Safety of bronchial thermoplasty in patients with severe refractory asthma

Background: Patients with severe refractory asthma treated with bronchial thermoplasty (BT), a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle, were followed up for 5 years to evaluate long-term safety of this procedure. Objectives: To assess long-term safety of BT for 5 years. Methods: Patients with asthma aged 18 to 65 years requiring high-dose inhaled corticosteroids (ICSs) (>750 μg/d of fluticasone propionate or equivalent) and long-acting β2-agonists (LABAs) (at least 100 μg/d of salmeterol or equivalent), with or without oral prednisone (≤30 mg/d), leukotriene modifiers, theophylline, or other asthma controller medications were enrolled in the Research in Severe Asthma (RISA) Trial. Patients had a prebronchodilator forced expiratory volume in 1 second of 50% or more of predicted, demonstrated methacholine airway hyperresponsiveness, had uncontrolled symptoms despite taking maintenance medication, abstained from smoking for 1 year or greater, and had a smoking history of less than 10 pack-years. Results: Fourteen patients (of the 15 who received active treatment in the RISA Trial) participated in the long-term follow-up study for 5 years. The rate of respiratory adverse events (AEs per patient per year) was 1.4, 2.4, 1.7, and 2.4, respectively, in years 2 to 5 after BT. There was a decrease in hospitalizations and emergency department visits for respiratory symptoms in each of years 1, 2, 3, 4, and 5 compared with the year before BT treatment. Measures of lung function showed no deterioration for 5 years. Conclusion: Our findings suggest that BT is safe for 5 years after BT in patients with severe refractory asthma. Trial Registration: clinicaltrials.gov Identifier: NCT00401986. © 2013 American College of Allergy, Asthma and Immunology. Published by Elsevier Inc. All rights reserved

Safety of bronchial thermoplasty in patients with severe refractory asthma.

BACKGROUND: Patients with severe refractory asthma treated with bronchial thermoplasty (BT), a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle, were followed up for 5 years to evaluate long-term safety of this procedure. OBJECTIVES: To assess long-term safety of BT for 5 years. METHODS: Patients with asthma aged 18 to 65 years requiring high-dose inhaled corticosteroids (ICSs) (>750 μg/d of fluticasone propionate or equivalent) and long-acting β2-agonists (LABAs) (at least 100 μg/d of salmeterol or equivalent), with or without oral prednisone (≤30 mg/d), leukotriene modifiers, theophylline, or other asthma controller medications were enrolled in the Research in Severe Asthma (RISA) Trial. Patients had a prebronchodilator forced expiratory volume in 1 second of 50% or more of predicted, demonstrated methacholine airway hyperresponsiveness, had uncontrolled symptoms despite taking maintenance medication, abstained from smoking for 1 year or greater, and had a smoking history of less than 10 pack-years. RESULTS: Fourteen patients (of the 15 who received active treatment in the RISA Trial) participated in the long-term follow-up study for 5 years. The rate of respiratory adverse events (AEs per patient per year) was 1.4, 2.4, 1.7, and 2.4, respectively, in years 2 to 5 after BT. There was a decrease in hospitalizations and emergency department visits for respiratory symptoms in each of years 1, 2, 3, 4, and 5 compared with the year before BT treatment. Measures of lung function showed no deterioration for 5 years. CONCLUSION: Our findings suggest that BT is safe for 5 years after BT in patients with severe refractory asthma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00401986

A multicenter RCT of Zephyr® Endobronchial Valve treatment in heterogeneous emphysema (LIBERATE)

RATIONALE: This is the first multicenter RCT to evaluate effectiveness and safety of Zephyr® Endobronchial Valve EBV® out to 12-months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation (CV) in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV: Standard-of-Care (SoC)) at 24 sites. Primary outcome at 12-months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of ≥15%. Secondary endpoints included absolute changes in post-BD FEV1, Six-Minute Walk Distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores. RESULTS: 190 subjects, 128 EBV and 62 SoC were randomized. At 12-months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 ≥15% (p<0.001). ΔEBV-SoC at 12-months was statistically and clinically significant: for FEV1 (L), 0.106L (p<0.001); 6MWD, +39.31m (p=0.002); and SGRQ, -7.05 points (p=0.004). Significant ΔEBV-SoC were also observed in hyperinflation (RV, -522ml; p<0.001), mMRC, -0.8 points (p<0.001), and the BODE Index (-1.2 points). Pneumothorax was the most common serious adverse event in the Treatment Period (procedure to 45 days), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12-months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea and quality of life out to at least 12-months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01796392

The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity

Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and H-3-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855+/-1389 sites/cell which was significantly lower (p0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport. (J. Endocrinol. Invest. 21: 656-661, 1998) (C)1998, Editrice Kurtis