Fluticasone

The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota's dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium's relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

BackgroundUmeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD). This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.MethodsPatients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg. Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.ResultsImprovements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p ConclusionsOnce-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.Trial registrationNCT01822899 Registration date: March 28, 2013.

PurposeTo characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.MethodsThe structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.ResultsSLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.ConclusionThe SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.

IntroductionThere is a paucity of comparative real-world evidence for fluticasone-based and beclometasone-based single-inhaler triple therapies in patients with chronic obstructive pulmonary disease (COPD).AimTo compare clinical outcomes of fluticasone/umeclidinium/vilanterol (a once-daily dry powder inhaler) and beclometasone/glycopyrrolate/formoterol (a twice-daily metered dose inhaler) in patients with COPD.MethodThis population-based cohort study enrolled patients with COPD who initiated fluticasone/umeclidinium/vilanterol or beclometasone/glycopyrrolate/formoterol from a nationwide Taiwanese database between 2019 and 2022. The effectiveness outcomes included severe and moderate exacerbations and the safety outcomes were pneumonia and composite cardiovascular events. Patients were followed from the first day after cohort entry to the earliest of each outcome occurrence, study treatment discontinuation or change, death, end of data (2022/12/31), or the 365th day after cohort entry. Cox regression models were employed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for each outcome comparing fluticasone/umeclidinium/vilanterol versus beclometasone/glycopyrrolate/formoterol after high-dimensional propensity score matching.ResultsThere were 12,971 initiators included in the high-dimensional propensity score matched cohort. The HR suggested a lower risk of severe and moderate exacerbations (0.80 [95% CI 0.69-0.93] and 0.80 [95% CI 0.74-0.87], respectively) and a marginally non-significant decreased risk of pneumonia (0.85 [95% CI 0.70-1.02]) associated with fluticasone/umeclidinium/vilanterol. However, both treatments showed a similar risk of composite cardiovascular events (0.96 [95% CI 0.69-1.35]). The results were generally consistent across several pre-specified sensitivity and subgroup analyses. Of note, among patients treated for ≥ 90 days (nearly 73% of the initiators), the differences in clinical outcomes of both treatments tended to be minimal, with an HR of 0.98 (95% CI 0.78-1.23) for severe exacerbations, 0.93 (95% CI 0.72-1.20) for pneumonia, and 1.07 (95% CI 0.64-1.77) for composite cardiovascular events. Nevertheless, fluticasone/umeclidinium/vilanterol remained having a lower risk of moderate exacerbations (0.86 [95% CI 0.74-0.98]).ConclusionThis cohort study conducted in an Asian COPD population suggests that fluticasone/umeclidinium/vilanterol may be a preferred initial treatment option over beclometasone/glycopyrrolate/formoterol. While among patients who are able to maintain their therapies for ≥ 90 days, both treatments may demonstrate more comparable effectiveness and safety profiles.