Chinese medical journal pulmonary and critical care medicine最新文献

Progressive lung fibrosis is characterized by dysregulated extracellular matrix (ECM) homeostasis. Understanding of disease pathogenesis remains limited and has prevented the development of effective treatments. While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation, factors that determine why fibrosis progresses rather than regular tissue repair occur are not fully explained. Within human lung fibrosis, there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial–mesenchymal transition (EMT), a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties. This review will focus on the role of EMT and dysregulated epithelial–mesenchymal crosstalk in progressive lung fibrosis.

Background

The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.

Methods

We used kinetic antibody data from the lopinavir–ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.

Results

From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (β −0.05, 95% CI [−0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50–1.00; P = 0.0508).

Conclusion

Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.

Alveoli serve as the functional units of the lungs, responsible for the critical task of blood–gas exchange. Comprising type I (AT1) and type II (AT2) cells, the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne particles. As such, preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial layer. Dysfunctions in these processes contribute to various lung diseases. Recent research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and regeneration. Additionally, endothelial cells, fibroblasts, and immune cells synergistically establish a nurturing microenvironment—or “niche”—that modulates these epithelial stem cells. This review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche, as well as the molecular mechanisms that govern them. Additionally, this article highlights diseases that arise due to perturbations in stem cell–niche interactions. We also discuss recent technical innovations that have catalyzed these discoveries. Specifically, this review underscores the heterogeneity, plasticity, and dynamic regulation of these stem cell–niche systems. It is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease (COPD), fibrosis, coronavirus disease 2019 (COVID-19), and lung cancer.

Asthma, a chronic respiratory disease with a global prevalence of approximately 300 million individuals, presents a significant societal and economic burden. This multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various factors. The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms. Omics technologies are employed to systematically screen for potential biomarkers, encompassing genes, transcripts, methylation sites, proteins, and even the microbiome components. This review provides an insightful overview of omics applications in asthma research, with a special emphasis on genetics, transcriptomics, epigenomics, and the microbiome. We explore the cutting-edge methods, discoveries, challenges, and potential future directions in the realm of asthma omics research. By integrating multi-omics and non-omics data through advanced statistical techniques, we aspire to advance precision medicine in asthma, guiding diagnosis, risk assessment, and personalized treatment strategies for this heterogeneous condition.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited airflow. COPD is characterized by chronic bronchitis and emphysema, and is often accompanied by malnutrition with fatigue, muscle weakness, and an increased risk of infection. Although the pulmonary function test is used as the gold criterion for diagnosing COPD, it is unable to identify early COPD or classify the subtypes, thereby impeding early intervention and the precise diagnosis of COPD. Recent evidence suggests that metabolic dysfunction, such as changes in lipids, amino acids, glucose, nucleotides, and microbial metabolites in the lungs and intestine, have a great potential for diagnosing COPD in the early stage. However, a comprehensive summary of these metabolites and their effects on COPD is still lacking. This review summarizes the metabolites that are changed in COPD and highlights some promising early diagnostic markers and therapeutic targets. We emphasize that intensified dietary management may be among the most feasible methods to improve metabolism in the body.

Immune checkpoint inhibitors (ICIs) are a class of antitumor medications that target immune checkpoints, which induce the activation of lymphocytes. These treatments effectively prolong the survival of patients with advanced tumors, especially lung cancer. However, in addition to tumor killing effects, ICIs may also cause an imbalance between immune tolerance and immunity. Over-activated lymphocytes may cause various types of damage to multiple organs throughout the body, called immune-related adverse events. In this review, we summarize the pathogenesis, pathological characteristics, biomarkers, and therapeutic agents for immune-related adverse events.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related fatalities, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancers. Over the past forty years, patients with NSCLC have had a 5-year survival rate of only 16%, despite improvements in chemotherapy, targeted therapy, and immunotherapy. Circulating tumor DNA (ctDNA) in blood can be used to identify minimal residual disease (MRD), and ctDNA-based MRD has been shown to be of significance in prognostic assessment, recurrence monitoring, risk of recurrence assessment, efficacy monitoring, and therapeutic intervention decisions in NSCLC. The level of MRD can be obtained by monitoring ctDNA to provide guidance for more precise and personalized treatment, the scientific feasibility of which could dramatically modify lung cancer treatment paradigm. In this review, we present a comprehensive review of MRD studies in NSCLC and focus on the application of ctDNA-based MRD in different stages of NSCLC in current clinical practice.