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      International Journal of COPD (submit here)

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      Patterns and characterization of COPD exacerbations using real-time data collection

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          Abstract

          Introduction

          Patients with chronic obstructive pulmonary disease often experience exacerbations. These events are important as they are a major cause of morbidity and mortality. Recently, it has been increasingly recognized that patients may experience symptoms suggestive of an exacerbation but do not seek treatment, which are referred to as unreported or untreated exacerbations. Symptom diaries used in clinical trials have the benefit of identifying both treated and untreated exacerbation events.

          Methods

          The Kamada study was a multicenter, double-blind randomized controlled trial of inhaled augmentation therapy in alpha-1 antitrypsin deficiency (AATD). A retrospective review of daily electronic symptom diary cards was undertaken from the two leading centers to identify symptomatic episodes consistent with a definition of an exacerbation. The aims were to explore the relationship between exacerbation events and classical “Anthonisen” symptoms and to characterize treated and untreated episodes.

          Results

          Forty-six AATD patients with airflow obstruction and history of exacerbations were included in the analysis. Two hundred thirty-three exacerbation episodes were identified: 103 untreated and 130 treated. Untreated episodes were significantly shorter (median 6 days; interquartile range [IQR] 3–10 days) than the treated episodes (median 10 days; IQR 5–18.25 days: P<0.001). Using logistic regression analysis, Anthonisen type and length of dyspnea were significant predictors of the treatment of an exacerbation event.

          Conclusion

          Real-time electronic diary cards provide valuable information about the characterization of exacerbations. Untreated episodes are common and are significantly shorter in duration than the treated episodes. Dyspnea is the most important single Anthonisen symptom in the prediction and/or driver of treatment.

          Most cited references8

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          Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD.

          To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture. Open, longitudinal study of sputum characteristics and acute-phase proteins. Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic. One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state. The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy. A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001). The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.
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            Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

            To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. Multicenter, cross-sectional, epidemiologic study. Pneumology units in six secondary or tertiary hospitals in Spain. Ninety-one patients with acute exacerbation of COPD were included. A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with 25 leukocytes per low magnification field (x 100). Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 50% (p 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.
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              Characterisation and impact of reported and unreported exacerbations: results from ATTAIN.

              The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians. "EXACT-identified" events were categorised as "EXACT-reported" (detected by EXACT and reported to the physician) and "EXACT-unreported" (detected but not reported). Health status was measured using the St George's Respiratory Questionnaire (SGRQ). Annualised EXACT-identified event rates were higher in all study arms (placebo 1.39, aclidinium 200 μg 1.00 and aclidinium 400 μg 0.98 per patient per year) versus HCRU (placebo 0.60, aclidinium 200 μg 0.43 and aclidinium 400 μg 0.40 per patient per year). Concordance between methods was low (kappa 0.16). Aclidinium reduced EXACT-identified events (rate ratio versus placebo: aclidinium 200 μg 0.72 and aclidinium 400 μg 0.71; both p<0.05); HCRU events were similarly reduced. At week 24, SGRQ scores improved (-6.6 versus baseline) in patients with no event during weeks 1-12; improvements were significantly smaller in patients with HCRU events (-3.4; p=0.036) or EXACT-unreported events (-3.0; p=0.002). Unreported events were more frequent than reported events. Both had similar negative impact on health status. Aclidinium reduced the frequency of both types of event.
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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
                2017
                25 January 2017
                : 12
                : 427-434
                Affiliations
                [1 ]Centre for Translational Inflammation Research, University of Birmingham
                [2 ]ADAPT Project, University Hospital Birmingham, Birmingham, UK
                [3 ]Leiden University Medical Centre, Leiden, the Netherlands
                [4 ]Independent consultant, Penn, UK
                Author notes
                Correspondence: Robert A Stockley, University Hospital Birmingham, ADAPT Project, Respiratory Department, Mindelsohn Way, Birmingham, B15 2GW, UK, Email rob.stockley@ 123456uhb.nhs.uk
                Article
                copd-12-427
                10.2147/COPD.S126158
                5279955
                28182151
                28f96f36-e873-436e-9b47-b6d853c26fc5
                © 2017 Ejiofor 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.

                History
                Categories
                Original Research

                Respiratory medicine
                exacerbations,alpha-1 antitrypsin deficiency,copd
                Respiratory medicine
                exacerbations, alpha-1 antitrypsin deficiency, copd

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