Higher FeNO Research Articles

Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry

Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis. We characterized biomarker expression in adults with severe asthma. Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/μL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables. Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV1) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis. There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics.

Comparison of fractional exhaled nitric oxide in asthmatics with and without allergic rhinitis

Purpose of the study The aim of this study was to measure the concentration of FeNO in asthmatics with and without allergic rhinitis (AR) and to determine usefulness of the test in the assessment of asthma control in the Polish population. The next objective of this study was to estimate the cut-off point of FeNO which might be a good indicator of uncontrolled asthma. Materials and methods The measurements were taken using the Hyp’Air FeNO in 303 adult patients with asthma, AR, comorbid AR and asthma, and non-diseased volunteers. Results FeNO level in healthy adults was similar to the FeNO concentration in AR as well as controlled asthmatic patients without and with AR. Patients with partly controlled and uncontrolled asthma with and without AR had higher FeNO (>60 ppb) levels when compared to adults with controlled disease. The optimal cut-off point of FeNO > 46 ppb and FeNO > 33 ppb was estimated for identification of uncontrolled asthmatics without and with AR, respectively. Conclusion In conclusion, we found a significant correlation between the FeNO concentration and the level of asthma symptom control in asthmatic patients with and without AR.

Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort.

As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8years in the PARIS birth cohort. Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8years. Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3months seem protected against asthma at 8years old.

The influence of smoking on asthma in the real-life

BackgroundAsthmatic smokers have reduced quality of life and need frequent specialist visits/hospitalization. Smoking habit represents for asthmatics a higher risk for comorbidities and lung function impairment. The impact of cigarette smoking on asthmatics should be addressed to evaluate the related risk factors. MethodsThis real-life observational study evaluated demographic, clinical/functional, and biological parameters of 521 asthmatic patients stratified as never (0 PY), light (1–10 PY), and heavy smokers (>10PY). ResultsThe heavy smokers with asthma were more frequently older, male, overweight, and non-allergic than other asthmatics. Although similar ICS dose and severity among groups, heavy smokers had more significant airflow limitation (FEV1/FVC = 0.65 ± 0.10, p < 0.01; FEV1%pred = 79.20 ± 21.20, p < 0.01), air trapping (RV %pred. = 135.6 ± 44.8, p < 0.05; RV/TLC = 0.48 ± 0.12, p < 0.05), and fixed airflow obstruction (post-bronchodilation FEV1/FVC = 0.66 ± 0.10; p = 0.01) than never and light smokers with asthma. Heavy smokers also demonstrated reduced blood eosinophils (p < 0.05) and FeNO (p < 0.01), increased frequency of type-2 low inflammation and LABA/LAMA use but had less frequently persistent rhinitis and chronic rhinosinusitis with nasal polyposis. Heavy smokers showed higher prevalence of paraseptal/bullous emphysema and arterial hypertension. Considering the risk analysis, heavy smokers showed less chance to have allergy (OR = 0.5), persistent rhinitis (OR = 0.6), chronic rhinosinusitis with nasal polyposis (OR = 0.3), or high FeNO (OR = 0.4), but they were prone to develop fixed airflow obstruction (post-bronchodilation FEV1%pred<80%, OR = 2.0, and post-bronchodilation FEV1/FVC≤0.70, OR = 2.0). ConclusionsHeavy smokers had more severe obstructive impairments than light and never smokers with similar ICS dose, showing a steroid insensitivity, but displayed less allergy with low FeNO and blood eosinophil count, thus being a definite phenotype.

Effectiveness of omalizumab on patient reported outcomes, lung function, and inflammatory markers in severe allergic asthma

BackgroundOmalizumab arose as a therapeutic option in patients suffering from moderate to severe refractory allergic asthma. It acts as a humanized monoclonal antibody neutralizing circulating IgE antibodies. Randomized clinical trials and real life clinical studies have already confirmed benefits, cost-effectiveness and applicability of the medication. MethodOur study retrospectively reports on the clinical outcomes and airway inflammation in 157 severe allergic asthmatics who were initiated with omalizumab between 2007 and 2019. ResultsAfter 4 months of therapy, 76% of the patients were judged to have benefited from omalizumab and were admitted to prolonged treatment. During follow-up, we observed an improvement in asthma control, quality of life and spirometric performance. There was also a sustained reduction in exacerbation rate over the years. As for T2 biomarkers, FeNO significantly decreased and, in a subgroup of patients who had repeated sputum inductions, there was also significant reduction in sputum eosinophils but no change in blood eosinophil count. Lastly, we found a correlation between high FeNO levels at baseline and reduction in ACQ scores at 1 year. ConclusionWe conclude that omalizumab shows effectiveness in severe allergic asthma in a real life setting, by reducing exacerbation rate, improving patient perspective outcomes and airway calibre, together with reducing type-2 airway inflammation.

The Effect of a five-Day Educational Program for Children with Asthma on Airway inflammation: A two-year study

The aim of this study was to investigate the effectiveness of a 5 day educational program in children with asthma on airway inflammation as measured by FeNO during 2 consecutive years. Ninety-four children with asthma were enrolled in Camp Wheez. Written consent was obtained for each participant. Children were educated on the early signs of asthma, identifying triggers and the use of controller medications. The curriculum was provided by the Asthma Camp consortium of the AAAAI. The NIOX Vero was used as a 6 to10 second, single breath, incentive quantitative measurement. We measured FeNO on day one (baseline) and day 5 (end of camp), 2018 and 2019. Ninety-four children were enrolled during the 5 day asthma camp 2018 and 2019. The average baseline FeNO was 36.3 ppb, compared to an average of 33.1 ppb on day 5. The average FeNO levels were the same at day 1 and day 5 in campers with a low (<20ppb) and intermediate FeNO (20-35 ppb.) However, in the 36 campers who had a high baseline FeNO >35 ppb there was a significant improvement in FeNO from an average 75 ppb down to 67 ppb. There was a 10% improvement overall at the end of camp. None of the campers were informed on their baseline levels nor received individual coaching. This 2 year study demonstrated the effectiveness of a 5-day asthma education program on 94 children with asthma. Our results showed a significant improvement in FeNo with a 10% improvement (p=.001) at the conclusion of asthma education.

Clinical significance of the bronchodilator response in children with severe asthma.

Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP). We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevereasthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1 ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility. We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1 % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1 % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility. Lung function, that is FEV1 % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.

Usefulness of mannitol challenge testing for diagnosing asthma in everyday clinical practice

Background: The mannitol test is widely used for assessment of airway responsiveness in patients with possible asthma, but our knowledge of the value in everyday clinical practice is limited.Objective: To investigate the diagnostic value of the mannitol test in a clinical setting.Methods: All patients having a mannitol challenge test as part of their diagnostic work-up for asthma at the respiratory outpatient clinic, Hvidovre Hospital, over a 5-year period were included in the present analysis. Case history, including previous diagnoses, spirometry, exhaled nitric oxide (FENO) was obtained. The mannitol challenge was performed according to guidelines, i.e. increasing doses of mannitol (from 5 to 635 mg) until maximum dose or a 15% decline in FEV1 (PD15) was achieved (positive test defined as a PD15 < 635 mg).Results: Our cohort comprised 566 patients (210 men). Post-challenge, 247 patients were diagnosed with asthma by a specialist in respiratory medicine, of whom 138 (56%) had a positive mannitol test. A diagnosis of asthma was ruled out by the specialist in 319 individuals, of whom 18 (6%) had a positive mannitol test and 77 (24%) previous doctor-diagnosed asthma (but with no evidence of a confirmatory test). The specificity and sensitivity of the test was 94% and 56%, respectively. Female gender (p = 0.005), increasing BMI (p < 0.001), exercise-induced cough (p = 0.002), night-time respiratory symptoms (p = 0.002), low FEV1/FVC ratio (p = 0.008) and high FENO (p < 0.001) were determinants for a positive mannitol test.Conclusion: In everyday clinical work-up of patients with possible asthma, the sensitivity and specificity of the mannitol challenge test is comparable to previous controlled trials.

Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III.

The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. To identify determinants of FE NO in men and women without lung diseases. Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. Exhaled NO levels were 21.3% higher in men compared with women P<0.001. Being in the upper age quartile (60.3-67.6years), men had 19.2ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3years) P=0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6years) had 15.4ppb (14.7, 16.2), P=0.03 and 16.4ppb (15.6, 17.1), P=<0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P<0.001) and 5% higher FE NO levels in women (P=0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (P<0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, P<0.001 for both. Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50years should take into account age and sex.

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.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

PROBLEMS ASSOCIATED WITH THE DIAGNOSIS OF PROLONGED/CHRONIC COUGH IN CLINICAL SETTINGS

Many patients visit primary care clinics or local hospitals with a complaint of prolonged/chronic cough. Among the different types of chronic cough, cough variant asthma (CVA) and postinfectious cough may be the most common types, and their differential diagnosis is difficult. Some physicians tend to prescribe inhaled corticosteroids before establishing a definitive diagnosis. We retrospectively investigated useful findings for diagnosis in 77 patients with a complaint of prolonged/ chronic cough to detect meaningful findings for differential diagnosis and to identify problems associated with diagnosis in clinical practice. CVA was diagnosed in 39 patients, and postinfectious cough was diagnosed in 19. Compared with postinfectious cough, CVA was associated with significant characteristics such as "diurnal variation of symptoms," "response to inhalation of short acting β2 agonist (SABA)," and "recurrent episodes of symptoms." CVA was associated with high FeNO levels as well, and high FeNO levels were specific to CVA. However, these useful characteristics were not significant in the patients who had been prescribed ICS before visiting our hospital. Medical examination and determination of FeNO levels are useful for the differential diagnosis of prolonged/chronic cough, before treatment with ICS.

Does FeNO Predict Clinical Characteristics in Chronic Cough?

PurposeTo evaluate whether exhaled nitric oxide measurement can facilitate in the assessment of chronic cough patients based on their airway inflammatory phenotype.MethodsWe have studied consecutive patients attending a specialist cough clinic. 30 patients with high FeNO (> 30 ppb) and 20 patients with low FeNO (< 20 ppb) were recruited.ResultsThere was a significant correlation between FeNO, B-Eos and sputum eosinophil count (p < 0.001). The number of recorded coughs in 24 h and HARQ scores were significantly (p < 0.05) higher in patients with a low FeNO. In contrast to the high FeNO group (48%), the greater proportion of these patients were women (90%). LCQ scores were worse in the low FeNO group but it was not significant.ConclusionA strong relationship between FeNO, blood eosinophils and sputum eosinophils confirming phenotypic identity was observed. Whether the observed gender disparity accounts for the different cough frequency characteristics is unknown.

Perspectives on exhaled nitric oxide

The history of nitric oxide (NO) in the respiratory field dates back to the beginning of the 1990s with the pioneering study by Lars Gustafsson et al describing the presence of endogenous NO in the exhaled breath of human beings. Soon after, independent studies showed that exhaled NO concentrations (FENO) is higher in asthmatics than in normal subjects. Not all asthmatics demonstrate a high FENO, reflecting the heterogeneity of asthma. High values of FENO are associated with over-expression of corticosteroid-sensitive iNOS isoform and allergic/eosinophilic inflammation. A major feature of elevated FENO in asthma is the prediction of inhaled corticosteroid (ICS) response, and FENO more than 50 ppb in adults is a strong indicator of likely ICS sensitivity. In addition, FENO values are elevated in asthma when asthma control deteriorates, identifying patients at risk of exacerbations, and, on the other hand, FENO reductions during ICS therapy precede improvement in respiratory symptoms and lung function, suggesting that FENO is a sensitive predictor of loss of asthma control. FENO also predicts the response to biological therapy (anti-IgE, -IL-5 and -IL-13 antibodies) in severe asthma but, interestingly, FENO values fall only after treatment with anti-IL-13 and -IL-4/IL-13 receptor antibodies. The use of FENO as a Type-2 inflammatory biomarker, in constellation with other Type-2 markers, could help to determine who might benefit from ICS and biological treatment. It remains to find out more precise cut-off values of FENO to identify potential ICS responders in specific phenotypes.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.

CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling

Objectives: Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. Methods: We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). Results: The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. Conclusions: The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.

Reduced clot retraction rate and altered platelet energy production in patients with asthma

Objective: Asthma enhances the risk of pulmonary embolism. The mechanism of this phenomenon is unclear. Methods: We evaluated the kinetics of clot formation, clot retraction rate (CRR), clot volume at 40 min, the rate of lactate production (a marker of aerobic glycolysis in platelets in contracting clots), blood eosinophil count (EOS), nitric oxide in exhaled breath (FENO), and spirometry (FEV1) in 50 healthy controls and in 81 allergic asthmatics (41 subjects with steroid-naïve asthma and 40 with steroid-treated asthma). Results: Thromboelastometry revealed that only steroid-treated asthmatics had slightly activated coagulation. Compared with healthy controls, whole asthmatics demonstrated (p < 0.05) reduced CRR, higher clot volume at 40 minutes, higher FENO, decreased FEV1, elevated EOS, and augmented lactate production in retracting clots. Reduced CRR was observed also in the absence of native plasma. In whole study population (asthmatics and healthy controls), CRR positively correlated with spirometry (rS = 0.668, p = <0.001) and negatively with FENO (rS = −0.543; p < 0.001), EOS (rS = −0.367, p < 0.002), and lactate production (rS = −0.791; p < 0.001). However, in steroid-treated asthmatics, the CRR did not correlate with FENO and EOS. In all study patients lactate production negatively correlated with FEV1 and positively with FENO. Conclusion: Collectively, this data is consistent with the hypothesis that, in asthmatics, reactive nitrogen species produced in the lungs may reduce platelet contractility (and CRR) through the diminution of platelet energy production. CRR inhibition would predispose asthmatics to pulmonary embolism.

Persistently high exhaled nitric oxide and loss of lung function in controlled asthma

BackgroundsIt remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. MethodsThis was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. ResultsA FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were −0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05). ConclusionsThis study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma.

Vitamin D and markers of airway inflammation in asthma

BackgroundVitamin D plays a role in the pathogenesis of asthma as it has a potent immunomodulatory effect acting on the cells of innate immunity. In asthmatic children low vitamin D levels are associated with poor asthma control, reduced lung function, increased medication intake, and exacerbations. Little is known about vitamin D in adult asthma patients or its association with asthma control and inflammatory markers of asthma. ObjectiveTo establish the relationship between vitamin D serum levels, pulmonary function, asthma control, IgE level and exhaled FENo. MethodsThis study comprised 55 subjects (15 healthy volunteers, 40 asthmatic patient) who underwent history taking, HRCT, pulmonary function test, FENO, total serum IGE level and serum 25(OH)D3 level. ResultsVitamin D deficiency and insufficiency were observed in uncontrolled asthmatic patients. Patients with vitamin D deficiency and insufficiency had lower pulmonary function, higher serum IgE level, FENO and higher number of exacerbations in the last year. Total serum IgE level, FENO, and number of exacerbations showed a negative correlation with serum 25(OH) vitamin D. Serum 25(OH)vitamin D showed a significant positive correlation with pulmonary function in asthmatic patients. ConclusionThe lower the vitamin D level deficiency or insufficiency, the more the asthma exacerbation, the less the asthma control, the higher the serum level of IgE and higher FENO. Also low vitamin D associated with airway remodeling is presented by small airway affection and HRCT findings.

P49 Can The Asthma Control Questionnaire (acq) And/or The Blood Eosinophil Count Accurately Detect Sputum Eosinophilia?

Induced sputum differential cell counts provide important information about airway inflammation and future risk in asthma, but are not universally available. We set out to ascertain the sensitivity and specificity of the Juniper Asthma Control Questionnaire (ACQ) and/or the peripheral blood eosinophil count to detect a sputum eosinophil count >3%. Methods We performed a retrospective, cross-sectional study of 165 subjects with asthma, aged 18–80, prescribed as-required bronchodilators, long-acting β-agonists, 0–4000 mcg inhaled beclometasone diproprionate equivalent or maintenance oral steroids (0–20 mg prednisolone) from our database. Current smokers were excluded. Spirometry, FeNO at 50 ml flow, sputum induction, Asthma Control Questionnaire (ACQ) and blood eosinophils (BEos) were recorded. Induced sputum eosinophils (SEos) defined eosinophilic (EA, SEos ≥3%) and non-eosinophilic (NEA, SEos 10 transformed and groups were compared with t-tests or Mann-Whitney-U using STATA and GraphPad. Receiver operating characteristic (ROC) curves determined cut-points of ACQ and BEos that identified SEos ≥3%, and these were tested retrospectively in a second population of adults with asthma (n = 48, 40% EA, mean FEV 1 82% predicted). Results The 31% with EA had a lower FEV 1 % predicted and FEV 1 /FVC ratio, a higher FeNO, BEos and ACQ compared to NEA (Table 1). There was a significant correlation between ACQ and sputum eosinophils (Pearson r 0.32, p The optimal cut-points of ACQ and BEos identifying a SEos of 3% were an ACQ >1.57 (sensitivity 55%, specificity 78%) and BEos ≥0.22 × 10 9 /L (sensitivity 84% and specificity 68%) respectively. Individuals with both ACQ of ≥1.57 AND a BEos of ≥0.22 the sensitivity was 45% and specificity of 100% for a SEos of 3%. Testing in the second population the ACQ≥1.57 had a sensitivity 47% and specificity 86% for SEos >3% while BEos ≥0.22 had sensitivity 68% and specificity 45%. The combination of ACQ ≥1.57 AND BEos ≥0.22 had a lower sensitivity of 37% but a high specificity of 93% and could be useful to exclude rather than identify the presence of sputum eosinophilia. Conclusion Combined testing using ACQ and BEos only identifies eosinophilia in 37% and can’t replace induced sputum, but may be useful to exclude sputum eosinophilia and prospective study is warranted.