Evaluation of antibody drug delivery efficiency via nebulizer in various airway models and breathing patterns.

BACKGROUND: Nebulizers are commonly used to treat respiratory diseases, which are a major cause of morbidity and mortality. While inhalation therapy with antibodies has been evaluated in preclinical studies and clinical trials for respiratory diseases, it has not yet been approved for treatment. Moreover, there is limited information regarding the delivery efficiency of therapeutic antibodies via nebulizer. METHODS: In this study, the nebulization characteristics and drug delivery efficiencies were compared when immunoglobulin G (IgG) was delivered by five nebulizers using two airway models and five breathing patterns. The study confirmed that the delivered dose and drug delivery efficiency were reduced in the child model compared to those in the adult model and in the asthma pattern compared to those in the normal breathing pattern. RESULTS: The NE-SM1 NEPLUS vibrating mesh nebulizer demonstrated the highest delivery efficiency when calculated as a percentage of the loading dose, whereas the PARI BOY SX + LC SPRINT (breath-enhanced) jet nebulizer had the highest delivery efficiency when calculated as a percentage of the emitted dose. CONCLUSION: The results suggest that the total inspiration volume, output rate, and particle size should be considered when IgG nebulization is used. We, therefore, propose a method for evaluating the efficiency of nebulizer for predicting antibody drug delivery.

[The use of oscillatory respiratory therapy with positive expiratory pressure (PEP-therapy) to restore the functional state of the lungs in patients after cardiac surgery]. / Primenenie ostsillyatornoi respiratornoi terapii s polozhitel'nym davleniem na vydokhe (PEP-terapii) dlya vosstanovleniya funktsional'nogo sostoyaniya legkikh u bol'nykh posle kardiokhirurgicheskikh operatsii.

Postoperative pulmonary complications in cardiac surgery patients occur in 10-35% of cases, depending on differences in their definition, patient characteristics and type of surgical intervention, most of them are associated with ineffective coughing and evacuation of bronchial secretions. OBJECTIVE: To determine the effectiveness of stimulating the evacuation of bronchial secretions with the help of oscillating PEP therapy carried out during the first three days. MATERIAL AND METHODS: A randomized prospective study of 60 adult patients after elective cardiac surgery was performed (Clinical Trials.gov. protocol number NCT05159401). Oscillatory PEP-therapy was performed in 30 patients using Acapella DHGreen device (SmithMedicalASD, USA) 10-12 hours after tracheal extubation 3 times a day for 3 days after surgery. The control group (30 patients). The inclusion criteria: age over 18 years, spontaneous breathing after tracheal extubation, clear consciousness and productive contact with the patient, the ability to maintain adequate gas exchange on the low-flow oxygen inhalation, adequate analgesia (<2 points of VAS). Exclusion criteria: the need for re-intubation and mechanical ventilation, non-invasive mask ventilation, high-flow oxygen therapy, acute cerebrovascular accident, ongoing bleeding, cardiac insufficiency (inotropic index >10), shocks syndrome of various etiologies, the use of any extracorporeal support, any neuromuscular disorders, pneumothorax, hydro-or hemothorax. Before each session and 20 minutes after its end, when breathing air, blood oxygen saturation was recorded using a pulse oximeter (SpO2), the maximum inspiratory capacity (MIC) was measured using a Coach-2 incentive spirometer from SmithsMedical and spirometry with a portable ultrasonic spirometer Spiro Scout (Schiller, Switzerland). For the purposes of this work, the total index of the spirometry maximum inspiratory capacity (SMIC) was used - the sum of the respiratory volume and the reserve volume of inspiration in ml. RESULTS: Difficulties in evacuation of sputum were noted in 90% of patients. Three-day sessions of oscillating PEP- therapy are accompanied by a significant improvement in the passage of sputum, as evidenced by a 3-fold increase in the number of patients with productive cough. The increase in MIC in the main group was 46.9% and 21.3%, respectively (p=0.042), and the number of patients with values greater than MICo. 1500 ml increased from 23.3% to 7.6% (p<0.001). The effectiveness of oscillatory PEP-therapy is confirmed by a 7-fold decrease in the frequency of radiological changes in the lungs at the end of sessions (p<0.001), while in the control group the frequency of their occurrence practically did not change and remained at a high level. The total number of patients with respiratory insufficiency (SpO2≤92%) decreased by 8.6 times after completion of all PEP- therapy sessions (p=0.001), however, without statistically significant difference with the control group. CONCLUSIONS: Oscillatory PEP- therapy in cardiac surgery patients has a positive effect on sputum passage, ventilation parameters and oxygenating lung function. The procedure was well tolerated and there were no complications associated with it.

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles.

Background: Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the in vitro dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with in vivo inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. Materials and Methods: Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. Results: Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. Conclusions: This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.