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Measuring distal airspace dimensions with nanoparticles. Initial development of a diagnostic method.

Aaltonen, H Laura LU (2019) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2019(49).
Abstract
Chronic obstructive pulmonary disease (COPD) consists of emphysema and bronchial disease. The pulmonary function tests currently used to diagnose COPD have poor sensitivity for early disease. This may delay diagnosis and lead to a poorer prognosis compared to establishing the diagnosis at an earlier stage.
The aim of this thesis was to investigate a new nanoparticle-based method, termed Airspace Dimension Assessment (AiDA), to chart distal airspace morphology, and to examine the technique as a possible diagnostic biomarker for
emphysema. In AiDA, inhaled nanoparticles’ deposition behavior is utilized to characterize distal airspace properties.
Nanoparticles, as opposed to larger particles, are able to penetrate into the distal... (More)
Chronic obstructive pulmonary disease (COPD) consists of emphysema and bronchial disease. The pulmonary function tests currently used to diagnose COPD have poor sensitivity for early disease. This may delay diagnosis and lead to a poorer prognosis compared to establishing the diagnosis at an earlier stage.
The aim of this thesis was to investigate a new nanoparticle-based method, termed Airspace Dimension Assessment (AiDA), to chart distal airspace morphology, and to examine the technique as a possible diagnostic biomarker for
emphysema. In AiDA, inhaled nanoparticles’ deposition behavior is utilized to characterize distal airspace properties.
Nanoparticles, as opposed to larger particles, are able to penetrate into the distal lung, where they deposit almost exclusively by diffusion. The particles’ likelihood to deposit is dependent on the diffusion distance. The thesis is
based on the hypothesis that in persons with enlarged, emphysematous airspaces, fewer particles will deposit, as opposed to healthy persons with narrower airspaces.
In paper I, significant nanoparticle deposition differences between 19 COPD-patients with mainly moderate-to advanced emphysema and 19 healthy controls were found. The deposition correlated to disease severity as measured by computed tomography (CT) densitometry and diffusion capacity for carbon monoxide (DL,CO).
In paper II, nanoparticle deposition was used to calculate distal airspace radius in 19 healthy volunteers. The radius correlated to lung density as measured by magnetic resonance imaging (MRI).
In paper III, the average radius in 403 individuals without previous pulmonary disease or respiratory symptoms was found to be 293 ± 36 μm. The radius and its variation in population was found to be approximately comparative to other methods. It was noted that the radius was on average 13 μm larger in male ever-smokers compared to never-smokers, which may reflect early smoking-related changes.
In paper IV, we concluded that in a population sample of 618 individuals, the persons with computed tomography evidence of emphysema (N = 47) had significantly larger distal airspace radii compared to persons without emphysema. We also showed that comorbidities did not significantly affect the results.
In conclusion, we suggest the AiDA radius is a promising biomarker candidate for emphysema. Further validating studies, including a diagnostic study in a population seeking health care attention with symptoms and history
indicative of COPD, are warranted. (Less)
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author
supervisor
opponent
  • Professor Verschakelen, Johny, KU Leuven, Belgium
organization
publishing date
type
Thesis
publication status
published
subject
keywords
nanoparticles, COPD, AiDA, biomarker
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2019
issue
49
pages
79 pages
publisher
Lund University: Faculty of Medicine
defense location
VO Bild och Funktion, rum 2005/2007, Carl-Bertil Laurells gata 9, Skånes Universitetssjukhus i Malmö
defense date
2019-05-15 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-778-3
project
Measuring distal airspace dimensions with nanoparticles
language
English
LU publication?
yes
id
543a4ee8-7955-4865-9484-9f17dfad09c9
date added to LUP
2019-04-14 16:03:59
date last changed
2021-04-15 15:00:53
@phdthesis{543a4ee8-7955-4865-9484-9f17dfad09c9,
  abstract     = {{Chronic obstructive pulmonary disease (COPD) consists of emphysema and bronchial disease. The pulmonary function tests currently used to diagnose COPD have poor sensitivity for early disease. This may delay diagnosis and lead to a poorer prognosis compared to establishing the diagnosis at an earlier stage.<br/>The aim of this thesis was to investigate a new nanoparticle-based method, termed Airspace Dimension Assessment (AiDA), to chart distal airspace morphology, and to examine the technique as a possible diagnostic biomarker for<br/>emphysema. In AiDA, inhaled nanoparticles’ deposition behavior is utilized to characterize distal airspace properties.<br/>Nanoparticles, as opposed to larger particles, are able to penetrate into the distal lung, where they deposit almost exclusively by diffusion. The particles’ likelihood to deposit is dependent on the diffusion distance. The thesis is<br/>based on the hypothesis that in persons with enlarged, emphysematous airspaces, fewer particles will deposit, as opposed to healthy persons with narrower airspaces.<br/>In paper I, significant nanoparticle deposition differences between 19 COPD-patients with mainly moderate-to advanced emphysema and 19 healthy controls were found. The deposition correlated to disease severity as measured by computed tomography (CT) densitometry and diffusion capacity for carbon monoxide (DL,CO). <br/>In paper II, nanoparticle deposition was used to calculate distal airspace radius in 19 healthy volunteers. The radius correlated to lung density as measured by magnetic resonance imaging (MRI). <br/>In paper III, the average radius in 403 individuals without previous pulmonary disease or respiratory symptoms was found to be 293 ± 36 μm. The radius and its variation in population was found to be approximately comparative to other methods. It was noted that the radius was on average 13 μm larger in male ever-smokers compared to never-smokers, which may reflect early smoking-related changes. <br/>In paper IV, we concluded that in a population sample of 618 individuals, the persons with computed tomography evidence of emphysema (N = 47) had significantly larger distal airspace radii compared to persons without emphysema. We also showed that comorbidities did not significantly affect the results.<br/>In conclusion, we suggest the AiDA radius is a promising biomarker candidate for emphysema. Further validating studies, including a diagnostic study in a population seeking health care attention with symptoms and history<br/>indicative of COPD, are warranted.}},
  author       = {{Aaltonen, H Laura}},
  isbn         = {{978-91-7619-778-3}},
  issn         = {{1652-8220}},
  keywords     = {{nanoparticles; COPD; AiDA; biomarker}},
  language     = {{eng}},
  number       = {{49}},
  publisher    = {{Lund University: Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Measuring distal airspace dimensions with nanoparticles. Initial development of a diagnostic method.}},
  url          = {{https://lup.lub.lu.se/search/files/63006174/e_spik_Laura_nr_2_med_paper_1_o_2.pdf}},
  volume       = {{2019}},
  year         = {{2019}},
}