FeNO Levels Research Articles

Astımlı Çocuklarda Serum Periostin ve Soluk Havasında Nitrik Oksit Düzeyi

Objective: Periostin is an extracellular matrix protein secreted by airway epithelium and pulmonary fibroblasts. Periostin was shown to play a role in eosinophilic airway inflammation. This study evaluated the serum periostin levels and exhaled nitric oxide (FeNO) in children with asthma.Materials and Methods: A total of 60 children with intermittent and mild persistent asthma (29 of them were allergic, and 31 of them were nonallergic) and a control group comprising 30 healthy children, ages between 7 and 17 years, were included in the study. Demographic and clinical data of the patients were recorded. The levels of FeNO and serum periostin were measured.Results: The serum periostin level was significantly correlated with age (59.08±12.79 ng/dL in 6–12 years and 46.18 ± 11.64 ng/dL in 13–18 years, p<0.001). No statistically significant difference was detected between the children with allergic and nonallergic asthma. The FeNO values were not different in the patient and the control groups. When the correlation between NO and periostin values of the only allergic patients was considered, no statistically significant difference was found (r = 0.327, p=0.077). Also, the serum periostin levels were higher in polysensitized children compared with only pollen sensitivity, but the “p” value was not at the significance level (58.2±15.1 and 44.65±8.3, p=0.065).Conclusion: In this study, serum periostin level was evaluated as a biomarker in children with asthma and it was correlated with age. No significant difference was detected in the serum periostin level of children with intermittent and mild-persistent asthma. Further studies are needed to evaluate serum periostin levels in children with moderate and severe-persistent asthma.

Persistently elevated exhaled nitric oxide fraction is associated with increased risk of exacerbation in COPD

Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently increased levels of exhaled nitric oxide (FeNO) during follow-up can identify a group of COPD patients at higher risk of AECOPD.To test this hypothesis, we measured FeNO levels (HypAir FeNO®, Medisoft; Sorinnes, Belgium) prospectively in 226 clinically stable COPD outpatients at recruitment and during follow-up (at 6 and 12 months). Patients were stratified according to the number of visits with FeNO ≥20 ppb.FeNO was <20 ppb in all three visits in 44.2% of patients, 29.6% in visit 1 and 26.1% in visit 2 or 3.These three groups suffered progressively higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively, p<0.001). After adjusting for potential confounding variables (log-rank test), the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049-2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter in these patients. Finally, there was no relationship between FeNO levels and circulating eosinophils.Persistent FeNO levels ≥20 ppb in clinically stable COPD outpatients are associated with a significantly higher risk of AECOPD.

How Could We Influence Systemic Inflammation in Allergic Rhinitis? The Role of H1 Antihistamines.

The aim of the study was the analysis of adhesion molecules' profile (ICAM-1, VCAM-1, and E-selectin) in patients with allergic rhinitis and the influence of H1 antihistamines on those markers. Seventy-nine patients with persistent allergic rhinitis (PAR) and 30 healthy volunteers were included in the study. The patients with PAR were treated with desloratadine 5 mg/day or levocetirizine 5 mg/day for 4 weeks. The clinical (rhinitis symptoms and total symptoms score (TSS), type of sensitization) and biological evaluation (total IgE, eosinophils, ICAM-1, VCAM-1, and E-selectin) as well as fractionate nitric oxide in exhaled air (FeNO) measurement was performed before and after treatment. The plasmatic levels of ICAM-1, VCAM-1, total IgE, and eosinophils and FeNO were significantly increased in patients with PAR compared to healthy volunteers. H1 antihistamines significantly improved TSS, with no differences between the investigated drugs. There was a significant decrease of eosinophils, total IgE, and FeNO after treatment. H1 antihistamines significantly decreased the plasmatic levels of ICAM-1 and E-selectin but not VCAM-1 compared to basal values. There is no difference between levocetirizine and desloratadine in the reduction of CAMs. A systemic inflammation characterized by increased levels of CAMs is present in patients with PAR. H1 antihistamines improve symptoms and reduce CAMs and FeNO levels after 1 month of treatment. H1 antihistamines might reduce the systemic inflammation which could be responsible to asthma occurrence in patients with PAR.

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.

Correlation of Fractional Exhaled Nitric Oxide Level With Severity of COPD

SESSION TITLE: COPD 3 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Nitric oxide (NO) is present in virtually all mammalian organ systems and is produced by the human lung. It is present in the exhaled breath of all humans. NO is recognized to play key roles in virtually all aspects of lung biology and has been implicated in the pathophysiology of lung diseases, including asthma. There is increasing evidence that endogenous nitric NO plays a key role in the physiological regulation of airways and is implicated in the pathophysiology of airway disease. The exact role of exhaled nitric oxide measurements in patients with established COPD remains to be defined. The airway inflammatory cell infiltrate may be mixed, including eosinophilic inflammation. We now seek to determine the association of fractional exhaled nitric oxide with the different severity of COPD patient based on GOLD classification. We believe that the correlation of of fractional exhaled nitric oxide (FeNO) in COPD severity will improve the morbidity and mortality rate of COPD patient. METHODS: This is a cross sectional, analytic study design. This was conducted at the Philippine Heart Center, Pulmonary and Critical care Medicine between April 2016 to December, 2016. All patient aged > 40 year old and above diagnosed with COPD through spirometry, including chronic bronchitis and emphysema. All patients who were referred to pulmonary laboratory with spirometry post bronchodilator FEV1/ FVC of < 70% which was confirm the diagnosis of COPD were included in the study. Clinical and demographic data were obtained. Spirometry value were collected, according to guidelines of Philippine College of Chest Physician, American Thoracic Society, European Respiratoy Society. Baseline exhaled nitric oxide was measured using Bedfont Nobreath device to which training of the use of the device were conducted by a study staff according to the manual operating procedure of the device. RESULTS: The clinical data and the COPD patients with different severity are summarized in table 1 which showed no significant difference between the 4 groups except for the two lung parameters (FEV1/FVC and FEV1) which showed significant difference. FeNO levels in exhaled air in patients with COPD Gold D (38.5 +7.7ppb) were significantly higher than in gold A (23.4 + 1.1ppb), gold B (24 +0.6 ppb), and gold C (28 +1.1ppb) ( p = <0.0001). There was weak negative correlation (r 0.21, p 0.231) between FEV1 and exhaled NO levels. CONCLUSIONS: FeNO level determination and may be use as a practical and noninvasive procedure to monitor the disease activity and progression in patient with COPD. Future study should be done to determine its response in different therapy for COPD which may with the result like aminophylline, vitamin D, etc. CLINICAL IMPLICATIONS: FeNo level may be used as a mean for monitoring disease activity of the respiratory tract. It is portable and can be done at home or in the clinic. It’s place in various disease in the lung is currently under intensive evaluation by many researchers. The finding of increasing FeNo level in as the severity of the COPD increases, is also seen in agreement with the observation done by Robbins et al. Hence, this may be used for monitoring disease activity or progression in COPD and may also be use in response to the treatment. DISCLOSURE: The following authors have nothing to disclose: Johnson See, Rommel Bayot No Product/Research Disclosure Information

The effect of monrustet on the exhalation of nitric oxide and inflammatory cytokines in patients with asthma combined with OSAHS

Objective:To study the effect of monrustet on fractional exhaled nitric oxide and inflammatory cytokines in the elderly with bronchial asthma combined obstructive sleep apnea hypopnea syndrome.Method:150 cases diagnosed as asthma were enrolled in this study. The patients were divided into bronchial asthma combined with OSAHS (n=72)and bronchial asthma (n=78). According to the different treatment methods , patients were divided into observation group and control group. Two groups were given common treatment with inhaled corticosteroids, and the observation group was taken orally montrast 10mg/night additionally. The fractional exhaled nitric oxide was detected before and after treatment. Serum were collected for detection of tumor necrosis factor alpha (TNR-α), Creactive protein (CRP) and interleukin 6 (IL-6), according to the sleep monitoring results, the sleep apnea low ventilation index (AHI) was calculated, and the changes of FeNO level,CRP,TNR-α,IL-6 and AHI were analyzed in the two groups.Result:Before treatment, the gender, age, degree of disease, FeNO level,TNR-α, CRP,IL-6 and AHI differences were not statistically significant in the two groups (P>0.05).After treatment, both groups of FeNO, TNR-α,CRP,IL-6 and AHI decreased before treatment (P < 0.05).The observation group was lower than the control group, and the difference was statistically significant (FeNO level, AHIP< 0.01,TNR-α, CRP,IL-6 P< 0.05).Conclusion::Montelukast can reduce the FeNO level, the expression of TNR-α, CRP, and IL-6 of patients of bronchial asthma combined with OSAHS. Further improvement of the patient's condition, and provide reference value for the clinical medicine of patients with asthma.

The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis

IntroductionBronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases. ObjectivesWe sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. MethodsWe evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. ResultsWe enrolled 40 subjects (21men, mean age 63.5yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic-eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL-8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL-13. Sputum IL-8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r=0.799), the extent of bronchiectasis in HRCT (r=0.765) and post-bronchodilator FEV1 (r=−0.416). Sputum IL-13 levels correlated with sputum eosinophils (r=0.656) and bronchodilator reversibility (r=0.441). Neutrophilic bronchiectasis exhibited comparable IL-8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL-13 levels compared to asthma. ConclusionsSputum cell counts and IL-8 and IL-13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non-invasively assessing inflammation in non-cystic fibrosis bronchiectasis.

Exhaled nitric oxide atopy, and spirometry in asthma and rhinitis patients in India.

Asthma is a chronic airway inflammatory disorder. Nitric oxide (NO) is non-invasively measured in exhaled breath (FeNO). The aim of the study was to investigate the anthropometric and physiologic factors that influence FeNO measurements. Also, to evaluate FeNO correlation with spirometry and inflammatory markers in asthma and rhinitis. The study was a prospective analysis of asthma (BA) and rhinitis (AR) in patients enrolled from outpatient clinics between 2011 and 2015. Healthy controls (HC) were enrolled from the community. All subjects underwent baseline spirometry with reversibility, FeNO measurements, skin prick tests, and blood sampling for absolute eosinophil counts and serum total IgE levels. Of 528 enrolled participants, 215 were BA, 248 were BA-AR and 65 were HC. The mean FeNO was higher in atopic versus nonatopic subjects (34.14 vs. 25.99; p < 0.001); asthmatics versus non-asthmatics (30.46 vs. 12.91; p < 0.001), and in participants with BA-AR, compared to those without BA-AR (32.56 vs. 30.46; p < 0.001). The odds ratio for FeNO in the study population showed a significant positive association with male gender, absolute eosinophil count (AEC), breathlessness, duration of symptoms, family history and atopy. In examining the diagnostic accuracy of FeNO for asthma, the AUC for FeNO value is 0.833 (95% confidence interval [CI], 0.717-0.901), with cut-off levels to screen for asthma being 19.45 at 71.2% sensitivity and 81.8% specificity (p < 0.001). The Positive Predictive Value 96.84% (95% CI: 94.43-98.23) and Negative Predictive Value 30% (95% CI: 23.78-37.05) for asthma prediction with FeNO. The study highlights the importance of estimation of anthropometric parameters and dyspnea assessment in the evaluation of FeNO levels. Also, the presence of atopy may influence the results in the interpretation of FeNO readings. Moreover, the study have demonstrated that spirometry and FeNO have no significant correlation, which further lays emphasis on them as being different physiological parameters of asthma. &nbsp.

The effects of mycoplasma pneumoniae infection on the exhaled nitric oxide level and lung function in asthma children

Objective To investigate the effects of mycoplasma pneumoniae(MP)infection on the exhaled nitric oxide level and lung function in asthmatic children, analyze the correlation between exhaled nitric oxide level and lung function and to provide reference for the treatment and monitoring of asthmatic children. Methods Sixty-eight children aged from 5 to 13 years old with mild or moderate asthma during June 2011 to January 2013 were collected.MP-IgG antibody, MP-IgM antibody, MP-DNA, total serum IgE, FeNO measurement and spirometry were examined on the next day morning.They were divided into two groups according to the pathogen: ashtma with MP group and ashtma without MP group.Then the levels of nitric oxide level and lung function indicators between the two groups were analyzed. Results The FeNO level in ashtma with MP group was significantly higher(P 0.05), but differnces were found in MEF75 and PEF(P<0.05). No correlation was found between FeNO levels and lung function parameters(FVC, FEV1, FEV1/Vcmax, MEF50, MEF25, MEF75 and PEF). Conclusion In asthma children with MP infection, the FeNO level was significantly increased and no correlation was found between FeNO levels and lung function. Key words: Asthma; Mycoplasma pneumoniae; Exhaled nitric oxide; Lung function

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.

Analysis of bronchial biopsies in chronic cough

BackgroundChronic cough is commonly associated with asthma, gastro-oesophageal reflux disease and postnasal drip, but in a significant proportion, no associated cause can be found. We determined whether examination of bronchial biopsies would be useful in determining the cause associated with chronic cough. Methods100 consecutive patients referred to a specialist cough clinic underwent a systematic assessment including a fiberoptic bronchoscopy for bronchial biopsies. ResultsIn 38 patients, treatment of associated causes led to amelioration of cough (‘explained’) and in 62, there was no association or improvement (‘idiopathic’). The latter group had a longer duration of cough, a lower FeNO levels and a more sensitive capsaicin cough response, with an increase in basement membrane thickness with no differences in goblet cell hyperplasia and seromucinous hyperplasia, and in lymphocyte, neutrophil and eosinophil counts. The duration of cough was inversely correlated with the degree of neutrophil infiltration. ConclusionWe conclude that pathological examination of bronchial biopsies is unlikely to be useful in the diagnosis of chronic cough in non-smokers.

Exhaled and nasal nitric oxide in relation to lung function, blood cell counts and disease characteristics in cystic fibrosis

Background. Patients with cystic fibrosis (CF) have similar or lower exhaled nitric oxide (FeNO) and lower nasal nitric oxide (nNO) levels than controls. There are divergent results on alveolar NO (CalvNO) concentrations in relation to CF. There are inconsistent results on correlation between different nitric oxide parameters and lung function and inflammation in CF. Aim. To compare FeNO, CalvNO and nNO levels between subjects with CF, asthma and healthy controls and to study whether these parameters are related to lung function, blood cell counts or clinical characteristics in CF patients. Material and methods. Measurements of FeNO at multiple exhalation flow rates, nNO and spirometry were done in 38 patients (18 adults) with CF. Blood cell counts and CF clinical characteristics were recorded. Thirty-eight healthy controls and 38 asthma patients, gender- and age-matched, were included as reference groups. Results. FeNO levels were lower in CF patients (7.2 [4.7–11.2] ppb) than in healthy controls (11.4 [8.3–14.6] ppb) and asthma patients (14.7 [8.7–24.7] ppb) (both p < 0.005). These differences were consistent in adults. No difference in CalvNO was seen between the groups. nNO levels in CF patients (319 [193–447] ppb) were lower than in healthy controls (797 [664–984] ppb) and asthma patients (780 [619–961] ppb) (both p < 0.001). FeNO positively related to FEV1 (rho = 0.51, p = 0.001) in CF patients and this was consistent in both adults and children. A negative correlation was found between FeNO and blood neutrophil counts (rho = −0.37, p = 0.03) in CF patients. Conclusion. CF patients have lower FeNO and nNO and similar CalvNO levels as healthy controls and asthma patients. Lower FeNO related to lower lung function in both adults and children with CF. Furthermore, in CF, lower FeNO also related to higher blood neutrophil counts.

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide

BackgroundWe previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. MethodsSteroid-naive bronchial asthma patients were classified into four phenotypes, including “Low inflammation” (35 patients), “Eosinophilic type” (58 patients), “Neutrophilic type” (15 patients), and “Mixed type” (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. ResultsThe median E/I LF value was highest in the “Mixed type” and lowest in the “Low inflammation” group. FeNO differentiated between the “Low inflammation” and “Eosinophilic type” groups, “Low inflammation” and “Neutrophilic type” groups, and “Neutrophilic type” and “Mixed type” (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the “Low inflammation” and “Eosinophilic type” groups (p = 0.006). E/I LF could distinguish the “Mixed type” group from the “Low inflammation” and “Eosinophilic type” groups (p = 0.002). ConclusionsA combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma.

Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea: A meta-analysis.

Exhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis. A systematic search was performed in the PubMed, EMBASE, the Cochrane Library, and MEDLINE databases to collect relevant studies published from 1996 to 2016. Eligible studies that reported eNO levels in patients with OSA were included. STATA (version 12.0) was used for data analysis. Two hundred eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 for the maximum airway wall flux of nitric oxide [J'awNO]). The FENO levels were significantly higher in patients with OSA compared with that in the control groups (6.32 ppb, 95% confidence interval [CI] 4.46-8.33, P < 0.001). Furthermore, FENO was significantly increased (4.00 ppb, 95% CI 1.74-6.27, P = 0.001) after overnight sleep in patients with OSA, but not in healthy controls. Additionally, long-term continuous positive airway pressure (CPAP) therapy reduced FENO levels (-5.82 ppb, 95% CI -9.6 to -2.01, P < 0.001). However, the CANO (-0.01 ppb, 95% CI -1.66 to 1.64, P = 0.989) and J'awNO levels (220.32 pl/s, 95% CI -49.31 to 489.94, P = 0.109) were not significantly different between the OSA groups and non-OSA groups. The results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy. J'awNO and CANO levels were not significantly different between the OSA groups and control groups.

Valor pronóstico del pH en el condensado de aire exhalado y de la fracción exhalada de óxido nítrico en la enfermedad pulmonar intersticial asociada a esclerosis sistémica

IntroductionInterstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. MethodsFraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. ResultsNo differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). ConclusionsEB and EBC could help to detect patients likely to present a deterioration on lung function during follow up.

Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients

ABSTRACTObjectives: The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. Methods: Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. Results: Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. Conclusions: Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease

IntroductionInterstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. MethodsFraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. ResultsNo differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4 years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (log Rank P=0.03 and P<0.01, respectively). ConclusionsEB and EBC could help to detect patients likely to present a deterioration on lung function during follow up.

Exhaled nitric oxide in a middle-aged Icelandic population cohort

The prevalence of atopy and asthma is relatively low in Iceland. The purpose of this study was to describe exhaled nitric oxide (FeNO) levels in the general population in correlation with demographic characteristics, smoking status, asthma, rhinitis, atopic status and lung function tests. Altogether 403 subjects, from the European Community Respiratory Health Survey (ECRHS) III who answered the main questionnaire and were checked by FeNO measurements, lung function testing, skin prick testing and measurement of total IgE and specific IgE were included. The geometric mean (95% CI) of FeNO was 16.2 ppb (15.2–17.1) and the prevalence of higher FeNO (⩾25 ppb) was 19.5% in the random sample. Subjects with higher FeNO levels were less likely to be current smokers and more likely to have asthma and rhinitis. Having higher FeNO values was also associated with higher total IgE, having specific IgE to at least one allergen and being skin prick test positive. Current smokers had significantly lower levels of FeNO, geometric mean (95% CI) 9.6 ppb (8.4–11.0), than ex-smokers 18.2 ppb (16.6–20.0) and never smokers 17.3 ppb (16.1–18.5). In multivariable models, having asthma (OR (95% CI) 2.10 (1.20–3.67)), having a specific IgE (OR 2.30 (1.25–4.23)) and being skin prick test positive (OR 2.06 (1.18–3.60)) were independently positively associated with a higher FeNO (⩾25) whereas current smoking was independently negatively associated with a higher FeNO (OR 0.19 (0.06–0.63)). Higher levels of FeNO (⩾25 ppb) were found in one out of five Icelanders; FeNO was positively associated with asthma and allergy and negatively with smoking.

Aging with higher fractional exhaled nitric oxide levels are associated with increased urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine concentrations in elder females.

Indoor air pollutants from environmental tobacco smoke and cooking fume can induce oxidative stress and inflammatory response, which generate oxidatively damaged DNA in human body. Among 2224 adults, levels of FENO and urinary 8-oxodG were measured using a nano coulomb nitric oxide analyzer and a high performance liquid chromatography system with electrochemical detector, respectively. Association between aging with higher FENO levels and urinary 8-oxodG levels were analyzed using multiple linear regression analysis. Nonsmoking women aged 64years and over, with higher FENO (≥ 25 part per billion) and self-catering but without passive smoking had a higher risk of increased urinary 8-oxodG (△% of urinary 8-oxodG: 81.3%, 95% CI: 27.4-158.0%) levels, particularly these elderly women with using liquefied petroleum gas for cooking, had a higher risk for increased urinary 8-oxodG levels (△% of urinary 8-oxodG: 100.2%, 95% CI: 95% CI: 35.3-196.3%), compared with those aged less than 64years, with lower FENO (< 25 part per billion). Cooking activity aggravated aging-related the aging-induced in urinary 8-oxodG excretion among nonsmoking women aged 64years and over but without passive smoking.

Study of the correlations between fractional exhaled nitric oxide in exhaled breath and atopic status, blood eosinophils, FCER2 mutation, and asthma control in Vietnamese children.

IntroductionFractional exhaled nitric oxide (FENO) is a biomarker of airway inflammation in asthma. The measurement of FENO is utilized to assist in the diagnosis and treatment of children with asthma, especially for those treated with inhaled corticosteroids.ObjectivesThe aims of this study were to evaluate the correlations between FENO and atopic status, blood eosinophil levels, FCER2 mutation, and asthma control in Vietnamese children.Subjects and methodsThis was a prospective and descriptive study approved by the local Ethical Board. All children with uncontrolled asthma, seen in the National Hospital of Pediatrics (Hanoi, Vietnam), were included. Exhaled breath FENO, blood eosinophils, skin prick test, total IgE, asthma control test (ACT), and FCER2 gene polymorphism were performed at inclusion. They were followed up at 3 months to evaluate clinical status, FENO levels, and ACT.ResultsForty-two children with uncontrolled asthma with a mean age of 10±3 years (6–16 years) were included. The male/female ratio was 2.5/1. The mean FENO levels were 26±25 ppb. FENO was significantly higher in patients with a positive skin prick test for respiratory allergens (P<0.05). FENO was significantly correlated with blood eosinophil levels (r=0.5217; P=0.0004). Five of the 32 subjects (15.6%) had a mutation of FCER2 gene (rs28364072 SNP). In this group, the levels of FENO were highest (37±10 ppb; P<0.05). The levels of FENO were significantly decreased after 3 months of treatment (17±8 ppb vs 26±25 ppb; P<0.05). Significant correlations between inhaled corticosteroid doses and FENO levels occurred at 1 and 3 months (r=0.415, P=0.007; r=0.396, P=0.010; respectively). There were no correlations between FENO levels, ACT, and daily use of salbutamol. After 3 months, asthma remained uncontrolled in 22.2% of children.ConclusionThe measurement of FENO levels is a useful and feasible tool to predict clinical, biological, and asthma control in Vietnamese children.