Adult Lung Research Articles

Pulmonary Surfactant: A Mighty Thin Film.

Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.

Prevalence of pulmonary arterial hypertension in post-tuberculosis lung fibrosis patients: A cross-sectional observational study

Introduction: Post-tuberculosis (TB) lung fibrosis is an infrequently reported cause of Pulmonary arterial hypertension (PAH). Pulmonary TB still being an important global health problem, especially in developing countries, PAH developing after pulmonary TB deserves attention. This study was undertaken to know the prevalence of PAH among patients with post-TB lung fibrosis. Methods: A cross-sectional observational study was carried out in two tertiary care hospitals in Kolkata over a period of 1 year. Sixty adult post-TB lung fibrosis patients without any cardiovascular or other pulmonary comorbidities were included in this study. Results: Out of the 60 patients with varying degrees of lung fibrosis confirmed radiologically, eight patients were found to have PAH (13.33% of the study population). Among the eight cases, six were males and two were females. Five of the males were smokers with a mean of 17.6 pack years of smoking. Out of the eight diagnosed PAH cases, three were mild PAH, four were moderate, and one case had severe PAH (grading based on 2D echocardiography findings). Pulmonary function test (PFT) revealed obstructive pattern in three cases, restrictive pattern in three cases, and mixed in two cases. On PFT, smokers with PAH exhibited obstructive pattern and mixed pattern, whereas the nonsmoker PAH cases exhibited restrictive pattern. Conclusion: All post-TB lung fibrosis cases must be followed up at regular intervals and screened to rule out PAH. Early diagnosis and prompt treatment of the cases will help to reduce morbidity and mortality of the disease which otherwise has a poor prognosis.

237 Durable fCFTRΔR transgene expression and efficient re-administration after rAAV2.5T-mediated gene transfer to adult ferret lungs

237 Durable fCFTRΔR transgene expression and efficient re-administration after rAAV2.5T-mediated gene transfer to adult ferret lungs

1736P Young adult lung cancer demands more attention in a low-resource area: Bangladesh perspective

1736P Young adult lung cancer demands more attention in a low-resource area: Bangladesh perspective

Preoperative risk factors of airway complications in adult lung transplant recipients: A systematic review and meta-analysis

Background: In this systematic review and meta-analysis, we aimed to identify recipient-related preoperative risk factors for airway complications following lung transplantation in adults. Methods: Articles published between November 1995 and February 2023 were searched by a thorough exploration of databases. Studies that addressed recipient-related risk factors for airway complications following adult lung transplantation, such as cohorts, case-control, or cross-sectional studies, were included. Fixed-effects or random-effects models were used to calculate the odds ratios (ORs) or mean differences (MDs) with 95% confidence interval (CI). Results: Twenty-one studies including a total of 38,321 recipients fulfilled the inclusion criteria. Based on the pooled analyses, taller height (MD=5.98, 95% CI: 5.69-6.27, I2=57.32%), intraoperative mechanical ventilation (OR=1.83, 95% CI: 1.41-2.38, I2=0%), male sex (OR=1.52, 95% CI: 1.33-1.74, I2 =15.91%), preoperative extracorporeal membrane oxygenation (OR=1.58, 95% CI: 1.1-2.26, I2=41.47%), and preoperative steroid use (OR=1.21, 95% CI: 1.04-1.41, I2=0%) elevated the risk of airway complications following lung transplantation. Conclusion: Taller height, intraoperative mechanical ventilation, male sex, preoperative extracorporeal membrane oxygenation, and preoperative steroid use can increase the risk of airway complications after lung transplantation. Identifying high-risk recipients or riskless situations can support the advancement of selective treatments or prevent the unnecessary avoidance of certain interventions.

Mechanosensitive Channels in Lung Health and Disease.

The lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents. Accordingly, understanding how mechanical forces are sensed in the lung, and the responses of cells and tissues in the context of normal development and health versus disease conditions becomes highly relevant. There is increasing recognition that transduction of mechanical forces into cellular responses involves a number of channels, some of which are inherently mechanosensitive. Such channels trigger mechanotransduction pathways that may further mediate cellular remodeling, inflammation, and other pathophysiologic mechanisms in response to stretch, stiffness, and inflammatory cascades. Two particularly important channel families have emerged in pulmonary pathophysiology: the transient receptor potential vanilloid family with focus on member TRPV4 and the recently identified Piezo (PZ) channels. Here, we explore current understanding of the contributions of TRPV4 and PZ channels in lung health and disease states, focusing on the interactions between these mechanosensitive channels and their local environment including immune cells, the extracellular matrix, and cellular cytoskeletal elements. We further discuss potential areas for future research to better understand the impact of mechanical channels on pulmonary health and disease. © 2023 American Physiological Society. Compr Physiol 13:5157-5178, 2023.

Esophageal Function and Reflux Evaluations in Lung Transplantation: A Nationwide Survey of UNOS-Accredited Transplant Centers in the United States.

Gastroesophageal reflux disease has been associated with worse lung transplant outcomes. We aimed to assess local practices for esophageal function testing (EFT) across transplant centers. This was a survey study of all United Network for Organ Sharing-accredited adult lung transplant centers regarding local EFT practice. Among 39/63 (60%) responded centers, 38.5% required any EFT (35.9% esophageal manometry, 15.4% pH monitoring, and 28.2% pH impedance), while another 28.2% may consider EFT based on symptoms. Five-year transplant volume was higher among centers requiring EFT (253 vs 159, P = 0.04). Only a minority of lung transplant centers routinely obtained EFT, supporting the need for guidelines for standardized reflux/esophageal assessment.

Safety and efficacy of delaying lung transplant surgery to a morning start

ObjectiveWe aimed to evaluate the safety and efficacy of delaying lung transplantation until morning for donors with cross-clamp times occurring after 1:30 am. MethodsAll consented adult lung transplant recipients between March 2018 and May 2022 with donor cross-clamp times between 1:30 am and 5 am were enrolled prospectively in this study. Skin incision for enrolled recipients was delayed until 6:30 am (Night group). The control group was identified using a 1:2 logistic propensity score method and included recipients of donors with cross-clamp times occurring at any other time of day (Day group). Short- and medium-term outcomes were examined between groups. The primary endpoint was early mortality (30-day and in-hospital). ResultsThirty-four patients were enrolled in the Night group, along with 68 well-matched patients in the Day group. As expected, donors in the Night group had longer cold ischemia times compared to the Day group (344 minutes vs 285 minutes; P < .01). Thirty-day mortality (3% vs 3%; P = .99), grade 3 primary graft dysfunction at 72 hours (8% vs 4%; P = .40), postoperative complications (26% vs 38%; P = .28), and hospital length of stay (15 days vs 14 days; P = .91) were similar in the 2 groups. No significant differences were noted between groups in 3-year survival (70% vs 77%; P = .30) or freedom from chronic lung allograft dysfunction (91% vs 95%; P = .75) at 3 years post-transplantation. The median follow-up was 752.5 days (interquartile range, 487-1048 days). ConclusionsLung transplant recipients with donor cross-clamp times scheduled after 1:30 am may safely have their operations delayed until 6:30 am with acceptable outcomes. Adoption of such a policy in clinically appropriate settings may lead to an alternative workflow and improved team well-being.

Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids

IntroductionThe lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. MethodsFetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. ResultsThe grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. ConclusionsImplanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.

Living-donor lobar lung transplantation

Living-donor lobar lung transplantation (LDLLT) is indicated for critically ill patients who would not survive the waiting period in the case of severe brain-dead donor shortage. It is essential to confirm that potential donors are willing to donate without applying psychological pressure from others. In standard LDLLT, the right and left lower lobes donated by 2 healthy donors are implanted into the recipient under cardiopulmonary support. LDLLT can be applied to various lung diseases including restrictive, obstructive, infectious, and vascular lung diseases in both adult and pediatric patients if size matching is acceptable. Functional size matching by measuring donor pulmonary function and anatomical size matching by 3-dimensional computed tomography volumetry are very useful. When 2 donors with ideal size matching are not available, various transplant procedures, such as single lobe, segmental, recipient lobe-sparing, and inverted lobar transplants are valuable options. There seems to be immunological advantages in LDLLT as compared to cadaveric lung transplantation (CLT). Unilateral chronic allograft dysfunction is a unique manifestation after bilateral LDLLT, which may contribute to better prognosis. The growth of adult lung graft implanted into growing pediatric recipients is suggested by radiologic evaluation. Although only 2 lobes are implanted, postoperative pulmonary function is equivalent between LDLLT and CLT. The long-term outcome after LDLLT is similar to or better than that after CLT. The author has performed 164 LDLLTs resulting in 71.6% survival rate at 10years. All living-donors returned to their previous life styles. Because of possible serious morbidity in donors, LDLLT should be applied only for critically ill patients.

Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung

Alveolar type 2 (AT2) cells function as stem cells in the adult lung and aid in repair after injury. The current study aimed to understand the signaling events that control differentiation of this therapeutically relevant cell type during human development. Using lung explant and organoid models, we identified opposing effects of TGFβ- and BMP-signaling, where inhibition of TGFβ- and activation of BMP-signaling in the context of high WNT- and FGF-signaling efficiently differentiated early lung progenitors into AT2-like cells in vitro. AT2-like cells differentiated in this manner exhibit surfactant processing and secretion capabilities, and long-term commitment to a mature AT2 phenotype when expanded in media optimized for primary AT2 culture. Comparing AT2-like cells differentiated with TGFβ-inhibition and BMP-activation to alternative differentiation approaches revealed improved specificity to the AT2 lineage and reduced off-target cell types. These findings reveal opposing roles for TGFβ- and BMP-signaling in AT2 differentiation and provide a new strategy to generate a therapeutically relevant cell type in vitro.

To decline or not to decline: Consequences of decision-making regarding lung offers from donors with hepatitis C

ObjectiveLung transplants from donors with hepatitis C (HCV D+) have excellent outcomes, but these organs continue to be declined. We evaluated whether (1) being listed to consider and (2) accepting versus declining HCV D+ offers provided a survival benefit to lung transplant candidates. MethodsUsing the Scientific Registry of Transplant Recipients, we identified all adult (≥18 years) lung transplant candidates 2016-2021 and compared waitlist mortality between those willing versus not willing to consider HCV D+ offers using competing risk regression. We identified all candidates offered an HCV D+ lung that was later accepted and followed them from offer decision until death or end-of-study. We estimated adjusted mortality risk of accepting versus declining an HCV D+ lung offer using propensity-weighted Cox regression. ResultsFrom 2016 to 2021, we identified 21,007 lung transplant candidates, 33.8% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 17% lower risk of waitlist mortality (subhazard ratio, 0.83; 95% confidence interval, 0.75-0.91, P < .001). Over the same period, 665 HCV D+ lung offers were accepted after being declined a total of 2562 times. HCV D+ offer acceptance versus decline was associated with a 20% lower risk of mortality (adjusted hazard ratio, 0.80; 95% confidence interval, 0.66-0.96, P = .02). ConclusionsConsidering HCV D+ lung offers was associated with a 17% lower risk of waitlist mortality, whereas accepting versus declining an HCV D+ lung offer was associated with a 20% lower risk of mortality. Centers and candidates should consider accepting suitable HCV D+ lung offers to optimize outcomes.

Racial Disparities in Waiting List Outcomes of Patients Listed for Lung Transplantation

BackgroundThe Lung Allocation Score, implemented in 2005, prioritized lung transplant candidates by medical urgency rather than waiting list time and was expected to improve racial disparities in transplant allocation. We evaluated whether racial disparities in lung transplant persisted after 2005. MethodsWe identified all wait-listed adult lung transplant candidates in the United States from 2005 through 2021 using the Scientific Registry of Transplant Recipients. We evaluated the association between race and receipt of a transplant by using a multivariable competing risk regression model adjusted for demographics, socioeconomic status, Lung Allocation Score, clinical measures, and time. We evaluated interactions between race and age, sex, socioeconomic status, and Lung Allocation Score. ResultsWe identified 33,158 candidates on the lung transplant waiting list between 2005 and 2021: 27,074 White (82%), 3350 African American (10%), and 2734 Hispanic (8%). White candidates were older, had higher education levels, and had lower Lung Allocation Scores (P < .001). After multivariable adjustment, African American and Hispanic candidates were less likely to receive lung transplants than White candidates (African American: adjusted subhazard ratio, 0.86; 95% CI, 0.82-0.91; Hispanic: adjusted subhazard ratio, 0.82; 95% CI, 0.78-0.87). Lung transplant was significantly less common among Hispanic candidates aged >65 years (P = .003) and non-White candidates from higher-poverty communities (African-American: P = .013; Hispanic: P =.0036). ConclusionsDespite implementation of the Lung Allocation Score, racial disparities persisted for wait-listed African American and Hispanic lung transplant candidates and differed by age and poverty status. Targeted interventions are needed to ensure equitable access to this life-saving intervention.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Defining and Promoting Pediatric Pulmonary Health: Assessing Lung Function and Structure.

Lifelong respiratory health is rooted in the structural and functional development of the respiratory system in early life. Exposures and interventions antenatally through childhood can influence lung development into young adulthood, the life stage with the highest achievable lung function. Because early respiratory health sets the stage for adult lung function trajectories and risk of developing chronic obstructive pulmonary disease, understanding how to promote lung health in children will have far reaching personal and population benefits. To achieve this, it is critical to have accurate and precise measures of structural and functional lung development that track throughout life stages. From this foundation, evaluation of environmental, genetic, metabolic, and immune mechanisms involved in healthy lung development can be investigated. These goals require the involvement of general pediatricians, pediatric subspecialists, patients, and researchers to design and implement studies that are broadly generalizable and applicable to otherwise healthy and chronic disease populations. This National Institutes of Health workshop report details the key gaps and opportunities regarding lung function and structure.

Histological and immunohistochemical characterization of mucosa-associated lymphoid tissue and antigen-presenting cells in trachea and lung of cattle.

The presence of bronchus-associated lymphoid tissue (BALT) and its structural components has been described in different healthy animal species and in animals with diseases of the respiratory tract. In contrast to normal mammals, BALT is absent in healthy human adult lungs, but has been found in the lungs of children. The histological characteristics of organized mucosa-associated lymphoid tissue (MALT), its subsets of immune cells and their in situ distribution in the lung of healthy subadult and adult cattle shows close similarities with BALT in humans and other animal species such as sheep, horses and pigs. This study clearly demonstrates that organized MALT also occurs in the tracheal mucosa of cattle. The absence of tracheal MALT and BALT in calves suggest that these structures are not constitutive. In the mucosa of bovine trachea, bronchi and bronchioli, MHC II+ and CD11c+ dendritic cells (DCs) are located in the epithelium and in the lamina propria mucosae. These DCs are already present in calves soon after birth. Examination of tangential epithelial sheets shows that in the bovine tracheal epithelium, like in man and rat, a dense network of MHC II+ and CD11c+ DCs exists and that their number is considerably higher than in conventional transverse sections. In the bovine tracheal and bronchial epithelium, MHC II+ DCs are extending their dendrites towards the lumen indicating that these DCs possibly are involved in sampling of luminal antigens. The presence of significantly higher numbers of MHC II+ DCs in the tracheal and bronchial/bronchiolar mucosa of older cattle in than in calves possibly results from local stimulation with exogenous antigens during postnatal life. Detection of DCs expressing the costimulatory molecules CD80 and CD86 in calves and cattle suggests maturation of DCs, which is most likely induced by stimulation with exogenous antigens.

Characteristics and outcomes of lung transplants performed with ex-situ lung perfusion

Ex-situ lung perfusion (ESLP) can be used to assess and rehabilitate donor lungs, potentially expanding the donor pool. We examined the characteristics and outcomes of lung transplants performed with ESLP in the United States. Retrospective review of the United Network for Organ Sharing registry of primary adult lung transplant recipients from February 28, 2018, to June 30, 2021, was performed, comparing baseline characteristics, in-hospital outcomes, and 1-year survival of ESLP vs no ESLP lung transplants. Of 8204 lung transplants, 426 (5.2%) were performed with ESLP. ESLP donors were older, more donation after circulatory death (DCD), and had lower PaO2:FiO2 (P:F) ratios. Recipients had lower lung allocation scores. ESLP lungs traveled further, had longer preservation times, and were more likely double lung transplants. Reintubation rates, extracorporeal membrane oxygenation at 72hours, and hospital length of stay were greater in the ESLP group. On multivariable analysis, ESLP was not an independent predictor of 1-year survival. However, further analysis showed that DCD lungs managed on ESLP had worse 1-year survival compared to DCD lungs preserved with standard cold storage or with donation after brain death donor lungs. ESLP is used in a small percentage of lung transplants in the US and is not independently associated with 1-year survival. ESLP combined with DCD lungs, however, is associated with worse 1-year survival and warrants further investigation.

Vascularization of the adult mouse lung grafted onto the chick chorioallantoic membrane

In the later stages of angiogenesis, the vascular sprout transitions into a functional vessel by fusing with a target vessel. Although this process appears to routinely occur in embryonic tissue, the biologic rules for sprout fusion and lumenization in adult regenerating tissue are unknown. To investigate this process, we grafted portions of the regenerating post-pneumonectomy lung onto the chick chorioallantoic membrane (CAM). Grafts from all 4 lobes of the post-pneumonectomy right lung demonstrated peri-graft angiogenesis as reflected by fluorescent plasma markers; however, fluorescent microsphere perfusion primarily occurred in the lobe of the lung that is the dominant site of post-pneumonectomy angiogenesis—namely, the cardiac lobe. Vascularization of the cardiac lobe grafts was confirmed by active tissue growth (p < .05). Functional vascular connections between the cardiac lobe and the CAM vascular network were demonstrated by confocal fluorescence microscopy as well as corrosion casting and scanning electron microscopy (SEM). Bulk transcriptional profiling of the cardiac lobe demonstrated the enhanced expression of many genes relative to alveolar epithelial cell (CD11b−/CD31−) control cells, but only the upregulation of Ereg and Fgf6 compared to the less well-vascularized right upper lobe. The growth of actively regenerating non-neoplastic adult tissue on the CAM demonstrates that functional lumenization can occur between species (mouse and chick) and across the developmental spectrum (adult and embryo).

Comparison of Lung Cancer Surgery Outcomes in Queensland for Indigenous and Nonindigenous Australians

IntroductionIndigenous Australians (Aboriginal and Torres Strait Islander) have lower overall survival from lung cancer compared with nonindigenous Australians. Indigenous Australians receive higher rates of chemotherapy and/or radiotherapy. The equity of peri-operative care and thoracic surgical outcomes in Australian indigenous populations have not been contemporarily evaluated. MethodsWe performed a retrospective registry analysis of the Queensland Cardiac Outcomes Registry Thoracic Database evaluating all adult lung cancer resections across Queensland from January 1, 2016 to April 20, 2022. Evaluating the time from diagnosis to surgery, operative data, and postoperative morbidity and mortality comparing Aboriginal and/or Torres Strait Islander people with nonindigenous Australians. ResultsThere were 31 patients (2.56%) of 1208 who identified as indigenous. The mean age at surgery was 68.2 years versus 66 years in the indigenous and nonindigenous, respectively (p = 0.23). There was female predominance among indigenous patients (n = 28, 90.32%, p < 0.01) and the average body mass index was lower (22.52 versus 27.09, p < 0.01). There was no variation in the surgical parameters or histopathologic distribution of cancer type between groups. Multivariable logistic regression analysis suggested that indigenous patients were at elevated risk of blood transfusion (relative risk 3.9, p = 0.014, OR = 9.01, 95% confidence interval [CI]: 2.25–36.33, p < 0.01) and had greater transfusion requirements (risk ratio 4.08, p = 0.0116 and OR = 12.67, 95% CI: 2.25–71.49, p < 0.01); however, the influence of low absolute number of transfusions must be acknowledged here. Indigenous status was not associated with increased intensive care unit admission (OR = 1.79, 95% CI: 0.17–18.80, p = 0.62), return to operating theater (OR = 2.1, 95% CI: 0.24–18.15, p = 0.50), new atrial fibrillation (OR = 0.52, 95% CI: 0.07–4.01, p = 0.55), prolonged air leak (OR = 0.29, 95% CI: 0.04– 2.16, p = 0.228), or pneumonia postoperatively (OR = 4.77, 95% CI: 0.55–41.71, p = 0.16). With only three deaths, no meaningful trends were observed. Time from diagnosis to surgery was comparable in the indigenous and nonindigenous groups (88.6 d, 95% CI: 54.26–123.24 versus 86.2 d, 81.40–91.02, p = 0.87). Postoperative length of stay was not numerically or statistically different between groups. (indigenous 7.54 d versus nonindigenous 7.13 d, p = 0.90). ConclusionsIndigenous patients are more likely to receive a blood transfusion than nonindigenous patients during lung resection. Reassuringly, the perioperative care provided to indigenous Australians undergoing lung resection in Queensland seems to be comparable to that of the nonindigenous population.

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.