While it is recognized that peripheral lung structure and ventilation heterogeneity change with age, the effects of age on aerosol deposition in the healthy adult lung is largely unknown. A series of aerosol bolus inhalations were repeatedly performed in four healthy subjects over a period of 19 years (years = 0, 9, 15 and 19). For each series, a bolus of 1 μm particles was inhaled at penetration volumes () ranging from 200 to 1200 mL. Aerosol bolus deposition (DE), dispersion (H), and mode shift (MS) were calculated along with the rate of increase in these parameters with increasing (slope-DE, slope-H, and slope-MS). Slope-DE significantly increased from 0.040 ± 0.014 (mean ± standard deviation) at year 0 to 0.069 ± 0.007%/mL at year 19 ( = 0.02) with no significant difference in DE at shallow depth ( = 200 mL; 14% ± 4% at year 0 vs. 15% ± 7% at year 19, = 0.25). There was no significant effect of age on either slope-H (0.44 ± 0.05 at year 0 vs. 0.47 ± 0.09 mL/mL at year 19, = 0.6) or dispersion at shallow depth (192 ± 36 mL at year 0 vs. 220 ± 54 mL at year 19, = 0.2). Slope-MS became significantly more negative with increasing age (-0.096 ± 0.044 at year 0 vs. -0.171 ± 0.027 mL/mL at year 19, = 0.001) with no significant difference in MS at shallow depth (12 ± 10 at year 0 vs. 7 ± 15 mL at year 19, = 0.3). These data suggest that (1) peripheral deposition increases with aging in the healthy lung, likely as a result of increasing closing volume with age; (2) alterations in the mechanical properties of healthy adult lungs with age occur uniformly; and (3) the significant increase in the magnitude of MS-slope with age is likely due to the concomitant increase in peripheral deposition and possible alterations in flow sequencing.
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http://dx.doi.org/10.1089/jamp.2019.1566 | DOI Listing |
Pharm Res
September 2024
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Surfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product.
View Article and Find Full Text PDFPharm Res
June 2024
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Aim: The aim of this in silico study was to investigate the effect of particle size, flow rate, and tidal volume on drug targeting to small airways in patients with mild COPD.
Method: Design of Experiments (DoE) was used with an in silico whole lung particle deposition model for bolus administration to investigate whether controlling inhalation can improve drug delivery to the small conducting airways. The range of particle aerodynamic diameters studied was 0.
Eur J Pharm Sci
May 2024
Clinical Trial Consultants AB, Dag Hammarskjölds väg 10B, Uppsala SE-752 37, Sweden; Department of Global Public Health, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Women's and Children's Health, Uppsala University, Stockholm, Sweden.
Background: In development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy.
View Article and Find Full Text PDFBMC Pediatr
September 2023
Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Introduction: Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce.
View Article and Find Full Text PDFPharmaceutics
August 2023
Department of Anaesthesiology and Critical Care Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68165 Mannheim, Germany.
Mechanically ventilated patients suffering from acute respiratory distress syndrome (ARDS) frequently receive aerosolized iloprost. Because of prostacyclin's short half-life, prolonged inhalative administration might improve its clinical efficacy. But, this is technically challenging.
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