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Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine quantitative ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate (p = 1e -4 for edema and p = 3e -7 for fibrosis) to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices., (© 2024. The Author(s).)

Acute lung injury (ALI) represents an aetiologically diverse form of pulmonary damage. Part of the assessment and diagnosis of ALI depends on skilled observer-based scoring of brightfield microscopy tissue sections. Although this readout is sufficient to determine gross alterations in tissue structure, its categorical scores lack the sensitivity to describe more subtle changes in lung morphology. To generate a more sensitive readout of alveolar perturbation we carried out high resolution immunofluorescence imaging on 200 μm lung vibratome sections from baseline and acutely injured porcine lung tissue, stained with a tomato lectin, Lycopersicon Esculentum Dylight-488. With the ability to resolve individual alveoli along with their inner and outer wall we generated continuous readouts of alveolar wall thickness and circularity. From 212 alveoli traced from 10 baseline lung samples we established normal distributions for alveolar wall thickness (27.37; 95% CI [26.48:28.26]) and circularity (0.8609; 95% CI [0.8482:0.8667]) in healthy tissue. Compared to acutely injured lung tissue baseline tissue exhibited a significantly lower wall thickness (26.86 ± 0.4998 vs 50.55 ± 4.468; p = 0.0003) and higher degree of circularityϕ≤ (0.8783 ± 0.01965 vs 0.4133 ± 0.04366; p < 0.0001). These two components were subsequently combined into a single more sensitive variable, termed the morphological quotient (MQ), which exhibited a significant negative correlation (R 2  = 0.9919, p < 0.0001) with the gold standard of observer-based scoring. Through the utilisation of advanced light imaging we show it is possible to generate sensitive continuous datasets describing fundamental morphological changes that arise in acute lung injury. These data represent valuable new analytical tools that can be used to precisely benchmark changes in alveolar morphology both in disease/injury as well as in response to treatment/therapy., (© 2024. The Author(s).)

Introduction: Bronchopulmonary dysplasia (BPD) impacts life expectancy and long-term quality of life. Currently, BPD mouse models exposed to high oxygen are frequently used, but to reevaluate their relevance to human BPD, we attempted an assessment using micro-computed tomography (µCT)., Methods: Newborn wildtype male mice underwent either 21% or 95% oxygen exposure for 4 days, followed until 8 wk. Weekly µCT scans and lung histological evaluations were performed independently., Results: Neonatal hyperoxia for 4 days hindered lung development, causing alveolar expansion and simplification. Histologically, during the first postnatal week, the exposed group showed a longer mean linear intercept, enlarged alveolar area, and a decrease in alveolar number, diminishing by week 4. Weekly µCT scans supported these findings, revealing initially lower lung density in newborn mice, increasing with age. However, the high-oxygen group displayed higher lung density initially. This difference diminished over time, with no significant contrast to controls at 3 wk. Although no significant difference in total lung volume was observed at week 1, the high-oxygen group exhibited a decrease by week 2, persisting until 8 wk., Conclusion: This study highlights µCT-detected changes in mice exposed to high oxygen. BPD mouse models might follow a different recovery trajectory than humans, suggesting the need for further optimization.

Background: While the development of CT imaging technique has brought cognition of in vivo organs, the resolution of CT images and their static characteristics have gradually become barriers of microscopic tissue research., Purpose: Previous research used the finite element method to study the airflow and gas exchange in the alveolus and acinar to show the fate of inhaled aerosols and studied the diffusive, convective, and sedimentation mechanisms. Our study combines these techniques with CT scan simulation to study the mechanisms of respiratory movement and its imaging appearance., Methods: We use 3D fluid-structure interaction simulation to study the movement of an ideal alveolus under regular and forced breathing situations and ill alveoli with different tissue elasticities. Additionally, we use the Monte Carlo algorithm within the OpenGATE platform to simulate the computational CT images of the dynamic process with different designated resolutions. The resolutions show the relationship between the kinematic model of the human alveolus and its imaging appearance., Results: The results show that the alveolus and the wall thickness can be seen with an image resolution smaller than 15.6 μm. With ordinary CT resolution, the alveolus is expressed with four voxels., Conclusions: This is a preliminary study concerning the imaging appearance of the dynamic alveolus model. This technique will be used to study the imaging appearance of the dynamic bronchial tree and the lung lobe models in the future., (© 2023 American Association of Physicists in Medicine.)

Understanding how the alveolar mechanics work in live lungs is essential for comprehending how the lung behaves during breathing. Due to the lack of appropriate imaging tools, previous research has suggested that alveolar morphologies are polyhedral rather than spherical based on a 2D examination of alveoli in fixed lungs. Here, we directly observe high-resolution 3D alveoli in live mice lungs utilizing synchrotron x-ray microtomography to show spherical alveolar morphologies from the live lungs. Our measurements from x-ray microtomography show high sphericity, low packing density, big alveolar size, and low osmotic pressure, indicating that spherical alveolar morphologies are natural in living lungs. The alveolar packing fraction is quite low in live lungs, where the spherical alveoli would behave like free bubbles, while the confinement of alveolar clusters in fixed lungs would lead to significant morphological deformations of the alveoli appearing polyhedral. Direct observations of the spherical alveolar shapes will help understand and treat lung disease and ventilation., (© 2023. The Author(s).)

Mechanical forces affect the alveolar shape, depending on location and tissue composition, and vary during the respiratory cycle. This study performs alveolar morphomics in different lobes of human lungs using models generated from three-dimensional (3-D) micro-computed tomography (microCT) images. Cylindrical tissue samples (1.6 cm × 2 cm) were extracted from two nontransplantable donor lungs (one ex-smoker and one smoker, 3 samples per subject) that were air-inflated and frozen solid in liquid nitrogen vapor. Samples were scanned with microCT (11 µm/voxel). Within representative cubic regions of interest (5.5 mm edge length), alveoli were segmented to produce corresponding 3-D models from which quantitative data were obtained. The surface of segmented alveoli (n&#95;alv&#95;total = 23,587) was divided into individual planar surfaces (facets) and angles between facet normals were calculated. Moreover, the number of neighboring alveoli was estimated for every alveolus. In this study, we examined intraindividual differences in alveolar morphology, which were reproducible in the lungs of two subjects. The main aspects are higher mean alveolar volumes (v&#95;alv: 6.64 × 10 6 and 6.63 × 10 6 µm 3 vs. 5.78 × 10 6 and 6.29 × 10 6 µm 3 ) and surface sizes (s&#95;alv: 0.19 and 0.18 mm 2 vs. 0.17 mm 2 in both lower lobes) in both upper lung lobes compared with the lower lobes. An increasing number of facets (f&#95;alv) from top to bottom (12 and 14 in the upper lobes; 14 and 15 in the lower lobes), as well as a decreasing number of alveolar neighbors (nei&#95;alv: 9 and 8 in the upper lobes; 8 and 7 in the lower lobes) from the upper lobes to the lower lobes were observed. We could observe an increasing ratio of alveolar entrance size to the surface size of the alveoli from top to bottom (S&#95;ratio&#95;alv: 0.71 and 0.64 in the upper lobes, 0.73 and 0.70 in the lower lobes). The angles between facet normals (ang&#95;alv) were larger in the upper lobes (67.72° and 62.44°) of both lungs than in the lower lobes (66.19° and 61.30°). By using this new approach of analyzing alveolar 3-D data, which enables the estimation of facet, neighbor, and shape characteristics, we aimed to establish the baseline measures for in-depth studies of mechanical conditions and morphology.

Coronavirus disease 2019 (COVID-19) is a novel infectious disease affecting the general population worldwide. A fever and cough are the common clinical presentations of COVID-19. In most of these patients, computed tomography (CT) shows bilateral peripheral ground-glass opacities. We herein report a case of hemoptysis and lung bulla in the convalescent phase of COVID-19. Based on the clinical observations, alveolar destruction was likely associated with hemoptysis and bulla formation. Therefore, we suggest the follow-up of COVID-19 patients whose clinical parameters indicate alveolar damage, even after their symptoms improve.

The application of stereology to lung casts and two-dimensional microscopy images is the gold standard for quantification of the human lung anatomy. However, these techniques are labor intensive, involving fixation, embedding, and histological sectioning of samples and thus have prevented comprehensive studies. Our objective was to demonstrate the application of stereology to volumetric multiresolution computed tomography (CT) to efficiently and extensively quantify the human lung anatomy. Nontransplantable donor lungs from individuals with no evidence of respiratory disease ( n = 13) were air inflated, frozen at 10 cmH 2 O, and scanned using CT. Systematic uniform random samples were taken, scanned using micro-CT, and assessed using stereology. The application of stereology to volumetric CT imaging enabled comprehensive quantification of total lung volume, volume fractions of alveolar, alveolar duct, and tissue, mean linear intercept, alveolar surface area, alveolar surface area density, septal wall thickness, alveolar number, number-weighted mean alveolar volume, and the number and morphometry of terminal and transitional bronchioles. With the use of this data set, we found that women and men have the same number of terminal bronchioles (last generation of conducting airways), but men have longer terminal bronchioles, a smaller wall area percentage, and larger lungs due to a greater number of alveoli per acinus. The application of stereology to multiresolution CT imaging enables comprehensive analysis of the human lung parenchyma that identifies differences between men and women. The reported data set of normal donor lungs aged 25-77 yr provides reference data for future studies of chronic lung disease to determine exact changes in tissue pathology. NEW & NOTEWORTHY Stereology has been the gold standard to quantify the three-dimensional lung anatomy using two-dimensional microscopy images. However, such techniques are labor intensive. This study provides a method that applies stereology to volumetric computed tomography images of frozen whole human lungs and systematic uniform random samples. The method yielded a comprehensive data set on the small airways and parenchymal lung structures, highlighting morphometric sex differences and providing a reference data set for future pathological studies.

The lung acinus is the most distal portion of the airway responsible for the gas exchange. The normal acini are not visible on conventional computed tomography (CT), but the advent of micro-CT improved the understanding of the microarchitecture of healthy acini. The comprehension of the acinar architecture is pivotal for the understanding of CT findings of diseases that involve the acini. Centriacinar emphysema, for example, presents as round areas of low attenuation due to the destruction of the most central acini with compensatory enlargement of proximal acini due to alveolar wall destruction. In pulmonary fibrosis, intralobular septal fibrosis manifests as acinar wall thickening with an overlap of acinar collapse and compensatory dilation of surrounding acini constituting the cystic disease typical of the usual interstitial pneumonia pattern. This is a state-of-the-art review to describe the acinar structure from the micro-CT perspective and display how the comprehension of the acinar structure can aid in the interpretation of its microarchitecture disruption on conventional CT.

Rationale and Objectives: Hyperpolarized xenon-129 magnetic resonance (MR) provides sensitive tools that may detect early stages of lung disease in smokers before it has progressed to chronic obstructive pulmonary disease (COPD) apparent to conventional spirometric measures. We hypothesized that the functional alveolar wall thickness as assessed by hyperpolarized xenon-129 MR spectroscopy would be elevated in clinically healthy smokers before xenon MR diffusion measurements would indicate emphysematous tissue destruction., Materials and Methods: Using hyperpolarized xenon-129 MR we measured the functional septal wall thickness and apparent diffusion coefficient of the gas phase in 16 subjects with smoking-related COPD, 9 clinically healthy current or former smokers, and 10 healthy never smokers. All subjects were age-matched and characterized by conventional pulmonary function tests. A total of 11 data sets from younger healthy never smokers were added to determine the age dependence of the septal wall thickness measurements., Results: In healthy never smokers the septal wall thickness increased by 0.04 μm per year of age. The healthy smoker cohort exhibited normal pulmonary function test measures that did not significantly differ from the never-smoker cohort. The age-corrected septal wall thickness correlated well with diffusion capacity for carbon monoxide (R 2  = 0.56) and showed a highly significant difference between healthy subjects and COPD patients (8.8 μm vs 12.3 μm; p < 0.001), but was the only measure that actually discriminated healthy subjects from healthy smokers (8.8 μm vs 10.6 μm; p < 0.006)., Conclusion: Functional alveolar wall thickness assessed by hyperpolarized xenon-129 MR allows discrimination between healthy subjects and healthy smokers and could become a powerful new measure of early-stage lung disease., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Magnetic resonance imaging of lung tissue is strongly influenced by susceptibility effects between spin-bearing water molecules and air-filled alveoli. The measured lineshape, however, also depends on the interplay between susceptibility effects and blood-flow around alveoli that can be approximated as pseudo-diffusion. Both effects are quantitatively described by the Bloch-Torrey-equation, which was so far only solved for dephasing on the alveolar surface. In this work, we extend this model to the whole range of physiological relevant air volume fractions. The results agree very well with in vivo measurements in human lung tissue., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Treatment of respiratory disease with a drug delivered via inhalation is generally held as being beneficial as it provides direct access to the lung target site with a minimum systemic exposure. There is however only limited information of the regional localization of drug retention following inhalation. The aim of this study was to investigate the regional and histological localization of salmeterol retention in the lungs after inhalation and to compare it to systemic administration. Lung distribution of salmeterol delivered to rats via nebulization or intravenous (IV) injection was analyzed with high-resolution mass spectrometry imaging (MSI). Salmeterol was widely distributed in the entire section at 5 min after inhalation, by 15 min it was preferentially retained in bronchial tissue. Via a novel dual-isotope study, where salmeterol was delivered via inhalation and d 3 -salmeterol via IV to the same rat, could the effective gain in drug concentration associated with inhaled delivery relative to IV, expressed as a site-specific lung targeting factor, was 5-, 31-, and 45-fold for the alveolar region, bronchial sub-epithelium and epithelium, respectively. We anticipate that this MSI-based framework for quantifying regional and histological lung targeting by inhalation will accelerate discovery and development of local and more precise treatments of respiratory disease.

Background and Objective: This work introduces an object-oriented computational model to study cardiopulmonary interactions in humans., Methods: Modeling was performed in object-oriented programing language Matlab Simscape, where model components are connected with each other through physical connections. Constitutive and phenomenological equations of model elements are implemented based on their non-linear pressure-volume or pressure-flow relationship. The model includes more than 30 physiological compartments, which belong either to the cardiovascular or respiratory system. The model considers non-linear behaviors of veins, pulmonary capillaries, collapsible airways, alveoli, and the chest wall. Model parameters were derisved based on literature values. Model validation was performed by comparing simulation results with clinical and animal data reported in literature., Results: The model is able to provide quantitative values of alveolar, pleural, interstitial, aortic and ventricular pressures, as well as heart and lung volumes during spontaneous breathing and mechanical ventilation. Results of baseline simulation demonstrate the consistency of the assigned parameters. Simulation results during mechanical ventilation with PEEP trials can be directly compared with animal and clinical data given in literature., Conclusions: Object-oriented programming languages can be used to model interconnected systems including model non-linearities. The model provides a useful tool to investigate cardiopulmonary activity during spontaneous breathing and mechanical ventilation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Lungs represent the essential part of the mammalian respiratory system, which is reflected in the fact that lung failure still is one of the leading causes of morbidity and mortality worldwide. Establishing the connection between macroscopic observations of inspiration and expiration and the processes taking place at the microscopic scale remains crucial to understand fundamental physiological and pathological processes. Here we demonstrate for the first time in vivo synchrotron-based tomographic imaging of lungs with pixel sizes down to a micrometer, enabling first insights into high-resolution lung structure. We report the methodological ability to study lung inflation patterns at the alveolar scale and its potential in resolving still open questions in lung physiology. As a first application, we identified heterogeneous distension patterns at the alveolar level and assessed first comparisons of lungs between the in vivo and immediate post mortem states.

Background: Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF)., Methods: Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (CALIPER) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185)., Results: In CHP, visual/CALIPER measures of reticular pattern, honeycombing, visual traction bronchiectasis, and CALIPER ILD extent were predictive of mortality (p < 0 · 05) on univariate analysis. PVV was strongly predictive of mortality on univariate (p < 0 · 0001) and multivariate analysis independent of age, gender and disease severity (represented by the CPI [p < 0 · 01]). CHP patients with a PVV threshold >6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185)., Conclusions: Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.

Purpose: To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized 3 He gas for whole lung morphometry with compressed sensing (CS)., Methods: A fully-sampled, two b-value, 3D hyperpolarized 3 He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the k y and k z phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled 3 He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value 3 He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (Lm D ) were validated against two-dimensional (2D) and 3D fully-sampled 3 He DW-MRI experiments., Results: Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and Lm D values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs., Conclusions: Accelerated CS acquisition has facilitated 3D multiple b-value 3 He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med 77:1916-1925, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: The interest in measurements of magnetic resonance imaging relaxation times, T1, T2, T2*, with intention to characterize healthy and diseased lungs has increased recently. Animal studies play an important role in this context providing models for understanding and linking the measured relaxation time changes to the underlying physiology or disease. The aim of this work was to study how the measured transversal relaxation time (T2) in healthy lungs is affected by normal respiration in mouse., Method: T2 of lung was measured in anaesthetized freely breathing mice. Image acquisition was performed on a 4.7 T, Bruker BioSpec with a multi spin-echo sequence (Car-Purcell-Meiboom-Gill) in both end-expiration and end-inspiration. The echo trains consisted of ten echoes of inter echo time 3.5 ms or 4.0 ms. The proton density, T2 and noise floor were fitted to the measured signals of the lung parenchyma with a Levenberg-Marquardt least-squares three-parameter fit., Results: T2 in the lungs was longer (p<0.01) at end-expiration (9.7±0.7 ms) than at end-inspiration (9.0±0.8 ms) measured with inter-echo time 3.5 ms. The corresponding relative proton density (lung/muscle tissue) was higher (p<0.001) during end-expiration, (0.61±0.06) than during end-inspiration (0.48±0.05). The ratio of relative proton density at end-inspiration to that at end-expiration was 0.78±0.09. Similar results were found for inter-echo time 4.0 ms and there was no significant difference between the T2 values or proton densities acquired with different interecho times. The T2 value increased linearly (p< 0.001) with proton density., Conclusion: The measured T2 in-vivo is affected by diffusion across internal magnetic susceptibility gradients. In the lungs these gradients are modulated by respiration, as verified by calculations. In conclusion the measured T2 was found to be dependent on the size of the alveoli., Competing Interests: The commercial company Antaros Medical (PHD) defines the authors’ current position and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Background: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs., Methods: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH2 O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2 O every 4 min, and a semi-complete scan performed at the end of each PEEP step., Results: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (β = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2 O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP., Conclusions: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Simulation of flow in the human lung is of great practical interest as a means to study the detailed flow patterns within the airways for many physiological applications. While computational simulation techniques are quite mature, lung simulations are particularly complicated due to the vast separation of length scales between upper airways and alveoli. Many past studies have presented numerical results for truncated airway trees, however, there are significant difficulties in connecting such results with respiratory airway models. This article presents a new modeling paradigm for flow in the full lung, based on a conjugate fluid-porous formulation where the upper airway is considered as a fluid region with the remainder of the lung being considered as a coupled porous region. Results are presented for a realistic lung geometry obtained from computed tomography (CT) images, which show the method's potential as being more efficient and practical than attempting to directly simulate flow in the full lung.

Background: With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case, the lung tissue density would decrease with inflation, whereas in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural issue, we measured the CT scan density in human subjects of widely varying size at two different lung volumes., Methods: Five hundred one subjects were enrolled in the study. They underwent a chest CT scan at full inspiration and another scan at end expiration. Spirometry, body plethysmography, and diffusing capacity of the lung for carbon monoxide were also measured., Results: There was a strong correlation between the size of the lungs measured at full inspiration on CT scan and the mean lung density (r = -0.72, P = .001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes., Conclusions: Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if larger lungs just had more alveoli. These observations suggest that the growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of greater air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

The gravity-dependent pleural pressure gradient within the thorax produces regional differences in lung inflation that have a profound effect on the distribution of ventilation within the lung. This study examines the hypothesis that gravitationally induced differences in stress within the thorax also influence alveolar density in terms of the number of alveoli contained per unit volume of lung. To test this hypothesis, we measured the number of alveoli within known volumes of lung located at regular intervals between the apex and base of four normal adult human lungs that were rapidly frozen at a constant transpulmonary pressure, and used microcomputed tomographic imaging to measure alveolar density (number alveoli/mm3) at regular intervals between the lung apex and base. These results show that at total lung capacity, alveolar density in the lung apex is 31.6 ± 3.4 alveoli/mm3, with 15 ± 6% of parenchymal tissue consisting of alveolar duct. The base of the lung had an alveolar density of 21.2 ± 1.6 alveoli/mm3 and alveolar duct volume fraction of 29 ± 6%. The difference in alveolar density can be negated by factoring in the effects of alveolar compression due to the pleural pressure gradient at the base of the lung in vivo and at functional residual capacity.

Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia remain the leading causes of preterm infant morbidity, mortality, and lifelong disability. Research to improve outcomes requires translational large animal models for RDS. Preterm pigs delivered by caesarian section at gestation days (GD) 98, 100, 102, and 104 were provided 24 h of neonatal intensive care, monitoring (pulse oximetry, blood gases, serum biomarkers, radiography), and nutritional support, with or without intubation and mechanical ventilation (MV; pressure control ventilation with volume guarantee). Spontaneous development of RDS and mortality without MV are inversely related with GD at delivery and correspond with inadequacy of tidal volume and gas exchange. GD 98 and 100 pigs have consolidated lungs, immature alveolar architecture, and minimal surfactant protein-B expression, and MV is essential at GD 98. Although GD 102 pigs had some alveoli lined by pneumocytes and surfactant was released in response to MV, blood gases and radiography revealed limited recruitment 1-2 h after delivery, and mortality at 24 h was 66% (35/53) with supplemental oxygen provided by a mask and 69% (9/13) with bubble continuous positive airway pressure (8-9 cmH2O). The lungs at GD 104 had higher densities of thin-walled alveoli that secreted surfactant, and MV was not essential. Between GD 98 and 102, preterm pigs have ventilation inadequacies and risks of RDS that mimic those of preterm infants born during the saccular phase of lung development, are compatible with standards of neonatal intensive care, and are alternative to fetal nonhuman primates and lambs., (Copyright © 2015 the American Physiological Society.)

Objective: To investigate the high-resolution computed tomographic (HRCT) features of infants with diffuse lung disease (DLD) for improving the diagnostic accuracy clinically., Method: Totally 75 infants under 2 years of age with DLD (2010-2013) were involved in this study. Among them, 56 were males and 19 females, aged from 2 days to 24 months (mean age was 10.9 months). According to the clinical or pathological data, the cases were enrolled into three groups, including systemic diseases-associated infantile DLD (30 cases), alveolar structure disorders-associated infantile DLD (23 cases), and infantile DLD specific to infancy (22 cases). Retrospectively, HRCT images, from the three groups respectively, were analyzed and compared. HRCT presentations including airway disorders, interstitial disorders and air space disorders were reviewed. Inter-reviewers consistency check was performed, the consistency between reviewers was good (K = 0.64;P = 0.03, < 0.05), as well as χ(2) test., Result: Among the three groups, some of the HRCT sings (bronchiectasis, thickened bronchiolar wall, mosaic sign, reticular, intralobular nodules and consolidations) had significant differences (χ(2) = 24.52, 6.08, 18.00, 12.56, 9.11 and 11.50, P < 0.05) ., Conclusion: The HRCT features of infantile pulmonary DLD/interstitial LD with different causes were as follows, compared to the other two groups, intralobular nodules was the main feature of the systemic diseases-associated infantile DLD, thickened bronchiolar wall, mosaic sign and consolidations were rare as well. Meanwhile, bronchiectasis was more common in alveolar structural disorders-associated infantile DLD, and reticular opacity was rarely seen. Associated clinical data, the HRCT presentations would help clinicians to make accurate diagnosis.

Objective: To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP)., Methods: The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized., Results: Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement., Conclusions: AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

Interstitial lung disease (ILD) is defined as a rare, heterogeneous group of parenchymal lung conditions that develop primarily because of underlying developmental or genetic disorders. Affected infants typically present with clinical syndromes characterized by dyspnea, tachypnea, crackles and hypoxemia. Until recently, the understanding of ILD in infants has been limited largely owing to a lack of evidence-based information of underlying pathogenesis, natural history, imaging findings and histopathological features. However, ILD in infants is now better understood and managed because of (1) advances in imaging methods that result in rapid and accurate detection, (2) improved thoracoscopic techniques for lung biopsy, (3) a consensus regarding the pathological criteria for these particular lung conditions and (4) a new classification system based on the underlying etiology of ILD. This article reviews the new classification system, imaging technique, clinical presentation and imaging findings of ILD in infants. Specialized knowledge of this new classification system in conjunction with recognition of characteristic imaging findings of ILD in infants has great potential for early and accurate diagnosis, which in turn can lead to optimal patient management.

Background: Maintenance of the open lung alveoli in the expiration on mechanical ventilation in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains challenging despite advances in lung imaging. The inspiratory lower inflection point (LIP) on the ventilator pressure-volume (P-V) curve estimates the required end-expiratory pressure for recruitment of alveolar consolidation. Alternatively, the end-expiratory pressure for recruitment of crater-like subpleural alveolar consolidation could be simply followed with ultrasound. These two methods for setting the ventilators positive end-expiratory pressure (PEEP) were compared., Methods: The observational study in surgical/neurosurgical intensive care between October 2009 and November 2011 included 17 deeply sedated or relaxed patients. LIP was measured with continuous low-flow method, as a pressure in cmH(2)O. Expiratory levelling between lower border of subpleural consolidation and adjacent pleural line, which means lung recruitment, was followed with linear ultrasound probe. PEEP in cmH(2)O at which the levelling occurs was compared with LIP pressure., Results: LIP pressure never exceeds the PEEP for recruitment of subpleural consolidations followed with ultrasound. A significant correlation (r = 0.839; p < 0.05) was found between two methods., Conclusions: In this study, positive end-expiratory pressures for recruitment of subpleural consolidations followed by ultrasound always exceed the pressures measured with LIP. Respecting this, ultrasound method could be the guide for PEEP lung recruitment.

We report a case of alveolar capillary dysplasia, wherein duodenal atresia was diagnosed during the third trimester. A 36-year-old mother was referred to our hospital for polyhydramnios at 31 weeks' gestation. Duodenal atresia was suspected from the ultrasonographic findings, which showed gastric dilation. Other findings noted were enlarged, highly echogenic lungs, a spherical heart and an increased lung-thorax transverse area ratio. A male infant was born at 37 weeks' gestation. The findings of serial radiography of the infant's upper gastrointestinal tract were compatible with the diagnosis of duodenal atresia; however, he developed persistent pulmonary hypertension of the newborn eight hours after birth and died at five days of age. The autopsy revealed alveolar capillary dysplasia and duodenal obstruction. We propose that the detection of duodenal atresia should prompt the physician to conduct a thorough ultrasonographic examination to rule out associated anomalies, such as alveolar capillary dysplasia, which can be detected by the presence of highly echogenic lungs., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Objective: Because the chest radiograph currently remains the routine choice of imaging for the examination of the chest in the intensive care unit, we compared lung ultrasonography with chest radiography., Study Design: Observational prospective study., Methods: An ultrasound examination and chest radiography were simultaneously ordered in 50 patients whose clinical exam justified a lung exploration. Each exam was interpreted independently by an intensivist. The abnormalities found were classified into interstitial syndrome, alveolar consolidation, and pleural effusion. An agreement analysis was performed between the results of the two techniques. The delay between the order and interpretation of both investigations, and the degree of interobserver agreement were also collected., Results: The kappa agreement between lung ultrasonography and chest radiography was 0.42. In total, 329 total abnormalities were detected, 156 abnormalities were found by both techniques, 31 by radiography alone, and 142 by ultrasonography alone. The interobserver agreement was 0.86. Ultrasonography was performed with a shorter delay (14.8 ± 6.9 min vs 44.2 ± 21.4 min)., Conclusion: There was only moderate agreement between lung ultrasonography and chest radiography for the diagnosis of interstitial syndrome, alveolar consolidation and pleural effusion in intensive care unit. This result is mainly explained by the higher number of ultrasound abnormalities. With the ability to provide fast diagnosis, good reproducibility and high feasibility, ultrasound scan could represent an alternative exam for chest exploration in intensive care unit., (Copyright © 2010. Published by Elsevier SAS.)

Background: Diffuse comet-tail B-line artifacts in lung ultrasound are a sign of alveolar-interstitial syndrome, but isolated transthoracic scans positive for B-lines (multiple B lines or B+) could be detected in other conditions. The aim was to assess the prevalence and distribution of this sonographic sign in patients with normal lung or isolated alveolar consolidation in chest radiography., Material/methods: Two hundred seventeen patients consecutively admitted to this emergency medicine unit with any diagnosis and without radiographic or clinical evidence of diffuse interstitial syndrome were analyzed. Each patient underwent chest radiography and lung sonographic examination with four anterolateral chest scans per side., Results: Of the 1736 sonographic scans performed, 13.2% were positive for the B+ pattern. Positive scans significantly corresponded to laterobasal areas or radiographic opacities due to lung alveolar consolidations (p<0.005). Twenty percent of the laterobasal scans of 145 patients with radiologically normal lung were positive. The negative predictive value of B+ was 83.9% (95% confidence interval: 78.2-89.7%), with a specificity of 90.3% (95%CI: 85.5-95.1%) for predicting any localized radiographic pulmonary opacity., Conclusions: B+ scans can be detected in the chest areas surrounding an isolated alveolar consolidation and in the laterobasal scans of a radiographic normal lung. These features should always be considered when lung ultrasound is performed to rule out the alveolar-interstitial syndrome in an emergency setting. Moreover, B+ patterns have a satisfactory negative predictive value for radiographic lung opacities, which could have added diagnostic value in the ED evaluation of dyspneic patients.

Positron emission tomography (PET) provides three-dimensional images of the distributions of radionuclides that have been inhaled or injected into the lungs. By using radionuclides with short half-lives, the radiation exposure of the subject can be kept small. By following the evolution of the distributions of radionuclides in gases or compounds that participate in lung function, information about such diverse lung functions as regional ventilation, perfusion, shunt, gas fraction, capillary permeability, inflammation, and gene expression can be inferred. Thus PET has the potential to provide information about the links between cellular function and whole lung function in vivo. In this paper, recent advancements in PET methodology and techniques and information about lung function that have been obtained with these techniques are reviewed.

Objective: To evaluate the value of static pressure-volume (P-V) curve during alveolar recruitment and derecruitment in mechanical ventilated rabbits with acute respiratory distress syndrome (ARDS), and to explore the lung protective ventilation strategies., Methods: The ARDS rabbit model was duplicated by warm-saline alveolar lavage. Dynamic CT scan was implemented to monitor the intrapulmonary gas volume and distribution during alveolar recruitment and derecruitment gradually. Static P-V curve was measured to reflect the features of alveolar recruitment and derecruitment., Results: Four aeration regions including nonaeration, insufficient aeration, normal aeration and overinflation regions, varied following airway pressure variation (t = 2.477 - 9.794, all P < 0.05). Recruitment of insufficient aeration region was found. Alveolar recruitment was divided two parts, alveolar open at nonaeration region and recruitment at insufficient aeration region. And alveolar derecruitment was divided two parts, alveolar close at nonaeration region and derecruitment at insufficient aeration region. Distribution frequency of alveolar open was different from inspiratory (r = 0.219, P = 0.220). And distribution frequency of alveolar close was different from expiratory (r = 0.094, P = 0.593). The compliance of P-V curve was only positively correlated with the volume of insufficient aeration region (inspiration r = 0.827, P = 0.006; expiration r = 0.792, P = 0.011). The airway pressure with the maximal compliance at inspiratory P-V curve [(16.2 +/- 3.5) cm H2O, 1 cm H2O = 0.098 kPa] was positively correlated with the alveolar opening pressure [(16.4 +/- 3.4) cm H2O, r = 0.900, P = 0.002], and the airway pressure with the maximal compliance at expiratory P-V curve [(11.9 +/- 2.4) cm H2O] was positively correlated with the alveolar closing pressure [(11.3 +/- 2.5) cm H2O, r = 0.887, P = 0.003]., Conclusions: During inspiration, alveolar recruitment takes place with alveolar overinflation. The compliance of P-V curve is correlated with insufficient region volume, and reflects the potential of lung recruitment, and can predict the alveolar opening pressure and closing pressure.

Purpose: Quantification of inhaled aerosols by planar gamma scintigraphy could be improved if a more comprehensive assessment of aerosol distribution patterns among lung airways were obtained. The analysis of planar scans can be quite subjective because of overlaying of small, peripheral airways with large, conducting airways. Herein, a computer modeling technique of the three-dimensional (3-D) branching structure of human lung airways was applied to assist in the interpretation of planar gamma camera images., Methods: Airway dimensions were derived from morphometric data, and lung boundaries were formulated from scintigraphy protocols. Central, intermediate, and peripheral regions were superimposed on a planar view of the 3-D simulations, and airways were then tabulated by type, number, surface area, and volume in each respective region., Results: These findings indicate that the central region, for example, consists mostly of alveolated airways. Specifically, it was found that alveolated airways comprise over 99% of the total number of airways, over 95% of the total airway surface area, and approximately 80% of the total airway volume in the central region., Conclusions: The computer simulations are designed to serve as templates that can assist in the interpretation of aerosol deposition data from scintigraphy images.

In order to evaluate the effectiveness of edge enhancement by refraction in computed tomography, images of a cross section of a euthanized mouse thorax were recorded at low (20 keV) and high (72 keV) x-ray energies at a spatial resolution of about 40 microm. Compared with the images obtained with the detector at 30 cm from an object, when the object was located at 113 cm from the detector, the contrast between tissues and air was improved at both energies. The improvement was more pronounced at 72 keV where the absorption contrast was weaker. This effect was due to refraction at the surfaces of alveolar membranes and small airways which creates areas with apparently high and low linear attenuation coefficients within tissues. The edge enhancement by refraction was also effective in images of a euthanized rabbit thorax at x-ray energies of 40 and 70 keV at a spatial resolution of about 0.15 mm. These results raise the possibility that the refraction contrast may be utilized to obtain a high-resolution tomographic image of human lung and bone with low dose.

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology characterized by accumulation of calcific concretions in the alveolar spaces. The paper reports a case of PAM in a 56-year-old male. The patient had persistent dry cough, and gradually progressive dyspnea on exertion. The diagnosis was established on the basis of roentgenography and confirmed by the sputum and transbronchial biopsy findings. Scintigraphy revealed the absence of Tc-99m methylenediphosphonate uptake of lungs. Familial occurrence was not observed. Chest roentgenogram, pulmonary function, and clinical status of the patient have remained stable for 41 months. Radiological and clinical follow-up of the disease continues.

The architecture of the lung is discussed with special focus on lung parenchyma. The lung parenchyma is mainly comprised of numerous air-containing passages and intervening fine structures, corresponding to alveolar ductal lumens and alveoli, as well as alveolar septa and small pulmonary vessels occupying 10% of total parenchymal volume. The shapes and relative arrangements of alveolar ducts and alveoli are discussed in detail, which is followed by a brief description of bronchial circulation and pulmonary lymphatics.

Purpose: To evaluate the feasibility of micro-computed tomography (CT) for analysis of the lung fine structure and its alterations during endotoxin-induced lung injury., Materials and Methods: Intravital perfusion-fixed rat lungs with (n = 5) and without (n = 5) endotoxin perfusion were scanned with micro-CT. Three imaging modalities (conventional histology, intravital microscopy, and electron microscopy) were used to document the effect of endotoxin and the in vivo application of contrast agent (a mixture of barium sulfate, gelatin, and thymol). The effect of endotoxin on structural changes of the lung was evaluated with analysis of variance., Results: Intravital microscopy, conventional histology, and electron microscopy demonstrated capillary perfusion of contrast agent, inflated alveoli, and no extravasation of barium sulfate in the extravascular space. Systemic application of endotoxin led to a significant increase in the soft-tissue volume of the lungs (ie, tissue edema) (58.09 microm(3)+/- 4.6 [standard error of the mean] vs 8.31 microm(3)+/- 1.63, P <.001) and significant thickening of the alveolar walls (34.01 microm +/- 4.5 vs 14.83 microm +/- 2.5, P <.001) at micro-CT. Simultaneously, endotoxin-treated rat lungs showed a significant reduction in total air space (49.74 microm(3)+/- 1.72 vs 100.99 microm(3)+/- 1.16, P <.001)., Conclusion: These findings indicate that micro-CT is feasible for structural evaluation of the lung fine structure and its alterations during endotoxin-induced lung injury., (Copyright RSNA, 2004)

Background: Lung auscultation and bedside chest radiography are routinely used to assess the respiratory condition of ventilated patients with acute respiratory distress syndrome (ARDS). Clinical experience suggests that the diagnostic accuracy of these procedures is poor., Methods: This prospective study of 32 patients with ARDS and 10 healthy volunteers was performed to compare the diagnostic accuracy of auscultation, bedside chest radiography, and lung ultrasonography with that of thoracic computed tomography. Three pathologic entities were evaluated in 384 lung regions (12 per patient): pleural effusion, alveolar consolidation, and alveolar-interstitial syndrome., Results: Auscultation had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung ultrasonography, in contrast to auscultation and chest radiography, could quantify the extent of lung injury. Interobserver agreement for the ultrasound findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and 0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and pleural effusion, respectively., Conclusions: At the bedside, lung ultrasonography is highly sensitive, specific, and reproducible for diagnosing the main lung pathologic entities in patients with ARDS and can be considered an attractive alternative to bedside chest radiography and thoracic computed tomography.

The effects of a deep inspiration (DI) in individuals with asthma differ from those observed in healthy subjects. It has been postulated that the beneficial effect of lung inflation is mediated by airway stretch. One hypothesis to explain the defects in the function of lung inflation in asthma is that a DI may be unable to stretch the airways. This may result from attenuation of the tethering forces between the airways and the surrounding parenchyma. In the current study, we used high-resolution computed tomography (HRCT) to examine the ability of a DI to distend the airways of subjects with asthma (n = 10) compared with healthy subjects (n = 9) at baseline and after increasing airway tone with methacholine (MCh). We found that both at baseline and after the induction of smooth muscle tone with MCh, a DI distended the airways of healthy and asthmatic subjects to a similar extent, indicating that abnormal interdependence between the lung parenchyma and the airways is unlikely to play a major role in the loss or attenuation of the beneficial effect of lung inflation that characterizes asthma. Furthermore, we observed that after constriction had already been induced by MCh, following a DI, bronchodilation occurred in the healthy subjects but further bronchoconstriction occurred in the subjects with asthma. Our findings suggest that an abnormal excitation contraction mechanism in the airway smooth muscle of subjects with mild asthma counteracts the bronchodilatory effect of a DI. Therefore, the mechanism for reduced bronchodilation after DIs in subjects with mild asthma could be intrinsic to the airway smooth muscle.

Propylthiouracil (PTU) has recently been observed to be associated with antineutrophil cytoplasmic antibody (ANCA)-positive small vessel vasculitis, resulting in crescentic glomerulonephritis and, infrequently, diffuse alveolar hemorrhage (DAH). We describe a case of a 23-year-old pregnant woman who developed a perinuclear ANCA and antimyeloperoxidase-positive small vessel vasculitis manifesting as DAH and crescentic glomerulonephritis after she began taking PTU. An open lung biopsy was consistent with pulmonary capillaritis. She responded to corticosteroid therapy and discontinuation of PTU. DAH can be caused by pulmonary capillaritis, bland hemorrhage, or diffuse alveolar damage. To our knowledge, this represents the first documentation of an underlying pulmonary capillaritis in a case of PTU-induced DAH.

Long-term retention of particles in airways is controversial. However, precise anatomic localization of the particles is not possible in people. In this study the anatomic location of retained particles after shallow bolus inhalation was determined in anesthetized, ventilated beagle dogs. Fifty 30-cm(3) boluses containing monodisperse 2.5-micron polystyrene particles (PSL) were delivered to a shallow lung depth of 81-129 cm(3). At 96 h before euthanasia, red fluorescent PSL were used; at 24 h, green fluorescent PSL and (99m)Tc-labeled PSL were used. Clearance of (99m)Tc-PSL was measured during the next 24 h. Sites of particle retention were determined in systematic, volume-weighted random samples of microwave-fixed lung tissue. Precise particle localization and distribution was analyzed by using gamma counting, conventional fluorescence microscopy, and confocal microscopy. Within 24 h after shallow bolus inhalation, 50-95% of the deposited (99m)Tc-PSL were cleared, but the remaining fraction was cleared slowly in all dogs, similar to previous human results. The three-dimensional deposition patterns showed particles across the entire cross-sectional plane of the lungs at the level of the carina. In these locations, 33 +/- 9.9% of the retained particles were found in small, nonrespiratory airways (0.3- to 1-mm diameter) and 49 +/- 10% of the particles in alveoli; the remaining fraction was found in larger airways. After 96 h, a similar pattern was found. These findings suggest that long-term retention in airways is at the bronchiolar level.

In order to assess the diagnostic yield of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) in pulmonary diseases with a ground-glass and/or alveolar pattern on high-resolution computed tomography (HRCT) scan, a prospective study was undertaken. Thirty-six patients (17 males, 19 females), mean age 53 yrs, selected on the basis of the presence of an alveolar and/or ground-glass pattern on chest HRCT scan, were submitted to fibreoptic bronchoscopy. All patients underwent BAL. TBBs were performed in 33 cases. A specific diagnosis was achieved, taking into account data obtained by means of serology, microbiology, cytology and histopathology in appropriate clinical settings. Twelve (33%) patients only had the appearance of a ground-glass opacity, whereas 24 (67%) had associated areas of airspace consolidation. BAL was performed in all cases and gave a definitive diagnosis in 21 (58%). The diagnostic yield of BAL in patients with only ground-glass opacities was no different from that in those patients also showing areas of alveolar consolidation (58 versus 58%). In eight patients (six with ground-glass opacity and two with alveolar consolidation), BAL provided useful but not definitive information. In these patients, a definitive diagnosis was achieved by means of TBB in seven cases and by open lung biopsy in one case. TBB was performed in 33 out of 36 patients and gave positive results in 25 (76%). The diagnostic yield of TBB in patients showing areas of alveolar consolidation was significantly higher than in those with pure ground-glass opacity, i.e. 95% (21 of 22) and 36% (4 of 11) respectively (p < 0.001). BAL and TBB were performed during the same bronchoscopy in 33 patients, and an accurate diagnosis was achieved in 30 (91%). Overall, the diagnostic yield of TBB (76%) and BAL (56%) did not differ significantly in the whole patient group (p = 0.12), or in patients with a ground-glass opacification (58 versus 36%, p = 0.3). However, in patients with areas of alveolar consolidation, the diagnostic sensitivity of TBB (95%) was significantly greater than the diagnostic sensitivity of BAL (54%) (p = 0.03). In conclusion this study shows that high-resolution computed tomography can be helpful in predicting the diagnostic accuracy of bronchological procedures, in particular of bronchoalveolar lavage and transbronchial biopsy, and that alveolar and/or ground-glass are favourable patterns for these diagnostic tools.

The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and compared between 21 patients with ALI and 10 healthy volunteers. Distribution of PEEP-induced alveolar recruitment along the anteroposterior and cephalocaudal axis and influence of the resting volume of nonaerated lower lobes were also assessed. Anteroposterior and transverse dimensions of the lungs of the patients were similar to those of healthy volunteers, whereas cephalocaudal dimensions were reduced by more than 15%. Total lung volume (aerated plus nonaerated lung) was reduced by 27%. Volumes of upper and lower lobes were 99 and 48% of normal values. In addition to an anteroposterior gradient in the distribution of aerated and nonaerated areas, a cephalocaudal gradient was also observed. Nonaerated areas were predominantly found in juxtadiaphragmatic regions. PEEP-induced alveolar recruitment was more pronounced in nondependent than in dependent regions and in cephalad than in caudal regions. A significant correlation between resting volume of nonaerated lower lobes and regional PEEP-induced alveolar recruitment was observed. In ALI, loss of lung volume involves predominantly lower lobes. The thorax shortens along its cephalocaudal axis. PEEP-induced alveolar recruitment predominates in nondependent and cephalad lung regions and is inversely correlated with the resting volume of nonaerated lung.

The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtained at FRC and at TLC with a positive airway pressure of 30 cm H2O. In patients, lung volumes were quantified by the analysis of the frequency distribution of CT numbers on the entire lung at zero end-expiratory pressure (ZEEP) and PEEP. In healthy volunteers at FRC, the distribution of the density histograms was monophasic with a peak at -791 +/- 12 Hounsfield units (HU). The lowest CT number observed was -912 HU. At TLC, lung volume increased by 79 +/- 35% and the peak CT number decreased to -886 +/- 26 HU. More than 70% of the increase in lung volume was located below -900 HU, suggesting that this value can be considered as the threshold separating normal aeration from overdistension. In patients with ALI, at ZEEP the distribution of density histograms was either monophasic (n = 3) or biphasic (n = 3). The mean CT number was -319 +/- 34 HU. At PEEP 13 +/- 3 cm H2O, lung volume increased by 47 +/- 19% whereas mean CT number decreased to -538 +/- 171 HU. PEEP induced a mean alveolar recruitment of 320 +/- 160 ml and a mean lung overdistension of 238 +/- 320 ml. In conclusion, overdistended lung parenchyma of healthy volunteers is characterized by a CT number below -900 HU. This threshold can be used in patients with ALI for differentiating PEEP-induced alveolar recruitment from lung overdistension.

The reformulation of asthma medications with non-ozone depleting propellants such as hydrofluoroalkane-134a (HFA) has provided the opportunity to apply new knowledge and inhaler technology to improve significantly the delivery of aerosol drugs to the respiratory tract. Beclomethasone dipropionate (BDP), the most commonly prescribed inhaled corticosteroid for asthma therapy, is effective therapy; however currently available chlorofluorocarbon (CFC)-BDP metered dose inhalers typically deliver no more than 10% of the inhaled drug to the lungs with the remainder deposited in the oropharynx. Compared with an average particle size of 3.5-4.0 microns for CFC-BDP, the new HFA-BDP formulation has an average particle size of 1.1 microns and a respirable fraction of approximately 60%. The lung deposition of 99mTc-radiolabelled HFA-BDP has been investigated in healthy volunteers and patients with asthma. Results showed that the HFA-BDP formulation reverses the pattern of distribution seen with CFC-BDP products, delivering most of the dose of inhaled steroid directly to the lungs rather than to the oropharynx and gut where it may lead to unwanted side-effects. As such, HFA-BDP is likely to achieve equivalent efficacy to existing CFC-BDP formulations with lower doses and with reduced potential for local adverse effects.

Study Objective: (1) To explore the interaction between mechanical ventilation and oleic acid (OA)-induced lung injury on indexes of pulmonary gas exchange and epithelial permeability, and (2) to compare this interaction using two different modes of ventilation: pressure-controlled inverse ratio ventilation (PCIRV) and volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP)., Design: Randomized animal study., Setting: Experimental laboratory investigation at Södersjukhuset, Stockholm, Sweden., Animals: Twenty-four New Zealand white rabbits., Interventions: (1) Ventilation with PCIRV (n=6) or VCV PEEP (n=6) for 6 h at equal end-expiratory alveolar pressure levels of 5 cm H2O followed by induction of lung injury (IV injection of OA 0.15 mL/kg). (2) Induction of lung injury followed by 6 h of ventilation with either PCIRV (n=6) or VCV PEEP (n=6) as described above., Measurements and Results: Lung mechanics, heart rate, BP, and gas exchange results were equal at baseline. In group A, after 1 h of ventilation, mean airway pressure was 11.9+/-4.4 with PCIRV and 8.3+/-1.0 cm H2O with VCV PEEP (p<0.05). Forty minutes after OA injection, PaO2/fraction of inspired oxygen (FIO2) was 24+/-10 kPa with PCIRV and 44+/-15 kPa with VCV PEEP (p<0.05). Mean airway pressure was higher and peak airway pressure was lower with PCIRV. In group B, after 6 h of ventilation, PaO2/FIO2 was 17+/-5 kPa with PCIRV and 43+/-8 kPa with VCV PEEP (p<0.01). Systemic BP was lower with PCIRV and mean airway pressure was higher. Technetium-99m diethylene triamine penta-acetic acid lung clearance: In group A, curves were monoexponential with both PCIRV (half-life time [T 1/2], 21+/-8 min and VCV PEEP (T 1/2, 126+/-59 min, p<0.005) until injection of OA. In the VCV PEEP-treated animals, a marked increase in clearance rate was observed within 60 s of OA injection (T 1/2, 13+/-9 min, p<0.001). Fifteen minutes after OA injections, T 1/2 had decreased to 38+/-17 min with VCV PEEP. In the animals treated with PCIRV, OA injection did not lead to a significant change in clearance rate, although the elimination pattern was observed to change from single-compartment to multicompartment type. In group B, clearance curves were monoexponential with both ventilatory modes. There was no significant difference in clearance rate between PCIRV (T 1/2, 25+/-9 min) and VCV PEEP (T 1/2, 36+/-16 min, not significant)., Conclusions: The observation that PaO2 was lower in the PCIRV-treated groups must be interpreted with caution in this animal study with relatively few observations. The finding may reflect differences in the effect of OA injection in the two ventilatory modes. It is also possible that externally applied PEEP is more effective than PCIRV in increasing oxygen tension, either because of a less inhomogenous distribution of ventilation and perfusion or for other reasons. The clearance results imply that PCIRV causes an alteration in lung epithelial or membrane function in comparison to VCV PEEP. This functional difference is most likely caused by the large time-weighted lung volume produced by pressure control in combination with a prolonged inspiration. Induction of high permeability lung injury with OA eliminates the difference between PCIRV and VCV PEEP. It remains to be established whether these findings are relevant with regard to ventilator-associated structural lung injury in man.

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.

Age is known to reduce the efficacy of body organs and systems, even in the absence of disease. The alveolar-capillary clearance (ACC) rate is representative of the alveolar-capillary barrier's functional state. We studied 29 healthy non-smokers, who were selected after clinical and radiographic evaluation. The patients were divided into three groups based on age: Group I, < or = 30 years (n = 10); Group II, 31-55 years (n = 9); Group III, > or = 56 years (n = 10). Each patient inhaled 750 MBq 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol generated by a Venticis nebulizer (particles with a mean diameter of 1.1 microns) for 5 min. Forty frames of 30 s duration each were acquired and the ACC rates for the right and left lungs determined using a computer program. The mean ACC rates for the three groups were as follows: Group I, 1.31% min-1; Group II, 1.08% min-1; Group III, 0.76% min-1. The differences between Groups I and III (P < 0.001) and Groups II and III (P = 0.03) were shown to be significant. There was no significant difference between Groups I and II. Possible explanations for an age-related reduction in ACC rates include a reduction in the internal alveolar surface, the closure of the small airways, a reduction in the lung blood capillaries and a reduction in cardiac output. We conclude that there appears to be an age-related reduction in ACC rates in healthy non-smokers, even in the absence of clinically and radiographically detectable lung disease. However, larger studies are required.