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      Predictive Value of Exhaled Nitric Oxide and Blood Eosinophil Count in the Assessment of Airway Eosinophilia in COPD

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          Fractional exhaled nitric oxide (F ENO 50) level and peripheral blood eosinophil count may serve as indicators of airway eosinophilia. The aim of this study was to estimate the diagnostic value of these markers for detecting airway eosinophilia in patients with stable chronic obstructive pulmonary disease (COPD) and those experiencing an acute exacerbation (AECOPD).

          Patients and Methods

          F ENO 50 levels, sputum and blood eosinophil counts were assessed in 53 clinically stable ex-smoker COPD patients and 67 ex-smoker COPD patients experiencing a severe exacerbation. In AECOPD, clinical variables were measured at the time of hospital admission and discharge following treatment.


          In stable COPD, blood eosinophil count but not F ENO 50 level was found to be a good predictor of airway eosinophilia (area under the receiver operating characteristic curve [ROC AUC]: ≥0.82). The sensitivity and the specificity of the test ranged between 75% and 98%, the negative predictive value (NPV) was high (>90%). In AECOPD, F ENO 50 was predictive for airway eosinophilia (ROC AUC: >0.8) with high NPV (>88%), but with lower sensitivity and specificity (64–70%). In contrast, the predictive accuracy of blood eosinophil count for airway eosinophilia in AECOPD was modest (ROC AUC: 0.54–0.63). The combined use of the two markers provided only limited additional benefit. Correlation analyses supported ROC curve findings.


          In stable COPD the peripheral blood eosinophil count, while in AECOPD the F ENO 50 level is a good surrogate marker of airway eosinophilia.

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          Most cited references 28

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          Exhaled nitric oxide in pulmonary diseases: a comprehensive review.

          The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FeNO to usual clinical guideline management including spirometry; however, significant design issues may exist. Overall, FeNO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases.
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            Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease.

            To determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.
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              A European Respiratory Society technical standard: exhaled biomarkers in lung disease.

              Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                25 August 2020
                : 15
                : 2025-2035
                [1 ]Department of Pathophysiology, National Koranyi Institute of Pulmonology , Budapest H-1121, Hungary
                [2 ]Department of Pulmonology, National Koranyi Institute of Pulmonology , Budapest H-1121, Hungary
                Author notes
                Correspondence: Balazs Antus Department of Pathophysiology, National Koranyi Institute of Pulmonology , Piheno ut 1, BudapestH-1121, HungaryTel +36 1 391 3309Fax + 36 1 200 7060 Email
                © 2020 Antus et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (

                Page count
                Figures: 3, Tables: 12, References: 40, Pages: 11
                Original Research

                Respiratory medicine

                surrogate, specificity, sensitivity, predictive, exacerbation, biomarker


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