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Considerations for new dual-acting bronchodilator treatments for chronic obstructive pulmonary disease.

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Considerations for new dual-acting bronchodilator treatments for chronic obstructive pulmonary disease.

Expert Opin Investig Drugs. 2014 Jan 7;

Authors: de Miguel-Díez J, Jiménez-García R

Abstract
Current guidelines recommend treatment with one or more bronchodilators for chronic obstructive pulmonary disease (COPD) patients. Combination therapy with long-acting muscarinic antagonists (LAMA) and long-acting β2-agonists (LABA) should be recommended in patients who are not fully controlled with one of them. In this article, two closely related approaches to provide long-acting treatments are compared: the LABA/LAMA fixed-dose combination therapy, and the dual-acting muscarinic receptor antagonist and β2-adrenoceptor agonist (MABA). The author in that study concludes that both approaches have been shown to provide clinically enhanced bronchodilator activity that is superior to that offered by current standard treatment. LAMA/LABA fixed-dose combinations are expected to become a new standard in the treatment of COPD. It is important to know the characteristics of the different LAMA or LABA, the inhalation device and the duration of action, because diversity can help to personalize the treatment. Dose-finding studies are required. It is also required to investigate the existence of pharmacodynamics or pharmacokinetic interactions between the components as well as the safety profile. MABA represent an alternative to these combinations, but there is little clinical data yet reported. They have the potential to act as a useful platform for the development of triple therapy in one inhaler.

PMID: 24392807 [PubMed - as supplied by publisher]

Association of Depression with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease.

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Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity.

METHODS: This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression.

RESULTS: Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = - 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37-9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI  1.04-6.06).

CONCLUSIONS: Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed.

C-reactive protein as a prognostic marker in chronic obstructive pulmonary disease.

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The present study aimed to evaluate whether circulating C-reactive protein (CRP) levels are a biomarker of systemic inflammation and a significant predictor of future chronic obstructive pulmonary disease (COPD) outcome.

During the study, 116 patients with stable COPD and 35 age- and gender-matched healthy subjects with normal pulmonary function were observed. Patient follow-up was also performed to evaluate the strength of the associations between CRP levels and future outcomes.

The observations from the present study showed that serum CRP levels were significantly higher in stable COPD patients than in control subjects (4.48±0.83 vs. 1.01±0.27 mg/l, respectively; P<0.05). In addition, it was identified that a serum CRP concentration of >3 mg/l is a poor prognostic variable of COPD compared with a CRP concentration of ≤3 mg/l [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.05-6.99; P<0.05]. A quantitative synthesis of four studies including 1,750 COPD patients was performed and statistically similar results were obtained (HR, 1.54; 95% CI, 1.14-2.07; P<0.01). The present study showed that circulating CRP levels are higher in stable COPD patients and, therefore, may be used as a long-term predictor of future outcomes.

These observations highlight the importance of high sensitivity CRP assays in patients with stable COPD.

Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease.

Individuals with chronic obstructive pulmonary disease (COPD) are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine.

METHODS: In this observational study, 34 subjects (20 COPD, 14 healthy) received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI) assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline) and the fold increase in antibody titer after vaccination.

RESULTS: Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036). Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity.

CONCLUSION: The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with a history of prior vaccination.

Non-anticoagulant derivatives of heparin for the management of asthma: distant dream or close reality?

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Non-anticoagulant derivatives of heparin for the management of asthma: distant dream or close reality?

Expert Opin Investig Drugs. 2014 Jan 3;

Authors: Shastri MD, Peterson GM, Stewart N, Sohal SS, Patel RP

Abstract
Introduction: Approximately 300 million people worldwide are currently affected by asthma. Improvements in the understanding of the mechanisms involved in such inflammatory airway disorders has led to the recognition of new therapeutic approaches. Heparin, a widely used anticoagulant, has been shown to be beneficial in the management of asthma. It belongs to the family of highly sulphated polysaccharides referred to as glycosaminoglycans, containing a heterogeneous mixture of both anticoagulant and non-anticoagulant polysaccharides. Experimental findings have suggested that heparin has potential anti-asthmatic properties owing to the ability of its non-anticoagulant oligosaccharides to bind and modulate the activity of a wide range of biological molecules involved in the inflammatory process. Areas covered: This review focuses on the potential mechanisms of action and clinical application of heparin as an anti-inflammatory agent for the management of asthma. Expert opinion: Heparin may play a significant role in the management of asthma. However, these properties are often hindered by the presence of anticoagulant oligosaccharides, which possess a significant risk of bleeding. Therefore, its therapeutic potential must be explored using well-designed clinical studies that focus on identifying and isolating the anti-inflammatory oligosaccharides of heparin and further elucidating the structure and mechanisms of actions of these non-anticoagulant oligosaccharides.

PMID: 24387080 [PubMed - as supplied by publisher]

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