Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is defined as an acute and clinically significant respiratory deterioration characterized by evidence of new, widespread alveolar abnormality. In the past, AE-IPF was considered to be idiopathic, which was hard to be prevented and its prognosis was hard to be obviously improved; the latest researches have shown that AE-IPF can be triggered by known causes, including pulmonary infection, aspiration, etc. This review summarizes the etiology or risk factors, treatment and prevention of AE-IPF according to the latest researches.
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic at the end of December 2019, more than 85% of the population in China has been infected. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly affects the respiratory system, especially the lungs. The mortality rate of patients with severe infection is high. A percentage of 6% to 10% of patients will eventually develop into COVID-related acute respiratory distress syndrome (CARDS), which requires mechanical ventilation and extracorporeal membrane oxygenation (ECMO) support. Some patients who survive acute lung injury will subsequently develop post COVID-19 pulmonary fibrosis (PCPF). Both fully treated CARDS and severe PCPF are suitable candidates for lung transplantation. Due to the special course, evaluation strategies are different from those used in patients with common end-stage lung disease. After lung transplantation in COVID-19 patients, special treatment is required, including standardized nucleic acid testing for the novel coronavirus, adjustment strategy of immunosuppressive drugs, and rational use of antiviral drugs, which is a big challenge for the postoperative management of lung transplantation. This consensus was evidence-based written and was reached by experts after multiple rounds of discussions, providing reference for assessment and postoperative management of patients with interstitial pneumonia after COVID-19 infection.
Objective To investigate the effects of sodium ferulate on lung mRNA expression of TGF-β1 signal transduction molecule in rats with pulmonary fibrosis，and explore the mechanism of sodium ferulate on pulmonary fibrosis.Methods A rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin (5 mg/kg).Thirty SD rats were randomly divided into three groups (n=10 in each group)，ie.a control group，a pulmonary fibrosis model group，and a sodium ferulate group.The lung histopathology and the expression of collagen was examined by HE staining and collagen fibril staining respectively.The expressions of TGF-βRII and Smad4 mRNA in the lung tissue were detected by situ hybridization.And the expression of TGF-β1 mRNA was detected by real-time fluorescence-quantification RT-PCR.Results Collagen fibril staining indicated that the expression of pulmonary collagen in the model group was significantly higher than that in the control group and sodium ferulate group (Plt;0.001).The mRNA expressions of pulmonary TGF-β1，TGF-βRII and Smad4 were significantly higher in the model group than those in the control group (all Plt;0.01)，and were significantly lower in the sodium ferulate group than those in the model group (all Plt;0.05).Conclusions Sodium ferulate can effectively reduce pulmonary fibrosis through inhibition of the mRNA expression of TGF-β1，TGF-βRII and Smad4 in the lung tissue，thus influence the TGF-β1/Smad4 signal transduction way and inhibit the target gene activation.
ObjectiveTo investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). MethodsGenome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and Finngen databases, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. ResultsIVW analysis results showed that Actinomycetes [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222,0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. ConclusionActinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.
ObjectiveTo systematically evaluate the prognostic prediction models for Idiopathic Pulmonary Fibrosis (IPF). MethodsA computer-based search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for literature relevant to the research objective, with the search period ranging from database inception to Jun 2025. Two researchers independently screened the articles. Data were extracted according to the key assessment and data extraction checklist for systematic reviews of prediction models (CHARMS). The risk of bias and applicability of the models were assessed using the PROBAST (Prediction model Risk of Bias Assessment Tool). The quality of model reporting was evaluated using the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) checklist. ResultsA total of 49 studies were included, of which 26 (53.06%) reported both model development and validation. The most common predictors included gender, age, diffusing capacity for carbon monoxide, forced vital capacity (FVC), and FVC percentage of predicted value. In terms of bias risk, 32 studies (65.31%) were classified as high risk of bias, mainly due to factors related to study subjects and predictors. Regarding applicability, 26 studies (53.06%) were rated as high risk, 11 studies (22.45%) were rated as unclear, and only 12 studies (24.49%) were rated as low risk, suggesting limited clinical applicability of the models. As for reporting quality, existing models showed generally insufficient adherence to the TRIPOD statement, especially in key areas such as research methods and result reporting, where normative issues were prominent. Of the 22 signaling questions in the TRIPOD checklist, most studies achieved only moderate reporting quality, with 8 signaling questions (1, 5c, 6b, 7b, 8, 11e, 13a, 14a) showing key information omissions or vague descriptions. ConclusionExisting prognostic prediction models for IPF generally exhibit high methodological bias risk and reporting deficiencies. Future studies should control for modeling biases based on the PROBAST framework, adhere to the TRIPOD guidelines for transparent reporting, and optimize clinical applicability through external validation.
ObjectiveTo study effects of two kinds of epidermal growth factor receptor kinase inhibitors on bleomycin-induced pulmonary fibrosis in mice, and regulation mechanism on oncostatin M (OSM) and downstream signaling pathways.MethodsForty Kunming female mice were randomly divided into a control group, a fibrosis group, a gefitinib group, and an erlotinib group. The mice in the control group were administered with saline aerosol intratracheally. The mice in the fibrosis group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally. The mice in the gefitinib group and the erlotinib group were administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally and then gastrically perfused with gefitinib (20 mg·kg–1·d–1) or erlotinib (25 mg·kg–1·d–1). All mice accepted computer tomography examination 14 days after the treatment and then were sacrificed, and the lungs were collected for further detection. The lungs were stained with hematoxylin eosin and Masson’s trichrome, examined with Western blot for pathological examination and expressions of α-smooth muscle actin (α-SMA), OSM, Janus kinase 1 (JAK1), phospho-JAK1 (p-JAK1), signal transducers and activators of transcription 3 (STAT3), and phospho-STAT3 (p-STAT3) proteins.ResultsThe pathological injury of the lung in the gefitinib group and the erlotinib group was significantly relieved compared with that in the bleomycin group. The expressions of α-SMA, OSM, p-JAK1/JAK1, and p-STAT3/STAT3 proteins were also significantly reduced. There were no differences between the above-mentioned indexes between the gefitinib group and the erlotinib group.ConclusionsGefitinib and erlotinib can significantly relieve bleomycin-induced pulmonary fibrosis in mice. The underlying mechanism may be involved in inhibiting expression of OSM and downstream JAK/STAT pathways.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
ObjectiveTo analyze the clinical characteristics and survival of pulmonary fibrosis (PF) patients complicated with lung cancer (LC) (PL-LC). MethodsFifty-three patients with PF diagnosed as LC from January 2008 to March 2014 in Nanjing Drum Tower Hospital were included in this study. Univariate analysis and Cox regression analysis were used to detect the effects of clinical variables on survival. Kaplan-Meier method was used to calculate the median survival time (MST) and overall survival (OS). ResultsMale patients (n=48, 90.6%) and patients with a history of smoking (n=42, 79.2%) were more easily suffered from PF-LC. The average age was 68.6±9.5 years. Cox multivariate analysis revealed that Velcro crackles (P=0.009) and clinical stage (P=0.013) were the independent risk factors of survival in the patients with PF-LC. The MST of 53 patients was 6.0 months.The survival rates of 1-year and 2-year were 34.1% and 22.0%, respectively. Forty-two (79.2%) patients were idiopathic pulmonary fibrosis (IPF) complicated with LC, and 11 (20.8%) patients were secondary pulmonary fibrosis (SPF) complicated with LC. OS difference between two groups was not significant (P=0.610). OS of NSCLC group (n=37) was significantly prolonged than that of SCLC group (n=6) and unclassified pathological pattern group (n=10) (P=0.035). OS of Ⅰ and Ⅱstage patients (n=13) was significantly longer than that of Ⅲ and Ⅳ stage patients (n=40) (P=0.002). MST and OS of patients with LC treated (n=31) were significantly better than those of untreated patients (n=22) (P < 0.001) and OS of patients treated by comprehensive therapy (n=11) was significantly prolonged than that of patients treated by mono-therapy (n=20) (P=0.036). ConclusionsVelcro crackles and clinical stages are the independent risk factors of prognosis in PF-LC patients. It is beneficial to survival if the PF patients with LC were treated by comprehensive therapy.
ObjectiveTo construct a luciferase reporter fusion containing the human connective tissue growth factor (CTGF) gene promoter.MethodsThe promoter region of the human CTGF gene (-835/+214) was amplified by polymerase chain reaction (PCR) using specially-designed primers, and subsequently cloned into the pGL3.0-Basic vector. Following screening and verification by single colony PCR, double digestion, and sequencing, the resulting pGL3.0-Basic-CTGF was used to transfect the human embryonic kidney cells 293T, human bronchial epithelial cells HBE and human lung epithelial cells A549, and its function in each cell line was determined by luciferase assay.ResultsSequence alignment showed 99.5% identity, suggesting successful construction of the pGL3.0-Basic-CTGF reporter fusion. Promoter activities were detected 48 hours after transfection of pGL3.0-Basic-CTGF into the 293T, HBE, and A549 cells, and the promoter activities were 2.416, 0.027, and 0.121, respectively (P<0.01). Moreover, the luciferase activity in the A549 cells was statistically higher than that in the HBE cells (P<0.01).ConclusionsThe human pGL3.0-Basic-CTGF luciferase reporter fusion has been successfully constructed. The construct exhibits promoter activity in the bronchial epithelial cells HBE and the lung epithelial cells A549, and can therefore serve as a useful tool for future research in transcriptional regulation.