PharmaFGP (Germany)

<bold>Introduction:</bold> Insufficient application pressure of pediatric valved holding chamber (VHC) face masks increases mask-to-face leakage. Regulatory standards recommend an application pressure of 16 Newtons (N) for in vitro testing. However, real-world data show that caregivers typically apply only around 4N, which is better tolerated by children. This study investigated how face mask leakage at low contact forces, such as 4N, affects the respirable dose of Budesonide. <bold>Methods:</bold> Two models from the Louis Infant Anatomical Face Model (LIAM) family - LIAM Baby (9 months) and LIAM Infant (2-3 years) - were used to evaluate five commercially available VHC face masks along with their respective chambers for babies and children. These models, based on 3D scans of children's faces, accurately replicate the facial geometry and varying tissue firmness of pediatric patients. Leakage and aerosol performance were measured using a validated test setup at 4N contact force. <bold>Results:</bold> Among baby masks, VORTEX demonstrates superior performance with minimal leakage and highest respirable dose. L‘Espace provides adequate sealing but does not deliver a high respirable dose. OptiChamber, RC Chamber and Aerochamber show higher leakage and lower respirable doses. Among child masks, VORTEX and RC Chamber exhibit the lowest leakage rates, ensuring high drug delivery. In contrast, L'Espace shows the highest leakage, correlating with the lowest respirable dose. OptiChamber and AeroChamber exhibit higher leakage rates but still deliver adequate respirable doses. <bold>Conclusion:</bold> Among all tested VHC masks, VORTEX had the lowest leakage and highest respirable dose, making it the most effective option for babies and children.

Background: IL-13 is a key cytokine in the pathogenesis of allergic asthma. Efficacy with systemically administered anti-IL-13 mAb therapies is mixed; inhaled mAbs may provide targeted treatment for patients. Aim: To investigate the efficacy of CDP7766, an inhaled anti-IL-13 mAb Fab fragment, in a cynomolgus macaque model of allergic asthma. Methods: Nebulised CDP7766 (0.1–60 mg/day) or vehicle was delivered via inhalation (days -2, -1, 1, 2 and 3) to cynomolgus macaques naturally sensitised to Ascaris suum. Concentrations of bronchoalveolar lavage (BAL) allergen-induced cytokines and chemokines were determined on days 1 and 2 using electrochemiluminescence immunoassay. CDP7766 was nebulised using a vibrating-membrane nebuliser based on eFlow® technology. The aerosol was analysed for particle size profile, biophysical and functional properties of CDP7766. Results: Inhaled CDP7766 was well tolerated (no adverse effects related to local irritation) and significantly inhibited BAL allergen-induced cytokine and chemokine upregulation (60 mg vs vehicle: eotaxin-3 p Conclusions: Inhaled CDP7766 inhibited allergen-induced lung and airway responses in cynomolgus macaques. This is the first report of an inhaled anti-IL-13 mAb in a non-human primate model and demonstrates the therapeutic potential of this mAb in allergic asthma. Funding: UCB Pharma.

Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2 accumulation within inhalation face masks has not been evaluated. Methods. We simulated airflow and CO2 concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK® Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated. Results. The maximum average modeled CO2 concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.) after approximately the 5th respiratory cycle. After steady state, the mean CO2 concentration inspired into the nostril was 2.24% and 2.26% for normal and distressed breathing patterns, respectively. Conclusion. The mask is predicted to cause minimal CO2 retention and rebreathing. Infants with normal and distressed breathing should tolerate the mask intermittently delivering aerosols over brief time frames.