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DAMPs activating innate and adaptive immune responses in COPD.

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DAMPs activating innate and adaptive immune responses in COPD.

Mucosal Immunol. 2013 Oct 23;

Authors: Pouwels SD, Heijink IH, Ten Hacken NH, Vandenabeele P, Krysko DV, Nawijn MC, van Oosterhout AJ

Abstract
Chronic obstructive pulmonary disease (COPD), a progressive lung disease characterized by sustained neutrophilic airway inflammation, is caused by chronic exposure to noxious stimuli, e.g., cigarette smoke. This chronic exposure can induce immunogenic cell death of structural airway cells, inducing the release of damage-associated molecular patterns (DAMPs). Levels of several DAMPs, including S100 proteins, defensins, and high-mobility group box-1 (HMGB1), are increased in extracellular lung fluids of COPD patients. As DAMPs can attract and activate immune cells upon binding to pattern recognition receptors, we propose that their release may contribute to neutrophilic airway inflammation. In this review, we discuss the novel role of DAMPs in COPD pathogenesis. Relevant DAMPs are categorized based on their subcellular origin, i.e. cytoplasm, endoplasmic reticulum, nucleus, and mitochondria. Furthermore, their potential role in the pathophysiology of COPD will be discussed.Mucosal Immunology advance online publication, 23 October 2013; doi:10.1038/mi.2013.77.

PMID: 24150257 [PubMed - as supplied by publisher]

COPD Exacerbation Frequency, Pharmacotherapy and Resource Use: An Observational Study in UK Primary Care.

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COPD Exacerbation Frequency, Pharmacotherapy and Resource Use: An Observational Study in UK Primary Care.

COPD. 2013 Oct 23;

Authors: Thomas M, Radwan A, Stonham C, Marshall S

Abstract
Abstract Chronic Obstructive Pulmonary Disease (COPD) management represents a significant health resource use burden. Understanding of current resource use, treatment strategies and outcomes can improve future COPD management, for patient benefit and to aid efficient service delivery. This study aimed to describe exacerbation frequency, pharmacotherapy and health resource use in COPD management in routine UK primary care. A retrospective, observational study using routine clinical records of 511 patients with COPD, was undertaken in 10 General Practices in England. Up to 3 years' patient data were collected and analysed. 75% (234/314) patients with mild-moderate COPD (≥50% predicted FEV1) received inhaled corticosteroids (ICS). 11% of patients (54/511) received ICS monotherapy. Mean (standard deviation) annual exacerbation frequency was 1.1 (1.2) in mild-moderate, 1.7 (1.6) in severe (30-49% predicted FEV1) and 2.2 (2.0) in very severe (<30% predicted FEV1) COPD. 14% patients (69/511) had a mean exacerbation frequency of ≥3/year ('frequent-exacerbators'); 9% (27/314) of patients with mild-moderate, 19% (27/145) with severe and 29% (15/52) with very severe COPD. 14% (10/69) of frequent-exacerbators failed to receive inhaled long-acting beta agonists (LABA), 25% (17/69) inhaled long-acting muscarinic antagonists (LAMA), and 12% (`/69) ICS. Frequent-exacerbators had a median of 6.67 primary care contacts/year, 1.0 secondary care visits/year and 21% were hospitalised for COPD/year. Inhaled therapy was frequently inappropriate, with over-use of ICS in patients with mild-moderate COPD. COPD exacerbations were associated with high health resource use and occurred at all levels of disease severity. COPD management strategies should encompass risk-stratification for both exacerbation frequency and physiological impairment.

PMID: 24152210 [PubMed - as supplied by publisher]

Chronic Obstructive Pulmonary Disease and Asthma-Patient Characteristics and Health Impairment.

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Chronic Obstructive Pulmonary Disease and Asthma-Patient Characteristics and Health Impairment.

COPD. 2013 Oct 23;

Authors: Pleasants RA, Ohar JA, Croft JB, Liu Y, Kraft M, Mannino DM, Donohue JF, Herrick HL

Abstract
Abstract Background: Persons with chronic obstructive pulmonary disease (COPD) and/or asthma have great risk for morbidity. There has been sparse state-specific surveillance data to estimate the impact of COPD or COPD with concomitant asthma (overlap syndrome) on health-related impairment. Methods: The North Carolina (NC) Behavioral Risk Factor Surveillance System (BRFSS) was used to assess relationships between COPD and asthma with health impairment indicators. Five categories [COPD, current asthma, former asthma, overlap syndrome, and neither] were defined for 24,073 respondents. Associations of these categories with health impairments (physical or mental disability, use of special equipment, mental or physical distress) and with co-morbidities (diabetes, coronary heart disease, stroke, arthritis, and high blood pressure) were assessed. Results: Fifteen percent of NC adults reported a COPD and/or asthma history. The overall age-adjusted prevalence of any self-reported COPD and current asthma were 5.6% and 7.6%, respectively; 2.4% reported both. In multivariable analyses, adults with overlap syndrome, current asthma only, and COPD only were twice as likely as those with neither disease to report health impairments (p < 0.05). Compared to those with neither disease, adults with overlap syndrome and COPD were more likely to have co-morbidities (p < 0.05). The prevalence of the five co-morbid conditions was highest in overlap syndrome; comparisons with the other groups were significant (p < 0.05) only for diabetes, stroke, and arthritis. Conclusions: The BRFSS demonstrates different levels of health impairment among persons with COPD, asthma, overlap syndrome, and those with neither disease. Persons reporting overlap syndrome had the most impairment and highest prevalence of co-morbidities.

PMID: 24152212 [PubMed - as supplied by publisher]

Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease.

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Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease.

BMJ Open. 2013;3(10):e003048

Authors: Watkins ML, Wilcox TK, Tabberer M, Brooks JM, Donohue JF, Anzueto A, Chen WH, Crim C

Abstract
OBJECTIVES: To test the reliability, validity and responsiveness of the 13-item Shortness of Breath with Daily Activities (SOBDA) questionnaire, and determine the threshold for response and minimal important difference (MID).
DESIGN: 6 week, randomised, double-blind, placebo-controlled study.
SETTING: 40 centres in the USA between 29 October 2009 and 1 July 2010.
PRIMARY AND SECONDARY OUTCOME MEASURES: 547 patients with chronic obstructive pulmonary disease (COPD) were enrolled and 418 entered the 2-week run-in period. Data from the run-in period were collected to test internal consistency, test-retest reliability, convergent validity and known-groups validity of the SOBDA. Three hundred and sixty six patients were randomised 2:2:1 to fluticasone propionate/salmeterol 250/50 µg, salmeterol 50 µg or placebo, twice daily. Results from the SOBDA questionnaire, Patient Global Assessment of Change Question, modified Medical Research Council Dyspnoea Scale (mMRC), Clinician Global Impression of Dysponea Severity (CGI-S), Clinician Global Impression of Change Question and Chronic Respiratory Disease Questionnaire self-administered standardised version (CRQ-SAS) were evaluated; spirometry and safety parameters were measured. Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA questionnaire in relation to the clinical criteria.
RESULTS: Internal consistency of the SOBDA questionnaire (Cronbach α) was 0.89. Test-retest reliability (intraclass correlation) was 0.94. The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC, CGI-S and CRQ-SAS dyspnoea domain scores (0.29, 0.24, 0.24 and -0.68, respectively). The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians. Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID.
CONCLUSIONS: The 13-item SOBDA questionnaire is reliable, valid and responsive to change in patients with COPD. On using anchor-based methods, the proposed responder threshold shows a -0.1 to -0.2 score change. A specific threshold value will be identified as more data are generated from future clinical trials.
TRIAL REGISTRATION: NCT00984659; GlaxoSmithKline study number: ASQ112989.

PMID: 24154513 [PubMed]

Risk factors associated with chronic obstructive pulmonary disease early readmission.

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Risk factors associated with chronic obstructive pulmonary disease early readmission.

Curr Med Res Opin. 2013 Oct 25;

Authors: Lin J, Xu Y, Wu X, Chen M, Lin L, Gong L, Feng J

Abstract
Abstract Background: The 31-day readmission rate is deemed to be an important indicator of the quality of medical care in China. The objectives of this study were to identify the readmission rate of acute exacerbation for chronic obstructive pulmonary disease (COPD) and to evaluate for associated risk factors. Methods: We retrospectively reviewed charts for patients with acute exacerbation of COPD (AECOPD) admitted to our hospital between January 2011 and November 2012. The early readmission group and non-early readmission group were determined by whether patients were readmitted within 31 days after discharge. Logistic regression analysis was performed to identify risk factors for early readmission following an AECOPD. Results: There were 692 patients with 925 admissions during the 23-month period, 63 (6.8%) admissions met our criteria for early readmission. Multivariate analysis showed that chronic cor pulmonale (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.26-3.64, p = 0.005), hypoproteinemia (OR 2.02, 95% CI 1.03-3.95, p = 0.040) and an elevated PaCO2 (OR 1.03, 95% CI 1.00-1.06, p = 0.027) were identified as risk factors for early readmission of AECOPD. Conclusion: The readmission rate for AECOPD was 6.8%. AECOPD patients with chronic cor pulmonale, hypoproteinemia, and a high PaCO2 are at higher risk for readmission with 31 days of hospital discharge, and medical care of these patients warrants greater attention.

PMID: 24156615 [PubMed - as supplied by publisher]

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