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Exhaled nitric oxide in stable chronic obstructive pulmonary disease  [cached]
Beg Mohammed,Alzoghaibi Mohammad,Abba Abdullah,Habib Syed
Annals of Thoracic Medicine , 2009,
Abstract: Study Objective : The objective of the study was to test the hypothesis that fraction of exhaled nitric oxide (FENO) is elevated in nonsmoking subjects with stable chronic obstructive pulmonary disease (COPD) and compare it with the results in patients with asthma and a control population. Design : Cross-sectional study. Materials and Methods : Pulmonology Clinic at a University Hospital. Twenty five control subjects, 25 steroid naοve asthmatics and 14 COPD patients were studied. All the patients were nonsmokers and stable at the time of the study. All subjects completed a questionnaire and underwent spirometry. Exhaled nitric oxide was measured online by chemiluminescence, using single-breath technique. Results : All the study subjects were males. Subjects with stable COPD had significantly higher values of FENO than controls (56.54±28.01 vs 22.00±6.69; P =0.0001) but lower than the subjects with asthma (56.54±28.01 vs 84.78±39.32 P = 0.0285).The FENO values in COPD subjects were inversely related to the FEV 1 /FVC ratio. There was a significant overlap between the FENO values in COPD and the control subjects. Conclusion : There is a significant elevation in FENO in patients with stable COPD, but the elevation is less than in asthmatic subjects. Its value in clinical practice may be limited by the significant overlap with control subjects.
Exhaled nitric oxide in diagnosis and management of respiratory diseases  [cached]
Abba Abdullah
Annals of Thoracic Medicine , 2009,
Abstract: The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO) in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.
Exhaled nitric oxide and airway hyperresponsiveness in workers: a preliminary study in lifeguards
Valérie Demange, Abraham Bohadana, Nicole Massin, Pascal Wild
BMC Pulmonary Medicine , 2009, DOI: 10.1186/1471-2466-9-53
Abstract: 39 lifeguards at six indoor pools were given a respiratory health questionnaire, FENO measurements, spirometry, and a methacholine bronchial challenge (MBC) test. Subjects were labeled MBC+ if the forced expiratory volume (FEV1) fell by 20% or more. The normalized linear dose-response slope (NDRS) was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. The relation between MBC and FENO was assessed using logistic regression adjusting on confounding factors. The association between NDRS and log-transformed values of FENO was tested in a multiple linear regression model.The prevalence of lifeguards MBC+ was 37.5%. In reactors, the median FENO was 18.9 ppb (90% of the predicted value) vs. 12.5 ppb (73% predicted) in non-reactors. FENO values ≥ 60% of predicted values were 80% sensitive and 42% specific to identify subjects MBC+. In the logistic regression model no other factor had an effect on MBC after adjusting for FENO. In the linear regression model, NDRS was significantly predicted by log FENO.In lifeguards working in indoor swimming pools, elevated FENO levels are associated with increased airway responsiveness.Airway inflammation is the hallmark of asthma[1]. Exposure to a variety of agents in the workplace can cause airway inflammation and occupational asthma. Thus, investigating airway inflammation from work exposure is important to elaborate preventive strategies.Airway hyperresponsiveness (AHR) can be considered as a surrogate marker of airway inflammation and is recognized as another characteristic finding of asthma[1]. In the general population, AHR is a risk factor for an accelerated decline in forced expiratory volume in one second (FEV1) and for the development of asthma and chronic obstructive pulmonary disease[2]. In working populations, AHR is an important determinant for the development of symptoms[3].Fractional concentration of exhaled nitric oxide (FENO) is another indirect marker of airway inflammation. FEN
Exhaled nitric oxide and clinical phenotypes of childhood asthma
Bruno Mahut, Séverine Peyrard, Christophe Delclaux
Respiratory Research , 2011, DOI: 10.1186/1465-9921-12-65
Abstract: We performed multivariate (exhaled NO as dependent variable) and k-means cluster analyses in a population of 169 asthmatic children (age ± SD: 10.5 ± 2.6 years) recruited in a monocenter cohort that was characterized in a cross-sectional design using 28 parameters describing potentially different asthma domains: atopy, environment (tobacco), control, exacerbations, treatment (inhaled corticosteroid and long-acting bronchodilator agonist), and lung function (airway architecture and tone).Two subject-related characteristics (height and atopy) and two disease-related characteristics (bronchodilator response and ICS dose > 200 μg/d) explained 36% of exhaled NO variance. Nine domains were isolated using principal component analysis. Four clusters were further identified: cluster 1 (47%): boys, unexposed to tobacco, with well-controlled asthma; cluster 2 (26%): girls, unexposed to tobacco, with well-controlled asthma; cluster 3 (6%): girls or boys, unexposed to tobacco, with uncontrolled asthma associated with increased airway tone, and cluster 4 (21%): girls or boys, exposed to parental smoking, with small airway to lung size ratio and uncontrolled asthma. FENO0.05 was not different in these four clusters.In conclusion, FENO0.05 is independently linked to two pathophysiological characteristics of asthma (ICS-dependant inflammation and bronchomotor tone) but does not help to identify a clinically relevant phenotype of asthmatic children.Numerous studies have evaluated exhaled nitric oxide (NO) correlates in asthma. For instance, exhaled NO fraction (FENO) has been linked to atopy rather than to asthma per se which could be due to the underlying relationship between FENO and eosinophilic inflammation of airways[1]. We and others have emphasized that FENO is also linked to other intrinsic dimensions of asthma such as airway reactivity/tone [2,3] and remodeling of airways[1,4]. All these relationships may explain the complex and still debated relationship between exhaled NO
Are exhaled nitric oxide measurements using the portable NIOX MINO repeatable?
Anna Selby, Bernie Clayton, Jane Grundy, Katy Pike, Kirsty Drew, Abid Raza, Ramesh Kurukulaaratchy, S Hasan Arshad, Graham Roberts
Respiratory Research , 2010, DOI: 10.1186/1465-9921-11-43
Abstract: Paired exhaled nitric oxide readings were obtained from 494 teenagers, aged 16-18 years, enrolled in an unselected birth cohort and 65 young people, aged 6-17 years, with asthma enrolled in an interventional asthma management study.The birth cohort participants showed a high degree of variability between first and second exhaled nitric oxide readings (mean intra-participant difference 1.37 ppb, 95% limits of agreement -7.61 to 10.34 ppb), although there was very close agreement when values were categorised as low, normal, intermediate or high (kappa = 0.907, p < 0.001). Similar findings were seen in subgroup analyses by sex, lung function and asthma status. Similar findings were seen in the interventional study participants.The reproducibility of exhaled nitric oxide is poor for absolute values but acceptable when values are categorised as low, normal, intermediate or high in children and teenagers. One measurement is therefore sufficient when using categorical exhaled nitric oxide values to direct asthma management but a mean of at least two measurements is required for absolute values.Asthma is a chronic inflammatory disorder of the airways associated with airway hyperresponsiveness and recurrent episodes of reversible airflow limitation that are accompanied by wheeze, shortness of breath, chest tightness and cough [1]. It is the most common chronic condition of childhood [2] affecting approximately 20% of school-aged children in the United Kingdom [3]. Decisions regarding asthma management are currently based on symptoms and conventional lung function tests. Exhaled nitric oxide (FeNO) has recently emerged as a potentially useful tool in the assessment of patients with asthma [4]. Exhaled nitric oxide measurements correlate well with measures of airway inflammation, including sputum levels of eosinophils [5], airway eosinophilia in bronchial biopsies [6] and allergen exposure [7]. Measurements can be made within minutes, even in young school children. Furthermore
Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics
Sushma Komakula, Sumita Khatri, Joel Mermis, Samira Savill, Shireen Haque, Mauricio Rojas, LouAnn Brown, Gerald W Teague, Fernando Holguin
Respiratory Research , 2007, DOI: 10.1186/1465-9921-8-32
Abstract: Observational study of the association of BMI, leptin, and adiponectin with exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients with moderate to severe persistent asthma during baseline conditions and 47 controls. Measurements included plasma levels of leptin, adiponectin, exhaled breath condensates for 8-isoprostanes, exhaled NO, pulmonary function tests, and questionnaires regarding asthma severity and control.In asthmatics, BMI and the ratio of leptin to adiponectin were respectively associated with reduced levels of exhaled NO (β = -0.04 [95% C.I. -0.07, -0.1], p < 0.003) and (β = -0.0018 [95% C.I. -0.003, -0.00034], p = 0.01) after adjusting for confounders. Also, BMI was associated with increased levels of exhaled 8-isoprostanes (β = 0.30 [95% C.I. 0.003, 0.6], p = 0.03) after adjusting for confounders. In contrast, we did not observe these associations in the control group of healthy non-asthmatics with a similar weight distribution.In adults with stable moderate to severe persistent asthma, but not in controls, BMI and the plasma ratio of leptin/adiponectin is associated with reduced exhaled NO. Also, BMI is associated with increased exhaled 8-isoprostanes. These results suggest that BMI in asthmatics may increase airway oxidative stress and could explain the BMI-related reductions in exhaled NO.In recent years, there has been a parallel increase in the prevalence of both asthma and obesity. This has led to the speculation that increased BMI is a risk factor for asthma [1]. Several cross sectional studies have shown higher odds for developing asthma among obese children and adults [2-5]; however, these studies were limited by their inability to address the direction of this association, and were susceptible to confounding factors [6]. Prospective studies have shown that increasing BMI antedates the diagnosis of asthma incidence and bronchial hyperresponsiveness. This temporal pattern supports the idea that obesity may actually cau
Elevated Exhaled Nitric Oxide in Allergen-Provoked Asthma Is Associated with Airway Epithelial iNOS  [PDF]
Abraham B. Roos, Michiko Mori, Reidar Gr?nneberg, Christina ?sterlund, Hans-Erik Claesson, Jan Wahlstr?m, Johan Grunewald, Anders Eklund, Jonas S. Erjef?lt, Jon O. Lundberg, Magnus Nord
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090018
Abstract: Background Fractional exhaled nitric oxide is elevated in allergen-provoked asthma. The cellular and molecular source of the elevated fractional exhaled nitric oxide is, however, uncertain. Objective To investigate whether fractional exhaled nitric oxide is associated with increased airway epithelial inducible nitric oxide synthase (iNOS) in allergen-provoked asthma. Methods Fractional exhaled nitric oxide was measured in healthy controls (n = 14) and allergic asthmatics (n = 12), before and after bronchial provocation to birch pollen out of season. Bronchoscopy was performed before and 24 hours after allergen provocation. Bronchial biopsies and brush biopsies were processed for nitric oxide synthase activity staining with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), iNOS immunostaining, or gene expression analysis of iNOS by real-time PCR. NADPH-d and iNOS staining were quantified using automated morphometric analysis. Results Fractional exhaled nitric oxide and expression of iNOS mRNA were significantly higher in un-provoked asthmatics, compared to healthy controls. Allergic asthmatics exhibited a significant elevation of fractional exhaled nitric oxide after allergen provocation, as well as an accumulation of airway eosinophils. Moreover, nitric oxide synthase activity and expression of iNOS was significantly increased in the bronchial epithelium of asthmatics following allergen provocation. Fractional exhaled nitric oxide correlated with eosinophils and iNOS expression. Conclusion Higher fractional exhaled nitric oxide concentration among asthmatics is associated with elevated iNOS mRNA in the bronchial epithelium. Furthermore, our data demonstrates for the first time increased expression and activity of iNOS in the bronchial epithelium after allergen provocation, and thus provide a mechanistic explanation for elevated fractional exhaled nitric oxide in allergen-provoked asthma.
Non-asthmatic patients show increased exhaled nitric oxide concentrations
Saraiva-Romanholo, Beatriz M.;Machado, Fabio S.;Almeida, Francine M.;Nunes, Maria do Patrocínio T.;Martins, Milton A.;Vieira, Joaquim E.;
Clinics , 2009, DOI: 10.1590/S1807-59322009000100002
Abstract: objective: evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm. introduction: intraoperative bronchospasm remains a challenging event during anesthesia. previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation. methods: a total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. bronchospasm was registered on 863 forms. from those, three groups were identified: 9 non-asthmatic patients (bronchospasm group), 12 asthmatics (asthma group) and 10 subjects with no previous airway disease or symptoms (control group). all subjects were submitted to exhaled nitric oxide measurements (parts/billion), spirometry and the induced sputum test. the data was compared by anova followed by the tukey test and kruskal-wallis followed by dunn's test. results: the normal lung function test results for the bronchospasm group were different from those of the asthma group (p <0.05). the median percentage of eosinophils in induced sputum was higher for the asthma [2.46 (0.45-6.83)] compared with either the bronchospasm [0.55 (0-1.26)] or the control group [0.0 (0)] (p <0.05); exhaled nitric oxide followed a similar pattern for the asthma [81.55 (57.6-86.85)], bronchospasm [46.2 (42.0 -62.6] and control group [18.7 (16.0-24.7)] (p< 0.05). conclusions: non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.
Airway biomarkers of the oxidant burden in asthma and chronic obstructive pulmonary disease: Current and future perspectives  [cached]
Noora Louhelainen,Marjukka Myllärniemi,Irfan Rahman,Vuokko L Kinnula
International Journal of COPD , 2008,
Abstract: Noora Louhelainen1, Marjukka Myll rniemi1, Irfan Rahman2, Vuokko L Kinnula11Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; 2Department of Environmental Medicine and the Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, New York, USAAbstract: The pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been claimed to be attributable to increased systemic and local oxidative stress. Detection of the oxidant burden and evaluation of their progression and phenotypes by oxidant biomarkers have proved challenging and difficult. A large number of asthmatics are cigarette smokers and smoke itself contains oxidants complicating further the use of oxidant biomarkers. One of the most widely used oxidant markers in asthma is exhaled nitric oxide (NO), which plays an important role in the pathogenesis of asthma and disease monitoring. Another oxidant marker that has been widely investigated in COPD is 8-isoprostane, but it is probably not capable of differentiating asthma from COPD, or even sensitive in the early assessment of these diseases. None of the current biomarkers have been shown to be better than exhaled NO in asthma. There is a need to identify new biomarkers for obstructive airway diseases, especially their differential diagnosis. A comprehensive evaluation of oxidant markers and their combinations will be presented in this review. In brief, it seems that additional analyses utilizing powerful tools such as genomics, metabolomics, lipidomics, and proteomics will be required to improve the specificity and sensitivity of the next generation of biomarkers.Keywords: sputum, condensate, smoking, nitric oxide, 8-isoprostane, biomarker
Reference values for exhaled nitric oxide (reveno) study
Mario Olivieri, Giorgio Talamini, Massimo Corradi, Luigi Perbellini, Antonio Mutti, Claudio Tantucci, Mario Malerba
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-94
Abstract: The aim of this study was to establish adult FENO reference values according to the international guidelines.FENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently.The main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women.We propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.The presence of nitric oxide (NO) in exhaled air was first described in 1991 by Gustafsson et al.[1], and this was soon followed by a number of publications reporting high fractional concentrations of orally exhaled NO (FENO) in subjects with various pulmonary diseases [2]. FENO is generally measured on line by having the subject blow directly into the analyser and obtaining immediate results [3], but breath can also be collected remotely into inert bags and analysed subsequently (off line) [3].Although the pathophysiological meaning is still unclear [4], it has been demonstrated that NO levels in exhaled air are higher in asthmatics than in healthy subjects, increase during spontaneous or induced asthma exacerbations, and decrease after anti-inflammatory treatment [5].Many studies have clearly demonstrated that a number of factors can affect FENO values, and so the European Respiratory Society (ERS) and American Thoracic Society (ATS) established particular recommendations for exhaled and nasal NO measurements in 2005 [6] in order to allow the comparison of data from different research centres.Clinicians and researchers seeking to apply FENO measurements in everyday practice are obviously interested in knowing what are normal FENO values in healthy subjects, but very few attempts
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