Table 5.
In vivo studies of radiolabelled aerosol deposition and distribution under neonatal ventilation conditions
| Study | Model, body weight | Nebulizer type and position | Nebulized substance | Particle size | Ventilation type | Interface | Lung deposition (% of the nominal dose) |
|---|---|---|---|---|---|---|---|
| Dubus et al. 2005 | Healthy macaques, 2.5–2.8 kg |
a) MistyNeb (Jet) at inspiratory limb b) Aeroneb Pro (VM) (continuous or sync) at Y-piece |
99mTc-DTPA |
MistyNeb = 4.6 μm Aeroneb Pro (cont.) = 4.8 μm Aeroneb Pro (sync) = 2.8 μm |
Mechanical ventilation | ET tube (ID = 3 mm) |
Mistyneb = 0.5 (0.4—1.3)* Aeroneb Pro (cont.) = 12.6 (9.6—20.6)* Aeroneb Pro (sync) = 14.0 (12.2 – 23.7)* |
| Linner et al. 2014 | Healthy newborn piglets, 1.2–2.2 kg | Investigational eFlow nebulizer (VM) at Y-piece | 99mTC-labelled Poractant alfa diluted 1:1 with saline | MMAD = 2.5–3.0 μm (GSD = 1.6) |
nCPAP (4 cmH2O) PPV |
Mask, prongs, and ET tube (ID = 2.5 or 3 mm) |
Mask (nCPAP) = 5 (3 – 13)* Prongs (nCPAP) = 14 (2 – 40)* ET tube (PPV) = 45 (25–56)* Intratracheal instillation = 88 (71–96)* |
| Réminiac et al. 2016 | Healthy macaques, 3.2–3.6 kg |
a) Cirrus2 (Jet) at inspiratory limb b) Aerogen Solo (VM) at inspiratory limb |
99mTc-DTPA |
Cirrus2 = 4.0 μm Aerogen Solo = 4.7 μm |
HNF (8, 4 and 2 L/min) | Nasal Cannula |
Cirrus2, 8 L/min = 0.03 ± 0.03§ Aerogen Solo, 8 L/min = 0.09 ± 0.04§ Aerogen Solo, 4 L/min = 0.49 ± 0.44§ Aerogen Solo, 2 L/min = 0.85 ± 0.57§ |
| Gregory et al. 2019 | Healthy macaques, 4.8–6.8 kg | Aerosurf delivery system (prototype) at Y-piece | 99mTC-labelled Lucinactant (surfactant) | MMAD = 2.91 μm (GSD = 1.81) | nCPAP (5 cmH2O) | Prongs with Affectair® | 7.52 (3.53 – 14.07)# |
| Nord et al. 2020 | Healthy newborn piglets, 1.2–2.2 kg | Customized eFlow nebulizer (VM) at Y-piece | 99mTC-labelled, undiluted Poractant alfa |
MMD = 3.0 μm GSD = 1.5 |
nCPAP (3 cmH2O) nIPPV (3 + 3 cmH2O) |
Prongs |
nCPAP = 15.9 ± 11.9§ nIPPV = 21.6 ± 10.0§ |
| Cunha-Goncalves et al. 2020 | Healthy newborn piglets, 1.3–2.2 kg (Treated either in supine, lateral decubitus, or prone position) | Customized eFlow nebulizer (VM) at Y-piece | 99mTC-labelled, undiluted Poractant alfa |
MMD = 3.0 μm GSD = 1.5 |
nCPAP (3 cmH2O) | Prongs |
Prone (right lung) = 21.0 ± 8.6§ Prone (left lung) = 10.7 ± 11.4§ Supine (right lung) = 10.7 ± 11.4§ Supine (left lung) = 4.5 ± 2.4§ Right side up (right lung) = 3.4 ± 1.0§ Right side up (left lung) = 15.3 ± 13.4§ Left side up (right lung) = 11.2 ± 9.8§ Left side up (left lung) = 1.8 ± 0.7§ |
VM, vibrating-mesh; 99mTc-DTPA, Technetium-99 m diethylenetriaminepentaacetic acid; MMAD, mass median aerodynamic diameter; GSD, geometric standard deviation; nCPAP, nasal continuous positive airway pressure; HNF, humidified nasal flow; MMD, mass median diameter; nIPPV, nasal intermittent positive pressure ventilation; ET tube, endotracheal tube; ID, internal diameter. *Median (range); § Mean ± SD; # Mean (range)