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.
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.
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.
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.
ObjectiveTo determine the diagnostic value of serum KL-6 level in patients with interstitial lung diseases (ILD). MethodsAll the ILD patients enrolled were hospitalized from April 2013 to April 2014. Patients with other pulmonary diseases and healthy subjects were chosen as control groups simultaneously. Serum KL-6 concentrations were measured by chemiluminescent enzyme immunoassay. The association with serum KL-6 level and pulmonary function was analyzed. ResultsThere were 149 ILD patients, 155 patients with other pulmonary diseases, and 64 healthy subjects. The average serum levels of KL-6 were (1 801.86±2 831.36) U/mL, (267.00±124.41) U/mL, (201.28±81.18) U/mL in the patients with ILD, the patients with other pulmonary diseases and the healthy controls, respectively. The sensitivity and the specificity of the serum KL-6 for the diagnosis of ILD was 83.89% and 92.24% respectively when the cut-off level was set at 500 U/mL. The Kappa value was 0.767 (P < 0.001). The best cut-off value of KL-6 was 469.5 U/mL. Serum KL-6 levels in the patients with ILD were significantly higher compared with the patients with chronic obstructive pulmonary disease, pneumonia, tuberculosis, bronchiectasis and the healthy controls, respectively (all P < 0.001). The KL-6 levels in the pulmonary alveolar proteinosis patients were significantly higher compared with the patients with cryptogenic organizing pneumonia (COP), the patients with idiopathic pulmonary fibrosis (IPF) and the patients with connective tissue disease (CTD-ILD) (all P < 0.001). While the KL-6 concentration in IPF and CTD-ILD were significantly higher than that in COP (P=0.003 and P=0.008, respectively). Significant negative correlations were found between the levels of serum KL-6 and vital capacity as a percentage of the predicted value, forced vital capacity as a percentage of the predicted value, forced expiratory volume in one second as a percentage of the predicted value and carbon monoxide diffusing capacity as a percentage of the predicted value (all P < 0.001). Follow-up study showed the levels of serum KL-6 were consistent with clinical efficacy. ConclusionSerum KL-6 level is a reliable serum marker for ILD, and is related with the severity of disease and clinical efficacy.
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.
Objective To investigate the prevalence of obstructive sleep apnea hypopnea syndrome ( OSAHS) in patients with idiopathic pulmonary fibrosis ( IPF) and its clinical significance. Methods Sleep quality and breathing disorders were measured by polysomnography and the relationship with lung function was analyzed in 20 IPF patients. Results Thirteen of 20 subjects ( 65% ) had OSAHS as defined by an AHI ≥5 events per hour. Three subjects ( 15% ) had mild OSAHS ( AHI,5 to 20 events per hour) , and 10 subjects ( 50% ) had moderate-to-severe OSAHS ( AHI≥20 events per hour) . The sleep architecture in these patients showed a reduction in sleep efficiency, rapid eye movement ( REM) sleep and slow wave sleep, and a marked sleep fragmentation due to an increased arousal index. The AHI was negatively correlated with FVC% pred ( r =-0.672, P=0.001) and FEV1% pred ( r =-0.659, P=0.002) , and positively correlated with body mass index ( BMI) ( r=0.791, Plt;0.0001) . Conclusions OSAHS is a common comorbidity in IPF. Early treatment of OSAHS may improve quality of life and the prognosis of patients with IPF.
Objective To investigate the impact and mechanisms of periostin (POSTN), Krebs von den Lungen-6 (KL-6), pulmonary surfactant protein A (SP-A), and pulmonary surfactant protein D (SP-D) on the diagnosis and disease assessment of idiopathic pulmonary fibrosis (IPF), and conduct a comparative analysis. Methods From October 2022 to October 2023, a total of 55 patients diagnosed with IPF and treated at the Third Affiliated Hospital of Anhui Medical University were enrolled as an IPF group. Additionally, 30 patients with bacterial pneumonia and 30 healthy individuals undergoing concurrent health examinations during the same period were selected as a pneumonia control group and a healthy control group, respectively. All participants underwent enzyme-linked immunosorbent assay to measure serum levels of POSTN, KL-6, SP-A, and SP-D, along with pulmonary function tests. The IPF patients also underwent high-resolution computed tomography (HRCT) and echocardiography to quantify HRCT scores and pulmonary artery systolic pressure (PASP). Receiver operating characteristic (ROC) curves were plotted to analyze the significance of serum POSTN, KL-6, SP-A, and SP-D levels in IPF diagnosis. Pearson and Spearman correlation tests were used to analyze the relationships between these biomarkers and pulmonary function, PASP, and HRCT scores. Results Serum concentrations of POSTN, KL-6, SP-A, and SP-D were significantly elevated in the IPF group compared with the pneumonia group and the healthy controls (P<0.05), while serum levels of SP-A and SP-D were notably higher in the pneumonia group compared with the healthy control group (P<0.05). Within the IPF group, serum POSTN levels were negatively correlated with forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) and diffusion capacity of the lung for carbon monoxide as a percentage of predicted value (DLCO%pred) (P<0.05); KL-6 and SP-D levels were also negatively correlated with FEV1%pred, forced vital capacity as a percentage of predicted value (FVC%pred), and DLCO%pred (P<0.05); and the concentration of SP-A was negatively correlated with DLCO%pred and positively correlated with PASP (P<0.05). Additionally, serum levels of POSTN, KL-6, and SP-A in the IPF group showed significant positive associations with HRCT scores (P<0.01). Conclusions POSTN is a valuable serum biomarker for IPF, exhibiting the highest sensitivity and specificity among the four serum markers, with diagnostic performance superior to KL-6, SP-A, and SP-D. POSTN, KL-6, SP-A, and SP-D can all be used for the diagnosis and assessment of IPF.