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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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      Optimization of Nebulized Budesonide in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

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          Abstract

          Background

          Clinical studies have suggested nebulized budesonide (NB) as an alternative to systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the optimal budesonide dose for AECOPD remains unclear.

          Objectives

          To compare the efficacy and safety of different doses of NB in the management of AECOPD.

          Patients and Methods

          A total of 321 AECOPD patients with moderate-to-severe exacerbation were randomly divided into three groups and treated with NB. The low dose group (L) was given 4 mg/day (n=95, 1 mg Q6h), while high-dose group 1 (H1, n=111, 2 mg Q6h) and high-dose group 2 (H2, n=115, 4 mg Q12h) were given 8 mg/day. Patients also received routine treatment including oxygen therapy, expectorant, nebulization bronchodilators, antibiotics, and fluid rehydration. The COPD assessment test (CAT), lung function, and artery blood gas were evaluated before and after 3 hrs and 5 days of treatment. In addition, hospital stay, frequency of acute exacerbations within 3 months of discharge, and adverse events during treatment were compared.

          Results

          H1 and H2 showed improved spirograms and CAT score faster than L. In H2, forced expiratory volume in 1 s (FEV 1%) at 3 hrs and FEV 1%, forced expiratory flow after 50% of the forced vital capacity has been exhaled (FEF 50%), mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF 25–75%) and CAT score at 5 days were significantly improved compared to L. FEV 1% improved most in H2, moderately in H1, and least in L, with significant differences between groups at 5 days. No differences between groups were observed in adverse effects, hospital stay, and frequency of exacerbations within 3 months of discharge.

          Conclusion

          Compared to the conventional dose (4 mg/day), a high dose (8 mg/day) of NB improved pulmonary function and symptoms more effectively in the early treatment of AECOPD, especially when given as 4 mg twice daily.

          Most cited references23

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          Non-genomic Effects of Glucocorticoids: An Updated View

          Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs 'rapidly' enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma. In this review article, we discuss (i) the non-genomic effects of GCs on pathways relevant to the pathogenesis of inflammatory diseases and (ii) the putative role of the membrane GC receptor. Since GC side effects are often considered to be generated through its genomic actions, understanding GC non-genomic effects will help design GCs with a better therapeutic index.
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            Corticosteroids contribute to muscle weakness in chronic airflow obstruction.

            Twenty-one patients with chronic obstructive pulmonary disease (COPD) or asthma, admitted to our division because of exacerbation of their conditions and requiring intensified treatment with corticosteroids, underwent pulmonary function tests, tests of respiratory muscle function, measurement of quadricep strength, and a variety of anthropometric and biochemical measurements. All tests were performed the 10th day after admission. As expected, muscle strength and pulmonary function were interrelated. Surprisingly, the average daily dose of steroids taken in the previous 6 mo, which ranged from 1.4 to 21.3 mg (average 4.3 mg), was significantly related to inspiratory muscle strength (PImax) and a similar tendency was present for expiratory muscle strength (PEmax). Multiple regression analysis of the relationship between PImax and quadriceps force (QF) and steroid dose revealed that the average daily dose independently explained 32% of the variance in PImax and up to 51% of the variance in QF. These relationships were independent of the degree of bronchial obstruction estimated by percentage predicted FEV1. Other significant determinants were age, sex, and COPD for PImax and age, sex, and body weight for QF. The present study demonstrates that in patients with COPD or asthma, respiratory and peripheral muscle strength and steroid treatment are interrelated despite the relatively low doses administered. This observation imposes further limitations on the prolonged treatment of chronic airflow obstruction with systemic corticosteroids.
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              Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment.

              Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after short-term, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 microg) corticotropin stimulation test. We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 microg corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 microg corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range. The adrenal response to 1 microg corticotropin was suppressed in 34 patients and normal in 41. Subsequent low-dose corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment. Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                26 February 2020
                2020
                : 15
                : 409-415
                Affiliations
                [1 ]Department of Respiratory Medicine, Affiliated Hospital of Xuzhou Medical College , Xuzhou, Jiangsu, People’s Republic of China
                Author notes
                Correspondence: Shuyang Zhu Department of Respiratory Medicine, Affiliated Hospital of Xuzhou Medical College , Xuzhou, West Huaihai Road #99, Xuzhou221000, People’s Republic of China Email shuyangzhu@126.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-7414-9623
                http://orcid.org/0000-0001-9121-3156
                http://orcid.org/0000-0002-6327-344X
                http://orcid.org/0000-0001-8957-6417
                http://orcid.org/0000-0003-0379-7038
                http://orcid.org/0000-0001-7992-3016
                http://orcid.org/0000-0002-6041-6433
                http://orcid.org/0000-0002-9998-6476
                Article
                235125
                10.2147/COPD.S235125
                7049770
                32161453
                8c4b08e9-37f1-491c-bc7b-d98754f5da00
                © 2020 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). 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 ( https://www.dovepress.com/terms.php).

                History
                : 25 October 2019
                : 20 December 2019
                Page count
                Tables: 5, References: 35, Pages: 7
                Categories
                Original Research

                Respiratory medicine
                obstructive pulmonary disease,exacerbation,nebulized budesonide,dose,pulmonary function

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