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COPD Exacerbations: Causes, Prevention, and Treatment.

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COPD Exacerbations: Causes, Prevention, and Treatment.

Immunol Allergy Clin North Am. 2013 Feb;33(1):95-115

Authors: Mackay AJ, Hurst JR

Abstract
The mechanisms of chronic obstructive pulmonary disease exacerbation are complex. Respiratory viruses (in particular rhinovirus) and bacteria play a major role in the cause of these events. A distinct group of patients seems susceptible to frequent exacerbations, irrespective of disease severity, and this phenotype is stable over time. Many current therapeutic strategies help reduce exacerbation frequency. Further work is required to develop novel anti-inflammatory therapies for exacerbation prevention and treatment. This article focuses on the cause of chronic obstructive pulmonary disease exacerbations, and the current preventative and acute interventions available.

PMID: 23337067 [PubMed - in process]

Influence of salmeterol/fluticasone via single versus separate inhalers on exacerbations in severe/very severe COPD.

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Influence of salmeterol/fluticasone via single versus separate inhalers on exacerbations in severe/very severe COPD.

Respir Med. 2013 Jan 18;

Authors: Hagedorn C, Kässner F, Banik N, Ntampakas P, Fielder K

Abstract
BACKGROUND: Patients with severe or very severe chronic obstructive pulmonary disease (COPD) frequently suffer repeated exacerbations generating high health care utilization costs. Combined corticosteroid and bronchodilator treatment using a single inhaler might - via improved compliance - reduce exacerbation rates. OBJECTIVES: Our aim was to obtain descriptive data on exacerbation rates in patients with severe or very severe COPD (GOLD Stages III and IV as per GOLD 2009 classification) receiving salmeterol xinafoate/fluticasone propionate via a single inhaler (SFC) or via separate inhalers (Sal/FP) in addition to individual existing therapy in order to investigate the potential benefit of a fixed combination device as compared with two separate devices due to potentially improved patients' compliance. METHODS: This prospective, randomized, open-label, parallel-group, multi-center, exploratory study was conducted in Germany in 2007-2009. Patients were required to have suffered ≥ 2 moderate/severe exacerbations in the preceding year. RESULTS: 213 patients (SFC: 108 patients, Sal/FP: 105 patients) from 23 centers were evaluated. Approximately 25% of patients showed COPD Stage IV. On average patients had suffered 2.3 ± 0.6 moderate/severe exacerbations in the preceding year. The annual rate of moderate/severe exacerbations observed in the study was similar in both treatment groups (SFC: 0.86 ± 0.13; Sal/FP: 0.86 ± 0.14; exacerbation rate ratio SFC/Sal/FP: 1.00; p = 0.73; negative binomial model). Compliance was high and comparable in both groups. Besides COPD exacerbations, pneumonia (5.6%) and nasopharyngitis (5.2%) were the most common adverse events. CONCLUSION: Observed exacerbation rates were lower than those reported at baseline. No substantial difference was observed between administration of salmeterol xinafoate/fluticasone propionate via a single inhaler and separate inhalers. Treatment was safe and well tolerated. ClinicalTrials.gov Identifier: NCT00527826.

PMID: 23337300 [PubMed - as supplied by publisher]

Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease.

Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease.

Pulm Pharmacol Ther. 2013 Jan 19;

Authors: Yasui H, Inui N, Furuhashi K, Nakamura Y, Uto T, Sato J, Yasuda K, Takehara Y, Suda T, Chida K

Abstract
BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), multidetector-row computed tomography (MDCT) showed that tiotropium dilated the inner diameters in airways from the third to the sixth generation of the bronchi. Here we aimed to evaluate the morphological effect by adding a budesonide/formoterol combination to tiotropium in COPD patients using three-dimensional MDCT. METHODS: Pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ) and MDCT imaging studies were performed at the beginning and after budesonide/formoterol combination treatment for 12 weeks in 14 patients with COPD. RESULTS: The median age was 73.5 years and the mean forced expiratory volume in 1 second (FEV(1)) as a percentage of the predicted value was 57.2 ± 18.3 %. The luminal area in the fifth generation bronchi and the emphysema volume/CT-derived total lung volume were significantly correlated with FEV(1) at baseline (r = 0.682, p < 0.02 and r = -0.868, p < 0.001, respectively). The average luminal area and wall area percentage in the third, fourth and fifth generations were correlated with the SGRQ total score. Budesonide/formoterol induced insignificant pulmonary function changes and significant symptoms improvement. CT images showed an increased inner luminal area and decreased wall area after budesonide/formoterol treatment. Average luminal area was significantly increased from 24.3 ± 9.7 to 26.0 ± 9.9 mm(2) in the third generation, 13.0 ± 6.5 to 14.7 ± 7.3 mm(2) in the fourth generation, 8.0 ± 4.8 to 9.4 ± 4.9 mm(2) in the fifth generation and 5.6 ± 2.7 to 6.7 ± 3.6 mm(2) in the sixth generation (p<0.01). The average increase of the third generation luminal area was correlated with the FEV(1) increase (r = 0.632, p < 0.03). The wall area percentage significantly decreased from 51.5 ± 9.2 to 49.1 ± 9.7 in the third generation, 56.1 ± 9.7 to 53.0 ± 11.1 in the fourth generation, and 62.3 ± 9.9 to 57.6 ± 9.8 in the fifth generation (p<0.05). Emphysema volume/CT-derived total lung volume was unchanged with treatment. CONCLUSION: MDCT demonstrated budesonide/formoterol-induced bronchodilation in the non-small airway. CT imaging can evaluate drug therapeutic effect and may provide additional insights into pharmacotherapy for COPD.

PMID: 23340058 [PubMed - as supplied by publisher]

Obstructive pulmonary disease in old age among individuals born preterm.

Obstructive pulmonary disease in old age among individuals born preterm.

Eur J Epidemiol. 2013 Jan 23;

Authors: Broström EB, Akre O, Katz-Salamon M, Jaraj D, Kaijser M

Abstract
There are only few studies of the association between preterm birth and risk of chronic lung disease in old age. The aim of this study was to assess the association between poor fetal growth, preterm birth, sex and risk of asthma and Chronic Obstructive Pulmonary Disease (COPD) in adulthood. We have followed up a cohort of all infants born preterm (<35 weeks) or with low birth weight (<2,000 and <2,100 g for girls and boys, respectively) and an equal number of controls in a source population of 250,000 individuals born from 1925 through 1949 in Sweden (6,425 subjects in total). Cases of asthma and COPD were identified through the Swedish Patient Register and we considered cohort subjects as cases if they had a main or additional discharge diagnosis of asthma or COPD. For any obstructive airways disease, there was a statistically significant increase in risk with decreasing birth weight and gestational duration among women but not among men. Compared to women born at term, women born before 32 weeks of gestation had a hazard ratio for any obstructive airways disease and asthma of 2.77 (95 % CI 1.39-5.54) and 5.67 (1.73-18.6), respectively. Low birth weight and preterm birth are risk factors for obstructive airways disease also among the old, but the importance of these risk factors differs between the sexes.

PMID: 23341027 [PubMed - as supplied by publisher]

Prolonged Infusion Antibiotics for Suspected Gram-Negative Infections in the ICU: A Before-After Study (February).

Prolonged Infusion Antibiotics for Suspected Gram-Negative Infections in the ICU: A Before-After Study (February).

Ann Pharmacother. 2013 Jan 22;

Authors: Arnold HM, Hollands JM, Skrupky LP, Smith JR, Juang PH, Hampton NB, McCormick S, Reichley RM, Hoban A, Hoffmann J, Micek ST, Kollef MH

Abstract
BACKGROUND:β-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical RESULTS: To determine whether prolonged infusion of β-Lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection.METHODS:We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011).RESULTS:A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329)CONCLUSIONS:Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

PMID: 23341160 [PubMed - as supplied by publisher]

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