Airspace Dimensions Research Articles

Enlarged airspaces in the distal lung in adolescents born very preterm as measured by aerosol

RationalePreterm infants diagnosed with bronchopulmonary dysplasia (BPD) are thought to have fewer and larger alveoli than their term peers, but it is unclear to what degree this persists later in...

Innovative airspace reflective tool for different building applications, part II: parametric study

Enclosed airspaces of different dimensions and inclinations that exist in buildings include double-pane windows, curtain walls, skylight devices, and reflective insulation assemblies for walls and roofing systems. Evaluating the energy performance of buildings requires accurate determination of the thermal resistance of enclosed airspaces in different climates. The parameters that affect enclosed airspace thermal resistances include the physical properties of air, the temperatures and emittances of airspace surfaces, airspace dimensions, and heat-flow direction. The Airspace Reflective Tool (ART) was developed for determining the thermal resistances of enclosed airspaces for a wide variety of conditions. In this article, for enclosed airspaces of various orientations and heat flow directions, the ART has been used to conduct a parametric study to quantify the effect on thermal resistance of: effective emittance, operating conditions such as temperature, orientation, dimensions (aspect ratio) and heat flow-direction. The calculated thermal resistances from the ART were compared with those in the ASHRAE Handbook of Fundamentals or calculated using ISO-6946 that are currently being used to obtain thermal resistances of enclosed airspaces and show the importance of the factors being considered.

Assessment of Left Lung Remodeling With Magnetic Resonance Imaging in a Murine Model Following Exposure to Douglas Fir Smoke.

Wildland firefighters (WLFFs) experience lung function decline due to occupational exposure to fire smoke. WLFFs typically do not wear respiratory personal protective equipment, and if they do, it is a simple bandana, which is not effective at filtering smoke. To pinpoint the biological underpinnings of abnormal respiratory function following 3-7 years of WLFF service, we exposed mice to Douglas fir smoke (DFS) over 8 weeks. Following exposure, we assessed changes in lung structure through Magnetic Resonance Imaging (MRI) and histological analysis, which was supported by immunohistochemistry staining. With MRI, we found that the signal decay time, T2*, from ultrashort echo time (UTE) images was significantly shorter in mice exposed to DFS compared to air controls. In addition, the variation in T2* was more heterogeneously distributed throughout the left lung in DFS-exposed mice, compared to air controls. As confirmed by histological analysis, shorter T2* was caused by larger parenchyma airspace sizes and not fibrotic remodeling. Destruction of the alveolar spaces was likely due to inflammation, as measured by an influx of CD68+ macrophages and destruction due to enhanced neutrophil elastase. In addition, measurements of airspace dimensions from histology were more heterogeneously distributed throughout the lung, corroborating the enhanced relative dispersion of T2*. Findings from this study suggest that the decline in lung function observed in WLFFs may be due to emphysema-like changes in the lung, which can be quantified with MRI.

An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models

BackgroundThe understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm.MethodsWe designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (rAiDA). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity).ResultsThe measured fractional deposition for 2.3 μm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (rAiDA) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model.ConclusionsWhole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations – a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that rAiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.

Ultrasound multifrequency strategy to estimate the lung surface roughness, in silico and in vitro results

Lung ultrasound (LUS) is an important imaging modality to assess the state of the lung surface. Nevertheless, LUS is limited to the visual evaluation of imaging artifacts, especially the vertical ones. These artifacts are observed in pathologies characterized by a reduction of dimensions of air-spaces (alveoli). In contrast, there exist pathologies, such as chronic obstructive pulmonary disease (COPD), in which an enlargement of air-spaces can occur, which causes the lung surface to behave essentially as a perfect reflector, thus not allowing ultrasound penetration. This characteristic high reflectivity could be exploited to characterize the lung surface. Specifically, air-spaces of different sizes could cause the lung surface to have a different roughness, whose estimation could provide a way to assess the state of the lung surface. In this study, we present a quantitative multifrequency approach aiming at estimating the lung surface’s roughness by measuring image intensity variations along the lung surface as a function of frequency. This approach was tested both in silico and in vitro, and it showed promising results. For the in vitro experiments, radiofrequency (RF) data were acquired from a novel experimental model. The results showed consistency between in silico and in vitro experiments.

Differential effects of two-hit models of acute and ventilator-induced lung injury on lung structure, function, and inflammation.

Acute respiratory distress syndrome (ARDS) and acute lung injury have a diverse spectrum of causative factors including sepsis, aspiration of gastric contents, and near drowning. Clinical management of severe lung injury typically includes mechanical ventilation to maintain gas exchange which can lead to ventilator-induced lung injury (VILI). The cause of respiratory failure is acknowledged to affect the degree of lung inflammation, changes in lung structure, and the mechanical function of the injured lung. However, these differential effects of injury and the role of etiology in the structure-function relationship are not fully understood. To address this knowledge gap we caused lung injury with intratracheal hydrochloric acid (HCL) or endotoxin (LPS) 2days prior to ventilation or with an injurious lavage (LAV) immediately prior to ventilation. These injury groups were then ventilated with high inspiratory pressures and positive end expiratory pressure (PEEP) = 0cmH2O to cause VILI and model the clinical course of ARDS followed by supportive ventilation. The effects of injury were quantified using invasive lung function measurements recorded during PEEP ladders where the end-expiratory pressure was increased from 0 to 15cm H2O and decreased back to 0cmH2O in steps of 3cmH2O. Design-based stereology was used to quantify the parenchymal structure of lungs air-inflated to 2, 5, and 10cmH2O. Pro-inflammatory gene expression was measured with real-time quantitative polymerase chain reaction and alveolocapillary leak was estimated by measuring bronchoalveolar lavage protein content. The LAV group had small, stiff lungs that were recruitable at higher pressures, but did not demonstrate substantial inflammation. The LPS group showed septal swelling and high pro-inflammatory gene expression that was exacerbated by VILI. Despite widespread alveolar collapse, elastance in LPS was only modestly elevated above healthy mice (CTL) and there was no evidence of recruitability. The HCL group showed increased elastance and some recruitability, although to a lesser degree than LAV. Pro-inflammatory gene expression was elevated, but less than LPS, and the airspace dimensions were reduced. Taken together, those data highlight how different modes of injury, in combination with a 2nd hit of VILI, yield markedly different effects.

Sensitive methods for assessment of lung health in welders and controls

BackgroundWelders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. MethodsThis study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). ResultsAccording to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. ConclusionsThis study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology.

Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.

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

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. 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. 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. AiDA parameters can provide information on early pulmonary peripheral changes that may not be seen with standard techniques used in screening of pulmonary function.

Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency.

Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (ELN), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18–55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in Eln+/− and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) were lower in adults with WS (p < 0.0001 and p < 0.05, respectively). The FEV1/FVC ratio was more frequently below the lower limit of normal in cases (p < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (p < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (p < 0.0001). In Eln+/− mice, ex vivo lung volumes were increased (p < 0.0001), with larger airspaces (p < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS.

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

BackgroundAirspace 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.MethodsAiDA 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.ResultsOur 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.ConclusionWe conclude that the AiDA method provides information about the lung that is inaccessible with more conventional lung function techniques.

Advanced Modeling of Enclosed Airspaces to Determine Thermal Resistance for Building Applications

Enclosed airspaces to reduce heat flow have been recognized for well over 100 years. Airspaces with one or more reflective surfaces define reflective insulation (RI) assemblies, a product type used in walls, roofs, windows with multiple panes, curtain walls and skylights. The thermal resistance (R value) of airspaces depends on the emittance of all surfaces, airspace dimensions and orientation, heat flow direction and surfaces temperatures. The modeling of RI now includes CFD coupled with radiation to quantify the total heat transfer. This study compares a validated model for airspace R values with existing methods such as ISO 6946 and hot-box results that provide the R values in the ASHRAE Handbook of Fundamentals. The existing methods do not include an airspace aspect ratio. This study showed that the aspect ratio can impact the R value by a factor of two. The impact of aspect ratio was calculated for double airspaces variation such as that for single airspaces. The present calculations are two-dimensional and also consider all the bounding airspace surfaces, while previous methods are one-dimensional and do not include surface temperature variations or detailed radiative transport.

Airspace Dimension Assessment (AiDA) by inhaled nanoparticles: benchmarking with hyperpolarised 129Xe diffusion-weighted lung MRI

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of distal airspaces from hyperpolarised 129Xe diffusion-weighted (DW)-lung magnetic resonance imaging (MRI). AiDA and 129Xe DW-MRI measurements were performed in 23 healthy volunteers who spanned an age range of 23–70 years. The relationship between the 129Xe DW-MRI and AiDA metrics was tested using Spearman’s rank correlation coefficient. Significant correlations were observed between AiDA distal airspace radius (rAiDA) and mean 129Xe apparent diffusion coefficient (ADC) (p < 0.005), distributed diffusivity coefficient (DDC) (p < 0.001) and distal airspace dimension (LmD) (p < 0.001). A mean bias of − 1.2 µm towards rAiDA was observed between 129Xe LmD and rAiDA, indicating that rAiDA is a measure of distal airspace dimension. The AiDA R0 intercept correlated with MRI 129Xe α (p = 0.02), a marker of distal airspace heterogeneity. This study demonstrates that AiDA has potential to characterize the distal airspace microstructures and may serve as an alternative method for clinical examination of the lungs.

An Analysis on Tradable Permit Models for Last-Mile Delivery Drones

Drones can play a game-changing role in reducing both cost and time in the context of last-mile deliveries. This paper addresses the last-mile delivery problem from a complex system viewpoint, where the collective performance of the drones is investigated. We consider a last-mile delivery system with a tradable permit model (TPM) for airspace use. Typically, in other research works regarding last-mile delivery drones, a fully cooperative centralized scenario is contemplated. In our approach, due to the TPM, the agents (i.e. drones) need to compete for airspace permits in a distributed manner. We simulate the system and evaluate how different parameters, such as the arrival rate and airspace dimensions, impact the system behavior in terms of the cost and time needed by the drones to acquire flight permits, and the airspace utilization. We use a simplified simulation model, where the agents' strategies are naïve, and the drones' flight dynamics are not accounted for. Nevertheless, the simulation's level of detail is adequate for capturing interesting properties from the agents' collective behavior, as our results support. The obtained results show that the system's performance is satisfactory, even with naïve agents and under high traffic conditions. Moreover, a real-world implementation of our competitive decentralized approach would lead to advantages, such as fast permit transactions, simple computational infrastructures, and error resilience.

In Vivo Morphometry of Distal Airspaces with Nanoparticles As a Proposed Biomarker for Emphysema

Background: Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airway morphology non-invasively. In this study, AiDA-derived airspace radii were measured in an unselected, cross-sectional study population. Persons with emphysema detected by computed tomography (CT) were compared to non-emphysematous subjects. Method: Nanoparticle inhalation tests, from which distal airspace radius (rAiDA) were calculated, were conducted on 618 individuals aged 50-64 years participating in the population-based Swedish CArdiopulmonary BioImaging Study (SCAPIS). The radius was studied in relation to visual and densitometric assessment of emphysema, as well as to lung function tests and symptoms. Findings: The forty-seven individuals with visually detected emphysema had a significantly larger rAiDA (326 ± 49 µm), compared to non-emphysematous persons (291 ± 36 µm), p = 0.00001. Odds ratio per 1 µm for emphysema, adjusted for age, sex, height and weight was 1·021 (1·013 - 1·028), p<0·0001. Similar results were found when other lung function measures were assessed. Interpretation: AiDA can indicate distal airspace enlargement and is a potential biomarker for emphysema. A diagnostic accuracy study in patients with suspected lung disease is needed to establish AiDA as a diagnostic technique. Funding: The study has received support from the Swedish Heart and Lung Foundation, The Swedish Research Council, FORTE, the Crafoord foundation, the Swedish Governmental Agency for Innovation Systems, the ERA-NET project EuroNanoMed2, and governmental funding of clinical research within the National Health Services. Declaration of Interest: The funders of the study had no commercial interests. Ethical Approval: The study was approved by the Regional Ethical Review Board in Umea, Sweden, 2010/228-31, and performed according to the Declaration of Helsinki.

On-demand assessment of air traffic impact of blocking airspace

ABSTRACTThe Federal Aviation Administration often blocks strategically located airspace volumes to ensure safety during a variety of operations that are potentially hazardous to aircraft, such as space launches. As the frequency of these operations increases, there is a growing need to deepen collaboration and transparency between stakeholders regarding the use of airspace. This collaboration can be supported by models and capabilities to quickly assess the impact of airspace closures, up to 12 months into the future. This paper presents a technique to enable a ‘what-if’ analysis capability coupled with a prediction model, whereby changes in airspace dimension, location, and activation time are reflected instantaneously as measures of projected impact. The technique can also be used for quick post-operations analysis using historical traffic data and to develop air traffic impact assessment capabilities accessible to a broad range of users outside of the air traffic domain. This research has three key components: developing a model to predict air traffic demand up to 12 months into the future, modelling air traffic impact to the affected traffic, and reducing this information into a data structure that can support on-demand analysis. The focus of this paper is on new techniques to predict demand using a large set of historical track data and further encode these projections to support the quick assessment of the impact of blocking various airspace volumes. Initial results show that the proposed data reduction scheme accurately represented the traffic crossing an airspace and resulted in data size reduction by over 50%. The projection model performed well, the actual number of impacted flights were within the estimated range of approximately 80% of the time. Finally, the responsiveness of the web-based prototype developed to illustrate the concept demonstrated the model’s ability to support an on-demand assessment of the air traffic impact of blocking airspace. A significant limitation of the projection model is that it is based on the historical traffic pattern within the U.S. airspace; separate analysis is needed to adapt it to other geographical location.

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.

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

BackgroundAirspace 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.MethodNineteen 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).ResultsThe 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).ConclusionThe 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.

Deposition of inhaled nanoparticles is reduced in subjects with COPD and correlates with the extent of emphysema: proof of concept for a novel diagnostic technique.

The diagnosis of chronic obstructive pulmonary disease (COPD) is often based on spirometry, which is not sensitive to early emphysema. We have recently described a method for assessing distal airspace dimensions by measuring recovery of nanoparticles in exhaled air after a single-breath inhalation followed by breath-hold. Recovery refers to the non-deposited particle fraction. The aim of this study was to explore differences in the recovery of exhaled nanoparticles in subjects with COPD and never-smoking controls. A secondary aim was to determine whether recovery correlates with the extent of emphysema. A total of 19 patients with COPD and 19 controls underwent three repeats of single-breath nanoparticle inhalation followed by breath-hold. Particle concentrations in the inhaled aerosol, and in an alveolar sample exhaled after breath-hold, were measured to obtain recovery. The patients with COPD had a significantly higher mean recovery than controls, 0·128±0·063 versus 0·074±0·058; P=0·010. Also, recovery correlated significantly with computed tomography (CT) densitometry variables (P<0·01) and diffusing capacity for carbon monoxide (DL,CO ; P=0·002). Higher recovery for emphysema patients, relative to controls, is explained by larger diffusion distances in enlarged distal airspaces. The nanoparticle inhalation method shows potential to be developed towards a tool to diagnose emphysema.

Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models.

During lung inflation, airspace dimensions are affected nonlinearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats (n = 7) and healthy controls (n = 7) were imaged with HP MRI. Gradual inflation was achieved by incremental changes to both inflation volume and airway pressure. The apparent diffusion coefficient (ADC) was measured at each level of inflation and fitted to the corresponding airway pressures as the second-order response equation, with minimizing residue (χ2 < 0.001). A biphasic ADC response was detected, with an initial ADC increase followed by a decrease at airway pressures >18 cmH2O. Discrimination between treated and control rats was optimal when airway pressure was intermediate (between 10 and 11 cmH2O). Similar findings were confirmed in mice following long-term exposure to cigarette smoke, where optimal discrimination between treated and healthy mice occurred at a similar airway pressure as in the rats. We subsequently explored the evolution of ADC measured at the intermediate inflation level in mice after prolonged smoke exposure and found a significant increase (P < 0.01) in ADC over time. Our results demonstrate that measuring ADC at intermediate inflation enhances the distinction between healthy and diseased lungs, thereby establishing a model that may improve the diagnostic accuracy of future HP gas diffusion studies.