Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes.

Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.

The respiratory system influences flight mechanics in soaring birds.

The subpectoral diverticulum (SPD) is an extension of the respiratory system in birds that is located between the primary muscles responsible for flapping the wing1,2. Here we survey the pulmonary apparatus in 68 avian species, and show that the SPD was present in virtually all of the soaring taxa investigated but absent in non-soarers. We find that this structure evolved independently with soaring flight at least seven times, which indicates that the diverticulum might have a functional and adaptive relationship with this flight style. Using the soaring hawks Buteo jamaicensis and Buteo swainsoni as models, we show that the SPD is not integral for ventilation, that an inflated SPD can increase the moment arm of cranial parts of the pectoralis, and that pectoralis muscle fascicles are significantly shorter in soaring hawks than in non-soaring birds. This coupling of an SPD-mediated increase in pectoralis leverage with force-specialized muscle architecture produces a pneumatic system that is adapted for the isometric contractile conditions expected in soaring flight. The discovery of a mechanical role for the respiratory system in avian locomotion underscores the functional complexity and heterogeneity of this organ system, and suggests that pulmonary diverticula are likely to have other undiscovered secondary functions. These data provide a mechanistic explanation for the repeated appearance of the SPD in soaring lineages and show that the respiratory system can be co-opted to provide biomechanical solutions to the challenges of flight and thereby influence the evolution of avian volancy.

Giant lungfish genome elucidates the conquest of land by vertebrates.

Lungfishes belong to lobe-fined fish (Sarcopterygii) that, in the Devonian period, 'conquered' the land and ultimately gave rise to all land vertebrates, including humans1-3. Here we determine the chromosome-quality genome of the Australian lungfish (Neoceratodus forsteri), which is known to have the largest genome of any animal. The vast size of this genome, which is about 14× larger than that of humans, is attributable mostly to huge intergenic regions and introns with high repeat content (around 90%), the components of which resemble those of tetrapods (comprising mainly long interspersed nuclear elements) more than they do those of ray-finned fish. The lungfish genome continues to expand independently (its transposable elements are still active), through mechanisms different to those of the enormous genomes of salamanders. The 17 fully assembled lungfish macrochromosomes maintain synteny to other vertebrate chromosomes, and all microchromosomes maintain conserved ancient homology with the ancestral vertebrate karyotype. Our phylogenomic analyses confirm previous reports that lungfish occupy a key evolutionary position as the closest living relatives to tetrapods4,5, underscoring the importance of lungfish for understanding innovations associated with terrestrialization. Lungfish preadaptations to living on land include the gain of limb-like expression in developmental genes such as hoxc13 and sall1 in their lobed fins. Increased rates of evolution and the duplication of genes associated with obligate air-breathing, such as lung surfactants and the expansion of odorant receptor gene families (which encode proteins involved in detecting airborne odours), contribute to the tetrapod-like biology of lungfishes. These findings advance our understanding of this major transition during vertebrate evolution.

Dry double-sided tape for adhesion of wet tissues and devices.

Two dry surfaces can instantly adhere upon contact with each other through intermolecular forces such as hydrogen bonds, electrostatic interactions and van der Waals interactions1,2. However, such instant adhesion is challenging when wet surfaces such as body tissues are involved, because water separates the molecules of the two surfaces, preventing interactions3,4. Although tissue adhesives have potential advantages over suturing or stapling5,6, existing liquid or hydrogel tissue adhesives suffer from several limitations: weak bonding, low biological compatibility, poor mechanical match with tissues, and slow adhesion formation5-13. Here we propose an alternative tissue adhesive in the form of a dry double-sided tape (DST) made from a combination of a biopolymer (gelatin or chitosan) and crosslinked poly(acrylic acid) grafted with N-hydrosuccinimide ester. The adhesion mechanism of this DST relies on the removal of interfacial water from the tissue surface, resulting in fast temporary crosslinking to the surface. Subsequent covalent crosslinking with amine groups on the tissue surface further improves the adhesion stability and strength of the DST. In vitro mouse, in vivo rat and ex vivo porcine models show that the DST can achieve strong adhesion between diverse wet dynamic tissues and engineering solids within five seconds. The DST may be useful as a tissue adhesive and sealant, and in adhering wearable and implantable devices to wet tissues.

Bronchial tree of the human embryo: Examination based on a mammalian model.

The symmetry of the right and left bronchi, proposed in a previous comparative anatomical study as the basic model of the mammalian bronchial tree, was examined to determine if it applied to the embryonic human bronchial tree. Imaging data of 41 human embryo specimens at Carnegie stages (CS) 16-23 (equivalent to 6-8 weeks after fertilization) belonging to the Kyoto collection were obtained using phase-contrast X-ray computed tomography. Three-dimensional bronchial trees were then reconstructed from these images. Bronchi branching from both main bronchi were labeled as dorsal, ventral, medial, or lateral systems based on the branching position with numbering starting cranially. The length from the tracheal bifurcation to the branching point of the labeled bronchus was measured, and the right-to-left ratio of the same labeled bronchus in both lungs was calculated. In both lungs, the human embryonic bronchial tree showed symmetry with an alternating pattern of dorsal and lateral systems up to segmental bronchus B9 as the basic shape, with a more peripheral variation. This pattern is similar to that described in adult human lungs. Bronchial length increased with the CS in all labeled bronchi, whereas the right-to-left ratio was constant at approximately 1.0. The data demonstrated that the prototype of the human adult bronchial branching structure is formed and maintained in the embryonic stage. The morphology and branching position of all lobar bronchi and B6, B8, B9, and the subsegmental bronchus of B10 may be genetically determined. On the other hand, no common structures between individual embryos were found in the peripheral branches after the subsegmental bronchus of B10, suggesting that branch formation in this region is influenced more by environmental factors than by genetic factors.

Clinical anatomy of pulmonary connections in young people.

OBJECTIVE: Aim: To study the clinical anatomy of the pulmonary ligaments of young people. PATIENTS AND METHODS: Materials and Methods: The study was carried out when performing 28 autopsies of young people aged 25 to 44 years. Methods of dissection of chest organocomplexes, macro-microscopy, morphometry and planimetry, and statistical processing were used. The shape and topography of the pulmonary ligaments was assessed, their area, the localization of lymph nodes was examined. RESULTS: Results: The pulmonary ligament is an anatomical formation, which is formed as a result of a combination of leaves of the mediastinal pleura, which, covering the surfaces of the roots of the lungs, descend towards the diaphragm and are located between the mediastinal organs and the lungs. Pulmonary connections on both sides have a few edges: the inner, outer and lower free. The pulmonary ligaments with lower free edges do not pass to the diaphragmatic surface of the pleura, but only with inner ones, which are located on the right along the esophagus, and on the left along the aorta. Pulmonary ligaments on both sides pass into the mediastinal part of the pleura, covering the pericardium. CONCLUSION: Conclusions: There are individual differences between the shape and size of the right and left pulmonary ligaments in males and females. There is no significant difference between the sizes of the right and left pulmonary ligaments, but such dimensions as: the width, the angle of inclination and the ratio of their lower free edge to the lower edge of the lungs are not found in all cases.

Topography of pleural epithelial structure enabled by en face isolation and machine learning.

Pleural epithelial adaptations to mechanical stress are relevant to both normal lung function and parenchymal lung diseases. Assessing regional differences in mechanical stress, however, has been complicated by the nonlinear stress-strain properties of the lung and the large displacements with ventilation. Moreover, there is no reliable method of isolating pleural epithelium for structural studies. To define the topographic variation in pleural structure, we developed a method of en face harvest of murine pleural epithelium. Silver-stain was used to highlight cell borders and facilitate imaging with light microscopy. Machine learning and watershed segmentation were used to define the cell area and cell perimeter of the isolated pleural epithelial cells. In the deflated lung at residual volume, the pleural epithelial cells were significantly larger in the apex (624 ± 247 µm2 ) than in basilar regions of the lung (471 ± 119 µm2 ) (p < 0.001). The distortion of apical epithelial cells was consistent with a vertical gradient of pleural pressures. To assess epithelial changes with inflation, the pleura was studied at total lung capacity. The average epithelial cell area increased 57% and the average perimeter increased 27% between residual volume and total lung capacity. The increase in lung volume was less than half the percent change predicted by uniform or isotropic expansion of the lung. We conclude that the structured analysis of pleural epithelial cells complements studies of pulmonary microstructure and provides useful insights into the regional distribution of mechanical stresses in the lung.

The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors.

Platelets are critical for haemostasis, thrombosis, and inflammatory responses, but the events that lead to mature platelet production remain incompletely understood. The bone marrow has been proposed to be a major site of platelet production, although there is indirect evidence that the lungs might also contribute to platelet biogenesis. Here, by directly imaging the lung microcirculation in mice, we show that a large number of megakaryocytes circulate through the lungs, where they dynamically release platelets. Megakaryocytes that release platelets in the lungs originate from extrapulmonary sites such as the bone marrow; we observed large megakaryocytes migrating out of the bone marrow space. The contribution of the lungs to platelet biogenesis is substantial, accounting for approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature megakaryocytes along with haematopoietic progenitors in the extravascular spaces of the lungs. Under conditions of thrombocytopenia and relative stem cell deficiency in the bone marrow, these progenitors can migrate out of the lungs, repopulate the bone marrow, completely reconstitute blood platelet counts, and contribute to multiple haematopoietic lineages. These results identify the lungs as a primary site of terminal platelet production and an organ with considerable haematopoietic potential.

Determinants of Lung Fissure Completeness.

Rationale: New advanced bronchoscopic treatment options for patients with severe chronic obstructive pulmonary disease (COPD) have led to increased interest for COPD phenotyping, including fissure completeness. Objectives: We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD. Methods: We used data from 9,926 participants of the COPDGene study who underwent chest computed tomographic (CT) scans. Fissure completeness was calculated from CT scans after quantitative CT analysis at baseline and 5-year follow-up. Clinical and environmental factors, including sex, race, smoking, COPD, emphysema, maternal smoking during pregnancy and maternal COPD, were tested for impact on fissure completeness. Genome-wide association analyses were performed separately in non-Hispanic White subjects and African American subjects. Measurements and Main Results: African American subjects had significantly higher fissure completeness than non-Hispanic White subjects for all three fissures (P < 0.001). There was no change in fissure completeness between baseline and 5-year follow-up. For all fissures, no clinically relevant differences in fissure completeness were found for other clinical or environmental factors, including COPD severity. Rs2173623, rs264866, rs2407284, rs7310342, rs4904145, rs6504172, and rs7209556 showed genome-wide significant associations with fissure completeness in non-Hispanic White subjects. In African American subjects, rs264866, rs4904145 and rs6504172 were identified as significant associations. Rs2173623, rs6504172, and rs7209556 lead to WNT5A and HOXB antisense RNA expression, which play an important role during embryogenesis. Conclusions: Fissure completeness is genetically determined and not dependent on age, sex, smoking status, the presence and severity of COPD (including exacerbation frequency), maternal smoking during pregnancy, or maternal COPD.

Anatomy of the left subsuperior segment for segmentectomy.

PURPOSE: The subsuperior segmental bronchi (B*) forms the subsuperior segment (S*) between the superior (S6) and basal segment (S7, S8, S9, S10) of the lung. However, the anatomical planes of S* remains undefined. The present study clarified the anatomical features of S*. METHODS: We reviewed the anatomical patterns of pulmonary vessels and the left lung bronchus in 539 patients using three-dimensional computed tomography. We report the anatomic structure in S*. RESULTS: A total of 537 patients were analyzed. B* was observed in 129 (24.0%) patients. The intersegmental vein between S6 and S* was complete in all cases. The absence of intersegmental veins of S* was observed in 77 (14.3%) patients, reaching 59.7% of B* cases. Twenty-two (4.1%) cases of B* diverged from the trunk of the basal bronchus, and about half of the B* branched to the dorsolateral (n = 77, 14.3%) or dorsal (n = 2, 0.37%) direction. CONCLUSION: Our study revealed the branching patterns of B* and anatomical intersegmental veins of S*. Our results provide useful information regarding anatomical segmentectomy including or adjusting to the left S*.

Pulmonary vessels and bronchus anatomy of the left upper lobe.

PURPOSES: The bronchopulmonary vascular bifurcation patterns in the upper lobe of the left lung are diverse. Therefore, it is important for general thoracic surgeons to understand the detailed anatomy of the pulmonary segments when performing thoracoscopic anatomical pulmonary resection. This study aimed to analyze the bronchovascular patterns of the left upper lobe and summarize the anatomical information associated with pulmonary anatomical pulmonary resection. METHODS: We reviewed the anatomical patterns of pulmonary vessels and the left lung bronchus of 539 patients using computed tomography imaging data including those obtained using three-dimensional computed tomography. We herein report the anatomic structure in the left upper lobe. RESULTS: Regarding the superior division bronchi, a pattern of trifurcation into B1+2, B3, lingular division bronchus was observed in nine patients (1.7%). A pattern of proximal bifurcation of B4 was found in eight patients (1.5%). Regarding the lingular veins (LV), patterns of LV drainage into the left lower pulmonary vein were observed in 22 patients (4.1%). Regarding the pulmonary artery, mediastinal lingular arteries (MLA) were found in 161 patients (29.9%). CONCLUSION: The bifurcation patterns of the bronchovascular region in the upper lobe of the left lung were clarified. These results should be carefully noted when performing anatomical pulmonary resection.

An antioxidant suppressed lung cellular senescence and enhanced pulmonary function in aged mice.

Oxidative stress is one of the major causes of cellular senescence in mammalian cells. The excess amount of reactive oxygen species generated by oxygen metabolism is pathogenic and facilitates tissue aging. Lung tissue is more susceptible to oxidative stress than other organs because it is directly exposed to environmental stresses. The aging of lung tissues increases the risk of chronic diseases. Senescent cells accumulate in tissues during aging and contribute to aging-associated morbidity; however, the roles of cellular senescence in lung aging and diseases have not yet been elucidated in detail. To clarify the physiological role of oxidative stress-induced cellular senescence in aging-associated declines in pulmonary function, we herein investigated the effects of the antioxidant N-acetyl-L-cysteine (NAC) on lung cellular senescence and aging in mice. The administration of NAC to 1-year-old mice reduced the expression of senescence-associated genes in lung tissue. Pulmonary function and lung morphology were partly restored in mice administered NAC. Collectively, these results suggest that oxidative stress is a major inducer of cellular senescence in vivo and that the control of oxidative stress may prevent lung aging and diseases.

X-ray Dark-Field Chest Imaging: Qualitative and Quantitative Results in Healthy Humans.

Background X-ray dark-field radiography takes advantage of the wave properties of x-rays, with a relatively high signal in the lungs due to the many air-tissue interfaces in the alveoli. Purpose To describe the qualitative and quantitative characteristics of x-ray dark-field images in healthy human subjects. Materials and Methods Between October 2018 and January 2020, patients of legal age who underwent chest CT as part of their diagnostic work-up were screened for study participation. Inclusion criteria were a normal chest CT scan, the ability to consent, and the ability to stand upright without help. Exclusion criteria were pregnancy, serious medical conditions, and changes in the lung tissue, such as those due to cancer, pleural effusion, atelectasis, emphysema, infiltrates, ground-glass opacities, or pneumothorax. Images of study participants were obtained by using a clinical x-ray dark-field prototype, recently constructed and commissioned at the authors' institution, to simultaneously acquire both attenuation-based and dark-field thorax radiographs. Each subject's total dark-field signal was correlated with his or her lung volume, and the dark-field coefficient was correlated with age, sex, weight, and height. Results Overall, 40 subjects were included in this study (average age, 62 years ± 13 [standard deviation]; 26 men, 14 women). Normal human lungs have high signal, while the surrounding osseous structures and soft tissue have very low and no signal, respectively. The average dark-field signal was 2.5 m-1 ± 0.4 of examined lung tissue. There was a correlation between the total dark-field signal and the lung volume (r = 0.61, P < .001). No difference was found between men and women (P = .78). Also, age (r = -0.18, P = .26), weight (r = 0.24, P = .13), and height (r = 0.01, P = .96) did not influence dark-field signal. Conclusion This study introduces qualitative and quantitative values for x-ray dark-field imaging in healthy human subjects. The quantitative x-ray dark-field coefficient is independent from demographic subject parameters, emphasizing its potential in diagnostic assessment of the lung. ©RSNA, 2021 See also the editorial by Hatabu and Madore in this issue.

Anatomy, ontogeny, and evolution of the archosaurian respiratory system: A case study on Alligator mississippiensis and Struthio camelus.

The avian lung is highly specialized and is both functionally and morphologically distinct from that of their closest extant relatives, the crocodilians. It is highly partitioned, with a unidirectionally ventilated and immobilized gas-exchanging lung, and functionally decoupled, compliant, poorly vascularized ventilatory air-sacs. To understand the evolutionary history of the archosaurian respiratory system, it is essential to determine which anatomical characteristics are shared between birds and crocodilians and the role these shared traits play in their respective respiratory biology. To begin to address this larger question, we examined the anatomy of the lung and bronchial tree of 10 American alligators (Alligator mississippiensis) and 11 ostriches (Struthio camelus) across an ontogenetic series using traditional and micro-computed tomography (µCT), three-dimensional (3D) digital models, and morphometry. Intraspecific variation and left to right asymmetry were present in certain aspects of the bronchial tree of both taxa but was particularly evident in the cardiac (medial) region of the lungs of alligators and the caudal aspect of the bronchial tree in both species. The cross-sectional area of the primary bronchus at the level of the major secondary airways and cross-sectional area of ostia scaled either isometrically or negatively allometrically in alligators and isometrically or positively allometrically in ostriches with respect to body mass. Of 15 lung metrics, five were significantly different between the alligator and ostrich, suggesting that these aspects of the lung are more interspecifically plastic in archosaurs. One metric, the distances between the carina and each of the major secondary airways, had minimal intraspecific or ontogenetic variation in both alligators and ostriches, and thus may be a conserved trait in both taxa. In contrast to previous descriptions, the 3D digital models and CT scan data demonstrate that the pulmonary diverticula pneumatize the axial skeleton of the ostrich directly from the gas-exchanging pulmonary tissues instead of the air sacs. Global and specific comparisons between the bronchial topography of the alligator and ostrich reveal multiple possible homologies, suggesting that certain structural aspects of the bronchial tree are likely conserved across Archosauria, and may have been present in the ancestral archosaurian lung.

Flow Rectification in Loopy Network Models of Bird Lungs.

We demonstrate flow rectification, valveless pumping, or alternating to direct current (AC-to-DC) conversion in macroscale fluidic networks with loops. Inspired by the unique anatomy of bird lungs and the phenomenon of directed airflow throughout the respiration cycle, we hypothesize, test, and validate that multiloop networks exhibit persistent circulation or DC flows when subject to oscillatory or AC forcing at high Reynolds numbers. Experiments reveal that disproportionately stronger circulation is generated for higher frequencies and amplitudes of the imposed oscillations, and this nonlinear response is corroborated by numerical simulations. Visualizations show that flow separation and vortex shedding at network junctions serve the valving function of directing current with appropriate timing in the oscillation cycle. These findings suggest strategies for controlling inertial flows through network topology and junction connectivity.

Texture Analysis of Computed Tomography Images in the Lung of Patients With Breast Cancer.

OBJECTIVE: The aim of this study was to investigate whether the texture features of lung computed tomography images were altered by primary breast cancer without pulmonary metastasis. METHODS: Texture analysis was performed on the regions of interest of lung computed tomography images from 36 patients with breast cancer and 36 healthy controls. Texture parameters between subjects with different clinical stages and hormone receptor (HR) statuses in patients with breast cancer were analyzed. RESULTS: Three texture parameters (mean, SD, and variance) were significantly different between patients with breast cancer and healthy controls and between preoperative and postoperative stages in patients with breast cancer. All 3 parameters showed an increasing trend under the tumor-bearing state. These parameters were significantly higher in the stage III + IV group than in the stage I + II group. The variance parameter was significantly higher in the HR-negative group than in the HR-positive group. CONCLUSIONS: Texture analysis may serve as a novel additional tool for discovering conventionally invisible changes in the lung tissue of patients with breast cancer.

Characterization of Lung Tumors that the Pulmonologist can Biopsy from the Esophagus with Endosonography (EUS-B-FNA).

BACKGROUND: According to guidelines, it is possible to biopsy lung tumors "immediately adjacent to the esophagus" with EUS-B-FNA. However, it is unknown what "immediately adjacent" exactly means. OBJECTIVE: to investigate the possibility of achieving EUS-B-FNA biopsies from a lung tumor depending on the distance from the esophagus and to establish the maximal allowable distance between the tumor and the esophagus. METHODS: In a prospective observational study, we included patients with a lung tumor located maximum 6 cm from the esophagus and indication of EUS-B-FNA from the tumor. The tumors were of different sizes. In a plot presenting the tumor size-distance relationship in cases with (biopsy) versus without (non-biopsy) successful EUS-B-FNA, a separation line representing the threshold between the groups were identified and a biopsy-index equation established. The maximal tumor-size corrected distance (TSCD) was calculated using the residuals to the separation line. RESULTS: In total, 70 patients were included. EUS-B-FNA from the lung tumor was possible in 46 patients. All tumors with a distance from the esophagus below 19 mm could be biopsied. The maximal allowable esophagus-tumor distance depended on tumor size. From the separation line, a biopsy-index equation was established with the sensitivity of 93.5%, a specificity of 100%, and total accuracy of 95.7%. The TSCD was 31 mm (sensitivity: 95.7%, specificity 75.0%, and accuracy: 88.6%). CONCLUSION: We established a biopsy-index equation to predict the achievability of a lung tumor using EUS-B-FNA depending on distance to esophagus and tumor size. A general maximal TSCD was 31 mm.

Three-stage segmentation of lung region from CT images using deep neural networks.

BACKGROUND: Lung region segmentation is an important stage of automated image-based approaches for the diagnosis of respiratory diseases. Manual methods executed by experts are considered the gold standard, but it is time consuming and the accuracy is dependent on radiologists' experience. Automated methods are relatively fast and reproducible with potential to facilitate physician interpretation of images. However, these benefits are possible only after overcoming several challenges. The traditional methods that are formulated as a three-stage segmentation demonstrate promising results on normal CT data but perform poorly in the presence of pathological features and variations in image quality attributes. The implementation of deep learning methods that can demonstrate superior performance over traditional methods is dependent on the quantity, quality, cost and the time it takes to generate training data. Thus, efficient and clinically relevant automated segmentation method is desired for the diagnosis of respiratory diseases. METHODS: We implement each of the three stages of traditional methods using deep learning methods trained on five different configurations of training data with ground truths obtained from the 3D Image Reconstruction for Comparison of Algorithm Database (3DIRCAD) and the Interstitial Lung Diseases (ILD) database. The data was augmented with the Lung Image Database Consortium (LIDC-IDRI) image collection and a realistic phantom. A convolutional neural network (CNN) at the preprocessing stage classifies the input into lung and none lung regions. The processing stage was implemented using a CNN-based U-net while the postprocessing stage utilize another U-net and CNN for contour refinement and filtering out false positives, respectively. RESULTS: The performance of the proposed method was evaluated on 1230 and 1100 CT slices from the 3DIRCAD and ILD databases. We investigate the performance of the proposed method on five configurations of training data and three configurations of the segmentation system; three-stage segmentation and three-stage segmentation without a CNN classifier and contrast enhancement, respectively. The Dice-score recorded by the proposed method range from 0.76 to 0.95. CONCLUSION: The clinical relevance and segmentation accuracy of deep learning models can improve though deep learning-based three-stage segmentation, image quality evaluation and enhancement as well as augmenting the training data with large volume of cheap and quality training data. We propose a new and novel deep learning-based method of contour refinement.

Predictions of inter- and intra-lobar deposition patterns of inhaled particles in a five-lobe lung model.

OBJECTIVE: To develop a stochastic five-lobe lung model and to compute particle deposition fractions in the five lobes, considering anatomical as well as ventilatory asymmetry. MATERIALS AND METHODS: The stochastic five-lobe lung model was derived from an existing stochastic model for the whole lung, which implicitly contains information on the lobar airway structure. Differences in lobar ventilation and sequential filling of individual lobes were simulated by a stochastic lobar ventilation model. Deposition fractions of inhaled unit density particles in the five lobes were calculated by an updated version of the Monte Carlo deposition code Inhalation, Deposition, and Exhalation of Aerosols in the Lung (IDEAL). RESULTS: Simulations for defined exposure and breathing conditions revealed that the two lower lobes receive higher deposition and the two upper lobes lower deposition, compared to the average deposition for the whole lung. The resulting inter-lobar distribution of deposition fractions indicated that the non-uniform lung morphometry is the dominating effect, while non-uniform ventilation only slightly enhances the lobar differences. The relation between average lobe-specific deposition fractions and corresponding average values for the whole lung allowed the calculation of lobe-specific deposition weighting factors. DISCUSSION: Comparison with limited deposition measurements for upper vs. lower (U/L) and left vs. right (L/R) lobes revealed overall agreement between experimental and theoretical data. Calculations of the L/R deposition ratio for inhaled aerosol boli confirmed the hypothesis of Möller et al. that the right lung is less able to expand at the end of a breath because of the restrictive position of the liver.