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Novel drug targets for asthma and COPD: Lessons learned from in vitro and in vivo models.

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Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as β-agonists and glucocorticoids, may be effective at reducing symptoms, they do not reduce disease progression. Thus, there is a need to identify new therapeutic targets.

In this review, we summarize the potential of novel targets or tools, including anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient receptor potential channels, vitamin D and protease inhibitors, for the treatment of asthma and COPD.

Surgery for parapneumonic pleural empyema - What influence does the rising prevalence of multimorbidity and advanced age has on the current outcome?

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Pleural empyema is a critical condition. In the western world the share of sufferers with multiple comorbidities and advanced age is rapidly increasing.

METHODS: This retrospective study comprises all patients who underwent surgery for parapneumonic pleural empyema at a major center for thoracic surgery in Germany between January 2006 and April 2013.

RESULTS: A total of 335 patients (mean age 60.4 years) were included. The average ASA grade was 2.8. Empyema stage 1, 2 and 3 (classification of the American Thoracic Society) was encountered in 30, 230 and 75 cases, respectively. The most common comorbidities were cardiac disorders (124), diabetes mellitus (76), COPD (66) and alcoholism (54). The mean Charlson index of comorbidity score was 2. Minimally invasive surgery was feasible in 290 cases. A total of 88 patients sustained pulmonary sepsis. The overall mortality was 29/335 (8.7%). The occurrence of pulmonary sepsis (OR: 17.95; 95% CI: 6.38-62.69; p < 0.001), respiratory failure (OR: 23.08; 95% CI: 8.52-73.35; p < 0.001) and acute renal failure (OR: 8.20; 95% CI: 3.18-20.80; p < 0.001) and Charlson score ≥ 3 (OR: 6.65; 95% CI: 2.76-17.33; p < 0.001) were associated with higher mortality. On the other hand, very elderly sufferers (≥80 years) showed neither higher odds for pulmonary sepsis (OR: 0.78) nor for fatal outcome (OR: 0.92; 95% CI: 0.22-2.86; p = 1).

CONCLUSIONS: Parapneumonic pleural empyema is still associated with considerable morbidity and mortality. Pre-existing comorbidity, the occurrence of pulmonary sepsis and sepsis related complications have a determining influence on the results whereas advanced age itself shows no higher risk for adverse outcome. Further improvement seems achievable by earlier surgical intervention before the onset of pulmonary sepsis.

Outpatient Palliative Care for Chronic Obstructive Pulmonary Disease: A Case Series.

Palliative-carePatients with chronic obstructive pulmonary disease (COPD) have well-documented symptoms that affect quality of life. Professional societies recommend palliative care for such patients, but the optimal way of delivering this care is unknown.

Objective: To describe an outpatient palliative medicine program for patients with COPD. Design: Retrospective case series. Setting/Subjects: Thirty-six patients with COPD followed in a United States academic outpatient palliative medicine clinic.

Measurements: Descriptive analysis of sociodemographic data, disease severity and comorbidities, treatments, hospitalizations, mortality, topic discussion, and symptom assessment.

Results: Thirty-six patients (representing 5% of the total number of patients with COPD seen in a specialty pulmonary clinic) were seen over 11 months and followed for 2 years. Seventy-seven percent of patients were Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3-4 and 72% were on oxygen at home. No patients had documented advanced directives at the initial visit but documentation increased to 61% for those who had follow-up appointments.

The most commonly documented topics included symptoms (100%), social issues (94%), psychological issues (78%), and advance care planning (75%). Of symptoms assessed, pain was the least prevalent (51.6%), and breathlessness and fatigue were the most prevalent (100%). Symptoms were often undertreated prior to the palliative care appointment. During the 3-year study period, there were 120 hospital admissions (median, 2) and 12 deaths (33%).

Conclusions: The patients with COPD seen in the outpatient palliative medicine clinic had many comorbid conditions, severe illness, and significant symptom burden. Many physical and psychological symptoms were untreated prior to the palliative medicine appointment. Whether addressing these symptoms through a palliative medicine intervention affects outcomes in COPD is unknown but represents an important topic for future research.

Describing drivers of and barriers to persistence with tiotropium in patients with chronic obstructive pulmonary disease: a mixed-methods approach.

To understand the factors influencing persistence with tiotropium in patients with chronic obstructive pulmonary disease (COPD).

METHODS: Patients classified as 'persistent' or 'non-persistent' with tiotropium were identified from pharmacy dispensing records. Patients were compared for health status, beliefs and behaviours using data from questionnaires and interviews.

KEY FINDINGS: Perceptions of the risks and benefits of medication, fear of worsening illness, and the GP's emphasis on the importance of the medication were key determinants of tiotropium persistence.

CONCLUSIONS: Perceptions, attitudes and beliefs of patients and doctors influence persistence with tiotropium. These complex interactions need to be targeted to improve persistence with medicines in COPD.

Cognitive function in chronic obstructive pulmonary disease: Relationship to global initiative for chronic obstructive lung disease 2011 categories.

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Cognitive_functionRecently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD.

METHODS: We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language.

RESULTS: Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores.

CONCLUSIONS: The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD.

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