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Inhaled Long-Acting β2-Agonists Do Not Increase Fatal Cardiovascular Adverse Events in COPD: A Meta-Analysis.

The cardiovascular safety of inhaled long-acting β2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta-analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD.

METHODS: A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated.

RESULTS: There were 24 trials included in this meta-analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96).

CONCLUSION: Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients.

Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD.

BACKGROUND: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD.

PATIENTS AND METHODS: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed.

RESULTS: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model.

CONCLUSION: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD.

Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease.

Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.

OBJECTIVE: We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.

METHODS: Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.

RESULTS: A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (-34.4±7.9 [group A]; -26.2±9.4 [group B]; -22.7±16.0 [group C]; and -24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (-32.3±7.2 vs -25.0±6.5 mL/year) (P=0.44) and the low risk group (-31.0±6.1 vs -23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.

CONCLUSION: There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification.

Fluticasone furoate/vilanterol combination for the treatment of COPD and asthma.

breo-ellipta_487161The critical role of the combination therapy of an inhaled corticosteroid (ICS) and a long-acting β-adrenoceptor agonist (LABA) in the treatment of patients suffering from asthma and also severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations explains why there is a strong interest within the pharmaceutical industry in developing a once-daily ICS/LABA fixed-dose combination (FDC), in an attempt to simplify the treatment and, consequently, increase adherence to the prescribed therapy, and also to overcome the loss of patent protection.

GlaxoSmithKline and Theravance have developed an inhaled FDC of the ICS fluticasone furoate (FF) and the LABA vilanterol (VI) as a once-daily treatment for asthma and COPD. FF/VI, by simplifying the dosing schedule, allows, for the first time, a shift from twice-daily to once-daily treatment, with an acceptable safety and tolerability profile that is consistent with the ICS/LABA class.

The decision to prescribe FF/VI rather than another ICS/LABA FDC is likely to be based on the patient's preference for the inhaler device, their ability to use the device correctly and the convenience of once-daily dosing frequency as well as comparative costs with other combination products. However, further studies are required to specifically assess these possibilities.

The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed pleural exudates

We assessed the utility of ultrasound to guide the selection of closed pleural biopsy technique and site and to assess the respective contributions of repeat thoracentesis and closed pleural biopsy in 100 consecutive patients with undiagnosed pleural exudates. Thoracentesis was more likely to be diagnostic in TB than malignancy (77.8% vs 31.0%, p<0.001). The addition of ultrasound-guided biopsy increased the combined yield for all diagnoses from 48.0% to 90.0% (p<0.001), for malignancy from 31.0% to 89.7% (p<0.001) and for TB from 77.8% to 88.9% (p=0.688). Our findings suggest that this minimally invasive approach has a high diagnostic yield. (Source: Thorax)

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