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.

A new method for measuring lung deposition efficiency of airborne nanoparticles in a single breath

“…Similarly to D L,CO , the particle recovery, R , is measured for air from a volumetric lung depth of about 1.5 L. As described earlier, particle recovery is expected to correlate with the diffusion distances of the distal lung units. AiDA might also reflect distal air space enlargement more specifically than D L,CO , as AiDA is expected to reflect the diffusion distances within the air spaces only, whereas D L,CO depends also on a number of other factors such as the properties of the blood-gas barrier and the capillary blood volume58. Judging from the limited number of measurements in this study, the precision of AiDA is comparable, or better, than that of D L,CO .…”

Airspace Dimension Assessment with nanoparticles reflects lung density as quantified by MRI

“…The apparatus as well as the theoretical background is described in detail elsewhere. 1,2 The measurements were performed in a sitting position, using a protocol and breathing manoeuver similar to measuring D L,CO . 7 The subjects inhaled nanoparticles through a mouthpiece to total lung capacity, held their breath for a given amount of time, and exhaled to residual volume.…”

“…Nanoparticle recovery was used to calculate the airspace radius as described by Löndahl. 1 Briefly, an exponential decay curve is fitted to the recovery values obtained by a series of breath holds of varying duration ( Figure 1). The airspace radius is calculated from the half-life of this decay, according to:…”

“…A non-invasive method to estimate distal airspace radius by a series of single breath-hold nanoparticle inhalations has recently been described. 1,2 This method, termed Airspace Dimension Assessment with nanoparticles (AiDA), is based on nanoparticle deposition behavior in distal airspaces. Nanoparticles deposit almost exclusively by diffusion; in a given time, the likelihood of deposition depends on the diffusion distance.…”

“…Nanoparticle versus micron-size particle recovery methods are extensively discussed by Löndahl. 1 A crucial difference between the two methods is that in AiDA, a simpler measurement procedure can be used, allowing for measurements without a set breathing flow rate. The deposition of nanoparticles is essentially independent of flow during inhalation.…”