RESUMO
BACKGROUND: Surgery is the main treatment option for destroyed-lung (DL) patients with life-threatening massive hemoptysis. However, short-term and long-term surgical safety and efficacy are unclear, prompting this study. METHODS: Data from 124 DL patients undergoing surgery between November 2001 and January 2022 at Beijing Chest Hospital were retrospectively analyzed. Data of the DL group (82 cases) and DL + massive hemoptysis group (42 cases) were compared with regard to clinical characteristics, long-term postoperative residual lung reinfection. RESULTS: As compared with DL group rates, The DL + massive hemoptysis group had greater incidence rates of postoperative complications, invasive postoperative respiratory support, long-term postoperative residual lung reinfection, and postoperative tuberculosis recurrence. Revealed risk factors for postoperative complications (Extent of lung lesion resection), postoperative invasive respiratory therapy (preoperative Hb < 9 g/L, severe intraoperative hemoptysis), and postoperative long-term residual lung reinfection (DL with massive hemoptysis). CONCLUSIONS: DL patients with massive hemoptysis had greater rate of invasive respiratory support therapy and postoperative complications. Extensive lesion removal, preoperative anaemia, severe intraoperative bleeding associated with recent postoperative complications for the patient.
Assuntos
Hemoptise , Pneumonectomia , Complicações Pós-Operatórias , Humanos , Hemoptise/etiologia , Hemoptise/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Pneumonectomia/efeitos adversos , Prognóstico , Idoso , Fatores de Risco , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/cirurgia , Pulmão/fisiopatologia , Pulmão/cirurgia , Recidiva , PequimRESUMO
Chronic obstructive pulmonary disease is a common chronic lung disease with an ever-increasing incidence. Despite years of drug research and approvals, we are still not able to halt progress or restore normal lung function. Our previous studies have demonstrated that liver growth factor-LGF has an effect on the repair of the affected tissue in a mouse model of cigarette smoke exposure, but by what pathways it achieves this is unknown. The present study aimed to identify differentially expressed genes between emphysematous mice treated with LGF to identify potential therapeutic targets for the treatment of pulmonary emphysema. The emphysema mouse model was induced by prolonged exposure to cigarette smoke. To determine the gene expression profile of the lung in smokers treated or not with LGF, lung messenger RNA gene expression was assessed with the Agilent Array platform. We carried out differentially expressed gene analysis, functional enrichment and validated in treated mouse lung samples. The treated group significantly improved lung function (~35%) and emphysema level (~20%), consistent with our previous published studies. Microarray analysis demonstrated 290 differentially expressed genes in total (2.0-fold over or lower expressed). Injury repair-associated genes and pathways were further enhanced in the lung of LGF treated mice. The expression trends of two genes (Zscan2 and Bag6) were different in emphysematous lungs treated with LGF compared to untreated lungs. Therefore, Zscan2 and Bag6 genes could play a role in regulating inflammation and the immune response in the lung that undergoes partial lung regeneration. However, further studies are necessary to demonstrate this causal relationship.
Assuntos
Modelos Animais de Doenças , Pulmão , Doença Pulmonar Obstrutiva Crônica , Fatores de Transcrição , Animais , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Camundongos , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Perfilação da Expressão Gênica , Camundongos Endogâmicos C57BL , Masculino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
In this paper, I will discuss recent studies using a cystic fibrosis pig model to better understand the origins of cystic fibrosis lung disease. Specifically, I will review our work investigating how loss of the cystic fibrosis transmembrane conductance regulator function (CFTR) impairs mucociliary transport in the cystic fibrosis airway. These studies reveal new insights into the early, underlying mechanisms of cystic fibrosis lung disease and could lead to novel therapeutic interventions.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Modelos Animais de Doenças , Depuração Mucociliar , Fibrose Cística/metabolismo , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Fibrose Cística/genética , Animais , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Suínos , Humanos , Pulmão/metabolismo , Pulmão/fisiopatologia , Mutação , Predisposição Genética para Doença , FenótipoRESUMO
Paraquat poisoning results in significant pulmonary damage, but current treatments are only minimally effective in repairing the injured lung tissues. Recent research has highlighted the promise of using stem cell therapy, namely mesenchymal stem cells, as a new method for treating paraquat toxicity. These cells have shown effectiveness in decreasing inflammation, apoptosis, and fibrosis in the mice lungs subjected to paraquat. The therapeutic implications of mesenchymal stem cells are believed to arise from their release of bioactive proteins and their capacity to regulate inflammatory responses. However, additional clinical study is required to validate these therapies' efficacy. This review thoroughly explores the pathophysiology of paraquat poisoning and the properties of mesenchymal stem cells. Additionally, it critically assesses the long-term safety and effectiveness of mesenchymal stem cell therapies, which is crucial for developing more dependable and effective treatment protocols. In summary, although mesenchymal stem cells offer promising prospects for treating lung injuries, more investigations are required to optimize their therapeutic promise and ensure their safe clinical application in the context of paraquat poisoning.
Assuntos
Lesão Pulmonar , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Paraquat , Paraquat/toxicidade , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Lesão Pulmonar/terapia , Lesão Pulmonar/induzido quimicamente , Pulmão/patologia , CamundongosRESUMO
BACKGROUND: The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques. METHODS: Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis). RESULTS: NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased. CONCLUSIONS: NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções por Mycobacterium não Tuberculosas/genética , Feminino , Pessoa de Meia-Idade , Idoso , Transcriptoma , Macrófagos/imunologia , Macrófagos/metabolismo , Pulmão/microbiologia , Pulmão/imunologia , Pulmão/patologia , Micobactérias não Tuberculosas/genética , Micobactérias não Tuberculosas/imunologia , Pneumopatias/genética , Pneumopatias/microbiologia , Pneumopatias/imunologia , Linfócitos T/imunologia , Perfilação da Expressão Gênica , Adulto , Bronquiectasia/imunologia , Bronquiectasia/genética , Bronquiectasia/microbiologiaRESUMO
BACKGROUND: Lung fibroblasts play a central role in maintaining lung homeostasis and facilitating repair through the synthesis and organization of the extracellular matrix (ECM). This study investigated the cross-talk between interleukin-1 alpha (IL-1α) and transforming growth factor-ß (TGF-ß) signaling, two key regulators in tissue repair and fibrosis, in the context of lung fibroblast repair in the healthy lung. RESULTS: Stimulation of lung fibroblasts with TGF-ß1 and TGF-ß2 induced collagen-I and fibronectin protein expression (p < 0.05), a response inhibited with co-treatment with IL-1α (p < 0.05). Additionally, TGF-ß1 and TGF-ß2 induced myofibroblast differentiation, and collagen-I gel contraction, which were both suppressed by IL-1α (p < 0.05). In contrast, interleukin (IL)-6, IL-8 and thymic stromal lymphopoietin induced by IL-1α, were unaffected by TGF-ß1 or TGF-ß2. Mechanistically, IL-1α administration led to the suppression of TGF-ß1 and TGF-ß2 signaling, through downregulation of mRNA and protein for TGF-ß receptor II and the downstream adaptor protein TRAF6, but not through miR-146a that is known to be induced by IL-1α. DISCUSSION: IL-1α acts as a master regulator, modulating TGF-ß1 and TGF-ß2-induced ECM production, remodeling, and myofibroblast differentiation in human lung fibroblasts, playing a vital role in balancing tissue repair versus fibrosis. Further research is required to understand the dysregulated cross-talk between IL-1α and TGF-ß signaling in chronic lung diseases and the exploration of therapeutic opportunities. METHODS: Primary human lung fibroblasts (PHLF) were treated with media control, or 1 ng/ml IL-1α with or without 50 ng/ml TGF-ß1 or TGF-ß2 for 1, 6 and 72 h. Cell lysates were assessed for the expression of ECM proteins and signaling molecules by western blot, miRNA by qPCR, mRNA by RNA sequencing and cell supernatants for cytokine production by ELISA. PHLFs were also seeded in non-tethered collagen-I gels to measure contraction, and myofibroblast differentiation using confocal microscopy.
Assuntos
Matriz Extracelular , Fibroblastos , Interleucina-1alfa , Pulmão , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Humanos , Interleucina-1alfa/metabolismo , Interleucina-1alfa/genética , Matriz Extracelular/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Pulmão/metabolismo , Pulmão/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/citologia , Diferenciação Celular , Miofibroblastos/metabolismo , Miofibroblastos/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fibronectinas/metabolismo , Fibronectinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta2RESUMO
Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70-0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.
Assuntos
Tubos Torácicos , Biópsia Guiada por Imagem , Pneumotórax , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/epidemiologia , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Idoso , Enfisema Pulmonar/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Fatores de Risco , RadiômicaRESUMO
BACKGROUND: Metamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach. AIMS: Our study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats. METHODS: Eighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues. RESULTS: Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups' lung and gastric tissues. CONCLUSION: Metamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.
Assuntos
Anti-Inflamatórios não Esteroides , Dipirona , Coração , Rim , Fígado , Pulmão , Estômago , Animais , Dipirona/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Anti-Inflamatórios não Esteroides/toxicidade , Masculino , Ratos , Coração/efeitos dos fármacos , Estômago/efeitos dos fármacos , Estômago/patologia , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Catalase/metabolismo , Miocárdio/patologia , Miocárdio/metabolismoRESUMO
BACKGROUND: A six-minute walk test (6MWT) is a reproducible, easily performed test, and is widely used to determine functional exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). However, there is currently a paucity of data on the clinical significance of baseline and serial 6-minute walk tests in patients with IPF, especially in Asian patients. OBJECTIVES: We aimed to investigate the clinical significance of serial 6MWT in patients with IPF, especially in Asian patients. DESIGN: This is a single-center retrospective cohort study. METHODS: Clinical data of patients diagnosed with IPF at a tertiary center in Korea were retrospectively analyzed. IPF diagnosis was defined according to the clinical guidelines of the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association. RESULTS: There were 216 patients diagnosed with IPF from December 2012 to January 2022, of whom 198 had a baseline of 6MWT data. The mean age of the cohort was 66.9 ± 8.6, and 89% were male. The non-survivors showed significantly lower six-minute walk distance (6MWD), minimum saturation of peripheral oxygen (SpO2) during 6MWT, forced vital capacity, and diffusing capacity of the lung for carbon monoxide than survivors at baseline. A multivariate Cox analysis demonstrated that lower minimum SpO2 was independently associated with increased mortality rates (Hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.024-1.142, p = 0.005). Higher mortality rates were also associated with echocardiographic-determined pulmonary hypertension (HR: 2.466, 95% CI: 1.149-5.296, p = 0.021) at diagnosis. Among 144 patients with 6MWT results at 12 months, patients with a decline of 50 m or more in the 6MWD showed poorer overall survival than others (median survival: 45.0 months vs 58.0 months, p < 0.001). CONCLUSIONS: Baseline lower minimum SpO2 during 6MWT was an independent prognostic factor in patients with IPF, and a decline in 6MWD in serial follow-up was also associated with a poorer prognosis. These findings suggest that both baseline 6MWT and follow-up data are important in the prognostication of patients with IPF.
Assuntos
Tolerância ao Exercício , Fibrose Pulmonar Idiopática , Teste de Caminhada , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/diagnóstico , Masculino , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , República da Coreia , Fatores de Tempo , Capacidade Vital , Valor Preditivo dos Testes , Prognóstico , Pulmão/fisiopatologia , Povo Asiático , Capacidade de Difusão PulmonarRESUMO
Chronic respiratory diseases often necessitate lung transplantation due to irreversible damage. Organ engineering offers hope through stem cell-based organ generation. However, the crucial sterilization step in scaffold preparation poses challenges. This study conducted a systematic review of studies that analysed the extracellular matrix (ECM) conditions of decellularised lungs subjected to different sterilisation processes. A search was performed for articles published in the PubMed, Web of Sciences, Scopus, and SciELO databases according to the PRISMA guidelines. Overall, five articles that presented positive results regarding the effectiveness of the sterilisation process were selected, some of which identified functional damage in the ECM. Was possible concluded that regardless of the type of agent used, physical or chemical, all of them demonstrated that sterilisation somehow harms the ECM. An ideal protocol has not been found to be fully effective in the sterilisation of pulmonary scaffolds for use in tissue and/or organ engineering.
Assuntos
Matriz Extracelular , Pulmão , Esterilização , Alicerces Teciduais , Esterilização/métodos , Humanos , Engenharia Tecidual/métodos , AnimaisRESUMO
Exosomes belong to a subgroup of extracellular vesicles secreted by various cells and are involved in intercellular communication and material transfer. In recent years, exosomes have been used as drug delivery carriers because of their natural origin, high stability, low immunogenicity and high engineering ability. However, achieving targeted drug delivery with exosomes remains challenging. In this paper, a phage display technology was used to screen targeted peptides, and different surface modification strategies of targeted peptide exosomes were reviewed. In addition, the application of peptide-targeted exosomes in pulmonary diseases was also summarised.
Assuntos
Sistemas de Liberação de Medicamentos , Exossomos , Pulmão , Peptídeos , Exossomos/química , Exossomos/metabolismo , Humanos , Peptídeos/química , Peptídeos/farmacologia , Pulmão/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Pneumopatias/tratamento farmacológico , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Técnicas de Visualização da Superfície Celular/métodosRESUMO
Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.
Assuntos
Proteínas de Ciclo Celular , Fibrose Pulmonar Idiopática , Proteínas Nucleares , Telomerase , Encurtamento do Telômero , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Telomerase/metabolismo , Telomerase/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fibroblastos/metabolismo , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Telômero/metabolismo , Telômero/genética , Regulação da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologiaRESUMO
BACKGROUND: This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. METHODS: All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. RESULTS: The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P<0.05). The incidence of pneumothorax (1.20%) and bleeding (10.84%) in the group of R-EBUS + ROSE were also less than those in the group of R-EBUS (P<0.05). The lesion's diameter ≥ 2 cm, the distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors are possibly relevant to a higher diagnostic yield. The diagnostic yield of PPLs those were adjacent to emphysema were lower than those PPLs which were away from emphysema (P = 0.048) in the group without ROSE, however, in the group of R-EBUS + ROSE, there was no such difference whether the lesion is adjacent to emphysema or not (P = 0.236). CONCLUSION: Our study found that the combination of R-EBUS and ROSE during bronchoscopy procedure was a safe and effective modality to improve diagnostic yield of PPLs with emphysema, especially for malignant PPLs. The distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors possibly indicated a higher diagnostic yield. Those lesions' position is adjacent to emphysema may reduce diagnostic yield but ROSE may make up for this deficiency.
Assuntos
Broncoscopia , Endossonografia , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Enfisema Pulmonar/diagnóstico por imagem , Endossonografia/métodos , Broncoscopia/métodos , China , Avaliação Rápida no Local , Sensibilidade e Especificidade , Pulmão/diagnóstico por imagem , Pulmão/patologia , Valor Preditivo dos Testes , Biópsia Guiada por Imagem/métodosRESUMO
Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.
Assuntos
COVID-19 , Citocinas , Pulmão , Macrófagos Alveolares , Macrófagos , SARS-CoV-2 , Humanos , COVID-19/virologia , COVID-19/imunologia , SARS-CoV-2/fisiologia , Pulmão/virologia , Pulmão/imunologia , Pulmão/patologia , Macrófagos/virologia , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos Alveolares/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Citocinas/metabolismo , Monócitos/virologia , Monócitos/metabolismo , Monócitos/imunologia , Masculino , Feminino , Análise de Célula Única , Pessoa de Meia-IdadeRESUMO
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.
Assuntos
Displasia Broncopulmonar , Modelos Animais de Doenças , Lactobacillus , Pulmão , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Animais , Neutrófilos/imunologia , Camundongos , Administração por Inalação , Humanos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Pulmão/imunologia , Pulmão/patologia , Pulmão/microbiologia , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/microbiologia , Camundongos Endogâmicos C57BL , Feminino , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Pneumonia/microbiologia , Pneumonia/imunologia , Masculino , Prolina/metabolismoRESUMO
BACKGROUND: Transbronchial cryobiopsy is a promising technique for biopsy of peripheral pulmonary lesions (PPL). However, cryobiopsy specimen retrieval can pose problems due to the risk of bleeding during the blind period when the bronchoscope and cryoprobe are removed en bloc. Artificial airways and prophylactic balloon placement are risk-reducing measures, but the latter is challenging in upper lobe PPL. Specimen retrieval through standard guide sheath (GS) system without the need for bronchoscope removal may now be feasible with the ultrathin cryoprobe. METHODS: Retrospective review of radial endobronchial ultrasound (rEBUS)-guided transbronchial cryobiopsy for PPL cases in which cryobiopsy specimen was retrieved through the GS over a 6-month period. RESULTS: Twenty patients were included with an overall median age of 66.50 (IQR: 53.0 to 76.7). The median procedural time was 30 (IQR: 25.0 to 33.7) minutes. Median target size was 3.20 (IQR: 2.17 to 4.84) cm with 85% of lesions demonstrated "within" rEBUS orientation. Overall technical feasibility was 85% with median cryoactivation of 4.0 (IQR: 3.0 to 4.0) seconds. No specimen was retrieved in 3 patients. The diagnostic yield for forceps and cryobiopsy was 70% and 60%, respectively, and the combined diagnostic yield was 85% (P<0.01 vs. forceps biopsy). Median aggregate size for forceps and cryobiopsy was 8.0 (IQR: 5.3 to 10.0) and 4.5 (IQR: 2.3 to 7.0) mm respectively (P<0.01). No pneumothorax was reported and mild self-limiting bleeding was encountered in 30% of cases. CONCLUSION: Retrieval of cryoprobe through standard GS appears to be a safe and feasible method that can simplify the transbronchial cryobiopsy procedure and complement forceps biopsy in specific cases.
Assuntos
Broncoscopia , Criocirurgia , Estudos de Viabilidade , Humanos , Idoso , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Broncoscopia/métodos , Broncoscopia/instrumentação , Criocirurgia/métodos , Criocirurgia/instrumentação , Biópsia/métodos , Biópsia/instrumentação , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Manejo de Espécimes/métodosRESUMO
Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal versus malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37 °C using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.
Assuntos
Neoplasias Pulmonares , Pulmão , Micro-Ondas , Humanos , Neoplasias Pulmonares/patologia , Animais , Suínos , Impedância Elétrica , Temperatura , Bovinos , Modelos Biológicos , Condutividade ElétricaRESUMO
BACKGROUND: Asthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance. METHODS: High-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund's adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung. RESULTS: HPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model. CONCLUSIONS: We have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype.
Assuntos
Remodelação das Vias Aéreas , Asma , Modelos Animais de Doenças , Animais , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Camundongos , Remodelação das Vias Aéreas/efeitos dos fármacos , Corticosteroides/uso terapêutico , Corticosteroides/farmacologia , Citocinas/metabolismo , Ayurveda , Líquido da Lavagem Broncoalveolar , Feminino , Camundongos Endogâmicos C57BL , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Extratos Vegetais/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Inflamação/tratamento farmacológico , Hipersensibilidade Respiratória/tratamento farmacológico , Pyroglyphidae/imunologiaRESUMO
RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.
Assuntos
Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinas de Partículas Semelhantes a Vírus , Proteínas Virais de Fusão , Proteínas da Matriz Viral , Animais , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Camundongos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/administração & dosagem , Feminino , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/administração & dosagem , Proteínas da Matriz Viral/genética , Imunidade nas Mucosas , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Pulmão/virologia , Pulmão/imunologia , Glicoproteínas/imunologia , Glicoproteínas/administração & dosagem , Administração através da Mucosa , Vírus Sinciciais Respiratórios/imunologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. METHODS: Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. RESULTS: We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. CONCLUSIONS: These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.
Lung adenocarcinoma (LUAD) is a disease that affects males and females differently. Biological sex not only influences chances of developing the disease, but also how the disease progresses and how effective various therapies may be. We analyzed sex-specific gene regulatory networks consisting of transcription factors and the genes they regulate in both healthy lung tissue and in LUAD and identified sex-biased differences. We found that genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females. We also found that several genes that are drug targets in LUAD, are also regulated differently between males and females. Importantly, these differences are also influenced by an individual's smoking history. Extending our analysis using a drug repurposing tool, we found candidate drugs with evidence that they might work better for one sex or the other. These results demonstrate that considering the differences in gene regulation between males and females will be essential if we are to develop precision medicine strategies for preventing and treating LUAD.