Search

Objectives: This systematic review aims to assess existing research concerning the use of robotic systems to execute percutaneous lung biopsy. Methods: A systematic review was performed and identified 4 studies involving robotic systems used for lung biopsy. Outcomes assessed were operation time, radiation dose to patients and operators, technical success rate, diagnostic yield, and complication rate. Results: One hundred and thirteen robot-guided percutaneous lung biopsies were included. Technical success and diagnostic yield were close to 100%, comparable to manual procedures. Technical accuracy, illustrated by needle positioning, showed less frequent needle adjustments in robotic guidance than in manual guidance ( P < .001): 2.7 ± 2.6 (range 1-4) versus 6 ± 4 (range 2-12). Procedure time ranged from comparable to reduced by 35% on average (20.1 ± 11.3 minutes vs 31.4 ± 10.2 minutes, P = .001) compared to manual procedures. Patient irradiation ranged from comparable to reduced by an average of 40% (324 ± 114.5 mGy vs 541.2 ± 446.8 mGy, P = .001). There was no significant difference in reported complications between manual biopsy and biopsies that utilized robotic guidance. Conclusion: Robotic systems demonstrate promising results for percutaneous lung biopsy. These devices provide adequate accuracy in probe placement and could both reduce procedural duration and mitigate radiation exposure to patients and practitioners. However, this review underscores the need for larger, controlled trials to validate and extend these findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Francois H. Cornelis is a consultant for GE Healthcare and XACT robotics.

Objectives: To investigate the diagnostic performance and complication rates of percutaneous transthoracic CT-guided coaxial core needle biopsy (PTCNB) in persistent consolidations and evaluate its safety in routine clinical practice., Methods: A total of 685 patients (404 males, 281 females) underwent PTCNB with coaxial core technique for persisted consolidation were reviewed in this study. According to histopathological and microbiological analysis, the results of biopsy specimens were categorized as follows: malignant, specific benign, non-specific benign and non-diagnostic. The final diagnosis was established through surgical resection or clinicoradiological follow-up for at least 12 months following biopsy. Diagnostic yield of PTCNB was defined as the percentage of the true diagnosis from biopsy as malignant and specific benign lesions., Results: With respect to the final diagnosis, 54 (54/685; 7.88%) cases were obtained by surgery and the remaining were by follow-up. The total accuracy, sensitivity, specificity of PTCNB for malignancy diagnosis was 94.45%, 84.87%, 100%, respectively. Diagnostic yield of PTCNB was 66.28%. Compared to lesions smaller than 3 cm, higher diagnostic yield (70.89%), lower complication incidence (38.22%) and shorter procedure time (8.78 min) were observed in lesions ≥ 3 cm group., Conclusion: PTCNB in persistent consolidation is a safe and effective procedure, which provide relatively high diagnostic yield and acceptable complication, especially in size over 3 cm lesions., Critical Relevance Statement: CT-guided coaxial needle biopsy for pulmonary consolidation is a safe and effective procedure. The coaxial needle biopsy yielded high diagnostic rates and low complication rates (including pneumothorax and intrapulmonary hemorrhage), especially in larger lesions., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Pulmonary hamartomas are the most common benign tumors of the lung, typically solitary with a diameter≤4 cm, and rarely undergo malignant transformation. We reported a case of multiple pulmonary hamartomas with malignant transformation of a giant pulmonary hamartoma (approximately 10 cm×12 cm in size). The patient was a 61-year-old female who sought medical attention for the discovery of multiple lesions in the right lung during a routine examination. Computed tomography revealed multiple soft tissue density lesions in the right lung. Surgical resection was performed to remove the lower lobe of the right lung and the lesion located in the posterior segment of the right upper lobe. The pathological results indicated that the right lower lobe lesion had undergone malignant transformation to a high-grade chondrosarcoma originating from a hamartoma, while the right upper lobe lesion remained a hamartoma. By analyzing this case together with the relevant literature, we aimed to emphasize the need for clinical awareness of the malignant potential of pulmonary hamartomas.

Pulmonary complications continue to cause significant morbidity and mortality in posthematopoietic stem cell transplantation (HSCT) settings. The histopathology of pulmonary diseases in the post-HSCT context is poorly characterized, especially in the pediatric population. We sought to characterize the pathologic spectrum of pulmonary disease post-HSCT in a pediatric cohort. Fifty-six specimens, including 53 biopsy specimens, corresponding to 53 patients, were identified. Biopsy slides were reviewed and assigned to diagnostic categories (infectious, graft-versus-host disease, vasculopathy, indeterminate, and others) by consensus among 3 pediatric pulmonary pathologists, taking into consideration pathologic, clinical, radiologic, and laboratory findings. The most common diagnostic category was infection (n=20). Vasculopathy, mostly in the form of fibromyxoid intimal expansion, was very common in the entire cohort (n=26) and was the sole finding in a small subset of patients (n=5), with particularly poor outcomes. A subset of biopsies remained indeterminate (n=10), and the findings in this cohort were dominated by acute lung injury. The latter group had a poor prognosis, with a short biopsy-to-death interval. The overall clinicopathologic concordance was 40%, most commonly agreeing in the infectious category. Finally, wedge biopsies led to a change in management in 69% of cases versus 23% of limited procedures (i.e., core needle biopsies). Our results suggest that while infectious complications continue to be common post-HSCT, other findings such as vasculopathy and acute lung injury portend a particularly poor prognosis and should be actively sought and reported., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies in this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis. Although our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease.

The histologic definition of peripheral pulmonary lesion (PPL) is critical for a correct diagnosis and appropriate therapy. Non-invasive techniques for PPL biopsy are imaging-guided, using endobronchial ultrasound (EBUS), computed tomography (CT), and electromagnetic navigation bronchoscopy (ENB). To assess the diagnostic accuracy of PPL biopsy and provide a framework for reporting data for accuracy studies of PPL biopsy. A systematic review was conducted on PubMed, Scopus, and Web of Science to identify all the articles assessing the accuracy of EBUS, CT, and ENB between January 2000 and June 2023 basing search queries on keywords emerging from PICO question. Only studies investigating biopsy of PPL and reporting accuracy or necessary data to calculate it independently were included. Risk of bias was based on QUADAS-2 tool. In total, 81 studies were included. Median accuracy was 0.78 (range=0.51-0.94) in the EBUS group, 0.91 (range=0.73-0.97) in the CT group, 0.72 (range=0.59-0.97) in the ENB group, and 0.77 (range=0.61-0.92) in the combined group. Sensitivity and NPV ranges were 0.35-0.94 and 0.26-0.88 in the EBUS group, 0.71-0.97 and 0.46-1.00 in the CT group, 0.55-0.96 and 0.32-0.90 in the ENB group, and 0.70-0.90 and 0.28-0.79 in the combined group. Specificity and PPV were 1.00 in almost all studies. Overall complication rate was 3%, 30%, 8%, and 5% in the EBUS, CT, ENB, and combined groups. CT-guided biopsy was the most accurate technique, although with the highest complication rate. When calculating accuracy, indeterminate results must be considered false negatives according to the "intention-to-diagnose" principle., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Topic Importance: Chest CT imaging holds a major role in the diagnosis of lung diseases, many of which affect the peribronchovascular region. Identification and categorization of peribronchovascular abnormalities on CT imaging can assist in formulating a differential diagnosis and directing further diagnostic evaluation., Review Findings: The peribronchovascular region of the lung encompasses the pulmonary arteries, airways, and lung interstitium. Understanding disease processes associated with structures of the peribronchovascular region and their appearances on CT imaging aids in prompt diagnosis. This article reviews current knowledge in anatomic and pathologic features of the lung interstitium composed of intercommunicating prelymphatic spaces, lymphatics, collagen bundles, lymph nodes, and bronchial arteries; diffuse lung diseases that present in a peribronchovascular distribution; and an approach to classifying diseases according to patterns of imaging presentations. Lung peribronchovascular diseases can appear on CT imaging as diffuse thickening, fibrosis, masses or masslike consolidation, ground-glass or air space consolidation, and cysts, acknowledging that some diseases may have multiple presentations., Summary: A category approach to peribronchovascular diseases on CT imaging can be integrated with clinical features as part of a multidisciplinary approach for disease diagnosis., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Pulmonary mucous gland adenomas (MGAs) originating in mucous-secreting cells in the bronchi are extremely rare benign tumours. Pulmonary chondroid hamartomas (PCHs) are the most common benign neoplasms of mesenchymal origin of the lung. This study reports an unusual case where MGA and PCH coexisted in a peripheral intra-parenchymal location. A patient with a 1-cm non-specific nodule in the left lung on a computed tomography scan underwent wedge resection. Microscopically, mesenchymal elements consisting of fat and cartilage tissue were observed. Mucous glands were present around these mesenchymal elements. No cellular atypia or mitosis was observed. This allowed for complete treatment without the need for a segmentectomy.

Background: With recent advancements in bronchoscopic procedures, data on the best modality to sample peripheral pulmonary lesions (PPLs) is lacking, especially comparing bronchoscopy with computed tomography-guided transthoracic biopsy or needle aspiration (CT-TBNA)., Methods: We performed a meta-analysis, pairwise meta-analysis and network meta-analysis on studies reporting diagnostic yield and complications with the use of CT-TBNA, radial endobronchial ultrasound (rEBUS), virtual bronchoscopy (VB), electromagnetic navigation (EMN) or robot-assisted bronchoscopy (RAB) to sample PPLs. The primary outcome was diagnostic yield and the secondary outcome was complications. We estimated the relative risk ratios using a random-effects model and used the frequentist approach for the network meta-analysis. We performed extensive analysis to assess the heterogeneity including reporting bias, publication bias, subgroup and meta-regressional analysis. We assessed the quality of the studies using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and QUADAS-Comparative (QUADAS-C)., Results: We included 363 studies. The overall pooled diagnostic yield was 78.1%, the highest with CT-TBNA (88.9%), followed by RAB (84.8%) and the least with rEBUS (72%). In the pairwise meta-analysis, only rEBUS showed inferiority to CT-TBNA. The network meta-analysis ranked CT-TBNA as likely the most effective approach followed by VB, EMN and RAB, while rEBUS was the least effective, with a low-GRADE certainty. CT-TBNA had the highest rate of complications., Conclusion: Although CT-TBNA is the most effective approach to sample PPLs, RAB has a comparable diagnostic yield with a lesser complication rate. Further prospective studies are needed comparing CT-TBNA and RAB., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Mitochondria, pivotal organelles governing cellular biosynthesis, energy metabolism, and signal transduction, maintain dynamic equilibrium through processes such as biogenesis, fusion, fission, and mitophagy. Growing evidence implicates mitochondrial dysfunction in a spectrum of respiratory diseases including acute lung injury/acute respiratory distress syndrome, bronchial asthma, pulmonary fibrosis, chronic obstructive pulmonary disease, and lung cancer. Consequently, identifying methods capable of ameliorating damaged mitochondrial function is crucial for the treatment of pulmonary diseases. Extracellular vesicles (EVs), nanosized membrane vesicles released by cells into the extracellular space, facilitate intercellular communication by transferring bioactive substances or signals between cells or organs. Recent studies have identified abundant mitochondrial components within specific subsets of EVs, termed mitochondrial extracellular vesicles (mitoEVs), whose contents and compositions vary with disease progression. Moreover, mitoEVs have demonstrated reparative mitochondrial functions in injured recipient cells. However, a comprehensive understanding of mitoEVs is currently lacking, limiting their clinical translation prospects. This Review explores the biogenesis, classification, functional mitochondrial cargo, and biological effects of mitoEVs, with a focus on their role in pulmonary diseases. Emphasis is placed on their potential as biological markers and innovative therapeutic strategies in pulmonary diseases, offering fresh insights for mechanistic studies and drug development in various pulmonary disorders.

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1β, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.

Pulmonary actinomycosis is a rare pulmonary infectious disease that is often challenging to diagnose early and has a high misdiagnosis rate. In some cases, it can be particularly difficult to distinguish pulmonary actinomycosis from lung cancer. We herein report a rare case of pulmonary actinomycosis in which the preoperative examinations strongly suggested lung cancer, leading to the patient undergoing right upper lung resection and bronchoplasty. The patient had a good postoperative recovery; however, the postoperative pathology report indicated pulmonary actinomycosis. In this report, we summarize the key aspects of the diagnosis and treatment of pulmonary actinomycosis to aid clinicians in reducing the likelihood of misdiagnosis., Competing Interests: Declaration of conflicting interestsNone of the authors has any conflict of interest to disclose.

Background: Transbronchial lung cryobiopsy (TBLC) is a new technique for obtaining high-quality and large-sized lung tissues, as compared to transbronchial forceps biopsy (TBFB), and is useful in the diagnosis of diffuse lung disease (DLD). We aimed to evaluate the safety of TBLC as compared to TBFB in DLD patients in Japan using a nationwide database., Methods: Data were retrospectively collected from the Japanese Diagnosis Procedure Combination database from April 1, 2020 to March 31, 2022. Eligible patients (n = 9673) were divided into the following two groups: those who underwent TBFB (TBFB group, n = 8742) and TBLC (TBLC group, n = 931). To compare the outcomes between the two groups, a stabilized inverse probability of treatment weighting (IPTW) was applied using propensity scores. The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, complications (mechanical ventilation, pneumothorax, and bleeding), and length of hospital stay after bronchoscopy., Results: The crude in-hospital mortality rates were 3.2% and 0.9% in the TBFB and TBLC groups, respectively. The stabilized IPTW analysis showed no significant difference in the in-hospital mortality rates between the two groups; the odds ratio of the TBLC group as compared with the TBFB group was 0.73 (95% confidence interval: 0.34-1.60; p = 0.44). Moreover, the secondary outcomes did not significantly differ between the two groups., Conclusions: TBLC for DLD patients had a similar mortality and complication rates as TBFB., Competing Interests: Declaration of competing interest Dr. H. Yasunaga reports receiving grants from the Ministry of Health, Labor, and Welfare, Japan and the Ministry of Education, Culture, Sports, Science, and Technology, Japan during the conduct of the study. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The diagnosis of peripheral pulmonary lesions (PPLs) remains challenging. Despite advancements in guided transbronchial biopsy (TBB) techniques, diagnostic yields haven't reached ideal levels. Optical coherence tomography (OCT) has been developed for application in pulmonary diseases, yet no data existed evaluating effectiveness in diagnosing PPLs., Research Design and Methods: This study included patients who underwent OCT and radial endobronchial ultrasound (R-EBUS)-guided TBB. OCT and R-EBUS imaging features were analyzed to differentiate between benign and malignant PPLs and subtypes of lung cancer., Results: A total of 89 patients were included in this study. The diagnostic yield of OCT-guided TBB stood at 56.18%, R-EBUS-guided TBB was 83.15% (P<0.01). The accuracy of OCT to judge the nature of lesions was 92.59%, while R-EBUS was 77.92%. The accuracy of OCT in predicting squamous carcinoma (SCC) and adenocarcinoma were both 91.30%., Conclusions: Although the diagnostic yield of OCT-guided TBB fell short of that achieved by R-EBUS, OCT possessed the capability to judge the nature of lesions and guide the pathological classification of malignant lesions. Further extensive prospective studies are necessary to thoroughly assess the characteristics of this procedure., Clinical Trial Registration: https://register.clinicaltrials.gov/ identifier is NCT06419114.

Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade, increasing evidence from preclinical models suggests that mesenchymal stromal cells, which are not normally resident in the lung, can be used to modulate immune responses after injury, but there have been challenges in translating these promising findings to the clinic. In parallel, there has been a surge in bioengineering studies investigating the use of artificial and acellular lung matrices as scaffolds for three-dimensional lung or airway regeneration, with some recent attempts of transplantation in large animal models. The combination of these studies with those involving stem cells, induced pluripotent stem cell derivatives, and/or cell therapies is a promising and rapidly developing research area. These studies have been further paralleled by significant increases in our understanding of the molecular and cellular events by which endogenous lung stem and/or progenitor cells arise during lung development and participate in normal and pathological remodeling after lung injury. For the 2023 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, scientific symposia were chosen to reflect the most cutting-edge advances in these fields. Sessions focused on the integration of "omics" technologies with function, the influence of immune cells on regeneration, and the role of the extracellular matrix in regeneration. The necessity for basic science studies to enhance fundamental understanding of lung regeneration and to design innovative translational studies was reinforced throughout the conference.

Recently, there has been increasing attention to bidirectional information exchange between the brain and lungs. Typical physiological data is communicated by channels like the circulation and sympathetic nervous system. However, communication between the brain and lungs can also occur in pathological conditions. Studies have shown that severe traumatic brain injury (TBI), cerebral hemorrhage, subarachnoid hemorrhage (SAH), and other brain diseases can lead to lung damage. Conversely, severe lung diseases such as acute respiratory distress syndrome (ARDS), pneumonia, and respiratory failure can exacerbate neuroinflammatory responses, aggravate brain damage, deteriorate neurological function, and result in poor prognosis. A brain or lung injury can have adverse effects on another organ through various pathways, including inflammation, immunity, oxidative stress, neurosecretory factors, microbiome and oxygen. Researchers have increasingly concentrated on possible links between the brain and lungs. However, there has been little attention given to how the interaction between the brain and lungs affects the development of brain or lung disorders, which can lead to clinical states that are susceptible to alterations and can directly affect treatment results. This review described the relationships between the brain and lung in both physiological and pathological conditions, detailing the various pathways of communication such as neurological, inflammatory, immunological, endocrine, and microbiological pathways. Meanwhile, this review provides a comprehensive summary of both pharmacological and non-pharmacological interventions for diseases related to the brain and lungs. It aims to support clinical endeavors in preventing and treating such ailments and serve as a reference for the development of relevant medications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Children's interstitial and diffuse lung disease (chILD) comprises a large number of diverse entities ranging from disorders of lung development, maturation and function unique in infancy to immune-mediated, environmental, vascular and other conditions overlapping with adult disease. Pathologic evaluation of the lung has played a central role in characterizing many of these disorders, resulting in revised nomenclature and classifications to help guide clinical management(1-4). Technological advancements are rapidly uncovering genetic and molecular underpinnings of these conditions, as well as widening the phenotypes which bridge adult disease, often reducing the perceived need for diagnostic lung biopsy. As such the decision to get a lung biopsy in chILD is frequently for rapid ascertainment of disease in a critically ill child or when clinical presentation, imaging and laboratory studies fail to provide a cohesive diagnosis needed for treatment. While there have been modifications in surgical procedures for lung biopsy that minimize postoperative morbidity, it remains a high-risk invasive procedure, especially in a medically complex patient(5). Thus, it is essential that the lung biopsy be handled properly to maximize diagnostic yield, including close communication between the clinician, radiologist, surgeon, and pathologist before biopsy to determine best sampling site(s) and prioritization of tissue utilization. This review provides an overview of optimal handling and evaluation of a surgical lung biopsy for suspected chILD, with emphasis on specific conditions in which pathologic features play a critical role in providing an integrated diagnosis and guiding management., (© 2023 Wiley Periodicals LLC.)

Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The endothelium is a cell monolayer that lines vessels and separates tissues from blood flow. Endothelial cells (ECs) have a multitude of functions, including regulating blood flow and systemic perfusion through changes in vessel diameter. When an injury occurs, the endothelium is affected by altering its functions and structure, which leads to endothelial dysfunction, a characteristic of many vascular diseases. Understanding the role that the endothelium plays in pulmonary vascular and cardiopulmonary diseases, and exploring new therapeutic strategies is of utmost importance to advance clinically. Currently, there are several treatments able to improve patients' quality of life, however, none are effective nor curative. This review examines the critical role of the endothelium in the pulmonary vasculature, investigating the alterations that occur in ECs and their consequences for blood vessels and potential molecular targets to regulate its alterations. Additionally, we delve into promising non-pharmacological therapeutic strategies, such as exercise and diet. The significance of the endothelium in cardiopulmonary disorders is increasingly being recognized, making ECs a relevant target for novel therapies aimed at preserving their functional and structural integrity.

Background: Cystic and nodular lung diseases encompass a broad spectrum of diseases with different etiologies and clinicoradiological presentations. Their differentiation is crucial for patient management but can be complex due to diseases with features of both categories and overlapping radiological patterns., Objective: This study aims to describe the imaging features of cystic and nodular lung diseases in high-resolution computed tomography (CT) in detail-primarily based on their etiology-in order to allow a more accurate differential diagnosis of these diseases., Materials and Methods: A narrative review based on current literature on the topic was conducted from a clinicoradiological perspective., Results: This paper systematically categorizes the differential diagnosis of cystic and nodular lung disease and provides insights into their radiological patterns and etiologies. It highlights the role of CT in the diagnosis of these diseases and emphasizes the importance of multidisciplinary panels combining expertise from radiology, pulmonology, rheumatology, and pathology., Conclusion: Reliable differential diagnosis of cystic and nodular lung diseases, particularly based on their radiological features alone, remains difficult due to their overlapping and dynamic nature. Multidisciplinary boards should be the clinical standard for accurate work-up of these diseases, as they combine the medical history, symptoms, radiological findings, and, if necessary, histopathological examinations, thus providing a more robust framework for diagnosis and management., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Transthoracic needle biopsy of lung lesions is a well-established procedure for the diagnosis of lung lesions. The literature focuses on the diagnosis of malignant lesions with an often reported accuracy rate of more than 90%. Experience showed that biopsy can identify sometimes incidentally, also benign lesions. There are many reasons why a biopsy is performed for a "benign lesion." First of all, it may be an unexpected diagnosis, as some benign pathologies may have misleading presentations, that are very similar to lung cancer, otherwise the reason is only to make a diagnosis of exclusion, which leads to the benign pathology already being considered in the differential diagnosis., Methods: This study was designed as a retrospective single-center study. We selected from our database all the lung biopsies performed under CT guidance, from 2015 to 2019 and retrospectively analysed the histological data. We selected only benign lesions describing the imaging feature and differential diagnosis with lung malignancy., Results: In our patient population, among the 969 of them that underwent biopsy, we identified 93 benign lesions (10%). Hamartomas, granulomas, slow-resolving pneumonia and cryptogenic organizing pneumonia are the pathologies that most frequently can misinterpratedas lung cancer., Conclusions: In this brief report we want to show the percentage and type of benign lesions that are found in our lung trans-thoracic biopsy population. Among these, we identified the three most frequent benign lesions that most frequently enter the differential diagnosis with lung malignant lesions describing the classic and atypical imaging findings.

Occupational lung/thoracic diseases are a major global public health issue. They comprise a diverse spectrum of health conditions with complex pathology, most of which arise following chronic heavy workplace exposures to various mineral dusts, metal fumes, or following inhaled organic particulate reactions. Many occupational lung diseases could become irreversible; thus accurate diagnosis is mandatory to minimize dust exposure and consequently reduce damage to the respiratory system. Lung biopsy is usually required when exposure history is inconsistent with imaging, in case of unusual or new exposures, in case of unexpected malignancy, and in cases in which there are claims for personal injury and legal compensation. In this paper, we provide an overview of the most frequent occupational lung diseases with a focus on pathological diagnosis. This is a paper that summarizes the expert opinion from a group of European pathologists, together with contributions from other specialists who are crucial for the diagnosis and management of these diseases. Indeed, tight collaboration of all specialists involved in the workup is mandatory as many occupational lung diseases are misdiagnosed or go unrecognized. This document provides a guide for pathologists in practice to facilitate the accurate diagnosis of occupational lung disease. The review article reports relevant topics discussed during an educational course held by expert pathologists, active members of the Pulmonary Pathology Working Group of the European Society of Pathology. The course was endorsed by the University of Padova as a "winter school" (selected project in the call for "Shaping a World-class University" 2022)., (© 2024. The Author(s).)

Background: Clinical differentiation between pulmonary metastases and noncalcified pulmonary hamartomas (NCPH) often presents challenges, leading to potential misdiagnosis. However, the efficacy of a comprehensive model that integrates clinical features, radiomics, and deep learning (CRDL) for differential diagnosis of these two diseases remains uncertain., Objective: This study evaluated the diagnostic efficacy of a CRDL model in differentiating pulmonary metastases from NCPH., Methods: The authors retrospectively analyzed the clinical and imaging data of 256 patients from the First Medical Centre of the General Hospital of the People's Liberation Army (PLA) and 85 patients from Shanghai Changhai Hospital, who were pathologically confirmed pulmonary hamartomas or pulmonary metastases after thoracic surgery. Employing Python 3.7 software suites, the authors extracted radiomic features and deep learning (DL) attributes from patient datasets. The cohort was divided into training set, internal validation set, and external validation set. The diagnostic performance of the constructed models was evaluated using receiver operating characteristic (ROC) curve analysis to determine their effectiveness in differentiating between pulmonary metastases and NCPH., Results: Clinical features such as white blood cell count (WBC), platelet count (PLT), history of cancer, carcinoembryonic antigen (CEA) level, tumor marker status, lesion margin characteristics (smooth or blurred), and maximum diameter were found to have diagnostic value in differentiating between the two diseases. In the domains of radiomics and DL. Of the 1130 radiomics features and 512 DL features, 24 and 7, respectively, were selected for model development. The area under the ROC curve (AUC) values for the four groups were 0.980, 0.979, 0.999, and 0.985 in the training set, 0.947, 0.816, 0.934, and 0.952 in the internal validation set, and 0.890, 0.904, 0.923, and 0.938 in the external validation set. This demonstrated that the CRDL model showed the greatest efficacy., Conclusions: The comprehensive model incorporating clinical features, radiomics, and DL shows promise for aiding in the differentiation between pulmonary metastases and hamartomas., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: In the past two decades, bronchoscopy of peripheral pulmonary lesions (PPLs) has improved its diagnostic yield due to the combination of various instruments and devices. Meanwhile, the application is complex and intertwined., Areas Covered: This review article outlines strategies in diagnostic bronchoscopy for PPLs. We summarize the utility and evidence of key instruments and devices based on the results of clinical trials. Future perspectives of bronchoscopy for PPLs are also discussed., Expert Opinion: The accuracy of reaching PPLs by bronchoscopy has improved significantly with the introduction of combined instruments such as navigation, radial endobronchial ultrasound, digital tomosynthesis, and cone-beam computed tomography. It has been accelerated with the advent of approach tools such as newer ultrathin bronchoscopes and robotic-assisted bronchoscopy. In addition, needle aspiration and cryobiopsy provide further diagnostic opportunities beyond forceps biopsy. Rapid on-site evaluation may also play an important role in decision making during the procedures. As a result, the diagnostic yield of bronchoscopy for PPLs has improved to a level comparable to that of transthoracic needle biopsy. The techniques and technologies developed in the diagnosis will be carried over to the next step in the transbronchial treatment of PPLs in the future.

The interactions between immune cells and epithelial cells influence the progression of many respiratory diseases, such as chronic obstructive pulmonary disease (COPD). In vitro models allow for the examination of cells in controlled environments. However, these models lack the complex 3D architecture and vast multicellular interactions between the lung resident cells and infiltrating immune cells that can mediate cellular response to insults. In this study, three complementary microphysiological systems are presented to delineate the effects of cigarette smoke and respiratory disease on the lung epithelium. First, the Transwell system allows the co-culture of pulmonary immune and epithelial cells to evaluate cellular and monolayer phenotypic changes in response to cigarette smoke exposure. Next, the human and mouse precision-cut lung slices system provides a physiologically relevant model to study the effects of chronic insults like cigarette smoke with the dissection of specific interaction of immune cell subtypes within the structurally complex tissue environment. Finally, the lung-on-a-chip model provides an adaptable system for live imaging of polarized epithelial tissues that mimic the in vivo environment of the airways. Using a combination of these models, a complementary approach is provided to better address the intricate mechanisms of lung disease., (© 2023 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

The lung is a highly mechanical organ as it is exposed to approximately 10 9 strain cycles, (where strain is the length change of tissue structure per unit initial length), with an approximately 4% amplitude change during quiet tidal breathing or 10 7 strain cycles at a 25% amplitude during heavy exercises, sighs, and deep inspirations. These mechanical indices have been reported to become aberrant in lung diseases such as acute respiratory distress syndrome (ARDS), pulmonary hypertension, bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), and asthma. Through recent innovations, various in vitro systems/bioreactors used to mimic the lung's mechanical strain have been developed. Among these, the Flexcell tension system which is composed of bioreactors that utilize a variety of programs in vitro to apply static and cyclic strain on different cell-types established as 2D monolayer cultures or cell-embedded 3D hydrogel models, has enabled the assessment of the response of different cells such as fibroblasts to the lung's mechanical strain in health and disease. Fibroblasts are the main effector cells responsible for the production of extracellular matrix (ECM) proteins to repair and maintain tissue homeostasis and are implicated in the excessive deposition of matrix proteins that leads to lung fibrosis. In this review, we summarise, studies that have used the Flexcell tension bioreactor to assess effects of the mechanical lung on the structure, function, and phenotype of lung fibroblasts in homeostatic conditions and abnormal environments associated with lung injury and disease. We show that these studies have revealed that different strain conditions regulate fibroblast proliferation, ECM protein production, and inflammation in normal repair and the diseased lung., (© 2024. The Author(s).)

Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cells (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to the basal ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury.

Currently, the global lifespan has increased, resulting in a higher proportion of the population over 65 years. Changes that occur in the lung during aging increase the risk of developing acute and chronic lung diseases, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer. During normal tissue homeostasis, cell proliferation and apoptosis create a dynamic balance that constitutes the physiological cell turnover. In basal conditions, the lungs have a low rate of cell turnover compared to other organs. During aging, changes in the rate of cell turnover in the lung are observed. In this work, we review the literature that evaluates the role of molecules involved in cell proliferation and apoptosis in lung aging and in the development of age-related lung diseases. The list of molecules that regulate cell proliferation, apoptosis, or both processes in lung aging includes TNC, FOXM1, DNA-PKcs, MicroRNAs, BCL-W, BCL-XL, TCF21, p16, NOX4, NRF2, MDM4, RPIA, DHEA, and MMP28. However, despite the studies carried out to date, the complete signaling pathways that regulate cell turnover in lung aging are still unknown. More research is needed to understand the changes that lead to the development of age-related lung diseases.

BACKGROUND. Concern may exist that pulmonary lesions associated with cystic airspaces are at risk of increased biopsy complications or lower biopsy accuracy given challenges in targeting tissue abutting or intermingled with the cystic airspaces. OBJECTIVE. The purpose of this study was to evaluate the safety and diagnostic performance of CT-guided core needle biopsy (CNB) of pulmonary lesions associated with cystic airspaces. METHODS. This retrospective study included 90 patients (median age, 69.5 years; 28 women, 62 men) who underwent CT-guided CNB of pulmonary lesions associated with cystic airspaces (based on review of procedural images) from February 2010 to December 2022 and a matched control group (2:1 ratio) of 180 patients (median age, 68.0 years; 56 women, 124 men) who underwent CNB of noncystic noncavitary lesions during the same period. The groups were compared in terms of complications, nondiagnostic biopsies (i.e., nonspecific benignities, atypical cells, or insufficient specimens), and CNB diagnostic performance for detecting malignancy using as reference the final diagnosis from a joint review of all available records. For lesions associated with cystic airspaces that underwent surgical resection after CNB, histologic slides were reviewed to explore the nature of the cystic airspace. RESULTS. The final diagnosis was malignant in 90% (81/90) of lesions associated with cystic airspaces and 92% (165/180) of noncystic noncavitary lesions. Patients with lesions associated with cystic airspaces and patients with noncystic noncavitary lesions showed no significant difference in frequency of complications (overall: 40% [36/90] vs 38% [68/180], p = .79; major: 4% [4/90] vs 6% [10/180], p = .78; minor: 36% [32/90] vs 32% [58/180], p = .59), frequency of nondiagnostic biopsies (12% [11/90] vs 9% [16/180], p = .40), or diagnostic performance (accuracy: 94% [85/90] vs 97% [175/180], p = .50; sensitivity: 94% [76/81] vs 97% [160/165], p = .50; specificity: 100% [9/9] vs 100% [15/15]; p > .99), respectively. All false-negative results for malignancy in both groups occurred in patients with nondiagnostic CNB results. Among lesions associated with cystic airspaces that were resected after CNB (all malignant), the cystic airspaces most commonly represented tumor degeneration (22/31 [71%]). CONCLUSION. CT-guided CNB is safe and accurate for assessing pulmonary lesions associated with cystic airspaces. CLINICAL IMPACT. CNB may help avoid a missed or delayed cancer diagnosis in pulmonary lesions with cystic airspaces.

Inhalation drug delivery is superior for local lung disease therapy. However, there are several unique absorption barriers for inhaled drugs to overcome, including limited drug deposition at the target site, mucociliary clearance, pulmonary macrophage phagocytosis, and systemic exposure. Moreover, the respiratory disease state can affect or even destroy the physiology of the lung, thus influencing the in vivo fate of inhaled particles compared with that in healthy lungs. Nevertheless, limited information is available on this effect. Thus, in this review, we present pathological changes of the lung microenvironment under varied respiratory diseases and their influence on the in vivo fate of inhaled particles; such insights could provide a basis for rational inhalation particle design based on specific disease states., (Copyright © 2024. Published by Elsevier Ltd.)

The gradually progressive solitary cystic-solid mass of chest CT scans is highly suggestive of lung cancer. We report a case of a 29-year-old woman with a persistent cystic-solid lesion in the right upper lobe. A chest CT scan showed a 35 mm × 44 mm × 51 mm focal cystic-solid mass in the anterior segment of the right upper lobe. The size of lesion had increased over 3 years, especially for the solid component. The right upper lobe pneumonectomy was performed. Postoperative pathological examination showed placental transmogrification of the lung, which is a rare cause of pulmonary cystic lesion., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Pulmonary hamartomas are benign lung lesions. Histopathologically, pulmonary hamartoma is composed of varying amounts of mesenchymal elements, including chondroid tissue, mature adipose tissue, fibrous stroma, smooth muscle, and entrapped respiratory epithelium. Most pulmonary hamartoma cases are asymptomatic and found incidentally during imaging. They usually appear as well-circumscribed lesions with the largest dimension of less than 4 cm. Asymptomatic giant pulmonary hamartomas that more than 8 cm are rare., Case Presentation: In the current case report, a 12.0 × 9.5 × 7.5 cm lung mass was incidentally noticed in a 59-year-old female during a heart disease workup. Grossly, the lesion was lobulated with pearly white to tan-white solid cut surface and small cystic areas. Microscopically, representative tumor sections demonstrate a chondromyxoid appearance with relatively hypocellular stroma and entrapped respiratory epithelium at the periphery. No significant atypia is noted. No mitosis is noted, and the proliferative index is very low (< 1%) per Ki-67 immunohistochemistry. Mature adipose tissue is easily identifiable in many areas. Histomorphology is consistent with pulmonary hamartoma. A sarcoma-targeted gene fusion panel was further applied to this case. Combined evaluation of microscopic examination and sarcoma-targeted gene fusion panel results excluded malignant sarcomatous transformation in this case. The mediastinal and hilar lymph nodes are histologically benign. After surgery, the patient had an uneventful postoperative period., Conclusions: Giant pulmonary hamartoma is rare; our case is an example of a huge hamartoma in an asymptomatic patient. The size of this tumor is concerning. Thus, careful and comprehensive examination of the lesion is required for the correct diagnosis and to rule out co-existent malignancy., (© 2024. The Author(s).)

The lung is regarded as having limited regenerative capacity, and there are few treatment options for refractory lung diseases, such as interstitial pneumonia. Lung transplantation is the final option available in some scenarios. Research in this area has been slow owing to the complex structure of the lung for efficient gas exchange between the alveolar spaces and capillaries as well as the difficulty in obtaining specimens from patients with progressive lung disease. However, basic research over the past decade in the field of mouse and human embryology using genetic lineage tracing techniques and stem cell biology using primary and pluripotent stem cell-derived alveolar organoids has begun to clarify the tissue response in various intractable lung diseases and the mechanisms underlying remodeling. Advancement in this area may expand potential therapeutic targets for alveolar regeneration, providing alternatives to lung transplantation, and contribute to the development of effective therapeutic methods that activate or repopulate stem cells in the lung. In this review, we cover research focused on alveolar epithelial cells and discuss methods expected to regenerate lungs that are damaged by diseases., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1 -related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants., Methods: Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis., Results: In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB., Conclusion: Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention., Competing Interests: Competing interests: Dr Hill is the owner of ResourcePath LLC, a company which does research and development of laboratory tests including for DICER1-related cancers. The work is unrelated to the information presented in this article. Dr Stewart provides telegenetics services for Genome Medical, Inc, in accordance with relevant National Cancer Institute policies. The remaining authors have no conflicts to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve the understanding of the disease. Methods: We retrospectively analyzed the clinical data of 23 PLCDD cases diagnosed by pathology in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023, a total of 11 cases of PLCDD secondary to SS(SS-PLCDD) were selected, the median age was 51 years old(range:36~74),10 female and 1 male, the clinical, imaging, and pathological features were summarized. Results: All 11 cases showed bilateral multiple pulmonary nodules on HRCT with 10 cases accompanied by cysts, 6 cases with vessels in the cystic wall or crossing the cysts. Microscopically, all 11 cases showed amorphous eosinophilic material with negative Congo red staining deposited in the lung, vascular involvement was common, with variable lymphocyte, plasma cell infiltration and multinucleated giant cell reaction, cysts formation was observed in 6 cases,1 case combined with pulmonary lymphoma. No extrapulmonary involvement in all 11 cases. Ten patients were treated with glucocorticoid and (or) immunosuppressants, 1 patient changed to bortezomib-dexamethasone chemotherapy after 1 year, with a mean follow-up of 50 months, 5 cases were stable on clinical and (or) HRCT findings, 2 cases showed remission on HRCT, 2 cases progressed on HRCT. Conclusions: SS-PLCDD affects predominantly middle-aged females with lesions confined to the lung; HRCT showed bilateral multiple nodules and thin-walled cysts. Pulmonary pathology presented as non-amyloid material with negative Congo red staining and interstitial changes associated with SS. The overall prognosis was good, but caution is advised regarding the underlying lymphoma.

Background: Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature., Case Presentation: A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern., Conclusions: This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors., (© 2024. The Author(s).)

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts., Competing Interests: YL, KC, JC, HC, HW, MT, BG, MK, MP, YM, WS No competing interests declared, (© 2023, Luo et al.)

Precision Cut Lung Slices (PCLS) have emerged as a sophisticated and physiologically relevant ex vivo model for studying the intricacies of lung diseases, including fibrosis, injury, repair, and host defense mechanisms. This innovative methodology presents a unique opportunity to bridge the gap between traditional in vitro cell cultures and in vivo animal models, offering researchers a more accurate representation of the intricate microenvironment of the lung. PCLS require the precise sectioning of lung tissue to maintain its structural and functional integrity. These thin slices serve as invaluable tools for various research endeavors, particularly in the realm of airway diseases. By providing a controlled microenvironment, precision-cut lung slices empower researchers to dissect and comprehend the multifaceted interactions and responses within lung tissue, thereby advancing our understanding of pulmonary pathophysiology., (© 2024. The Author(s).)

Competing Interests: Declaration of interests We declare no competing interests.

Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes., Competing Interests: Disclosure No disclosures or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Therapeutic options for steroid-resistant non-type 2 inflammation in obstructive lung diseases are limited. Bronchial epithelial cells are key in the pathogenesis by releasing the central proinflammatory cytokine interleukine-8 (IL-8). Olfactory receptors (ORs) are expressed in various cell types. This study examined the drug target potential of ORs by investigating their impact on associated pathophysiological processes in lung epithelial cells., Methods: Experiments were performed in the A549 cell line and in primary human bronchial epithelial cells. OR expression was investigated using RT-PCR, Western blot, and immunocytochemical staining. OR-mediated effects were analyzed by measuring 1) intracellular calcium concentration via calcium imaging, 2) cAMP concentration by luminescence-based assays, 3) wound healing by scratch assays, 4) proliferation by MTS-based assays, 5) cellular vitality by Annexin V/PI-based FACS staining, and 6) the secretion of IL-8 in culture supernatants by ELISA., Results: By screening 100 potential OR agonists, we identified two, Brahmanol and Cinnamaldehyde, that increased intracellular calcium concentrations. The mRNA and proteins of the corresponding receptors OR2AT4 and OR2J3 were detected. Stimulation of OR2J3 with Cinnamaldehyde reduced 1) IL-8 in the absence and presence of bacterial and viral pathogen-associated molecular patterns (PAMPs), 2) proliferation, and 3) wound healing but increased cAMP. In contrast, stimulation of OR2AT4 by Brahmanol increased wound healing but did not affect cAMP and proliferation. Both ORs did not influence cell vitality., Conclusion: ORs might be promising drug target candidates for lung diseases with non-type 2 inflammation. Their stimulation might reduce inflammation or prevent tissue remodeling by promoting wound healing., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Knobloch has received research grants, speaker fees and fees for participation on advisory boards from AstraZeneca, and has received research grants from Sanofi. J. Kronsbein has received speaker fees and fees for participation on advisory boards from AstraZeneca, Sanofi, Novartis and GlaxoSmithKline., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Placental transmogrification of the lung (PTL) is a rare pulmonary condition characterized by the presence of immature placental villous structures. The etiology and molecular mechanisms underlying this disease remain largely unknown. This functional study aimed to identify the molecular signatures in the pathogenesis of PTL via comprehensive transcriptome analysis. Comparative transcriptomic assessment of PTL tissue and stromal cells showed differential expression of 257 genes in PTL tissue and 189 genes in stromal cells. Notably, several transcription factors and regulators, including FOSB, FOS, JUN, and ATF3, were upregulated in PTL tissue. Additionally, genes associated with the extracellular matrix and connective tissue, such as COL1A1, MMP2, and SPARC, were significantly altered, indicating possible fibrotic changes. Gene set enrichment analysis highlighted the role of vascular development and extracellular matrix organization, and the Activator Protein-1 (AP-1) transcription factor was significantly activated in PTL tissue. Furthermore, the analysis highlighted an overlap of 25 genes between PTL tissue and stromal cells, underscoring the importance of shared molecular pathways in the pathogenesis of PTL. Among the shared genes, JUND, COL4A2, COL6A2, IGFBP5, and IGFBP7 were consistently upregulated, highlighting the possible involvement of AP-1-mediated signaling and fibrotic changes in the pathogenesis of PTL. The present findings pave the way for further research into the molecular mechanisms underlying PTL and offer novel insights for therapeutic interventions. Given the rarity of PTL, these molecular findings represent a significant step forward in our understanding this enigmatic disease., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)