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Introduction Appropriate timing for dual bronchodilator therapy initiation in chronic obstructive pulmonary disease (COPD) management is uncertain. Combination therapy is recommended as step-up from monotherapy or first-line treatment in patients with persistent symptoms. In this setting, umeclidinium/vilanterol (UMEC/VI) demonstrated improved lung function and reduced rescue medication use over tiotropium/olodaterol (TIO/OLO). This subgroup analysis explored efficacy differences between these combinations in patients naïve to COPD maintenance therapy before study entry. Methods Post hoc analysis of an 8-week, randomized, open-label, assessor-blind, two-period crossover study (204990; NCT02799784) comparing UMEC/VI 62.5/25 mcg and TIO/OLO 5/5 mcg, focused on maintenance-naïve (MN) patients with moderate COPD and persistent symptoms (modified Medical Research Council dyspnea score ≥ 2). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), percentage of FEV1 responders (CFB ≥ 100 ml), rescue medication use and safety were evaluated. Results The MN population comprised 63% of the intent-to-treat (ITT) population (148/236 patients) and had similar baseline demographics. At week 8, adjusted mean (standard error) improvements in trough FEV1 from baseline were clinically meaningful for both combinations (UMEC/VI: 167 [17] ml; TIO/OLO 110 [18] ml; adjusted mean difference [95% confidence interval (CI)]: 57 [23–92] ml; p = 0.001; %CFB: 11 vs. 8%). Proportion of FEV1 responders was greater with UMEC/VI versus TIO/OLO at week 8 (60 vs. 42%; odds ratio [95% CI] 1.90 [1.12–3.22]; p = 0.018). Reduction in rescue medication use was 0.20 (95% CI 0.07–0.34) puffs/day greater with UMEC/VI versus TIO/OLO over weeks 1–8 (p = 0.003). Adverse events incidence was similar (UMEC/VI: 24%; TIO/OLO: 29%). Conclusions These results highlight that the efficacy difference between UMEC/VI and TIO/OLO demonstrated in the ITT population is maintained in MN patients. Greater lung function improvements with UMEC/VI versus TIO/OLO were accompanied by symptom improvements, as reflected in a significantly lower need for supplemental rescue medication. Funding GSK. Trial registration NCT02799784

Introduction We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD. Methods This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy. Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa. The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed. Results In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28–77 mL); p

Depression is a prevalent comorbidity in COPD and has an impact on the prognosis of these patients, thereby making it important to study the factors associated with depression in patients with COPD.A multicenter, observational and cross-sectional study was conducted to study the factors associated with depression in patients with COPD measured by the hospital anxiety and depression (HAD) questionnaire. We analyzed anthropometric variables and the number of exacerbations in the previous year and calculated the 6-min walking test and the body mass index, airflow obstruction, dyspnea, and exercise (BODE) index. All the patients completed the quality of life EQ-5D and the LCADL physical activity questionnaires. The relationship of these variables with depression was evaluated with two multiple logistic regression models.One hundred fifteen patients were evaluated (93 % male) with a mean age of 66.9 years (SD 8.8) and a mean FEV1 % of 44.4 % (SD 15.7 %). 24.3 % presented symptoms of depression (HAD-D 8). These latter patients had worse lung function, greater dyspnea, reduced exercise capacity, a higher score in the BODE index, poorer quality of life, reduced physical activity, and more exacerbations. In the first logistic regression model, quality of life and the BODE index were associated with depression (AUC: 0.84; 0.74-0.94). In the second model including the variables in the BODE index, quality of life and dyspnea measured with the MRC scale (AUC: 0.87; 0.79-0.95) were associated with depression.Nearly one-quarter of the patients with COPD in this study presented clinically significant depression associated with worse quality of life, reduced exercise capacity, greater dyspnea, and a higher score in the BODE index.

To date, no evidence exists in the literature as to the effects of inhaled corticosteroids (ICs) on salivary composition in patients with bronchial asthma. The aim of this study was to assess the effect of ICs on salival composition. Adult patients attending an outpatient respiratory clinic who were classified into two groups (controls and patients with bronchial asthma receiving ICs), were recruited in this cross-sectional study. For each participant, data of clinical records, baseline history of asthma, and regular IC dose were recorded. A sample of stimulated saliva was collected and processed for investigation of mucin 5B (MUC5B), lipoxygenase (LPO), total antioxidant capacity, and 8-hydroxydeoxyguanosine (8-OHdG) levels. Overall, 103 patients (49 controls and 54 patients receiving regular treatment with ICs) were recruited. No differences in comorbidities or smoking habits were observed. Patients treated with high-doses of ICs showed lower levels of salival MUC5B compared with those treated with medium IC doses or those not treated with ICs (1.60 vs. 2.20 vs. 2.53 ng/mL; p = 0.042). In patients with asthma, treatment with high-doses of ICs is associated with reduced levels of salivary MUC5B. This effect can explain some of the effects of ICs on oral health.