Airspace Dimension Assessment for early detection of lung function impairment in the peripheral airways of firefighters.

Introduction: Firefighters have increased risk of chronic respiratory disease. Standard clinical techniques used in medical checkups may not detect the earliest microstructural changes in peripheral airways. A new technique called Airspace Dimension Assessment (AiDA) has been shown to enable early detection of emphysema in COPD. This method may be useful in the occupational setting to detect early pulmonary changes and enable prevention. The aim of the present study was to evaluate whether AiDA detects changes in the most peripheral airways of firefighters. Methods: AiDA, measuring the effective airspace radius (r AiDA) and zero-second recovery (R 0), was used as a complement to other standardised lung function measures in 21 male firefighters and 16 age-matched male controls. Results: There were significant differences in r AiDA and R 0 between firefighters (mean±sd r AiDA 0.301±0.024 mm; mean±sd R 0 0.336±0.116 arbitrary units) and controls (mean±sd r AiDA 0.276±0.044 mm; mean±sd R 0 0.5760.168 arbitrary units), p=0.03 and p<0.001, respectively. Higher forced vital capacity was found in firefighters (mean 101% of predicted) than in controls (mean 93% of predicted; p=0.03). No significant differences were found with regard to either the ratio between forced expiratory volume in 1 s and forced vital capacity or forced expiratory volume in 1 s. The majority of firefighters had diffusing capacity of the lung for carbon monoxide, oscillometry and single-breath nitrogen washout values within the normal ranges. Conclusion: AiDA parameters can provide information on early pulmonary peripheral changes that may not be seen with standard techniques used in screening of pulmonary function.

Airspace Dimension Assessment with Nanoparticles (AiDA) in Comparison to Established Pulmonary Function Tests.

Background: Airspace Dimensions Assessment with nanoparticles (AiDA) is a new method for non-invasive measurement of pulmonary distal airspaces. The aim of this study was to compare AiDA measurements with other pulmonary function variables to better understand the potential of AiDA in a clinical context. Methods: AiDA measurements and pulmonary function tests were performed in 695 subjects as part of the Swedish CArdioPulmonary bioImage Study. The measurement protocol included spirometry, measurement of diffusing capacity of carbon monoxide, oscillometry and pulmonary computed tomography. AiDA indices were compared to all other pulmonary examination measurements using multivariate statistical analysis. Results: Our results show that AiDA measurements were significantly correlated with other pulmonary function examination indices, although covariance was low. We found that AiDA variables explained variance in the data that other lung function variables only influenced to a minor extent. Conclusion: We conclude that the AiDA method provides information about the lung that is inaccessible with more conventional lung function techniques.

Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema.

Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 µm vs 291±36 µm); OR for emphysema per 10 µm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 µm vs 291 µm±26 µm); OR per 10 µm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.

Inhalation and Dermal Uptake of Particle and Gas-Phase Phthalates-A Human Exposure Study.

Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine-disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labeled airborne phthalates: particle-phase D4-DEHP (di(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone and combined inhalation + dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014 ± 0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 h exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation + dermal was 0.0067 ± 0.0045 and 0.00073 ± 0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles and highlight the importance of considering the deposited dose in particle uptake studies.

Charting the human respiratory tract with airborne nanoparticles: evaluation of the Airspace Dimension Assessment technique.

Airspace Dimension Assessment (AiDA) is a technique to assess lung morphology by measuring lung deposition of inhaled nanoparticles. Nanoparticles deposit in the lungs predominately by diffusion, and average diffusion distances, corresponding to effective airspace radii (rAiDA), can be inferred from measurements of particle recovery after varied breath holds. Also, particle recovery after a 0-s breath hold (R0) may hold information about the small conducting airways. This study investigates rAiDA at different volumetric sample depths in the lungs of healthy subjects. Measurements were performed with 50-nm polystyrene nanospheres on 19 healthy subjects aged 17-67 yr. Volumetric sample depths ranged from 200 to 5,000 ml and breath-hold times from 5 to 20 s. At the examined volumetric sample depths, rAiDA values ranged from ~200-600 µm, which correspond to dimensions of the bronchiolar and the gas-exchanging regions of the lungs. R0 decreased with volumetric sample depth and showed more intersubject variation than rAiDA. Correlations were found between the AiDA parameters, anthropometry, and lung function tests, but not between rAiDA and R0. For repeated measurements on 3 subjects over an 18-mo period, rAiDA varied on average within ± 7 µm (± 2.4%). The results indicate that AiDA has potential as an efficient new in vivo technique to assess individual lung properties. The information obtained by such measurements may be of value for lung diagnostics, especially for the distal lungs, which are challenging to examine directly by other means.NEW & NOTEWORTHY This is the first study to measure effective airspace radii (rAiDA) at volumetric sample depths 200-5,000 ml in healthy subjects by Airspace Dimension Assessment (AiDA). Observed rAiDA were 200-600 µm, which corresponds to airspaces for the bronchiolar and the gas-exchanging regions around airway generation 14-17. rAiDA correlated with lung function tests and anthropometry. Measurements of rAiDA on 3 subjects over 11-18 mo were within ± 7 µm.

Altered deposition of inhaled nanoparticles in subjects with chronic obstructive pulmonary disease.

BACKGROUND: Respiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease. METHODS: Lung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests. RESULTS: We found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001-0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p < 0.05), FEV1/VC%Pred (p < 0.01) and DL,CO (p < 0.0005) when all subjects were included. Furthermore, for subjects with emphysema, deposition fraction correlated strongly with DL,CO (Pearson's r = 0.80-0.85, p < 0.002) while this correlation was not found within the other groups. CONCLUSIONS: Lower deposition fraction was observed for emphysematous subjects and this can be explained by enlarged distal airspaces in the lungs. As expected, deposition increases for smaller particles and deeper inhalation. The observed results have implications for exposure assessment of air pollution and dosimetry of aerosol-based drug delivery of nanoparticles.

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

BACKGROUND: Airspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings. METHOD: Nineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI). RESULTS: The distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = -0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149). CONCLUSION: The AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated.

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

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 (DL,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.

Assessment of respiratory tract deposition of nanoparticles is a key link to understanding their health impacts. An instrument was developed to measure respiratory tract deposition of nanoparticles in a single breath. Monodisperse nanoparticles are generated, inhaled and sampled from a determined volumetric lung depth after a controlled residence time in the lung. The instrument was characterized for sensitivity to inter-subject variability, particle size (22, 50, 75 and 100 nm) and breath-holding time (3-20 s) in a group of seven healthy subjects. The measured particle recovery had an inter-subject variability 26-50 times larger than the measurement uncertainty and the results for various particle sizes and breath-holding times were in accordance with the theory for Brownian diffusion and values calculated from the Multiple-Path Particle Dosimetry model. The recovery was found to be determined by residence time and particle size, while respiratory flow-rate had minor importance in the studied range 1-10 L/s. The instrument will be used to investigate deposition of nanoparticles in patients with respiratory disease. The fast and precise measurement allows for both diagnostic applications, where the disease may be identified based on particle recovery, and for studies with controlled delivery of aerosol-based nanomedicine to specific regions of the lungs.