【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.
After pirfenidone and nintedanib showed efficacy, drug treatment for idiopathic pulmonary fibrosis began to focused on anti-fibrosis. Current research on idiopathic pulmonary fibrosis mainly focus on the pathogenesis and therapeutic targets, and more targeted drugs are gradually entering clinical trials. This article summarizes the results of recent studies on the treatment of idiopathic pulmonary fibrosis with pirfenidone and nintedanib alone or in combination by searching the literature, and reviews the mechanism and test results of the new target anti-fibrosis drugs based on molecular biology that are currently undergoing clinical research in various phases, and aims to provide a basis for how to choose drugs to treat idiopathic pulmonary fibrosis.
Objective To improve the awareness of acute exacerbation of idiopathic pulmonary fibrosis ( AEIPF) and discuss its clinical characteristics, diagnosis, treatment and outcome. Methods The clinical data of patients with AEIPF from June 2006 to June 2011 in 11 hospitals in Jiangsu were collected and analyzed. Resluts There were 18 males and 3 females in the AEIPF patients with mean age of ( 67.4 ± 8.1) years. The duration from IPF diagnosis was ( 7.4 ±8.2) months. The duration of acute symptom before admission was ( 7.0 ±5.3) days. The distribution pattern of new groud-glass opacity was peripheral in 3 patients,multifocal in 5 patients, and diffuse in13 patients. All patients were treated with corticosteroid pulse therapy. Nine patients survived and 12 patients died. The mortality rate was 57.1% . Conclusions AEIPF progresses quickly and the mortality rate is very high. Corticosteroid pulse therapy is the mainstay of therapy in AEIPF 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.
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.
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.
ObjectiveTo systematically review the efficacy and safety of N-acetylcysteine (NAC) for patients with idiopathic pulmonary fibrosis (IPF). MethodsWe electronically searched PubMed, EMbase, The Cochrane Library (Issue 2, 2014), CNKI, WanFang Data and VIP databases from the date of establishment to February 2014 for all randomized controlled trials (RCTs) on the use of NAC in patients with IPF. Manual search in relevant journals were also performed. The data extraction and quality assessment of included RCTs were conducted by two reviewers independently. Then, meta-analysis was conducted using RevMan 5.1 software. ResultsA total of 13 RCTs involving 713 patients were included. The results of meta-analysis indicated that the NAC group was better than the control group in clinical effectiveness (RR=1.34, 95%CI 1.19 to 1.51, P < 0.000 1). After treatment, the lung function was also improved in the NAC group than in the control group in the following index:PaO2 (MD=6.06, 95%CI 3.79 to 8.32, P < 0.000 01), vital capacity (VC) (%) (MD=4.79, 95%CI 0.35 to 9.24, P=0.03) and diffusing capacity of carbon monoxide (Dlco) (%) (MD=5.74, 95%CI 2.67 to 8.81, P=0.000 2). However, no significant difference was found between groups in total lung capacity (TLC) (%) (MD=5.56, 95%CI-1.73 to 12.86, P=0.14). No serious or frequently-happened adverse effect was reported in the NAC group. ConclusionThe current evidence suggests that NAC in long term use could improve clinical conditions, PaO2 and lung function of IPF patients, with less adverse effects.
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 characteristics on chest high-resolution computed tomography (HRCT) of patients with interstitial pneumonia with positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-IP). Methods The extent of fibrosis and subtypes of emphysema on HRCT of MPO-IP patients were retrospectively analyzed and compared with idiopathic pulmonary fibrosis (IPF) cases admitted in the same period. Results From July 2014 to March 2016, 10 patients was diagnosed with IPF and 10 patients was diagnosed with MPO-IP. Emphysema was not different between two groups. Among the MPO-IP patients, 8 patients presented with a usual interstitial pneumonia (UIP) pattern. There existed statistical difference in the bronchial bifurcation level, the fibrosis score of lungs in the MPO-IP patients presented with UIP was lower than that in the IPF patients. Conclusions UIP is the predominant radiologic type of MPO-IP patients. Fibrosis in IPF is more serious than that in MPO-IP with UIP. Paraseptal and centrilobular emphysema are main forms in MPO-IP patients.
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.