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      Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients

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          Abstract

          Background

          A new approach to the treatment of COPD includes controlling inflammation because of its important role in exacerbation of the disease. Recently, roflumilast has been added as a therapeutic option for COPD. Roflumilast is an oral phosphodiesterase-4 inhibitor that targets inflammatory cells involved in triggering exacerbations of COPD. The objective of the current study was to evaluate roflumilast for its contribution to phagocytic activity in COPD patients.

          Methods

          Twenty-one patients diagnosed with COPD received roflumilast once daily for 6 months in combination with fluticasone (an inhaled corticosteroid), salmeterol (a long-acting β2-agonist), and tiotropium (a long-acting muscarinic antagonist) or combinations of these agents. The main inclusion criterion was stable disease for at least the previous 30 days. Neutrophils and spirometric changes, ie, forced expiratory volume in 1 second (FEV 1) and forced vital capacity (FVC), were measured in the COPD patients at indicated time points. The first sample was taken before receiving roflumilast, the second 3 months later, and the third after 6 months. Examination of defective phagocytosis was done by flow cytometry using a FagoFlowEx ® kit. The statistical analysis was performed using Statistica software.

          Results

          Our results indicate that phagocytic activity was increased after 3 and 6 months of treatment when compared with baseline ( P<0.001). Similarly, FVC and FEV 1 were also increased during the 6-month period, but only FVC differed significantly from baseline ( P<0.001).

          Conclusion

          Although the number of patients in this study was limited, our results indicate that roflumilast induces phagocytic activity, which improves lung function.

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          Most cited references 27

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          Chronic obstructive pulmonary disease: molecular and cellular mechanisms.

          Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
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            The cytokine network in chronic obstructive pulmonary disease.

             Peter Barnes (2009)
            Multiple cytokines play a role in the orchestration of inflammation in inflammatory airway diseases, such as chronic obstructive pulmonary disease, through the recruitment, activation and survival of inflammatory cells. Lymphokines secreted from T cells regulate the pattern of inflammation, whereas proinflammatory cytokines amplify and perpetuate the inflammatory response. Multiple chemokines recruit inflammatory cells from the circulation into the lungs and many growth factors maintain this inflammation and lead to characteristic structural changes in the airways. There are several therapeutic approaches that target cytokine-mediated inflammation in chronic obstructive pulmonary disease, but blocking specific cytokines may not provide clinical benefit, whereas broad-spectrum anti-inflammatory approaches are more likely to be clinically effective.
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              Patient understanding, detection, and experience of COPD exacerbations: an observational, interview-based study.

              This study was conducted to gain insight into patients' comprehension, recognition, and experience of exacerbations of COPD, and to explore the patient burden associated with these events. A qualitative, multinational, cross-sectional, interview-based study. Patients' homes. Patients (n = 125) with predominantly moderate-to-very severe COPD (age > or = 50 years; with two or more exacerbations during the previous year). Patients underwent a 1-h face-to-face interview with a trained interviewer. During the preceding year, patients experienced a mean +/- SD of 4.6 +/- 5.4 exacerbations, after which 19.2% (n = 24) believed they had not fully recovered. Although commonly used by physicians, only 1.6% (n = 2) of patients understood the term exacerbation, preferring to use simpler terms, such as chest infection (16.0%; n = 20) or crisis (16.0%; n = 20) instead. Approximately two thirds of patients stated that they were aware of when an exacerbation was imminent and, in most cases, patients recounted that symptoms were consistent from one exacerbation to another. Some patients (32.8%; n = 41), however, reported no recognizable warning signs. At the onset of an exacerbation, 32.8% of patients (n = 41) stated that they reacted by self-administering their medication. Some patients spontaneously mentioned a fear of dying (12.0%; n = 15) or suffocating (9.6%; n = 12) during exacerbations, and effects on activities, mood, and personal/family relationships were frequently reported. Physicians tended to underestimate the psychological impact of exacerbations compared with patient reports. This study shows that patients with frequent exacerbations have a poor understanding of the term exacerbation. Patient recollections suggest that exacerbation profiles vary enormously between patients but that symptoms/warning signs are fairly consistent within individuals, and are generally recognizable. Exacerbations appear to have a significant impact on patient well-being, including psychological well-being, and this may be underestimated by physicians.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2015
                15 June 2015
                : 10
                : 1123-1128
                Affiliations
                [1 ]Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [2 ]Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [3 ]Pulmonary Department, Immunology and Histocompatibility Laboratory, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                Author notes
                Correspondence: Paul Zarogoulidis, Pulmonary Department, Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, EXOHI 1100, 57010, Thessaloniki, Greece, Tel +30 003 069 7727 1974, Fax +30 23 1099 2424, Email pzarog@ 123456hotmail.com
                Article
                copd-10-1123
                10.2147/COPD.S83205
                4474389
                © 2015 Porpodis et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                phosphodiesterase-4 inhibitors, copd, roflumilast

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