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

Sammanfattning: 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 foremphysema. 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 isbased 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 historyindicative of COPD, are warranted.