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Background The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. [ABSTRACT FROM AUTHOR]

Summary Background The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. Methods AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov , numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. Findings We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0·8 [95% CI −3·1 to 4·7], p=0·68) in AIR-BX1, but was significant (4·6 [1·1 to 8·2], p=0·011) in AIR-BX2. The 4·6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. Interpretation AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. Funding Gilead Sciences. [ABSTRACT FROM AUTHOR]

Background: Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis. Methods: Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months. Results: Eighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1-3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1-3]) compared to the control group (2[1-3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047). Conclusions: Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months. Trial registry: ClinicalTrials.gov (NCT00885521). [ABSTRACT FROM AUTHOR]

Background: The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery. Methods: Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation--after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study. Results: DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs -0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events. Conclusions: Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population. [ABSTRACT FROM AUTHOR]

The authors reflect on the significance of stem cell therapy in the treatment of lung diseases. The authors say that respiratory diseases cause 7% of deaths, representing 4% of the global burden of lung disease. They explain the limitations of existing therapies including inhaled bronchodilators, corticosteroids, and endothelial restitution. It discusses several types of stem cells such as mesenchymal stem cells (MSC), embryonic stem cells (ESC), and induced pluripotent cells (iPS).