Related Articles

Effect of dual bronchodilation with QVA149 on cardiac safety in healthy volunteers.

Int J Clin Pharmacol Ther. 2014 Feb 26;

Authors: Drollmann A, Brown M, Sechaud R, Perry S, Hara H, Jones I, Febbraro S

Abstract
Objectives: QVA149 is a dual bronchodilator, containing a fixed-dose combination of the long-acting β2-agonist indacaterol and long-acting muscarinic antagonist glycopyrronium, for the treatment of chronic obstructive pulmonary disease (COPD). Here we assess the potential of QVA149 (440/200 μg) at 4-fold the therapeutic dose for causing cardiac pharmacodynamic (PD) effects. Methods: This double-blind, randomized study estimated the time-matched largest heart rate (HR) change and average HR change (over 24 hours) from baseline for QVA149 vs. placebo in healthy subjects. Similar analyses were done for QVA149 vs. indacaterol 600 μg, glycopyrronium 200 μg, and salmeterol 200 μg. The time-matched and average change from baseline in QT interval corrected for HR using Fridericia's formula (QTcF), effects on serum potassium and blood glucose, pharmacokinetic (PK) parameters, and safety were also assessed. Results: Of 50 subjects randomized, 43 completed the study. QVA149, when compared with placebo, showed the time-matched largest mean increase and decrease in HR of 5.69 bpm and -2.51 bpm, respectively, and average HR change from baseline of 0.62 bpm. QVA149 showed no tachycardic potential compared with indacaterol and no relevant tachycardic effect compared with glycopyrronium. No consistent differences were seen in the time-matched largest mean change and average change from baseline in QTcF for QVA149 vs. other treatments. There were no relevant effects of QVA149 on serum potassium and blood glucose. There was no apparent PK/PD relationship between the observed exposures to indacaterol and glycopyrronium in QVA149 on HR and QTcF. There were no deaths or serious adverse events. Conclusion: Overall, short-term administration of QVA149 showed a good cardiovascular safety and tolerability profile in healthy subjects.

PMID: 24569129 [PubMed - as supplied by publisher]

Time course of inflammation resolution in patients with frequent exacerbations of chronic obstructive pulmonary disease.

Med Sci Monit. 2014;20:311-20

Authors: Chang C, Yao W

Abstract
Background When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations. Material and Methods Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10-14), and 8 weeks after discharge. Results We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10-14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators. Conclusions Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life.

PMID: 24569299 [PubMed - in process]

Impact of switching to new spirometric reference equations on severity staging of airflow obstruction in COPD: a crosssectional observational study in primary care.

Prim Care Respir J. 2014 Feb 25;

Authors: Sluga R, Smeele IJ, Lucas AE, Thoonen BP, Grootens-Stekelenburg JG, Heijdra YF, Schermer TR

Abstract
BACKGROUND: Severity of airflow obstruction in chronic obstructive pulmonary disease (COPD) is based on forced expiratory volume in one second expressed as percentage predicted (FEV1%predicted) derived from reference equations for spirometry results.
AIMS: To establish how switching to new spirometric reference equations would affect severity staging of airflow obstruction in the Dutch primary care COPD patient population.
METHODS: Spirometry tests of 3,370 adults aged >40 years with obstruction (postbronchodilator FEV1/forced vital capacity (FVC) <0.70) were analysed. The presence and severity of obstruction were defined using Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Postbronchodilator FEV1%predicted was calculated using three reference equations: corrected European Community of Steel and Coal (ECSC) (currently recommended in Dutch primary care), Swanney et al., and Global Lung Initiative (GLI). Discordances between severity classifications based on these equations were analysed.
RESULTS: We studied 1,297 (38.5%) females and 2,073 males. Application of contemporary reference equations (i.e. Swanney and GLI) changed the GOLD severity stages obtained with the ECSC equations, mostly into milder stages. Severity of airflow obstruction was staged differently in 14.0% and 6.3%, respectively, when the Swanney et al. and GLI reference equations were applied.
CONCLUSIONS: Compared with the (corrected) ECSC equations, switching to more contemporary reference equations would result in lower FEV1 predicted values and affect interpretation of spirometry by reclassifying 6-14% of primary care COPD patients into different (mostly milder) severity stages. If and how this will affect GPs' treatment choices in individual patients with COPD requires further investigation.

PMID: 24570083 [PubMed - as supplied by publisher]

Related Articles

The prevalence of obstructive sleep apnea in patients hospitalized for COPD exacerbation.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014 Feb 25;

Authors: Turcani P, Skrickova J, Pavlik T, Janousova E, Orban M

Abstract
BACKGROUND: The concurrence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is generally identified as an overlap syndrome. Only limited evidence is available on the prevalence of OSA in patients with stable COPD, and essentially no data on the prevalence of OSA in patients hospitalized for COPD exacerbation. The aims of the study were to determine the ratio of concurrence of OSA in patients hospitalized for COPD exacerbation and to identify the confounders of OSA detected in COPD subjects.
METHODS: 101 patients were hospitalized for COPD exacerbation at the Department of Respiratory Diseases in the course of four months. Seventy-nine consecutive patients were enrolled in the study and in 35 of these subjects polygraphy was performed. Descriptive statistics, Mann-Whitney test, Kruskal-Wallis test, Spearman correlation and Fisher's test were used to summarize and evaluate results.
RESULTS: In 18 (51.4%) subjects with polygraphy examination, the apnea-hypopnea index (AHI) ≥ 5 indicated the presence of OSA. The AHI value, and thus the severity of the sleep disorder, correlated with the class of the Mallampati score, presence of snoring, apnea, coronary heart disease, diabetes mellitus in patient's history, height, body mass index, neck, waist and hip circumferences, and the value of the Epworth sleepiness scale.
CONCLUSION: Polygraphy performed in patients hospitalized for exacerbation of COPD indicated an increased prevalence of OSA compared to the general population and stable COPD patients.

PMID: 24572486 [PubMed - as supplied by publisher]