Evaluation of Aerosol Therapy during the Escalation of Care in a Model of Adult Cystic Fibrosis

Abstract

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the escalation of care using a bench model of adult CF. Droplet size analysis of selected antibiotics was completed in tandem with the delivered aerosol dose (% of total dose) assessments in simulations of various interventions providing oxygen supplementation or ventilatory support. Results highlight the variability of aerosolised dose delivery. In the homecare setting, the vibrating mesh nebuliser (VMN) delivered significantly more than the jet nebuliser (JN) (16.15 ± 0.86% versus 6.51 ± 2.15%). In the hospital setting, using VMN only, significant variability was seen across clinical interventions. In the emergency department, VMN plus mouthpiece (no supplemental oxygen) was seen to deliver (29.02 ± 1.41%) versus low flow nasal therapy (10 L per minute (LPM) oxygen) (1.81 ± 0.47%) and high flow nasal therapy (50 LPM oxygen) (3.36 ± 0.34%). In the ward/intensive care unit, non-invasive ventilation recorded 19.02 ± 0.28%, versus 22.64 ± 1.88% of the dose delivered during invasive mechanical ventilation. These results will have application in the design of intervention-appropriate aerosol therapy strategies and will be of use to researchers developing new therapeutics for application in cystic fibrosis and beyond.

Aerosol release, distribution, and prevention during aerosol therapy: a simulated model for infection control

“…Supplemental gas flow rates of 0, 2 and 6 liters per minute (LPM), were considered. Supplemental air is often prescribed in combination with aerosol therapy to increase oxygen levels in the blood and ease the work of breathing of the patient (Fernández Fernández et al., 2021 ; Saeed et al., 2021 ). The flow rates considered in this study were those recommended as suitable for use by the manufacturer.…”

Molecular Insight into the Therapeutic Effects of Stem Cell-Derived Exosomes in Respiratory Diseases and the Potential for Pulmonary Delivery

“…Currently, there are three prevalent aerosol generator technologies in commercial use, with many new technologies under development or as of yet not commercially available: (I) pressurized metered-dose inhalers (pMDIs); (II) dry powder inhalers; and (III) medical nebulizers [ 110 ]. The choice of device should consider the required target lung dose and the likely patient intervention at the time of administration, as both have been shown to have significant influence [ 111 , 112 ]. The pMDIs are the most prescribed device for lung diseases such as COPD and asthma, but regarding clinical research, nebulizers are the most used instrument [ 113 ].…”

Cellular Therapy for the Treatment of Paediatric Respiratory Disease

“…Jet nebulisers require compressed gas to draw the drug from a reservoir through a baffle, which allows for smaller particles to be delivered, with the gas exiting towards the patient, whilst larger particles collide and are drawn back into the reservoir [101]. Jet nebulisers are reported to have low and varying levels of dose efficiency between brands and have a significant residual volume of the drug remaining in the device once dosing is complete (~40%) [102,103], due to the suspension buffer being easily aerosolised owing to its low viscosity; therefore, jet nebulizers are generally considered unsuitable for cells in suspension [104]. VMNs have been designed with an aperture plate with uniform-sized holes that vibrates to create a uniform dosage for delivery to the patient [101].…”

“…VMNs have minimal residual drug volume following use and have shown to have increased efficiency for drug delivery; however, no data yet exists demonstrating successful delivery of cells using VMN [102,105]. Nebuliser choice will be somewhat directed through the selection of patient intervention, with some nebuliser types either deemed unsuitable for use during certain interventions, e.g., JN being unsuitable for use during high flow nasal therapy, or delivery will be too low to economically or clinically rationalise its choice [104,[106][107][108][109].…”