Chiesi (United Kingdom)

<h3></h3> Current guidelines recommend anti-inflammatory reliever (AIR) therapies that combine inhaled corticosteroids (ICS) and formoterol for newly diagnosed asthma and patients treated with SABA only. Budesonide-formoterol (BUD-F) is the only combination licensed for as-needed AIR in the UK; however, beclometasone-formoterol (BDP-F) may be used as an alternative in the real-world setting. We conducted a non-inferiority study (pre-specified 20% non-inferiority margin; IRR 1.20) for exacerbation prevention of BDP-F (Fostair) AIR compared with BUD-F (Symbicort) AIR. We compared exacerbations pre- and post-AIR initiation, oral corticosteroid (OCS) use, and risk of acute cardiovascular (CVD) events. A historical cohort study using the Optimum Patient Care Research Database, UK. Adults with asthma, no other chronic respiratory condition, and ≥1 year GP registration who initiated BDP-F AIR or BUD-F AIR (‘likely intent’ based on prescription instructions and ≤1 SABA inhaler at follow-up) for the first time (index date) after July 2012 were followed up for ≤1 year. Inverse probability treatment weighting (IPTW), adjustment and prior event rate ratio (PERR) methods controlled for baseline differences between groups. Non-inferiority of exacerbations used Poisson regression (incident rate ratios [IRR] with bootstrapped confidence intervals [95% CI]). Changes in OCS use and incidence of acute CVD events post-initiation of AIR were also compared. Among 8,750 adult patients, 1,630 (18.6%) were initiated onto BDP-F AIR and 7,120 (81.4%) BUD-F AIR between Jul 2012 and Apr 2025. BDP-F AIR was found to be non-inferior to BUD-F AIR for exacerbation prevention: IRR=0.85 (0.61,1.16). The percentage of people with ≥1 exacerbation at baseline reduced by 7.0% after initiation of BDP-F AIR (relative reduction: 67.5% [57.1,79.8]; p&lt;0.001) and 3.3% after initiation of BUD-F AIR (relative reduction: 76.9% [66.2,88.9]; p&lt;0.001). OCS use reduced with both AIR regimens, but the reduction was significantly greater in the BDP-F AIR group (0.24 mg vs 0.05 mg; p&lt;0.001). Incidence of CVD events post-initiation of AIR was similar for both groups: IRR=1.04 for BDP-F vs BUD-F [0.46,2.34]). BDP-F AIR is non-inferior to BUD-F AIR for exacerbation prevention, results in significantly lower OCS use, and has comparable outcomes for acute cardiovascular events.

BackgroundInhalers are widely used for the management of asthma and chronic obstructive pulmonary disease. However, there is little knowledge about the extent to which an inhaler is used and when it is disposed of, despite the implications for an individual’s health (when used beyond the recommended number of doses (overused)), and medicine wastage, healthcare costs and the environment (when discarded with remaining doses (underused)). To explore inhaler use, we assessed the number of doses remaining in pressurised metered-dose inhalers (pMDIs) returned via a Chiesi Inhaler Recycling scheme.MethodspMDIs were dismantled, and components recycled where possible. Each canister was weighed and the mass of the formulation remaining was calculated. pMDIs were categorised based on number of doses remaining (underused, used, empty (indicating correct use) and overused) and by dose counter presence/absence. A separate online survey was used to obtain patient feedback on inhaler use and disposal behaviours.ResultsOverall, 2614 pMDIs were analysed (55.9% maintenance, 44.1% reliever inhalers); 1015 (38.8%) had an integrated dose counter. The proportion of pMDIs returned empty was greater for inhalers with dose counters than for those without (51.3% vs 25.1%; p<0.0001); the proportion of pMDIs returned underused was lower for inhalers with dose counters than for those without (5.2% vs 33.2%; p<0.0001). The proportion of pMDIs returned overused was substantial and similar for devices with and without dose counters (34.0% vs 23.2%; p>0.01). Most respondents (55.2%) using devices without a dose counter reported that they were not confident in identifying when their inhaler was empty. Furthermore, many respondents (20.6%) who used inhalers with a dose counter reported continued use beyond ‘zero’.ConclusionsOur study suggests that many inhalers are returned underused or overused, with inadequate knowledge among patients about the number of therapeutic doses remaining in the device and appropriate inhaler disposal. These have concerning implications for patient health and the environment and highlight a need for high-quality education for patients and healthcare professionals.

Dry powder inhalers (DPIs) are commonly used devices for delivering inhalable pharmaceuticals. The overall efficacy of any inhalable pharmaceutical is a function of total and regional dose, and the bioavailability of the active pharmaceutical ingredient upon deposition in the lung. Thus, a detailed understanding of the dissolution dynamics of particles from a DPI from the point of generation through to deposition in the lung may shed additional insights into the interpretation of the pharmacokinetic effects, resulting in the design of improved formulations. We present the design and benchmarking of a novel technology that directly measures the dissolution dynamics of dry aerosol particles in situ, where the relative humidity and temperature are directly comparable to the highly humid conditions within the lungs. The rate of water uptake (mass) as well as changes in the physical structure of the particle are directly measured using a combination of electrodynamics and laser light scatter. This technique offers unique insights into the dissolution dynamics of DPI starting formulations.

BackgroundThe complexity of standard chronic obstructive pulmonary disease (COPD) therapy regimens can lead to treatment non-adherence, negatively impacting on health-related quality of life (HRQoL) and long-term outcomes.TriOptimize is the first global real-world study to evaluate HRQoL and treatment adherence in patients with poorly-controlled, moderate-to-severe COPD, treated with fixed triple therapy. Here we present the final analysis from the UK study cohort.MethodsTriOptimize-UK (NCT04355546) is a prospective, non-interventional study investigating an extrafine formulation single-inhaler triple therapy (beclometasone;BDP/formoterol: FF/glycopyrronium;G [Trimbow® pMDI 87/5/9]) on HRQoL in patients with COPD.The primary objective was change in HRQoL (measured by COPD assessment test [CAT]) after prescription of BDP/FF/G, between baseline (Visit1 [V1]) and month 6 (Visit 3 [V3]) stratified by previous COPD therapy. Secondary measures included Test of Adherence to Inhalers (TAI), change in CAT items, and CAT total score at month 3 (Visit 2 [V2]).The plan was to recruit 3,800 patients worldwide, with 200 from the UK; UK patient recruitment and follow-up was restricted by the COVID-19 pandemic.ResultsA total of 100 patients were enrolled, 94 patients were included in the safety analysis and full analysis sets; 76 (80.9%) patients completed the study and 91.8% planned to continue BDP/FF/G.In the six months prior to enrolment, 69 patients (73.4%) were treated with ICS/LABA/LAMA (fixed or open inhaled triple therapy combinations); 12 (12.8%) and 13 (13.8%) patients were treated with ICS/LABA or LAMA/LABA, respectively.After six months treatment with BDP/FF/G CAT total score improved from 23.7 to 21.0 (figure 1); a significant mean change from baseline of -3.6 (P<0.0001); 66.7% of patients were CAT responders (score improvement ≤-2 between V1-V3).All CAT items improved significantly from V1-V2; mean change in CAT total score at V2 was -4.7, P<0.0001. An improvement in adherence was observed; mean change in TAI domain score V1-V2 of 0.7 (P=0.0126), and a positive trend between V1-V3 of 0.6 (P=0.1159).ConclusionTriOptimize-UK has demonstrated a positive impact of Trimbow® in patients with poorly-controlled COPD, with significant improvements in HRQoL and the potential to enhance treatment adherence, important for long-term disease control and outcomes.Please refer to page A292 for declarations of interest related to this abstract. P209 Figure 1CAT total score distribution at a) baseline (V1) and b) after 6 months (V3) The CAT total score is the sum of its single items and ranges between 0 (best possible condition) to 40 (worst possible condition). If one item is missing CAT cannot be calculated. CAT ranges for assessment of impact level of COPD on patient‘s life were predefined: >30, very high impact; 21–30, high impact; 10–20 medium impact; and <10, low impact. Number of patients at V1, n=72; number of patients at V3, n=76.

As pulmonary drug deposition is a function of aerosol particle size distribution, it is critical that the dynamics of particle formation and maturation in pMDI sprays in the interim between generation and inhalation are fully understood. This paper presents an approach to measure the evaporative and condensational fluxes of volatile components and water from and to solution pMDI droplets following generation using a novel technique referred to as the Single Particle Electrodynamic Lung (SPEL). In doing so, evaporating aerosol droplets are shown capable of acting as condensation nuclei for water. Indeed, we show that the rapid vaporisation of volatile components from a volatile droplet is directly correlated to the volume of water taken up by condensation. Furthermore, a significant volume of water is shown to condense on droplets of a model pMDI formulation (hydrofluoroalkane (HFA), ethanol and glycerol) during evaporative droplet ageing, displaying a dramatic shift from a core composition of a volatile species to that of predominantly water (non-volatile glycerol remained in this case). This yields a droplet with a water activity of 0.98 at the instance of inhalation. The implications of these results on regional and total pulmonary drug deposition are explored using the International Commission of Radiological Protection (ICRP) deposition model, with an integrated semi-analytical treatment of hygroscopic growth. Through this, droplets with water activity of 0.98 upon inhalation are shown to produce markedly different dose deposition profiles to those with lower water activities at the point of inspiration.

IntroductionRespiratory distress syndrome is a condition seen in preterm infants primarily due to surfactant insufficiency. European guidelines recommend the dose and method of surfactant administration. However, in routine practice, clinicians often use a ‘whole vial’ approach to surfactant dosing. The aim of this study is to assess whether in preterm infants of gestational age 36+6 weeks+days or less, a low first dose of surfactant (100–130 mg/kg) compared with a high first dose (170–200 mg/kg) affects survival with no mechanical ventilation on either on postnatal days 3 and 4, and other outcomes.Methods and analysisIn this prospective, observational study, we will use the National Neonatal Research Database as the main data source. We will obtain additional information describing the dose and method of surfactant administration through the neonatal EPR system. We will use propensity scores to form matched groups with low first dose and high first dose for comparison.Ethics and disseminationThis study was approved by the West Midlands—Black Country Research Ethics Committee (REC reference: 18/WM/0132; IRAS project ID: 237111). The results of the research will be made publicly available through presentations at local, national or international conferences and will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03808402; Pre-results.