Diffuse alveolar hemorrhage (DAH) is a severe complication that can occur post- hematopoietic stem cell transplantation (HSCT). So far, the precise pathogenesis and risk factors of DAH post-HSCT remain elusive, diagnostic criteria have not reached a consensus, and the efficacy of existing therapeutic measures is far from satisfactory. At present, it is believed that the core mechanism of DAH post-HSCT is a vicious cycle initiated by endothelial injury, accompanied by a series of subsequent inflammatory and cellular responses. Treatment primarily focuses on managing inflammation, promoting hemostasis, and improving oxygenation. This paper reviews recent advances in understanding the pathogenesis, risk factors, clinical manifestations, diagnosis, and treatment of DAH following HSCT.
Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hemorrhage/etiology* ; Pulmonary Alveoli ; Lung Diseases/etiology* ; Risk Factors

Mechanical ventilation (MV) is currently widely used in the treatment of respiratory failure and anesthesia surgery, and is a commonly used respiratory support method for critically ill patients; however, improper usage of MV can lead to ventilator-induced lung injury (VILI), which poses a significant threat to patient life. Alveolar epithelial cell (AEC) has the functions of mechanosensation and mechanotransduction. Physiological mechanical stretching is beneficial for maintaining the lineage homeostasis and normal physiological functions of AEC cells, while excessive mechanical stretching can cause damage to AEC cells. Damage to AEC cells is an important aspect in the occurrence and development of VILI. Understanding the effects of mechanical stretching on AEC cells is crucial for developing safe and effective MV strategies, preventing the occurrence of VILI, and improving the clinical prognosis of VILI patients. From the perspective of cell mechanics, this paper aims to briefly elucidate the mechanical properties of AEC cells, mechanosensation and mechanotransduction of mechanical stretching in AEC cells, and the injury and repair of AEC cells under mechanical stretch stimulation, and potential mechanisms with the goal of helping clinical doctors better understand the pathophysiological mechanism of VILI caused by MV, improve their understanding of VILI, provide safer and more effective strategies for the use of clinical MV, and provide theoretical basis for the prevention and treatment of VILI.
Humans ; Mechanotransduction, Cellular ; Ventilator-Induced Lung Injury ; Stress, Mechanical ; Alveolar Epithelial Cells ; Respiration, Artificial/adverse effects* ; Epithelial Cells ; Pulmonary Alveoli/cytology* ; Animals

Humans ; Lupus Erythematosus, Systemic/diagnosis* ; Hemorrhage/etiology* ; Lung Diseases/etiology* ; Pulmonary Alveoli

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with major clinical manifestations of hemoptysis, anemia, and diffuse infiltration in the lung. DAH has a high mortality rate in the acute stage and is a life-threatening emergency in clinical practice. Compared with adult DHA, childhood DHA tends to have a specific spectrum of underlying diseases. It has long been believed that idiopathic pulmonary hemosiderosis (IPH) is the main cause of childhood DAH; however, with the increase in reports of childhood DAH cases, the etiology spectrum of childhood DAH is expanding. The treatment and prognosis of DAH with different etiologies are different. This review article gives a general outline of childhood DAH, with focuses on DAH caused by IPH, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-related vasculitis, COPA syndrome, or IgA vasculitis.
Antibodies, Antineutrophil Cytoplasmic ; Child ; Hemorrhage ; Humans ; Lung Diseases ; Pulmonary Alveoli ; Vasculitis

The inhalation and deposition of particles in human pulmonary acinus region can cause lung diseases. Numerical simulation of the deposition of inhaled particles in the pulmonary acinus region has offered an effective gateway to the prevention and clinical treatment of these diseases. Based on some important affecting factors such as pulmonary acinar models, model motion, breathing patterns, particulate characteristics, lung diseases and ages, the present research results of numerical simulation in human pulmonary acinus region were summarized and analyzed, and the future development directions were put forward in this paper, providing new insights into the further research and application of the numerical simulation in the pulmonary acinus region.
Aerosols ; Computer Simulation ; Humans ; Lung ; physiology ; Models, Biological ; Particle Size ; Pulmonary Alveoli ; physiology

OBJECTIVETo study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.

METHODSEighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.

RESULTSCompared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).

CONCLUSIONSHyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; metabolism ; pathology ; CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Cell Proliferation ; Disease Models, Animal ; Hyperoxia ; complications ; pathology ; Ki-67 Antigen ; analysis ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley ; Sumoylation

We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test result was 212 pg/ml (reference value of negative is < 14 pg/ml), Mycobacterium tuberculosis culture was positive, and tuberculin skin test (PPD) was negative (skin induration < 5 mm). The patient was treated with several courses of antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed disease progression. Bronchoscopy yielded negative results. PET-CT scans showed negative results. A percutaneous lung biopsy revealed mucin-secreting cells lining the alveolar walls. IMA with a lepidic-predominant pattern was diagnosed after invasiveness was found after experimental treatments. Simultaneous occurrence of pulmonary tuberculosis and lung cancer are common; however, the present case of IMA having a lepidic-predominant pattern and coexisting with active tuberculosis has not been reported yet.
Adenocarcinoma, Mucinous ; diagnosis ; pathology ; Aged, 80 and over ; Antibiotics, Antitubercular ; therapeutic use ; Disease Progression ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Male ; Mycobacterium tuberculosis ; isolation & purification ; Positron Emission Tomography Computed Tomography ; Pulmonary Alveoli ; pathology ; Tuberculosis, Pulmonary ; diagnosis ; drug therapy

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9 basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9 BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9 BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient's lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9 BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.
Bronchiectasis ; genetics ; metabolism ; Humans ; Pulmonary Alveoli ; cytology ; metabolism ; SOX9 Transcription Factor ; genetics ; metabolism ; Stem Cell Transplantation ; methods ; Stem Cells ; cytology ; metabolism

A 35-year-old man presented with progressive dyspnea and hemoptysis. His blood pressure was 230/140 mmHg and serum creatinine level was 20.13 mg/dL. Chest radiography and computed tomography revealed pulmonary hemorrhage. His renal function was low, thus emergent renal replacement therapy was required. Malignant hypertension and acute kidney injury were diagnosed, and antihypertensive therapy and hemodialysis started immediately. Renal biopsy was performed to examine the underlying disease. Typical pathological changes of malignant hypertension, fibrinoid necrosis of the afferent arterioles, and proliferative endoarteritis at the interlobular arteries were observed. His renal function improved gradually and pulmonary hemorrhage completely disappeared with administration of antihypertensive agents. Here, we report this rare case of malignant hypertension with pulmonary alveolar hemorrhage and speculate that the hemorrhage may be related to vascular injuries at the alveolar capillary level caused by malignant hypertension.
Acute Kidney Injury ; Adult ; Antihypertensive Agents ; Arteries ; Arterioles ; Biopsy ; Blood Pressure ; Capillaries ; Creatinine ; Dialysis* ; Dyspnea ; Hemoptysis ; Hemorrhage* ; Humans ; Hypertension, Malignant* ; Necrosis ; Pulmonary Alveoli ; Radiography ; Renal Dialysis ; Renal Replacement Therapy ; Thorax ; Vascular System Injuries