10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Phenotyping of Chronic Obstructive Disease, COPD, from Deposition Fractions of Inhaled Nanoparticles
JAKOB LÖNDAHL, Jonas Jakobsson, H Laura Aaltonen, Eeva Piitulainen, Per Wollmer, Lund University, Sweeden
Abstract Number: 1498 Working Group: Aerosols in Medicine
Abstract COPD is one of our most common diseases, globally causing about three million deaths each year and an economic loss of more than two trillion USD. The disease is characterized by poor airflow and shortness of breath, often resulting from smoking or long-term exposure to air pollution. Two major phenotypes of COPD are predominantly bronchial disease with narrowing of the conducting airways, and emphysema, which is damage and enlargement of the terminal airways including the alveoli. A precise diagnosis is important for treatment, but currently there is a lack of cheap and specific methods to diagnose COPD – especially in the form of emphysema.
We have previously suggested that inhaled nanoparticles can be used as a probe to assess dimensions of the small airspaces in the lung (Löndahl et al. 2017). The method, named Airspace Dimension Assessment (AiDA), derives dimensions of the peripheral airspaces from the half-life time of airborne nanoparticles. Enlarged airspaces result in a decreased deposition and hence a longer half-life. The objective of this study was to investigate if AiDA can provide information about emphysema.
AiDA measurements were carried out on 66 subjects: 25 healthy, 23 smokers with COPD and 18 subjects with alpha-1 antitrypsin deficiency (AATD). AATD is a genetic disorder that greatly increases the risk to develop emphysema. This group differs from smokers with COPD, which are likely to have both bronchial disease and emphysema. A comprehensive investigation of lung function was carried out for all subjects, including spirometry, diffusion capacity of the lung for carbon monoxide (DL,CO) and forced oscillation technique (FOT). Computed tomography (CT) scans of the chest were made for the smokers and the AATD group.
An instrument for deposition measurements of nanoparticles has been developed as described in detail elsewhere (Jakobsson et al. 2017). Measurements were carried out with 50 nm particles sampled from a volumetric lung depth of 1100-1300 ml after a single breath-hold. To obtain the half-life time of the particles, six measurements were performed for each subject with breath-holds varying between 5-10 s. Data were aggregated into two numbers: an airspace dimension calculated from the nanoparticle half-life and a parameter named intercept, which is related to particle losses in the conducting airways.
In a first analysis of the data, the peripheral airspace dimensions derived from AiDA were 0.27±0.03 mm, 0.37±0.07 mm and 0.34±0.08 mm for healthy, smokers and AATD subjects, respectively. Both groups with disease differed significantly from the healthy subjects (p<0.001), which indicate presence of emphysema. The AiDA intercept was 0.50±0.18, 0.33±0.18 and 0.50±0.22, for the three groups: healthy, smokers and AATD. Thus, the AATD group had almost identical intercept as the healthy subjects, while the smokers deviated significantly (p<0.01), which imply that the smokers, but not the AATD group, had changes in the conducting airways compared to the healthy subjects. AiDA data correlated significantly with measures of emphysema from DL,CO and CT.
In conclusion, this study shows that AiDA has potential as a new method for detection and phenotyping of lung disease. The method is less expensive than CT and does not involve radiation. It is more specific to lung geometry than DL,CO and is in no need of pressurized CO. Thus, it has ability to be more widely available in healthcare, which would facilitate early discovery of COPD.
This work was supported by Swedish Research Council, Vinnova, EU EuroNanoMed, The Swedish Heart and Lung Foundation and the Crafoord foundation.
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