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Objective: Treatment with fluticasone furoate/vilanterol (FF/VI), an inhaled corticosteroid/ long-acting β 2 -agonist therapy, reduces the risk of severe asthma exacerbations and improves lung function and symptom control in patients with asthma. However, real-world data remain limited among asthma patients in the United States (US). Methods: This retrospective cohort study propensity score (PS) matched adult asthma patients initiating once-daily FF/VI 100/25 mcg with patients initiating twice-daily budesonide/ formoterol (B/F) 160/4.5 mcg using a US claims database (January 1, 2015-December 31, 2018). Asthma control was measured by the mean number of short-acting β 2 -agonist (SABA) canisters dispensed per patient-year (PPY) during follow-up. Time to first, and rates of, overall and severe asthma exacerbations were also measured. Results: After PS matching, 18,531 patients receiving FF/VI were matched to 18,531 patients receiving B/F. Mean SABA canisters dispensed PPY was significantly lower for FF/VI users compared with B/F users (FF/VI: 1.47, B/F: 1.64; p < 0.001). FF/VI use resulted in 13% significantly lower risk of having an overall asthma-related exacerbation and 22% lower risk of a severe exacerbation versus B/F use (overall exacerbation hazard ratio [HR] [95% confidence interval (CI)]: 0.87 [0.82-0.92], p < 0.001; severe exacerbation HR [95% CI]: 0.78 [0.63-0.97], p = 0.027). Asthma-related exacerbation rates per 100 patient-days were also significantly lower for the FF/VI group compared with the B/F group (overall: 0.0475 vs. 0.0558, p < 0.001; severe: 0.0026 vs. 0.0033, p = 0.020). Conclusions: In real-world practice, initiation of once-daily FF/VI 100/25 mcg in adults with asthma was associated with lower use of SABA and fewer asthma-related exacerbations, which may indicate better asthma control, when compared with use of twice-daily B/F 160/4.5 mcg.

ORCID ID: 0000-0001-7054-794X (J.L.I.). AbstractElastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV 1 , 89 6 3% predicted) and 30 normal control subjects (FEV 1 , 102 6 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC 20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV 1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV 1 /FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

Introduction Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are at risk of further readmissions, increased treatment costs, and excess mortality. This study evaluated inpatient admissions and readmissions in patients receiving initial maintenance therapy with umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO). Methods This retrospective, matched cohort study identified patients with COPD who initiated maintenance therapy with UMEC/VI or TIO from Optum’s de-identified Clinformatics Data Mart database between January 1, 2013, and December 31, 2018 (index date defined as earliest dispensing). Eligibility criteria included: ≥ 1 medical claim for COPD pre-index or on the index date; ≥ 12 months of continuous eligibility pre-index; age ≥ 40 years at index; no pre- or post-index asthma diagnosis; and no pre-index claims for medications containing inhaled corticosteroids, long-acting β2-agonists, or long-acting muscarinic antagonists. Outcomes included time to first on-treatment COPD-related inpatient admission, rate of on-treatment COPD-related admissions, and rate of all-cause and COPD-related readmissions within 30 and 90 days. Propensity score matching was used to adjust for potential confounders. Results Matched UMEC/VI and TIO cohorts each included 7997 patients and were balanced on baseline characteristics (mean age 70.9 years; female 47.1–47.6%). Over 12 months, patients initiating UMEC/VI had significantly reduced risk (hazard ratio [95% CI]: 0.87 [0.79, 0.96]; p = 0.006) and rates (rate ratio [95% CI]: 0.80 [0.72, 0.92]; p = 0.008) of COPD-related inpatient admissions compared with TIO. While all-cause readmission rates were similar between treatment cohorts, readmission rates among patients with an initial admission length of stay of 1–3 days were numerically lower for UMEC/VI versus TIO (30-day readmissions: 10.5% vs. 12.4%; 90-day readmissions: 15.5% vs. 19.8%). Similar patterns were observed for COPD-related readmissions. Conclusions These findings highlight the real-world benefits of dual therapy with UMEC/VI versus TIO in reducing inpatient admissions and readmissions in patients with COPD, which may translate to lower healthcare costs.