An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models
Rissler, Jenny LU ; Sjögren, Madeleine Peterson LU ; Linell, Julia LU ; Hurtig, Amalia Larsson LU ; Wollmer, Per LU and Löndahl, Jakob LU
(2023)
In Particle and Fibre Toxicology
20.
- Abstract
Background: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm.
Methods: We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while... (More)
Background: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm.
Methods: We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (r AiDA). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity).
Results: The measured fractional deposition for 2.3 μm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (r AiDA) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model.
Conclusions: Whole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations – a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that r AiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.
(Less)
- author
- Rissler, Jenny
LU
; Sjögren, Madeleine Peterson
LU
; Linell, Julia
LU
; Hurtig, Amalia Larsson
LU
; Wollmer, Per
LU
and Löndahl, Jakob
LU
- organization
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- AiDA, Health effects of aerosols, Inhaled dose, Lung deposition, Particle deposition, Pulmonary, Respiratory tract
- in
- Particle and Fibre Toxicology
- volume
- 20
- article number
- 40
- pages
- 14 pages
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:37875960
- scopus:85174821180
- ISSN
- 1743-8977
- DOI
- 10.1186/s12989-023-00551-9
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This research was supported by Formas [prn 2018 − 00693], the Swedish Research Council, VR [2021–03265] and the Swedish Heart and Lung Foundation [20200855]. The funding bodies did not have any influence on the design of the study, collection, analysis, interpretation of data, or in writing the manuscript. Funding Information: The authors would like to acknowledge Haris Zilic, Shakilla Modaber, and Eva Assarsson for performing the clinical lung function tests and AiDA. We also want to acknowledge Bo Olsson (Emmace Consulting) for help with lung deposition modelling and for access to the Mimetikos Preludium software. This research was supported by the Swedish Research Council for Environmental, Agricultural Sciences and Spatial Planning, FORMAS (grant number 2018 − 00693), the Swedish Research Council, VR (2021–03265) and the Swedish Heart and Lung Foundation (20200855).
- id
- 14f179b6-77e4-4cc3-88ce-3dda759a9273
- date added to LUP
- 2023-11-08 16:19:23
- date last changed
- 2024-04-20 08:25:14
@article{14f179b6-77e4-4cc3-88ce-3dda759a9273,
abstract = {{<p>Background: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm. </p><p>Methods: We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (r <sub>AiDA</sub>). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity). </p><p>Results: The measured fractional deposition for 2.3 μm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (r <sub>AiDA</sub>) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model. </p><p>Conclusions: Whole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations – a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that r <sub>AiDA</sub>, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.</p>}},
author = {{Rissler, Jenny and Sjögren, Madeleine Peterson and Linell, Julia and Hurtig, Amalia Larsson and Wollmer, Per and Löndahl, Jakob}},
issn = {{1743-8977}},
keywords = {{AiDA; Health effects of aerosols; Inhaled dose; Lung deposition; Particle deposition; Pulmonary; Respiratory tract}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{Particle and Fibre Toxicology}},
title = {{An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models}},
url = {{http://dx.doi.org/10.1186/s12989-023-00551-9}},
doi = {{10.1186/s12989-023-00551-9}},
volume = {{20}},
year = {{2023}},
}