Inhaled drug delivery: a randomized study in intubated patients with healthy lungs.

BACKGROUND: The administration technique for inhaled drug delivery during invasive ventilation remains debated. This study aimed to compare in vivo and in vitro the deposition of a radiolabeled aerosol generated through four configurations during invasive ventilation, including setups optimizing drug delivery. METHODS: Thirty-one intubated postoperative neurosurgery patients with healthy lungs were randomly assigned to four configurations of aerosol delivery using a vibrating-mesh nebulizer and specific ventilator settings: (1) a specific circuit for aerosol therapy (SCAT) with the nebulizer placed at 30 cm of the wye, (2) a heated-humidified circuit switched off 30 min before the nebulization or (3) left on with the nebulizer at the inlet of the heated-humidifier, (4) a conventional circuit with the nebulizer placed between the heat and moisture exchanger filter and the endotracheal tube. Aerosol deposition was analyzed using planar scintigraphy. RESULTS: A two to three times greater lung delivery was measured in the SCAT group, reaching 19.7% (14.0-24.5) of the nominal dose in comparison to the three other groups (p < 0.01). Around 50 to 60% of lung doses reached the outer region of both lungs in all groups. Drug doses in inner and outer lung regions were significantly increased in the SCAT group (p < 0.01), except for the outer right lung region in the fourth group due to preferential drug trickling from the endotracheal tube and the trachea to the right bronchi. Similar lung delivery was observed whether the heated humidifier was switched off or left on. Inhaled doses measured in vitro correlated with lung doses (R = 0.768, p < 0.001). CONCLUSION: Optimizing the administration technique enables a significant increase in inhaled drug delivery to the lungs, including peripheral airways. Before adapting mechanical ventilation, studies are required to continue this optimization and to assess its impact on drug delivery and patient outcome in comparison to more usual settings.

Association of forced oscillation technique measurements with respiratory system compliance and resistance in a 2-compartment physical model.

BACKGROUND: The forced oscillation technique (FOT) may be useful for diagnosis and follow-up of respiratory diseases. It is unclear how global or regional alterations in airway resistance (Raw) and lung compliance (CL) alter FOT measurements. METHODS: A 2-compartment physical model of the respiratory system allowed to simulate variations in Raw, CL, and their heterogeneity during tidal breathing in an adult human. Five-Hz respiratory system resistance (Rrs5) and reactance (Xrs5), area of reactance (AX), resonance frequency (Fresp) and intrabreath variation in Rrs5 and Xrs5 were measured by FOT. Frequency dependance of resistance could not be studied in this model. Relationships between model characteristics (Raw, CL, and heterogeneity) and FOT measurements were explored by multiple regression. RESULTS: Rrs5 and intrabreath variation in Rrs5 and Xrs5 strongly associated with model characteristics (R2=0.753, 0.5 and 0.658). Associations of Xrs5, AX, and Fresp with model characteristics were weak (R2=0.214, 0.349 and 0.076). Raw heterogeneity was the main determinant of Rrs5 (Coeff=0.594), AX (Coeff=0.566) and intrabreath variation in Rrs5 and Xrs5 (Coeff=0.586 and 0.732). Regional extremes in Raw strongly determined Rrs5 (Coeff=1.006). Xrs5 did not strongly associate with any model characteristic. CONCLUSION: Raw heterogeneity and maximal regional Raw were the main determinants of FOT measurements, in particular Rrs5. Associations between CL and FOT measurements were weak.

Controlled Heat and Humidity-Based Treatment for the Reuse of Personal Protective Equipment: A Pragmatic Proof-of-Concept to Address the Mass Shortage of Surgical Masks and N95/FFP2 Respirators and to Prevent the SARS-CoV2 Transmission.

Background: The coronavirus infectious disease-2019 (COVID-19) pandemic has led to an unprecedented shortage of healthcare resources, primarily personal protective equipment like surgical masks, and N95/filtering face piece type 2 (FFP2) respirators. Objective: Reuse of surgical masks and N95/FFP2 respirators may circumvent the supply chain constraints and thus overcome mass shortage. Methods, design, setting, and measurement: Herein, we tested the effects of dry- and moist-air controlled heating treatment on structure and chemical integrity, decontamination yield, and filtration performance of surgical masks and FFP2 respirators. Results: We found that treatment in a climate chamber at 70°C during 1 h with 75% humidity rate was adequate for enabling substantial decontamination of both respiratory viruses, oropharyngeal bacteria, and model animal coronaviuses, while maintaining a satisfying filtering capacity. Limitations: Further studies are now required to confirm the feasibility of the whole process during routine practice. Conclusion: Our findings provide compelling evidence for the recycling of pre-used surgical masks and N95/FFP2 respirators in case of imminent mass shortfall.

Low-Frequency Intrapulmonary Percussive Ventilation Increases Aerosol Penetration in a 2-Compartment Physical Model of Fibrotic Lung Disease.

In patients with fibrotic pulmonary disease such as idiopathic pulmonary fibrosis (IPF), inhaled aerosols deposit mostly in the less affected region of the lungs, resulting in suboptimal pharmacokinetics of airway-delivered treatments. Refinement of aerosol delivery technique requires new models to simulate the major alterations of lung physiology associated with IPF, i.e., heterogeneously reduced lung compliance and increased airway caliber. A novel physical model of the respiratory system was constructed to simulate aerosol drug delivery in spontaneously breathing (negative pressure ventilation) IPF patients. The model comprises upper (Alberta ideal throat) and lower airway (plastic tubing) models and branches into two compartments (Michigan lung models) which differ in compliance and caliber of conducting airway. The model was able to reproduce the heterogeneous, compliance-dependent reduction in ventilation and aerosol penetration (using NaF as a model aerosol) seen in fibrotic lung regions in IPF. Of note, intrapulmonary percussive ventilation induced a 2-3-fold increase in aerosol penetration in the low-compliance/high airway caliber compartment of the model, demonstrating the responsiveness of the model to therapeutic intervention.