FeNO Levels Research Articles

CT and Functional MRI to Evaluate Airway Mucus in Severe Asthma

Intraluminal contributor(s) to airflow obstruction in severe asthma are patient-specific and must be evaluated to personalize treatment. The occurrence and functional consequence of airway mucus in the presence or absence of airway eosinophils remain undetermined. The objective of this study was to understand the functional consequence of airway mucus in the presence or absence of eosinophils and to identify biomarkers of mucus-related airflow obstruction. Mucus plugs were quantified on CT scans, and their contribution to ventilation heterogeneity (using MRI ventilation defect percent [VDP]) was evaluated in 27 patients with severe asthma. Patients were dichotomized based on sputum eosinophilia such that the relationship between mucus, eosinophilia, and ventilation heterogeneity could be investigated. Fractional exhaled nitric oxide (Feno) and related cytokines in sputum were measured. Mucus plugging was present in 100%of asthma patients with sputum eosinophils and 36%of those without sputum eosinophils (P= .0006) and was correlated with MRI VDP prebronchodilator (r= 0.68; P= .0001) and postbronchodilator (r= 0.72; P< .0001). In a multivariable regression, both mucus and eosinophils contributed to the prediction of postbronchodilator MRI VDP (R2= 0.75; P< .0001). Patients with asthma in whom the mucus score was high had raised Feno (P= .03) and IL-4 (P= .02) values. Mucus plugging correlated with Feno (r= 0.63; P= .005). Both airway eosinophils and mucus can contribute to ventilation heterogeneity in patients with severe asthma. Patients in whom mucus is the dominant cause of airway obstruction have evidence of an upregulated IL-4/IL-13 pathway that could be identified according to increased Feno level.

The effect of passive smoking on exhaled nitric oxide in asthmatic children

To date, some studies suggest that passive smoking (PS) may be an important determinant of FeNO levels in children but sill there is a need of investigations using objective methods of PS exposure.The aim of our study was to examine the effect of PS, measured by urine cotinine levels, on FeNO and lung function (FEV1) in allergic and non-allergic asthmatic children. MethodsIt was a prospective, non-interventional study. 140 children, aged 4–17, newly diagnosed with asthma were recruited into two study groups (exposed group, unexposed group), according to smoking exposure/unexposure based on the questionnaire. There was one study visit. Subjects underwent a medical history (including history of atopy), physical examination, spirometry, FeNO and urinary cotinine measurement. Results70 individuals had been exposed to tobacco smoke. The patients exposed to tobacco smoke were characterized by statistically significantly higher urine concentration of cotinine, 10,80 ng/mL, than their counterparts who had not been exposed to tobacco smoke, 1,56 ng/mL (P = 0,019). In the group of individuals unexposed to tobacco smoke the mean value of FeNO was 34,99 ppb, while in the group of patient who had been exposed to tobacco smoke, the corresponding mean value was significantly lower, it amounted to 22,41 ppb (P = 0,001) (Table 1). As regards to FEV1 measurements, there were not any statistically significant differences by study groups unexposed/exposed to tobacco smoke (P = 0,179 and P = 0,074, respectively). FeNO levels (ppb) in the studied patients allergic to cat, grass or trees, exposed to tobacco smoke were significantly lower than in those children unexposed to tobacco smoke.Our results suggest a clinically important issue, that FeNO results should be interpreted in the context of environmental tobacco smoke exposure. Additionally allergy to cat dander, grass or tree may be potential confounding factor, which should be taken into consideration.

Predictive and Diagnostic Value of Fractional Exhaled Nitric Oxide in Patients with Chronic Rhinosinusitis.

BackgroundFractional exhaled nitric oxide (FeNO) participates in the local defense of the upper respiratory tract. Abnormal FeNO level is directly related to the occurrence of nasal diseases. However, the clinical value of FeNO in the upper airway is limited, which greatly impedes the diagnosis and treatment of nasal diseases. Here, we assessed the level of FeNO and evaluated the diagnostic accuracy of FeNO for chronic rhinosinusitis.Material/MethodsWe enrolled 35 patients with confirmed nasal inflammation and 30 healthy subjects from December 2016 and June 2017. The FeNO level was measured using a fractional exhaled nitric oxide detector. The level of FeNO in patients with different clinicopathological factors was compared. The diagnostic potential of FeNO for chronic rhinosinusitis was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsFeNO level was significantly lower in patients with nasal inflammation than in healthy subjects (P<0.05). For nasal inflammation diagnosis, FeNO had the highest area under the curve (AUC) at 0.760, with a sensitivity of 93.30% and a specificity of 68.60%. FeNO level was significantly downregulated in chronic rhinosinusitis patients relative to chronic rhinitis patients (P<0.05). FeNO had a good ability to discriminate between chronic rhinosinusitis patients and chronic rhinitis patients, with higher AUC, sensitivity, and specificity of 0.760, 93.30%, and 68.60%, respectively. However, FeNO levels were not significantly different between different histological types of chronic rhinosinusitis (P>0.05).ConclusionsOur results show that FeNO is a useful marker for discriminating chronic rhinosinusitis, and has potential to provide valuable information in the early diagnosis of chronic rhinosinusitis.

The Fraction Exhaled Nitric Oxide as a Biomarker of Asthma Control.

Introduction and Objective:The main goal of asthma treatment is to achieve and maintain clinical control of the disease. The exhaled fraction nitric oxide (FeNO) level is a biomarker of T-helper cell type 2 (Th2) inflammation of the airways. Our objective was to determine whether the FeNO level can be used to discriminate between patients with controlled, partially controlled, and uncontrolled asthma.Materials and Methods:The FeNO level and asthma control were evaluated in a retrospective and analytic cross-sectional study through data collected from asthmatic patients who were assessed by clinical history, asthma control, physical examination, spirometry, and FeNO level. Asthma control was determined by the criteria of the Global Initiative for Asthma and classified as controlled asthma, partially controlled asthma, and uncontrolled asthma. The FeNO values were classified as low (<25 ppb) or intermediate/high (⩾25 ppb) based on the American Thoracic Society recommendations.Results:The symptoms of 81 asthmatic patients were classified as controlled (34 [42%] patients), partially controlled (27 [33.3%] patients), and uncontrolled (20 [24.7%] patients). The FeNO level discriminated between the uncontrolled and controlled groups (P = .01) and between the uncontrolled and partially controlled groups (P = .01), but not between the controlled and partially controlled groups (P = .98). An FeNO level >30 ppb was associated with uncontrolled asthma (P = .0001) with an area under the receiver operating characteristic curve of 0.78 (95% confidence interval = 0.65-0.89).Conclusions:FeNO level could be helpful in determining asthma control as >30 ppb was associated with uncontrolled asthma.

The relationship between serum vitamin D level and asthma.

OBJECTIVE:Several studies have established a relationship between low serum vitamin D levels and the onset of asthma in childhood. In this study, we aim to assess the relationship between vitamin D and asthma.METHODS:This study included 29 mild and 30 moderate persistent asthma and 38 healthy control group. Evaluation of the three groups was carried out in respect of serum vitamin D levels, Respiratory Function Test (RFT), and Exercise Provocation Test (EPT). The two asthma groups were also examined using the Asthma Control Test (ACT) and Nitric Oxide in Exhaled Breath (FeNO) level.RESULTS:The vitamin D levels of the mild and the moderate persistent asthma groups were determined to be lower than the vitamin D levels of the control group (p=0.007). A significant negative correlation was determined in all cases between the vitamin D levels and the broncho-reversibility percentage (p=0.0002). The negative correlation between the vitamin D levels and the broncho-reversibility percentage was more evident in the moderate persistent asthma group (p=0.0001). In the moderate persistent asthma group, a significant positive correlation was determined between the lowness of the maximum forced expiratory volume in EPT and a low vitamin D level (p=0.009). The ACT scores were lower, and the FeNO levels were higher in the moderate asthma group compared to the mild asthma group (p=0.0001).CONCLUSION:The findings showed that low serum vitamin D levels were observed more often in children with asthma, and there was a correlation with increased broncho-reversibility in the RFT and increased bronchial hyper-reactivity in the EPT.

"T2-high" in severe asthma related to blood eosinophil, exhaled nitric oxide andserum periostin.

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort.The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs.37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild-moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (F eNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. F eNO (≥30 ppb) and blood eosinophils (≥300 cells·µL-1) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression.T2-high severe asthma can be predicted to some extent from raised levels of F eNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.

The level of exhaled nitric oxide and its clinical significance in children with Mycoplasma pneumoniae pneumonia

Objective To investigate the changes of levels of exhaled nitric oxide and the clinical significance in children with Mycoplasma pneumoniae pneumonia(MPP). Methods From June 2014 to March 2017, 95 children with MPP and 64 children with bronchial pneumonia in Jinshan Branch of The Sixth People's Hospital of Shanghai were collected, 32 healthy children were enrolled as controls.According to the imaging examination, patients with MPP were further grouped into lobar pneumonia group, bronchopneumonia group and interstitial pneumonia group.FeNO and lung function were measured in all children. Results The level of FeNO in the MPP group was (7.25±3.41) ppb, which was lower than that in the non-MPP group and control group[(11.24±3.52)ppb, (10.51±4.23)ppb](t=5.82, 5.77, all P 0.05). The FEV1, FEV1/FVC%, FEF25%-75% of the MPP group[(66.23±13.21), (84.62±6.73), (58.65.±19.43)]were lower than those of the control group and non-MPP group[(91.81±11.36), (93.80±8.91), (86.80±20.71); (85.43±10.32), (90.18±11.35), (74.73±17.91)](t=4.35, 3.62, 4.78; 4.56, 7.12, 5.06, all P 0.05). In the MPP group, the FEV1, FEV1/FVC%, FEF25%-75% were not associated with FeNO level(r=-0.15, P>0.05; r=-0.06, P>0.05; r=0.07, P>0.05). Conclusion The level of FeNO in children with MPP is lower, and the level of FeNO is not significantly correlated with the parameters of lung function, and FeNO can be used as an inflammatory marker to evaluate the correlation between MP infection and airway inflammation. Key words: Pneumonia, mycoplasma; Nitric oxide; Maximal midexpiratory flow rate; Forced expiratory volume; Child

Association of short-term exposure to ambient air pollutants with exhaled nitric oxide in hospitalized patients with respiratory-system diseases

BackgroundPrevious studies have suggested that exposure to ambient air pollutants may adversely affect human health. However, few studies have examined the health effects of exposure to ambient air pollutants in hospitalized patients. ObjectivesTo evaluate the association between short-term exposure to ambient air pollutants and exhaled nitric oxide fraction (FeNO) in a large cohort of hospitalized patients. MethodsFeNO was detected for 2986 hospitalized patients (ages 18–88 years). Daily average concentrations of SO2, NO2, O3, CO, PM2.5 and PM10 in 2014 and 2015 were obtained from nine fixed-site monitoring stations. Multiple linear regression models were chosen to assess the associations of exposure to ambient air pollutants with FeNO while adjusting for confounding variables. Lagged variable models were selected to determine the association between FeNO and ambient air pollutants concentrations with lags of up to 7 days prior to FeNO testing. ResultsInterquartile-range (IQR) increases in the daily average SO2 (8.00 μg/m3) and PM2.5 (37.0 μg/m3) were strongly associated with increases in FeNO, with increases of 3.41% [95% confidence interval (CI), 0.94–5.93%] and 2.72% (95%CI, −0.09% to 5.61%), respectively. However, FeNO levels were not statistically associated with PM10, NO2, O3 or CO. In the two-pollutant models, the maximum correlation was for ambient SO2. We also found that FeNO was associated with IQR increases in daily average ambient concentrations of SO2 up to 3 and 4 days after the exposure events. ConclusionsShort-term exposure to SO2 and PM2.5 were positively correlated with FeNO levels in hospitalized patients in Shanghai.

DUPILUMAB EFFICACY IN UNCONTROLLED, MODERATE-TO-SEVERE ALLERGIC ASTHMA IN THE PHASE 3 LIBERTY ASTHMA QUEST STUDY

Introduction Dupilumab, a fully human interleukin (IL)-4 receptor-α monoclonal antibody inhibiting IL-4/IL-13 signaling pathways, key drivers of Type 2 inflammation, is approved for treating adults with inadequately controlled moderate-to-severe atopic dermatitis. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), dupilumab 200mg and 300mg administered every 2 weeks versus matched placebo reduced annualized severe exacerbation rates and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma (≥12 years, without minimum baseline Type 2 inflammatory biomarkers). This post-hoc analysis assessed the efficacy of dupilumab in patients with and without allergic asthma. Methods Allergic asthma was defined as total serum IgE ≥30 kU/L and ≥1 positive perennial aeroallergen-specific IgE (≥0.35 kU/L) at baseline. Endpoints were annualized severe exacerbation rates over the 52-week treatment period and change from baseline to Week 12 in pre-bronchodilator FEV1 (L). Results 56% (n=1,066) of the intent-to-treat population met the criteria for allergic asthma. In patients with and without allergic asthma, dupilumab vs placebo significantly reduced annualized severe exacerbation rates during the treatment period (all P1 (L) at Week 12 (all PFigure). In both subgroups, improvements were greater with higher baseline blood eosinophil and FeNO levels. The most frequent adverse event in the dupilumab-treated groups versus placebo was injection-site reactions (15%/18% versus 5%/10%, respectively). Conclusions Add-on dupilumab reduced severe exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated. Figure. Change from baseline to Week 12 in pre-bronchodilator FEV1 (L) and annualized severe exacerbation rate during the 52-week treatment period in patients with and without allergic asthma and in subgroups defined by baseline blood-eosinophil counts and FeNO levels.

REFRACTORY NASAL POLYPOSIS TREATED WITH OMALIZUMAB IN A CHILD

Introduction Current treatment of inflammatory nasal polyposis consists of nasal/oral glucocorticoid therapy and surgical management if unresponsive to pharmacotherapy. The etiology is often multifactorial and requires combination management with both pharmacotherapy and surgery. We present a case of refractory nasal polyposis in a child treated with omalizumab, preventing the need for repeat surgical intervention. Case Description A 12-year old male with history of severe asthma, allergic rhinitis and allergic fungal sinusitis requiring functional endoscopic sinus surgery, developed worsening nasal polyposis despite maximal medical therapy. Physical and endoscopic exam revealed left sided nasal polyps, bilateral inferior turbinate hypertrophy, vocal cord nodules and hoarse voice. FeNO was uptrending, ranging from 98-175 ppb over the past year. Management included allergen immunotherapy, oral leukotriene-receptor antagonist, high-dose inhaled corticosteroid/long-acting beta agonist, oral antihistamine, intranasal antihistamines, high-dose intranasal steroid rinses, and oral steroids. His asthma was well controlled. Repeat surgical intervention was anticipated. Given his rising FeNO levels despite oral steroids, omalizumab was initiated in an attempt to decrease his nasal inflammatory process. Significant symptomatic improvement was noted after two omalizumab injections and his FeNO decreased to 65 ppb, the lowest value in the previous 3 years. Six months later, his FeNO has declined further to 29 ppb. Endoscopic exam showed polyp regression. This has prevented need for nasal surgery with continued use. Discussion Off-label use of omalizumab for atopic nasal polyposis should be considered in patients nonresponsive to traditional pharmacotherapies.

Usefulness of serum biopterin as a predictive biomarker for childhood asthma control: A prospective cohort study

BackgroundPteridines are metabolites of tetrahydrobiopterin, which serves as co-enzyme of nitric oxide synthase. We sought to investigate the usefulness of pteridines as biomarkers for childhood asthma control. MethodsWe conducted a single-center prospective cohort study involving 168 asthmatic children aged 4–17 years who visited the periodical asthma checkup program. Serum neopterin and biopterin levels were measured as pteridines at each visit along with measurement of FeNO, respiratory function tests, nasal eosinophil test, blood eosinophil count, and IgE level. We calculated coefficients for relation between pteridines and asthma control, which was assessed by questionnaires (JPAC: Japanese Pediatric Asthma Control Program). ResultsA total of 168 participants aged 10.3 ± 3.39 years (mean ± SD) with asthma were recruited. The participants in this study contained 58 patients (34.5%) of complete-controlled based on JPAC, 132 patients (76.0%) of well-controlled group based on GINA. FeNO and serum neopterin level did not correlate with following period's JPAC scores. In contrast, serum biopterin level significantly correlated with following period's JPAC total score (Coefficients 0.398; 95% CI 0.164 to 0.632; p value 0.001) and frequency of wheezing during exercise (Coefficients 0.272; 95% CI 0.217 to 0.328; p value < 0.001). ConclusionsWe found serum biopterin effected the following period's control status of asthmatic children, thus monitoring biopterin level will be a useful for management of asthma to adjust treatment.

FRACTION OF EXHALED NITRIC OXIDE (FENO) IN METABOLIC SYNDROME

SESSION TITLE: Systemic Disease and the Lung 1 SESSION TYPE: Original Investigations PRESENTED ON: 10/07/2018 01:00 PM - 02:00 PM PURPOSE: Metabolic syndrome (MetS) is a pro-inflammatory status that affects different body systems including the pulmonary system. Many studies showed an association between MetS and abnormal pulmonary function. Knowing that FENO has been proven as a marker for eosinophilic airway inflammation, the aim of this study is to compare FENO levels in individuals with MetS, with the rest of the population to know whether they have higher degree of eosinophilic airway inflammation. Since MetS is associated with obesity, and as obesity is associated with abnormal pulmonary function, we studied three groups: MetS, obese without MetS, and non-obese without MetS. METHODS: This is a cross-sectional analysis using the National Health and Nutrition Examination Surveys (NHANES lll) collected from 2007 to 2012. We included 3,871 adult participants with the following variables: age, gender, ethnicity, smoking status, MetS components, asthma status, body mass index (BMI), and FENO. We identified three groups: non-obese without MetS, obese without MetS (obese group), and MetS group (regardless of the BMI). MetS was defined using the current Adult Treatment Panel III criteria. Obesity was defined as having BMI ≥ 30 kg/m2. We compared FENO means by group using analysis of variance. Multiple variable linear regression was used to adjust for age, gender, ethnicity, smoking status, and asthma status. RESULTS: The MetS group had the highest FENO mean, followed by the obese group, and then the non-obese without MetS group (15.64 parts per billion [ppb], 14.01 ppb, and 13.44 ppb, respectively; p=0.003). Crude analysis was followed by adjustments for age, gender, smoking status, and asthma status. Interestingly, the association stayed significant after adjusting for all the above-mentioned factors except age (p=0.002). When age was included, the association was attenuated (p=0.09). Inclusion of an interaction term between age and group revealed a differential association for FENO and age by group (p =0.048). Stratification for age was performed using the sample median age of 45-years as a cutoff. In ≥ 45-year-old participants, the association between FENO and group was non-significant (p=0.645). In < 45-year-old participants, there was a trend, but not an association, between FENO and group (p = 0.08). CONCLUSIONS: MetS participants had the highest FENO mean, and therefore the highest degree of eosinophilic airway inflammation. However, their mean is considered within low FENO range ( < 25 ppb) and therefore of unclear clinical significance. Age attenuated the association with FENO, especially in the ≥ 45-year-old participants. This is important in supporting the association between age and FENO in adults as there was less agreement on this association in the previous studies. CLINICAL IMPLICATIONS: Though the association between MetS and FENO is statistically significant, its clinical significance is unclear and warrants more studies. DISCLOSURES: No relevant relationships by Charles Eaton, source=Admin input No relevant relationships by Faeq Kukhon, source=Web Response no disclosure on file for Franklin McCool; No relevant relationships by Mahmoud Mowafy, source=Web Response No relevant relationships by Ibrahim Othman, source=Web Response No relevant relationships by Mary Roberts, source=Web Response

Time-Lag Pattern of Short-Term Exposure to Traffic-Related Air Pollution and Changes in Exhaled Nitric Oxide in Asthmatic Children

Background/Aim: Short-term exposure to traffic-related air pollution (TRAP) has been associated with asthma exacerbation and increases in exhaled nitric oxide (FeNO), a biomarker of airway inflammation, with time lags ranging from several hours to a few days. Very few studies have examined TRAP-FeNO associations on less than 24-hour timescale. Moreover, most of the previous studies have used central-site exposure data. We aimed to investigate the lag structure of changes in FeNO in response to black carbon (BC), a marker for diesel exhaust particulate matter exposure, at hourly resolution measured by personal monitors from 35 asthmatic children in seaport-adjacent communities in New Jersey.Methods: Thirty five children with mild-to-moderate physician-diagnosed asthma wore micro-aethalometers (AE51, Aethlabs) for around 30 days (1071 observations in total). FeNO was measured daily in late afternoon using a NIOX MINO. Linear-mixed effect model was applied to quantify the BC-FeNO association after adjusting for day-of-week, temperature, age and gender. The lag was stratified as every two hours within 24-hour before the time of FeNO measurement.Results: Based on data from the first 9 subjects, FeNO level was positively associated with 24-hour average BC exposure (0.69% [95%CI: -1.62%, 3.05%] per one &amp;#956;g/m3 increase in BC) in the adjusted model. However, we observed inverse associations between BC and FeNO within 24 hour prior to FeNO measurement, and the association was strongest at lag 14-16 hours (-5.5% [95%CI: -9.38%, -1.44%] per one &amp;#956;g/m3 increase in BC) The strength of negative associations increased from lag 4-6 hours to lag 16-18 hours, and then decreased and becoming positive, over lags 18-20, 20-22 and 22-24 hours.Conclusions: Given the known high spatial and temporal variation in exposure to TRAP, the preliminary results support the need for further study of time-lag patterns between exposure to TRAP and acute asthma outcomes.

Childhood Pulmonary Function, Exercise Capacity, and Exhaled Nitric Oxide Levels: Outcomes following Neonatal Treatment with Inhaled Nitric Oxide to Prevent Bronchopulmonary Dysplasia.

The goal was to determine if inhaled nitric oxide (iNO) for 3 weeks during neonatal care of high-risk preterm infants was associated with improved pulmonary function and exercise capacity or altered exhaled nitric oxide (FeNO) levels in later childhood. Thirty-four very preterm children previously enrolled in a randomized, neonatal trial of iNO to prevent chronic lung disease, were assessed in follow-up at 7 to 9 years of age, including pulmonary function testing (PFT), exercise testing, and measurement of FeNO. There were no differences in PFTs or exercise capacity between iNO treated and controls. FeNO levels showed large interpatient variability but tended to be lower in the iNO treated. Findings indicate no overall differences in pulmonary function or exercise capacity for children who had neonatal iNO treatment compared with placebo.

Value of Exhaled Nitric Oxide (FeNO) And Eosinophilia During the Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospital Admission

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3–6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.

Biomarkers of respiratory allergy in laboratory animal care workers: an observational study.

Laboratory animal allergy is a highly prevalent occupational disease among exposed workers. The aim of the study was to validate the biomarkers of airway inflammation in laboratory animal (LA) care workers. All of the participants in this observational study (63 LA care workers and 64 controls) were administered a clinical questionnaire, underwent spirometry and a skin prick or radioallergosorbent test for common and occupational aeroallergens, and the fraction of exhaled nitric oxide (FeNO50), exhaled breath condensate hydrogen peroxide (EBC H2O2) and serum pneumoprotein levels were measured. Multivariate analysis (ANCOVA) was used to assess the interactions of the variables. FeNO50 levels correlated with exposure (p = 0.002), sensitisation (p = 0.000) and age (p = 0.001), but there was no interaction between exposure and sensitisation when age was considered in the model (p = 0.146). EBC-H2O2 levels were higher in the sensitised workers than in the sensitised controls [0.14 (0.08-0.29) µM vs 0.07 (0.05-0.12) µM; p < 0.05]. Serum surfactant protein A (SP-A) levels were unaffected by exposure, sensitisation or age, although higher levels were observed in symptomatic workers; however, SP-D levels were influenced by exposure (p = 0.024) and age (p = 0.022), and club cell 16 levels were influenced by sensitisation (p = 0.027) and age (p = 0.019). The presence of the clinical symptoms associated with LA exposure and high FeNO levels should prompt further medical assessments in LA workers. Although EBC-H2O2 levels do not seem to reflect eosinophilic inflammation, serum SP-A levels could be used to monitor progression from rhinitis to asthma.

Serum level of eosinophilic cationic protein in relation to eosinophilia and to exhaled nitric oxide value in children with atopic asthma and aeroallergens sensitization

Aim. To assess the correlation between the serum level of eosinophilic cationic protein (S-ECP) and the occurrence of eosinophilia, respectively the exhaled nitric oxide value (FeNO), in children with atopic asthma and aeroallergens sensitization. Material and method. A prospective study including 63 children with atopic asthma and aeroallergens sensitization aged 5-18 years old, conducted in Pediatric Department of Children Clinical Hospital “Dr. Victor Gomoiu”, between April 2016 and July 2017. The S-ECP level, occurrence of eosinophilia and FeNO value were initially determined. Thereafter the statistically significance of the correlation between S-ECP and the occurrence of eosinophilia, respectively FeNO value, was assessed. Results. 22 patients had normal S-ECP level; among them only 8 had eosinophilia. 41 patients had increased S-ECP level; among them 28 had eosinophilia. Using the statistical function Pearson Chi-Square Test to assess the significance of the correlation between increased S-ECP level and eosinophilia we have obtained a p value = 0.0146 (statistically significant). 15 of those 22 patients with normal S-ECP level had at the same time a normal FeNO level; the other 7 patients had increased FeNO level. 17 of those 41 patients with increased S-ECP value had normal FeNO level; the other 24 patients had increased FeNO level. Using the statistical function Pearson Chi-Square Test to assess the significance of the correlation between S-ECP level and FeNO value we have obtained a p value = 0.0432 (statistically significant). Conclusion. Increased S-ECP level is correlated with the occurrence of eosinophilia and also with the increased FeNO value in atopic children with aeroallergens sensitization.

Accuracy of a New Algorithm to Identify Asthma–COPD Overlap (ACO) Patients in a Cohort of Patients with Chronic Obstructive Airway Disease

ObjectivesWe aimed to characterize the clinical, functional and inflammatory features of patients diagnosed diagnosed with ACO according to a new algorithm and to compare them with those of other chronic obstructive airway disease (COAD) categories (asthma and COPD). MethodsACO was diagnosed in a cohort of COAD patients in those patients with COPD who were either diagnosed with current asthma or showed significant blood eosinophilia (≥300cells/μl) and/or a very positive bronchodilator response (>400ml and >15% in FEV1). ResultsEighty-seven (29.8%) out of 292 patients fulfilled the ACO diagnostic criteria (12.8% asthmatics who smoked <20 pack-years, 100% of asthmatics who smoked ≥20 pack-years, 47.7% of COPD with >200eosinophils/μl in blood and none with non-eosinophilic COPD). ACO, asthma and COPD patients showed no differences in symptoms or exacerbation rate. Mean pre-bronchodilator FEV1 in ACO and asthma were similar (1741 vs 1771ml), higher than in COPD (1431ml, p<0.05). DLCO was lower in ACO than in asthma (68.1 vs 84.1%) and similar to COPD (64.5%). Mean blood eosinophil count was similar in ACO and asthma (360 vs 305cells/μl) and higher than in COPD (170cells/μl). Periostin levels were similar in ACO to COPD (36.6 and 36.5IU/ml) and lower than in asthma (41.5IU/ml, p<0.05), whereas FeNO levels in ACO were intermediate. ConclusionThis algorithm classifies as ACO all smoking asthmatics with non-fully reversible airway obstruction and a considerable proportion of e-COPD patients, highlighting those who can benefit from inhaled corticosteroids.

Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients

BackgroundSome studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients.MethodsThis is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis.ResultsA total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49–5.84; p = 0.002), greater severity of asthma (OR, 2.43; 95% CI, 1.29–4.57; p = 0.006), at least one previous episode of pneumonia (OR, 2.42; 95% CI, 1.03–5.69; p = 0.044), and lower levels of FeNO (OR, 0.98; 95% CI, 0.97–0.99; p = 0.016). The NOPES score was developed on the basis of these variables (FeNO[cut off point 20.5 ppb], Pneumonia, Expectoration and asthma Severity), and it ranges from 0 to 4 points, where 0 means “no risk” and 4 corresponds to “high risk”. The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%.ConclusionsAlmost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma.

Association between (CCTTT)n repeat polymorphism in NOS2 promoter and asthma exacerbations

Association between (CCTTT)n repeat polymorphism in NOS2 promoter and asthma exacerbations