Chinese medical journal pulmonary and critical care medicine最新文献

Asthma is a chronic respiratory disease, and clinically, asthma exacerbations remain difficult to treat. The disease is caused by combinations of and interactions between genetic and environmental factors. Genomic and genetic approaches identified many novel genes to treat asthma and brought new insights into the disease. The products of the genes have functional roles in regulating physiological or pathophysiological processes in airway structural cells and immune system cells. Genetic factors also interact with environmental factors such as air pollutants, and bacterial and viral infections to trigger the disease. Thymic stromal lymphopoietin (TSLP), orosomucoid-like 3 (ORMDL3), and gasdermin B (GSDMB) are three genes identified by genetic studies to have a great potential as therapeutic targets of asthma. TSLP is an important driver of type 2 inflammation. ORMDL3 mediates cell stress, sphingolipid synthesis, and viral and bacterial infections. GSDMB regulates cell pyroptosis through its N and C terminals and can bind sulfatides to influence inflammatory response. Investigating inhibitors or modulators for these pathways would bring a new landscape for therapeutics of asthma in future.

Background

Liver dysfunction was common in coronavirus disease 2019 (COVID-19), but its association with clinical features and poor prognosis has not been fully delineated. Our study aimed to determine the role of liver dysfunction in COVID-19 and understand the predictors for worse outcomes in patients with liver injury.

Methods

We conducted this multicenter, retrospective study in five designated hospitals for COVID-19 management. Laboratory-confirmed COVID-19 patients were enrolled and classified into the normal live function group and liver dysfunction group according to liver enzymes, bilirubin, and albumin on admission, respectively. Data of baseline, clinical manifestations, and outcomes were collected and compared in the paired groups.

Results

Of the 649 included COVID-19 patients, 200 (30.8%), 69 (10.6%), and 267 (41.1%) patients had elevated liver enzymes, increased bilirubin, and low-level albumin, respectively. Fever, cough, and dyspnea were the most common symptoms and showed an increased proportion in the liver dysfunction group. Compared with patients in the normal liver function group, patients with liver dysfunction manifested decreased lymphocytes, higher level of leukocytes, neutrophils, inflammatory indicators, and cytokines, as well as more severe impairment in kidney function and myocardium. They were more likely to show bilateral involvement and more pulmonary lobes involved according to chest images. With increased proportion of patients who developed severe/critical conditions and needed mechanical ventilation and systemic glucocorticoid therapy, patients with liver dysfunction on admission showed significantly higher in-hospital mortality. Moreover, cardiac troponin I ≥1.5 ng/mL was identified as an independent mortality predictor in the elevated liver enzymes group.

Conclusion

Patients with liver dysfunction on admission had worse clinical manifestation, and resulted in higher rate of severe/critical type, receiving mechanical ventilation and in-hospital mortality.

Background

The aim of this review is to summarize the current evidence regarding small airway disease in asthma, focusing on recent advances in small airway pathophysiology, assessment and therapeutic implications.

Methods

A search in Medline was performed, using the keywords “small airways”, “asthma”, “oscillometry”, “nitrogen washout” and “imaging”. Our review was based on studies from adult asthmatic patients, although evidence from pediatric populations is also discussed.

Results

In asthma, inflammation in small airways, increased mucus production and airway wall remodelling are the main pathogenetic mechanisms of small airway disease. Small airway dysfunction is a key component of asthma pathophysiology, leading to increased small airway resistance and airway closure, with subsequent ventilation inhomogeneities, hyperresponsiveness and airflow limitation. Classic tests of lung function, such as spirometry and body plethysmography are insensitive to detect small airway disease, providing only indirect measurements. As discussed in our review, both functional and imaging techniques that are more specific for small airways, such as oscillometry and the multiple breath nitrogen washout have delineated the role of small airways in asthma. Small airways disease is prevalent across all asthma disease stages and especially in severe disease, correlating with important clinical outcomes, such as asthma control and exacerbation frequency. Moreover, markers of small airways dysfunction have been used to guide asthma treatment and monitor response to therapy.

Conclusions

Assessment of small airway disease provides unique information for asthma diagnosis and monitoring, with potential therapeutic implications.

Background

Although examinations and therapies for bronchial lung cancer, also called lung cancer (LC), have become more effective and precise, the morbidity and mortality of LC remain high worldwide. Describing the changing profile of LC characteristics over time is indispensable. This study aimed to understand the changes in real-world settings of LC and its characteristics in China.

Methods

In this study, 119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital. The patients’ medical records were extracted from the hospital's database. Demographic characteristics, general clinicopathological information, and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal–Wallis, Nemenyi, chi-squared, and Bonferroni tests. Changes in demographic characteristics during the 8-year study period, namely dynamic changes among different stages and different pathological types, were evaluated.

Results

The percentages of female (from 38.50% [323/839] in 2012 to 48.29% [5112/10,585] in 2020) and non-smoking LC (from 69.34% [475/685] to 80.48% [8055/10,009]) patients increased significantly during the study period, with a trend toward a younger age at diagnosis (from 3.58% [30/839] to 8.99% [952/10,585]). Over the study period, the proportion and absolute number of lung adenocarcinoma cases increased (from 67.97% [433/637] to 76.31% [6606/8657]) while the proportion of lung squamous cell carcinoma decreased (from 21.19% [135/637] to 12.08% [1046/8657]). Comprehensive driver gene mutation examination became more common, and epidermal growth factor receptor (EGFR) mutation occurred more frequently in female vs. male (62.03% [12793/20625] vs. 29.90% [8207/27,447]) and non-smoking vs. smoking (53.54% [17,203/32,134] vs. 23.73% [3322/13,997]) patients (both P < 0.001). The distribution of the common driver genes differed among different stages of LC. EGFR mutation was detected most frequently at each stage, and other driver gene alterations were more common in advanced stages (P <0.001). The combination of chemotherapy, targeted therapy, and immunotherapy, as a comprehensive management regimen, gradually became predominant over the study period (P < 0.001). A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion, indicated by significantly elevated levels of d-dimer, fibrinogen, and fibrinogen degradation products.

Conclusions

This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.

Trial registration: ClinicalTrials.gov, NCT05423236.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tobacco smoking and air pollution are believed to be responsible for more than 90% of lung cancers. Respiratory pathogens are also known to be associated with the initiation and development of lung cancer. Despite the fact that the bacterial biomass in the lungs is lower than that in the intestinal tract, emerging evidence indicates that the lung is colonized by a diverse array of microbes. However, there is limited knowledge regarding the role of dysbiosis of the lung microbiota in the progression of lung cancer. In this review, we summarize the current information about the relationship between the microbiome and lung cancer. The objective is to provide an overview of the core composition of the microbiota in lung cancer as well as the role of specific dysbiosis of the lung microbiota in the progression of lung cancer and treatment of the disease.

Lung cancer has the highest mortality rate among all cancers in the world. Hence, early diagnosis and personalized treatment plans are crucial to improving its 5-year survival rate. Chest computed tomography (CT) serves as an essential tool for lung cancer screening, and pathology images are the gold standard for lung cancer diagnosis. However, medical image evaluation relies on manual labor and suffers from missed diagnosis or misdiagnosis, and physician heterogeneity. The rapid development of artificial intelligence (AI) has brought a whole novel opportunity for medical task processing, demonstrating the potential for clinical application in lung cancer diagnosis and treatment. AI technologies, including machine learning and deep learning, have been deployed extensively for lung nodule detection, benign and malignant classification, and subtype identification based on CT images. Furthermore, AI plays a role in the non-invasive prediction of genetic mutations and molecular status to provide the optimal treatment regimen, and applies to the assessment of therapeutic efficacy and prognosis of lung cancer patients, enabling precision medicine to become a reality. Meanwhile, histology-based AI models assist pathologists in typing, molecular characterization, and prognosis prediction to enhance the efficiency of diagnosis and treatment. However, the leap to extensive clinical application still faces various challenges, such as data sharing, standardized label acquisition, clinical application regulation, and multimodal integration. Nevertheless, AI holds promising potential in the field of lung cancer to improve cancer care.

Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite the recent advances in cancer therapies, the 5-year survival of non-small cell lung cancer (NSCLC) patients hovers around 20%. Inherent and acquired resistance to therapies (including radiation, chemotherapies, targeted drugs, and combination therapies) has become a significant obstacle in the successful treatment of NSCLC. c-Myc, one of the critical oncoproteins, has been shown to be heavily associated with the malignant cancer phenotype, including rapid proliferation, metastasis, and chemoresistance across multiple cancer types. The c-Myc proto-oncogene is amplified in small cell lung cancers (SCLCs) and overexpressed in over 50% of NSCLCs. c-Myc is known to actively regulate the transcription of cancer stemness genes that are recognized as major contributors to tumor progression and therapeutic resistance; thus, targeting c-Myc either directly or indirectly in mitigation of the cancer stemness phenotype becomes a promising approach for development of a new strategy against drug resistant lung cancers. This review will summarize what is currently known about the mechanisms underlying c-Myc regulation of cancer stemness and its involvement in drug resistance and offer an overview on the current progress and future prospects in therapeutically targeting c-Myc in both SCLC and NSCLC.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. Acute exacerbation of COPD (AECOPD) is an acute worsening of respiratory symptoms, which needs additional treatment and can result in worsening health status, increasing risks of hospitalization and mortality. Therefore, it is necessary to early recognize and diagnose exacerbations of COPD. This review introduces the updated definition of COPD exacerbations, the current clinical assessment tools, and the current potential biomarkers. The application of mobile health care in COPD management for early identification and diagnosis is also included in this review.

Steroid resistance represents a major clinical problem in the treatment of severe asthma, and therefore a better understanding of its pathogenesis is warranted. Recent studies indicated that histone deacetylase 2 (HDAC2) and interleukin 17A (IL-17A) play important roles in severe asthma. HDAC2 activity is reduced in patients with severe asthma and smoking-induced asthma, perhaps accounting for the amplified expression of inflammatory genes, which is associated with increased acetylation of glucocorticoid receptors. Neutrophilic inflammation contributes to severe asthma and may be related to T helper (Th) 17 rather than Th2 cytokines. IL-17A levels are elevated in severe asthma and correlate with the presence of neutrophils. Restoring the activity of HDAC2 or targeting the Th17 signaling pathway is a potential therapeutic approach to reverse steroid insensitivity.

Tissue inhibitors of metalloproteases (TIMPs) have caught the attention of many scientists due to their role in various physiological and pathological processes. TIMP-1, 2, 3, and 4 are known members of the TIMPs family. TIMPs exert their biological effects by, but are not limited to, inhibiting the activity of metalloproteases (MMPs). The balance between MMPs and TIMPs is critical for maintaining homeostasis of the extracellular matrix (ECM), while the imbalance between MMPs and TIMPs can lead to pathological changes, such as cancer. In this review, we summarized the current knowledge of TIMP-1 in several pulmonary diseases namely, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pneumonia, asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and pulmonary fibrosis. Considering the potential of TIMP-1 serving as a non-invasive diagnostic and/or prognostic biomarker, we also reviewed the circulating TIMP-1 levels in translational and clinical studies.