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      Relationship between Fractional Exhaled Nitric Oxide Level and Efficacy of Inhaled Corticosteroid in Asthma-COPD Overlap Syndrome Patients with Different Disease Severity

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          Abstract

          This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO 2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO 2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.

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          Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.

          The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments.
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            Current evidence and future research needs for FeNO measurement in respiratory diseases.

            Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.
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              Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children.

              Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. eNO was significantly correlated with peripheral blood eosinophils (r =.51, P <.0001), IgE (r =.48, P <.0001), and serum eosinophil cationic protein (r =.31, P =.0003) but not with urinary leukotriene E4 (r =.16, P =.08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r =.45, P <.0001). eNO did not correlate with FEV1% predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P =.032), bronchodilator response (r =.20, P =.023), and FEV1 PC20 methacholine (r = -.31, P =.0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of.52 (eosinophils [P <.0001], IgE [P =.0023], age [P <.0001], months of inhaled corticosteroid use in the year before study entry [P =.01], and FEV1 PC20 [P =.0061]). These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                March 2017
                29 December 2016
                : 32
                : 3
                : 439-447
                Affiliations
                Department of Respiratory Medicine, Taizhou Hospital of Zhejiang Province, Linhai, China.
                Author notes
                Address for Correspondence: You-Zu Xu MD. Department of Respiratory Medicine, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, No. 150 Ximen Road, Linhai, Taizhou 317000, Zhejiang, China. Youzuxu@ 123456163.com
                Author information
                http://orcid.org/0000-0003-4814-8648
                http://orcid.org/0000-0002-2576-3827
                http://orcid.org/0000-0003-2510-9064
                http://orcid.org/0000-0003-0035-0003
                http://orcid.org/0000-0003-0070-0931
                http://orcid.org/0000-0002-3115-3988
                http://orcid.org/0000-0002-1252-9564
                Article
                10.3346/jkms.2017.32.3.439
                5290103
                28145647
                a6263b15-31bd-4e97-94dc-a005a6539f21
                © 2017 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 April 2016
                : 30 October 2016
                Categories
                Original Article
                Respiratory Diseases

                Medicine
                fractional exhaled nitric oxide,inhaled corticosteroid,asthma-chronic obstructive pulmonary disease overlap syndrome,efficacy

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