Inhibitor of PD-1/PD-L1: a new approach may be beneficial for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a globally prevalent, progressive disease with limited treatment options and poor prognosis. Because of its irreversible disease progression, IPF affects the quality and length of life of patients and imposes a significant burden on their families and social healthcare services. The use of the antifibrotic drugs pirfenidone and nintedanib can slow the progression of the disease to some extent, but it does not have a reverse effect on the prognosis. The option of lung transplantion is also limited owing to contraindications to transplantation, possible complications after transplantation, and the risk of death. Therefore, the discovery of new, effective treatment methods is an urgent need. Over recent years, various studies have been undertaken to investigate the relationship between interstitial pneumonia and lung cancer, suggesting that some immune checkpoints in IPF are similar to those in tumors. Immune checkpoints are a class of immunosuppressive molecules that are essential for maintaining autoimmune tolerance and regulating the duration and magnitude of immune responses in peripheral tissues. They can prevent normal tissues from being damaged and destroyed by the immune response. While current studies have focused on PD-1/PD-L1 and CTLA-4, PD-1/PD-L1 may be the only effective immune checkpoint IPF treatment. This review discusses the application of PD-1/PD-L1 checkpoint in IPF, with the aim of finding a new direction for IPF treatment.

Prognostic significance of peripheral blood S100A12, S100A8, and S100A9 concentrations in idiopathic pulmonary fibrosis.

BACKGROUND: S100A12, S100A8, and S100A9 are inflammatory disease biomarkers whose functional significance in idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the significance of S100A12, S100A8, and S100A9 levels in IPF development and prognosis. METHODS: The dataset was collected from the Gene Expression Omnibus (GEO) database and differentially expressed genes were screened using GEO2R. We conducted a retrospective study of 106 patients with IPF to explore the relationships between different biomarkers and poor outcomes. Pearson's correlation coefficient, Kaplan-Meier, Cox regression, and functional enrichment analyses were used to evaluate relationships between these biomarkers' levels and clinical parameters or prognosis. RESULTS: Serum levels of S100A12, S100A8, and S100A9 were significantly elevated in patients with IPF. The two most significant co-expression genes of S100A12 were S100A8 and S100A9. Patients with levels of S100A12 (median 231.21 ng/mL), S100A9 (median 57.09 ng/mL) or S100A8 (median 52.20 ng/mL), as well as combined elevated S100A12, S100A9, and S100A8 levels, exhibited shorter progression-free survival and overall survival. Serum S100A12 and S100A8, S100A12 and S100A9, S100A9 and S100A8 concentrations also displayed a strong positive correlation (rs2 = 0.4558, rs2 = 0.4558, rs2 = 0.6373; P < 0.001). S100A12 and S100A8/9 concentrations were independent of FVC%, DLCO%, and other clinical parameters (age, laboratory test data, and smoking habit). Finally, in multivariate analysis, the serum levels of S100A12, S100A8, and S100A9 were significant prognostic factors (hazard ratio 1.002, P = 0.032, hazard ratio 1.039, P = 0.001, and hazard ratio 1.048, P = 0.003). CONCLUSIONS: S100A12, S100A8, and S100A9 are promising circulating biomarkers that may aid in determining IPF patient prognosis. Multicenter clinical trials are needed to confirm their clinical value.

Anti­PD­1/PD­L1 and anti­CTLA­4 associated checkpoint inhibitor pneumonitis in non­small cell lung cancer: Occurrence, pathogenesis and risk factors (Review).

Immune checkpoint inhibitors (ICIs) play a significant anti­tumor role in the management of non­small cell lung cancer. The most broadly used ICIs are anti­programmed death 1 (PD­1), anti­programmed cell death­ligand 1, and anti­cytotoxic T lymphocyte­associated antigen­4 monoclonal antibody. Compared with traditional chemotherapy, ICIs have the advantages of greater efficiency and more specific targeting. However, the resulting immune­related adverse events limit the clinical application of ICIs, especially checkpoint inhibitor pneumonitis (CIP). CIP chiefly occurs within 6 months of administration of ICIs. Excessive activation and amplification of cytotoxic T lymphocytes, helper T cells, downregulation of regulatory T cells, and over­secretion of pro­inflammatory cytokines are the dominant mechanisms underlying the pathophysiology of CIP. The dysregulation of innate immune cells, such as an increase in inflammatory monocytes, dendritic cells, neutrophils and M1 polarization of macrophages, an increase in IL­10 and IL­35, and a decrease in eosinophils, may underlie CIP. Although contested, several factors may accelerate CIP, such as a history of previous respiratory disease, radiotherapy, chemotherapy, administration of epidermal growth factor receptor tyrosine kinase inhibitors, PD­1 blockers, first­line application of ICIs, and combined immunotherapy. Interestingly, first­line ICIs plus chemotherapy may reduce CIP. Steroid hormones remain the primary treatment strategy against grade ≥2 CIP, although cytokine blockers are promising therapeutic agents. Herein, the current research on CIP occurrence, clinical and radiological characteristics, pathogenesis, risk factors, and management is summarized to further expand our understanding, clarify the prognosis, and guide treatment.

Genomic Fingerprint Associated with Familial Idiopathic Pulmonary Fibrosis: A Review.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease; although the recent introduction of two anti-fibrosis drugs, pirfenidone and Nidanib, have resulted in a significant reduction in lung function decline, IPF is still not curable. Approximately 2-20% of patients with IPF have a family history of the disease, which is considered the strongest risk factor for idiopathic interstitial pneumonia. However, the genetic predispositions of familial IPF (f-IPF), a particular type of IPF, remain largely unknown. Genetics affect the susceptibility and progression of f-IPF. Genomic markers are increasingly being recognized for their contribution to disease prognosis and drug therapy outcomes. Existing data suggest that genomics may help identify individuals at risk for f-IPF, accurately classify patients, elucidate key pathways involved in disease pathogenesis, and ultimately develop more effective targeted therapies. Since several genetic variants associated with the disease have been found in f-IPF, this review systematically summarizes the latest progress in the gene spectrum of the f-IPF population and the underlying mechanisms of f-IPF. The genetic susceptibility variation related to the disease phenotype is also illustrated. This review aims to improve the understanding of the IPF pathogenesis and facilitate his early detection.

Protective role of zinc in the pathogenesis of respiratory diseases.

Respiratory diseases remain a major cause of morbidity and mortality worldwide. An imbalance of zinc, an essential trace element, is associated with a variety of lung diseases. We reviewed and summarized recent research (human subjects, animal studies, in vitro studies) on zinc in respiratory diseases to explore the protective mechanism of zinc from the perspective of regulation of oxidative stress, inflammation, lipid metabolism, and apoptosis. In the lungs, zinc has anti-inflammatory, antioxidant, and antiviral effects; can inhibit cancer cell migration; can regulate lipid metabolism and immune cells; and exerts other protective effects. Our comprehensive evaluation highlights the clinical and experimental effects of zinc in the pathogenesis of respiratory diseases. Our analysis also provides insight into the clinical application of zinc-targeted therapy for respiratory diseases.

How Ginsenosides Trigger Apoptosis in Human Lung Adenocarcinoma Cells.

Panax ginseng is a natural medicine that has been used globally for a long time. Moreover, several studies have reported the effective activity of ginseng in treating malignancies. Various agents containing ginseng were widely used as an antitumor treatment nowadays. Lung cancer is the most common fatal cancer in China, and lung adenocarcinoma is the most common histological type of non-small cell lung cancer (NSCLC). What's worse, many patients may have a failed response to conventional therapy including chemotherapy, radiotherapy, or molecule-targeted therapy due to drug resistance. Apoptosis is a highly ordered cellular suicidal process that plays an essential role in maintaining normal homeostasis. The pharmacological mechanism of many antineoplastic drugs involves triggering of apoptotic process. In several recent studies, ginsenosides are regarded as major active components of ginseng that have the potential to control lung cancer. Most of these results have proved that ginsenosides induce apoptosis in lung cancer cells through many different signaling pathways such as PI3K/Akt, NF-κB, EGFR, and so on. This study is aimed at reviewing the signaling pathways that underlie ginsenosides-triggered apoptotic process and encourage further studies to target promising agents against lung cancer treatment.

Pulmonary fibrosis: a possible diabetic complication.

Diabetic complications affect many organs in diabetic patients. Emerging evidence indicates that diabetes can increase the risk of pulmonary dysfunction. Early epidemiological studies from different populations on whether diabetes was an independent risk for pulmonary dysfunction were inconclusive. Recent epidemiological studies and systematic reviews clearly indicate that diabetes is an independent risk factor for pulmonary dysfunction. Given that pulmonary fibrosis is an important predictor of mortality in people with this chronic disease, whether diabetes directly causes pulmonary fibrosis is an important unresolved clinical question. This review combines recent epidemiological data with findings from basic research to indicate that diabetes induces pulmonary fibrosis. We then discuss the possible underlying mechanisms for the histological and biochemical pathology. At the end of this review, we emphasize that diabetic pulmonary fibrosis as a potential diabetic complication warrants more attention.