was a significant association between both prebronchodilator forced expiratory volume in 1 s (FEV1) and the presence of reversibility with levels of BA control. There was no significant difference in the FeNO value between the levels of BA control (P=0.5). Combined assessment of BA using low FEV1 with high FeNO showed a significant difference between BA control groups. Conclusion A combination of FeNO and FEV1 provides a better method in detecting the level of BA control. It may be very important for patients with higher airway reversibility to consistently monitor disease control and then to modify therapeutic strategy.

Relationship between exhaled nitric oxide and biomarkers of atopy in children and adolescents with allergic rhinitis

IntroductionMeasurement of the exhaled nitric oxide fraction (FeNO) has been proposed as an indirect and non-invasive method to detect eosinophilic airway inflammation. Allergic rhinitis (AR) is frequently associated with high levels of FeNO. Allergic sensitization can contribute to the recruitment of eosinophils in the airway and the consequent increase in FeNO. ObjectiveTo correlate FeNO values with inflammatory and atopic sensitization biomarkers in patients with AR. Patients and methodsObservational, analytical, cross-sectional study. Children and adolescents with AR without asthma were included. FeNO, blood eosinophil count, total serum IgE were determined and skin tests with aeroallergens were performed by calculating the scores for PPC1 (number of positive allergens), STS2 (sum of millimeters of positive papules) and the atopy index (ratio between STS2/STS1). Spearman's correlation test was used between FeNO and variables of inflammation and atopy. ResultsTwenty-eight patients between 6 and 17 years old were included. There was a significant positive correlation between FeNO and blood eosinophils (r=.38; p=.047) and between FeNO and the atopy index (r=.40; p=.03). No correlation was found between FeNO and total serum IgE (r=.24; p=.21), STS1 (r=.20; p=.32) and STS2 (r=.34; p=.08). ConclusionIn children and adolescents with AR, FeNO was correlated with the atopy index and the blood eosinophil count. These last biomarkers could be used as alternatives for FeNO as biomarkers of lower airway inflammation in patients with AR.

HSP70 upregulation in nasal mucosa of symptomatic children with allergic rhinitis and potential risk of asthma development

Allergic rhinitis and asthma are the most common causes of chronic inflammation of the upper and lower airways in childhood. However, a nasal biomarker that can link to pulmonary inflammation is yet to be found. The present paper aims to investigate the possible role in inflammation of two inducible 70-kDa Heat Shock Proteins (HSP70) members, HSPA1A/B and HSPA6, in nasal mucosa cells of allergic children through their mRNA expression analysis, and their correlation to both spirometric and FeNO values. The relationship between FeNO in lower airways and ∆Cts of HSPA1A/B in nasal mucosa seems to be influenced by clinical symptoms regardless of age, sex, and sensitization patterns. Therefore, HSP70 expression, as well as FeNO levels, could have a predictive capability to identify lower airways inflammation and thus to recognize rhinitic children having a potential risk of asthma development.

Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study.

Introduction: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies have been conducted so far to evaluate the role of the leukotriene cysLT/cysLTr1 axis in the management of clinical and inflammatory outcomes within a population of patients with severe asthma and bronchiectasis. The aim of our study was to verify in this population the effect of leukotriene receptor antagonist (LTRA) therapy in clinical and inflammatory control before and after 6 months of introduction of biologic therapy. Methods: We retrospectively enrolled, from eight different severe asthma centers’ outpatients, 36 atopic patients with the simultaneous presence of non-cystic fibrosis (non-CF) and non-allergic bronchopulmonary aspergillosis (non-ABPA) bronchiectasis and severe asthma. The first biological injection was performed at baseline (T0 time). Patients who were already taking LTRA therapy at time T0 were recorded, and no new prescriptions were made. We observed our population over a 6-month period (T1 time). At the baseline we collected the following data: baseline characteristics, clinical history, high resolution computed tomography and bronchiectasis-related parameters and skin prick test. At both times T0 and T1 we collected the following data: asthma control test (ACT), asthma control questionnaire (ACQ), immunoglobulin E (IgE) level, blood count, fractional exhaled nitric oxide 50 (FeNO 50) and flow-volume spirometry. The study was retrospectively registered. Results: Our population had a mean age of 59.08 ± 11.09 and 50% were female. At T1, patients on LTRA therapy had a significantly lower FeNO value (33.03 ± 23.61 vs. 88.92 ± 77.96; p = 0.012). We assessed that the value of ΔFeNO (FeNO 50 T1 − FeNO 50 T0) and the number of unplanned specialist visits allowed a discrimination of 66.7% in the presence of LTRA therapy. We also verified how low FeNO values at time T1 were statistically significant predictors of LTRA therapy (ODD = 9.96 (0.94–0.99); p = 0.032). Conclusion: The presence of LTRA in therapy in a population of severe asthmatics with coexisting non-ASBPA bronchiectasis and non-cystic fibrosis, acting simultaneously on the T helper type 2 (TH2) pathway and probably on the neutrophilic component of bronchiectasis, would allow a further amplification of the beneficial effects of biological therapy, leading to a reduction in the number of unplanned visits to specialists.

Longitudinal Nitric Oxide Levels and Infections by Ultrastructure and Genotype in Primary Ciliary Dyskinesia

We hypothesized that differences in nasal nitric oxide (nNO) and fractional exhaled nitric oxide (Feno) relate to prognosis in primary ciliary dyskinesia (PCD). What is the relationship between baseline values and longitudinal evolution of nNO and Feno and ultrastructure, genotype, and respiratory infections in PCD? Prospective, longitudinal, single-center study in adults and children evaluated biannually for up to 10 years. We compared cross-sectional and longitudinal values of nNO and Feno in ultrastructural (inner dynein arm [IDA] and microtubular disorganization [MTD]) and genetic (CCDC39 and CCDC40) groups known to have worse pulmonary function with patients within the ultrastructural and genetic groups with a better prognosis. Linear mixed-effects models were used to evaluate longitudinal associations. One hundred forty-one patients with PCD underwent 1,014 visits. At enrollment, no differences were found in children in nNO or Feno between the IDA and MTD group and the other ultrastructural groups. In adults, nNO (P= .038) and Feno (P= .032) were significantly lower in the IDA and MTD group than in all other combined ultrastructural groups. Feno values were significantly lower in the CCDC39 and CCDC40 group than in the DNAH5 and DNAH11 combined genotype group (P= .033) and in all other genotypes (P= .032). The IDA and MTD group showed a significant decline in nNO with age (P< .01) compared with other ultrastructural groups who showed stable levels. The CCDC39 and CCDC40 group showed the steepest decline in nNO over time (P< .01) compared with all other genotypes. A higher nNO was associated with lower likelihood of any positive bacterial isolate from the lower respiratory tract (P= .008). Changes in Feno over time did not differ between structural groups or genotypes. Lower nNO in patients with PCD with genetic and ultrastructural changes associated with greater lung function decline may be related to worse prognosis, but whether a low nNO is causal needs further study. If lower nNO directly results in a poorer prognosis, strategies augmenting upper airway nitric oxide production may be worth evaluating.

Assessment of plasma lipid parameters, exhaled nitric oxide fraction, and systemic immune-inflammation index on stable asthma patients

Asthma is a chronic disease characterized by the presence of inflammatory agents in the airways, and diagnosis and treatment are based on clinical questioning, physical examination, laboratory results, and spirometric analysis. This study investigated the effect of asthma alone on routine laboratory parameters in adults and whether an idea about the course of the disease can be obtained using these parameters. Two hundred and fourteen patients with known asthma history, diagnosed, and treated according to guidelines, were included in our study. Among all patients and between gender-specific groups, total cholesterol (CHOL), HDL, LDL, VLDL, triglyceride (TG), albumin, total protein (TP), lactate dehydrogenase (LDH), glucose, urea, creatinine, C reactive protein (CRP), FeNO, SII, INR, and complete blood count value parameters of the patients were analyzed. When we consider all asthma patients, we found that the mean glucose, LDH, CRP, TG, FeNO, and INR values outpaced the upper limit of the reference range. In contrast, the mean HDL value was below the reference range for all patients. In addition, our study found a significant correlation between triglyceride levels within the biochemical parameters with FeNO and SII). Finally, when we compared the mean values of gender-specific groups, we found a statistically significant difference between VLDL, HDL, TG, CRP, FeNO, creatinine, lymphocyte, eosinophile, basophile, and hemoglobin. CRP, LDH, TG, FeNO, SII, and INR levels may help clinicians in adult patients with stable asthma. In addition, differences depending on gender could be observed in the biochemical parameters of asthma patients.

Clinical Profile, Feno Value and Cortical Steroid Reactivity Evaluation of Patients with Chronic Cough

Clinical Profile, Feno Value and Cortical Steroid Reactivity Evaluation of Patients with Chronic Cough