ObjectiveTo understand the genetic polymorphisms of MUC5B and TOLLIP in Chinese patients with idiopathic pulmonary fibrosis (IPF), and to explore whether gene polymorphism variation in Chinese IPF patients can be used as a genetic biomarker for accurate treatment and prognosis judgment.MethodsA total of one hundred and twenty-six patients with IPF were enrolled in this study. The baseline characteristics, total lung capacity (TLC), forced vital capacity (FVC), carbon monoxide diffusion function (DLCO), imaging changes of the patients were followed up. The levels of serum sputum glycosylated antigen-6 (Krebs Von den Lungen-6, KL-6) and B lymphocyte chemotactic factor C-X-C motif chemokine 13 (CXCL13) were detected by chemiluminescent enzyme immunoassay and enzyme-linked immunosorbent assay. The gene MUC5B rs35705950 and TOLLIP rs5743890, rs5743894 single nucleotide polymorphism (SNP) were determined by polymerase chain reaction.ResultsOne hundred and twenty-six patients with IPF were found with AA type by TOLLIP rs5743890 and rs5743894 SNP, accounting for 100.0%; MUC5B rs35705950 SNP was expressed as 116 patients (92.1%) with GG type, and 10 patients (7.9%) with GT type, no TT patients were detected. There was no significant difference in clinical characteristics between the two groups in age and non-smokers (P>0.05). Compared with group G, annual decrease of lung function (FVC, DLCO, and TLC), serum biomarkers (KL-6 and CXCL13), annual increase of reticular and honeycombing lesions, and mortality were significantly lower in group T (P<0.05). The median survival time of IPF patients carrying the MUC5B SNP rs35705950 minor allele (gene phenotype GT) heterozygous was significantly higher than that of homozygous IPF patients with a genetic phenotype of GG.ConclusionsThere are genetic polymorphisms in Chinese patients with IPF. MUC5B rs35705950 and TOLLIP rs5743890, rs5743894 gene subtypes have low mutation rates in the cohort. Compared with homozygous patients of MUC5B SNP rs35705950, heterozygous patients have smaller changes in lung function and radiological image, lower levels of serum KL-6 and CXCL13, and better prognosis.
美国胸科协会(ATS)和欧洲呼吸学会(ERS)联合发表的共识中，将特发性肺纤维化(IPF)定义为原因不明并以普通型间质性肺炎(UIP)为特征性病理改变的一种慢性纤维化性间质性肺疾病。在2000年ATS／ERS的IPF共识意见 及2003年中华医学会呼吸病学分会IPF的诊断和治疗指南(草案) 中均推荐的治疗方案为糖皮质激素，或与细胞毒制剂(环磷酰胺及硫唑嘌呤)联合使用。但目前尚缺乏循证医学证据支持该治疗方案能够提高IPF患者生活质量或生存率 。近年来随着对IPF的发病机制认识的深入，越来越多的临床医师和研究者对IPF患者是否需要用糖皮质激素等药物的治疗提出了质疑。
Objective To explore the imaging features of acute exacerbation of idiopathic pulmonary fibrosis ( IPF) under high-resolution computed tomography ( HRCT) . Methods The HRCT imaging features of six patients who met the criteria for acute exacerbation of IPF were analyzed retrospectively. Results The manifestations of IPF on HRCT scan were various in forms and distribution, as multifocal, ground-glass opacity, reticular shadow, honeycombing densities, capillary bronchiectasis,subpleural lines, traction bronchiolectasis and emphysema. The characteristic lesions were newly diffuse bilateral ground-glass opacity at the time of acute exacerbation, superimposed on subpleural reticular and honeycombing densities. Conclusions Chest HRCT findings in acute exacerbation of IPF are characteristic.HRCT is accurate and superior in diagnosis of IPF and in determining acute exacerbation of IPF.
ObjectiveTo evaluate the clinical efficacy and safety of pirfenidone in Chinese patients with idiopathic pulmonary fibrosis (IPF). MethodsIn a multicenter,randomized,double-blind,comparative clinical trial,87 patients with IPF were randomly divided into two groups. Group A (43 patients) were treated with pirfenidone (1 200 mg per day) for 48 weeks,while Group B (44 patients) were treated with placebo. Clinical features were compared between two groups including efficacy indicators (pulmonary function,6MWT,and quality of life scores) and safety indicators (incidence of adverse events). ResultsForced vital capacity (FVC) was increased by (90±410)mL in Group A and decreased by (70±310)mL in Group B (P<0.05);In Group A,forced expiratory volume in 1 second was raised by (100±330)mL and (110±240)mL following 12 and 24 weeks after treatment,significantly different from group B (P<0.05). There were significant differences in 6MWT between two groups 36 and 48 weeks after treatment respectively(both P<0.05). Quality of life scores,including the St. George's score (excluding symptoms) and dyspnea score,were significantly higher in Group A than Group B (both P<0.05). There was no significant difference in the incidence of adverse events between Groups A and B (83.72% vs. 72.73%,P>0.05). ConclusionDomestic pirfenidone is clinically effective and safe for the treatment of IPF in Chinese patients.
Objective To explore the correlation and mechanism of ferroptosis with pulmonary fibrosis. Methods Pulmonary fibrosis tissue sequencing data were obtained from Gene Expression Omnibus and FerrDb databases from January 2019 to December 2023. Differentially expressed genes (DEGs) between the normal control group and the pulmonary fibrosis group were analyzed by bioinformatic method, and DEGs related to pulmonary iron addiction were extracted. The hub genes were screened by enrichment analysis, protein-protein interaction (PPI) analysis and random forest algorithm. The mouse model of pulmonary fibrosis was made for exercise intervention, and the expression of hub genes was verified by real-time quantitative reverse transcription polymerase chain reaction. Results A comparison of 103 patients with idiopathic pulmonary fibrosis and 103 normal lung tissues showed that 13 up-regulated genes and 7 down-regulated genes were identified as ferroptosis-related DEGs. PPI results showed that there was an interaction between these ferroptosis-related genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment and Genome Ontology enrichment analysis showed that ferroptosis-related genes were involved in organic anion transport, hypoxia response, oxygen level reduction response, hypoxia-inducible factor-1 signaling pathway, renal cell carcinoma, and arachidonic acid metabolic signaling pathway. Genes identified by PPI analysis and random forest algorithm included CAV1, NOS2, GDF15, HNF4A, and CDKN2A. Real-time fluorescence quantitative polymerase chain reaction results of mouse fibrotic lung tissue showed that compared with the exercise group, the mRNA levels of NOS2, PTGS2 and GDF15 were up-regulated and the mRNA levels of CAV1 and CDKN2A were down-regulated in the bleomycin group (P<0.05); compared with the bleomycin group, the expression of CAV1 and CDKN2A increased and the expression of NOS2, PTGS2 and GDF15 decreased in the bleomycin + exercise group (P<0.05). Conclusions Bioinformatic analysis identifies 20 potential genes associating with ferroptosis in pulmonary fibrosis. CAV1, NOS2, GDF15, and CDKN2A influence the development of pulmonary fibrosis by modulating ferroptosis. Treadmill training can reduce ferroptosis in fibrotic tissues, thereby reducing lung inflammation.
ObjectivesTo compare the clinical features of combined pulmonary fibrosis and emphysema (CPFE) and idiopathic pulmonary fibrosis (IPF).MethodsEighty-three patients diagnosed as CPFE or IPF for the first time were retrospectively analyzed from June 2014 to July 2018 in Nanjing Drum Tower Hospital, including 47 patients in the CPFE group and 36 in the IPF group. The demographic characteristics, clinical manifestations, pulmonary function, cardiac ultrasound, blood gas analysis and prognosis of the two groups were compared.ResultsThe proportion of smokers in the CPFE group was higher than IPF group (P<0.05), but dyspnea was lower (P<0.05). The FVC, FVC%pred, FEV1, FEV1%pred and VC% of the CPFE group were higher than IPF group (P<0.05), while FEV1/FVC%pred in the IPF group was higher than CPFE group (P<0.05). DLCO/VA%pred of CPFE group decreased more significantly than IPF group (P<0.05), RV/TLC%pred of CPFE group increased annually, while decreased annually in IPF group (P<0.01). The RV%pred of CPFE increased annually, while that of IPF group decreased annually (P<0.05). There was no significant difference in arterial oxygen pressure and pulmonary artery pressure between the two groups. As for prognosis, the 1- and 3-year survival rate of the CPFE group were 87.9% and 73.8% respectively, those of the IPF group were 84.1% and 65.8% respectively, and no significantly difference was observed between two groups (P=0.95).ConclusionsCompared with IPF, patients with CPFE usually have more smokers, less proportion of dyspnea, almost normal lung volume, more rapidly decreased DLCO/VA%pred, and no significant difference in prognosis.
【Abstract】 Objective To evaluate the relationship between multiple tumor biomarkers and idiopathic pulmonary fibrosis ( IPF) , and analyze the prognostic value of these biomarkers in IPF. Methods Clinical data of 43 confirmed IPF patients with no evidence of malignant disaeses, admitted in Peking Union Medical College Hospital between January 2000 and June 2010, were retrospectively analyzed. All IPF patients had detected serum alpha fetoprotein ( AFP) , cancer antigen 50 ( CA50) , cancer antigen 24-2( CA24-2) , carcinoembryonic antigen ( CEA) , carbohydrate antigen 19-9 ( CA19-9) , cancer antigen 125( CA125) , cancer antigen 15-3 ( CA15-3) , tissue polypeptide antigen ( TPA) , neuron specific enolase( NSE) , and cytokeratin-19-fragment ( Cyfra211) . Results The serum levels of CEA, CA19-9, CA125,CA15-3, and TPA were obviously higher than normal range, while the serum levels of AFP, CA50, CA24-2,NSE, and Cyfra211 were within normal range. Neither tumor biomarkers had correlation with 6-minute walk distance, FVC% pred, TLC% pred, DLCO/VA, PaO2 , PaO2 /FiO2 , P( A-a) O2 , BALF cell differentiation counting,or CD4 /CD8. The patients with increased CA19-9 level had shorter survival time than those with normal CA19-9 level ( P lt; 0. 05) . There was no significant difference in survival time between the patients with increased CEA/TPA levels and those with normal CEA/TPA levels( P gt;0. 05) , neither between the patients with glucocorticoid treatment and those with non-glucocorticoid treatment ( P gt; 0. 05) . Conclusions Multiple tumor biomarkers, especially CA19-9, increase in IPF patients. The degrees of those increases arenot associated with the severity of disease, but closely relate to prognosis, and may also indicate the progression. The increases of multiple tumor biomarkers may be a sign of poor prognosis of IPF with no evidence of malignant disaeses.
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.
ObjectiveAlthough evidence links idiopathic pulmonary fibrosis (IPF) and diabetes mellitus (DM), the exact underlying common mechanism of its occurrence is unclear. This study aims to explore further the molecular mechanism between these two diseases. MethodsThe microarray data of idiopathic pulmonary fibrosis and diabetes mellitus in the Gene Expression Omnibus (GEO) database were downloaded. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify co-expression genes related to idiopathic pulmonary fibrosis and diabetes mellitus. Subsequently, differentially expressed genes (DEGs) analysis and three public databases were employed to analyze and screen the gene targets related to idiopathic pulmonary fibrosis and diabetes mellitus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. In addition, common microRNAs (miRNAs), common in idiopathic pulmonary fibrosis and diabetes mellitus, were obtained from the Human microRNA Disease Database (HMDD), and their target genes were predicted by miRTarbase. Finally, we constructed a common miRNAs-mRNAs network by using the overlapping genes of the target gene and the shared gene. ResultsThe results of common gene analysis suggested that remodeling of the extracellular matrix might be a key factor in the interconnection of DM and IPF. Finally, hub genes (MMP1, IL1R1, SPP1) were further screened. miRNA-gene network suggested that has-let-19a-3p may play a key role in the common molecular mechanism between IPF and DM. ConclusionsThis study provides new insights into the potential pathogenic mechanisms between idiopathic pulmonary fibrosis and diabetes mellitus. These common pathways and hub genes may provide new ideas for further experimental studies.
ObjectiveBased on real-word data, and compared with two common chronic respiratory diseases, interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), this case-control study plans to investigate the risk factors and clinical characteristics of patients with combined pulmonary fibrosis and emphysema syndrome (CPFE).MethodsA retrospective case-control study was carried out to screen the clinical data of 96 patients with CPFE, 133 patients with COPD and 164 patients with ILD, analyze their demographics, clinical data, complications and related clinical indicators. Univariate analysis was used to compare the differences among the three groups, and multivariate logistic analysis was used to screen for risk factors.ResultsAll three groups were in old age with the average age of above 71 years. In terms of male ratio and smoking rate, the CPFE group (93.8%, 85.4%) was higher than the ILD group (75.0%, 64.0%), but there was no significant difference when compared with the COPD group (90.2%, 82.0%). Regarding comorbid disease, the proportion of connective tissue disease (CTD) in the CPFE group (10.4%) and the ILD group (13.4%) was higher than that in the COPD group (1.5%). The proportion of hyperlipidemia in the CPFE group (8.3%) was higher than that in the COPD group (1.5%) and the ILD group (1.2%). There were differences in the abnormal proportion of antinuclear antibody among the three groups, but no significant difference was found when compared with the CPFE group alone. The CPFE group (46.9%, 12.5%) and the ILD group (54.9%, 9.8%) were significantly higher than the COPD group (34.6%, 2.3%) in terms of carcinoembryonic antigen (CEA) abnormal proportion and cancer rate. In terms of the prevalence of pulmonary hypertension, the CPFE group (41.7%) > the COPD group (33.1%) > the ILD group (32.9%) was shown, but no statistical significance was found among the three groups.ConclusionsMale and smoking are not only risk factors for COPD but also for CPFE. At the same time, the suffering of CPFE may be affected by immune factors and hyperlipidemia. The proportion of CPFE patients complicated with cancer and CEA abnormalities is higher than COPD patients. The severity of pulmonary hypertension in CPFE patients is significantly higher than the other two diseases.