Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?

Abstract

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4-1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (D_L,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology.

Keywords: AiDA; COPD; emphysema; lung particle interaction; nanoaerosols; respiratory diagnosis.

Figure 1

Available experimental data for patients with COPD.– The four studies are different with respect to aerosol type, breathing pattern, classification of disease, and experimental methodology. Ellipses are added for clarity (indicating data from Brown et al and Möller et al45). Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 2

Comparison of gravitational settling velocity and root mean square Brownian displacement in 1 s. The calculation is made for body temperature (37°C) with unit density spherical particles. Abbreviation: s, second.

Figure 3

The fraction of particles deposited in the pulmonary region as calculated by the Multiple Path Particle Dosimetry model. The simulated breathing patterns correspond to those used in diagnostic procedures, with a 2,000 mL inhalation followed by a 10 s breath-hold. Abbreviation: s, second.

Figure 4

Deposition fraction at different generations of the respiratory tract for 0.05 µm particles (left) and 1 µm particles (right) as calculated with the Multiple Path Particle Dosimetry model for a healthy adult during oral breathing without breath-hold. Abbreviation: s, second.

Figure 5

Estimated half-life, t_½, of inhaled particles during a breath-hold for airways with a radius of 200, 300, and 400 µm, respectively, which corresponds with the airspace sizes in the periphery of healthy lungs and of patients with mild pulmonary emphysema. Abbreviation: s, second.