Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Identification of potential biomarkers for idiopathic pulmonary fibrosis and validation of TDO2 as a potential therapeutic target

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.

Acute exacerbation of idiopathic pulmonary fibrosis treated using the Feibi recipe:Two case reports

BACKGROUND Rationale:No other treatment besides lung transplant is effective for idiopathic pulmonary fibrosis(IPF).Patients with IPF have poor prognosis,which may eventually lead to death.Patient concerns:Two female patients were diagnosed with IPF.In our recent follow-up,both these patients maintained a good quality of life.CASE SUMMARY Diagnosis:Both patients had dry cough and progressive dyspnea.Interventions:The first patient was treated with prednisone,and the second patient was treated with prednisone and tripterygium glycosides.However,the symptoms did not improve and fibrosis was not controlled.Thus,the Feibi recipe was used.Outcomes:No deterioration was observed after the treatment,and the dry cough and its effect were ameliorated.Furthermore,they are still alive and the quality of their lives has improved.CONCLUSION These two cases suggest that the Feibi recipe and other traditional Chinese medicine therapies could be beneficial for IPF treatment.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a serious and fatal pulmonary inflammatory disease with an increasing incidenceworldwide.The drugs nintedanib and pirfenidone,are listed as conditionally recommended drugs in the“Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis”.However,these two drugs have many adverse reactions in clinical application.Salvianolic acid B(Sal B),a water-soluble component of Salvia miltiorrhiza,could alleviate bleomycin-induced peroxidative stress damage,and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease’s progression.However,Sal B is poorly absorbed orally,and patient compliance is poor when administered intravenously.Therefore,there is an urgent need to find a new non-injection route of drug delivery.In this study,Sal B was used as model drug and l-leucine(LL)as excipient to prepare Sal B dry powder inhaler(Sal B-DPI)by spray drying method.Modern preparation evaluation methods were used to assess the quality of Sal B-DPI.Sal B-DPI is promising for the treatment of IPF,according to studies on pulmonary irritation evaluation,in vivo and in vitro pharmacodynamics,metabolomics,pharmacokinetics,and lung tissue distribution.

Correlation Analysis between Idiopathic Pulmonary Fibrosis and Tumor Markers

The purpose of this study was to investigate the correlation between idiopathic pulmonary fibrosis(IPF)and tumor markers to provide evidence for early screening of precancerous lesions.In our hospital from July 2017 to May 2019,40 patients with IPF treatment were selected as the IPF group,and 40 patients with idiopathic pulmonary fibrosis with lung cancer(IPF-LC)were selected as the IPF-LC group.In the same period,40 healthy physical examinees were used as control group.Different types of patients in the IPF-LC group were divided into lung adenocarcinoma group,small cell lung cancer group and l squamous carcinoma group.The expression levels of tumor markers were detected in the three groups,the positive rates of tumor markers in IPF group,IPF-LC group and their subgroups were compared.The results showed that the levels of neuron specific enolase(NSE),antigen CYFRA211,carcinogenic antigen(CEA)and cancer antigen 125(CA125)in IPF and IPF-LC groups were significantly higher than those in control group(P<0.05).There was no significant difference in CEA and CYFRA211 between IPF-LC group and IPF group.The level of NSE in IPF-LC group was significantly higher than that in IPF group,while the level of CA125 was significantly lower than that in IPF group(P<0.0.5).The difference of positive rate of NES and CA125 in IPF-LC group and IFP group was statistically significant(P<0.05),there was no statistically significant difference in the positive rate of other indicators(P>0.05)The NSE positive rate of IPF group was significantly lower than that of IPF-LC group(P<0.05),the positive rates of other tumor markers were significantly lower than those of each subgroup of IPF-LC group(P<0.05).Therefore,tumor markers in IPF patients showed different degrees of increase,which is worthy of clinical attention.Among them,NSE can be used as an early screening indicator for IPF precancerous lesions.

Progress of Radix Astragali and Radix Angelicae Sinensis in the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.

Integrated bioinformatics analysis of key candidate genes and therapeutic drugs for idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis is a form of fibrotic and fatal lung disease worldwide with unknownetiology and mechanisms. This manuscript focused on clarifying the core protein-protein interaction network, genesand related pathways correlated with idiopathic pulmonary fibrosis in detail. Methods: Gene chip (GSE24206) wasacquired from the Gene Expression Omnibus database. GEO2R was a R-based online tool to screen differentialexpressed genes. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were utilized toascertain gene function and key signaling pathways. The Search Tool for the Retrieval of Interacting Genes was usedto construct the protein-protein interaction network. Key genes and module analysis were screened out usingCytohubba and MCODE plugin. The candidate therapeutic molecular drugs were searched for IPF using DGIdbdatabase. Results: A cohort of 240 differential expression of genes (113 up-regulated and 127 down-regulated) wereknocked out. Gene Ontology enrichment analysis indicated that some differential expression of genes were involvedin extracellular matrix and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathways werepredominantly involved in chemokine signaling pathway and ECM-receptor interactions. Two significant modulesand 5 hub genes were strongly implicated in idiopathic pulmonary fibrosis from protein-protein interaction network.The 2 module genes were primarily enriched in the cytokine-cytokine receptor, TNF signaling pathway, toll-likesignaling pathway, and Wnt signaling pathway. Finally, 41 small molecules were identified by DGIdb database as thepotential drugs of idiopathic pulmonary fibrosis. Conclusion: To conclude, in this study, the hub genes, signalingpathways, and small molecules will conduce to better understanding the mechanisms and may provide new methodsto the therapy of idiopathic pulmonary fibrosis.

Serum biomarkers in evaluation and management of idiopathic pulmonary fibrosis

Despite there has greater understanding of the pathophysiology in idiopathic pulmonary fibrosis,idiopathic pulmonary fibrosis still remains a challenge in clinical practice and translational research due to its heterogeneity.Improvements in molecular techniques have identified potential pathways and targets for diagnosis and therapeutic intervention.Several types of idiopathic pulmonary fibrosis biomarkers such as KL-6,SP-A,SP-D,MMP7 and other potential ones have been studied extensively.In addition,many studies have confirmed that levels of some tumor markers such as CA 19-9,CA 15-3,CEA,CA 125,CYFRA 21-1 are useful for idiopathic pulmonary fibrosis.The present study focuses on serum biomarkers including tumor markers to provide an overview on the current roles of these biomarkers in the setting of diagnosis,prediction as well as response to therapy in idiopathic pulmonary fibrosis.

Research progress of Chinese medicine in treatment of IPF(idiopathic pulmonary fibrosis)

Idiopathic pulmonary interstitial fibrosis is one of the respiratory refractory diseases,and the incidence rate is on the rise.At present,the effect of western medicine is not ideal and the side effects are obvious,while the traditional Chinese medicine shows good curative effect on the disease.This paper makes a summary on the traditional Chinese medicine theory in treating idiopathic pulmonary interstitial fibrosis in recent years.

Early pirfenidone treatment enhances lung function in idiopathic pulmonary fibrosis patients

This editorial comments on the study by Lei et al investigating the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis(IPF)published.This study evaluates the efficacy of early treatment with pirfenidone on lung function in patients with IPF.The early and advanced stages of IPF are defined,highlighting the drug's benefits.While prior research indicates pirfenidone's effectiveness in advanced IPF,this study focuses on its advantages in early stages.The study emphasizes the importance of computed tomography imaging alongside biochemical data and lung function tests for a comprehensive analysis of symptom relief.Results show that early intervention with pirfenidone significantly reduces disease progression and preserves lung function,underscoring its potential as a critical treatment strategy in early IPF.

Potential biomarkers for diagnosis and disease evaluation of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia.IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration;thus,a differential diagnosis remains challenging.Several biomarkers have been identified to achieve a differential diagnosis;however,comprehensive reviews are lacking.This review summarizes over 100 biomarkers which can be divided into six categories according to their functions:differentially expressed biomarkers in the IPF compared to healthy controls;biomarkers distinguishing IPF from other types of interstitial lung disease;biomarkers differentiating acute exacerbation of IPF from stable disease;biomarkers predicting disease progression;biomarkers related to disease severity;and biomarkers related to treatment.Specimen used for the diagnosis of IPF included serum,bronchoalveolar lavage fluid,lung tissue,and sputum.IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF.Currently,the physiological measurements used to evaluate the occurrence of acute exacerbation,disease progression,and disease severity have limitations.Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF.Most biomarkers described in this review are not routinely used in clinical practice.Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis:An exploratory randomized controlled trial

Background:Acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF)is an important occurrence in the natural history of idiopathic pulmonary fibrosis(IPF),associated with high hospitalization rates,high mortality and poor prognosis.At present,there is no effective treatment for AE-IPF.Chinese herbal medicine has some advantages in treating IPF,but its utility in AE-IPF is unclear.Objective:The treatment of AE-IPF with Kangxian Huanji Granule(KXHJ),a compound Chinese herbal medicine,lacks an evidence-based justification.This study explores the efficacy and safety of KXHJ in patients with AE-IPF.Design,setting,participants and interventions:Wedesigned a randomized,double-blind,placebo-controlled,exploratory clinical trial.A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo;the treatment included a 10 g dose,administered twice daily for 4 weeks,in addition to conventional treatment.Participants were followed up for 12 weeks after the treatment.Main outcome measures:The primary endpoints were treatment failure rate and all-cause mortality.Secondary endpoints included the length of hospitalization,overall survival,acute exacerbation rate,intubation rate,the modified British Medical Research Council(mMRC)score,and the St George’s Respiratory Questionnaire for IPF(SGRQ-I)score.Results:The rate of treatment failure at 4 weeks was lower in the intervention groupcompared to the control group(risk ratio[RR]:0.22;95%confidence interval[CI]:0.051 to 0.965,P=0.023).There was no significant difference in all-causemortality at 16 weeks(RR:0.75;95%CI:0.179 to 3.138;P>0.999)or in the acute exacerbation rate during the 12-week follow-up period(RR:0.69;95%CI:0.334 to 1.434;P=0.317).The intervention group had a shorter length of hospitalization than the control group(mean difference[MD]:–3.30 days;95%CI,–6.300 to–0.300;P=0.032).Significant differences in the mean change from baseline in the mMRC(between-group difference:–0.67;95%CI:–0.89 to–0.44;P<0.001)and SGRQ-I score(between-group difference:–10.36;95%CI:–16.483 to–4.228;P=0.001)were observed after 4 weeks,and also in the mMRC(between-group difference:–0.67;95%CI:–0.91 to–0.43;P<0.001)and SGRQ-I(between-group difference:–10.28;95%CI,–15.838 to–4.718;P<0.001)at 16 weeks.The difference in the adverse events was not significant.Conclusion:KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF.As a preliminary exploratory study,our results provide a basis for further clinical research.

A novel pulmonary fibrosis murine model with immune-related liver injury

Idiopathic pulmonary fibrosis(IPF),characterized by aggravated alveolar destruc-tion and fibrotic matrix deposition,tendentiously experiences the stage called acute exacerbation IPF(AE-IPF)and progresses to multiple organ damage,especially liver injury.Recent studies have found a variety of immune microenvironment disorders associated with elevated IPF risk and secondary organ injury,whereas current animal models induced with bleomycin(BLM)could not completely reflect the pathologi-cal manifestations of AE-IPF patients in clinic,and the exact underlying mechanisms are not yet fully explored.In the current study,we established an AE-IPF model by tracheal administration of a single dose of BLM and then repeated administrations of lipopolysaccharide in mice.This mouse model successfully recapitulated the clinical features of AE-IPF,including excessive intrapulmonary inflammation and fibrosis and extrapulmonary manifestations,as indicated by significant upregulation of Il6,Tnfa,Il1b,Tgfb,fibronectin,and Col1a1 in both lungs and liver and elevated serum aspartate transaminase and alanine transaminase levels.These effects might be attributed to the regulation of Th17 cells.By sharing this novel murine model,we expect to pro-vide an appropriate experimental platform to investigate the pathogenesis of AE-IPF coupled with liver injury and contribute to the discovery and development of targeted interventions.

Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure.Recently, phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3 K/AKT in fibrotic processes is increasingly prominent, with PI3 K/AKT inhibitors currently under clinical evaluation in IPF. Therefore,PI3 K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3 K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3 K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.

MicroRNAs in idiopathic pulmonary fibrosis: involvement in pathogenesis and potential use in diagnosis and therapeutics

MicroRNAs(miRNAs) are a class of phylogenetically conserved, non-coding short RNAs,19–22 nt in length which suppress protein expression through base-pairing with the 30-untranslated region of target m RNAs. mi RNAs have been found to participate in cell proliferation, differentiation and apoptosis. Idiopathic pulmonary fibrosis(IPF) is a chronic, progressive, and high lethality fibrotic lung disease for which currently there is no effective treatment. Some mi RNAs have been reported to be involved in the pathogenesis of pulmonary fibrosis. In this review, we discuss the role of mi RNAs in the pathogenesis, diagnosis and treatment of IPF.

Role of various imbalances centered on alveolar epithelial cell/fibroblast apoptosis imbalance in the pathogenesis of idiopathic pulmonary fibrosis

There have been recent extensive studies and rapid advancement on the pathogenesis underlying idiopathic pulmonary fibrosis(IPF),and intricate pathogenesis of IPF has been suggested.The purpose of this study was to clarify the logical relationship between these mechanisms.An extensive search was undertaken of the PubMed using the following keywords:"etiology,""pathogenesis,""alveolar epithelial cell(AEC),""fibroblast,""lymphocyte,""macrophage,""epigenomics,""histone,"acetylation,""methylation,""endoplasmic reticulum stress,""mitochondrial dysfunction,""telomerase,""proteases,""plasminogen,""epithelial-mesenchymal transition,""oxidative stress,""inflammation,""apoptosis,"and"idiopathic pulmonary fibrosis."This search covered relevant research articles published up to April 30,2020.Original articles,reviews,and other articles were searched and reviewed for content;240 highly relevant studies were obtained after screening.IPF is likely the result of complex interactions between environmental,genetic,and epigenetic factors:environmental exposures affect epigenetic marks;epigenetic processes translate environmental exposures into the regulation of chromatin;epigenetic processes shape gene expression profiles;in turn,an individual’s genetic background determines epigenetic marks;finally,these genetic and epigenetic factors act in concert to dysregulate gene expression in IPF lung tissue.The pathogenesis of IPF involves various imbalances including endoplasmic reticulum,telomere length homeostasis,mitochondrial dysfunction,oxidant/antioxidant imbalance,Th1/Th2 imbalance,M1-M2 polarization of macrophages,protease/antiprotease imbalance,and plasminogen activation/inhibition imbalance.These affect each other,promote each other,and ultimately promote AEC/fibroblast apoptosis imbalance directly or indirectly.Excessive AEC apoptosis and impaired apoptosis of fibroblasts contribute to fibrosis.IPF is likely the result of complex interactions between environmental,genetic,and epigenetic factors.The pathogenesis of IPF involves various imbalances centered on AEC/fibroblast apoptosis imbalance.

Idiopathic pulmonary fibrosis will increase the risk of lung cancer

Objective To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis （IPF）.Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included.Study selection We identified,retrieved and reviewed the information on the frequency,risk factors,anatomical features,histological types,clinical manifestations,computed tomography findings and underlying mechanisms of lung cancer in IPF patients.Results The prevalence rates of lung cancer in patients with IPF （4.8％ to 48％） are much higher than patients without IPF （2.0％ to 6.4％）.The risk factors for lung cancer in IPF include smoking,male gender,and age.Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant.Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF.Radiologic features of these patients include peripherally located,ill-defined mass mimicking air-space disease.The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood,but may include the inflammatory response,epithelial injury and/or abnormalities,aberrant fibroblast proliferation,epigenetic and genetic changes,reduced cell-to-cell communication,and activation of specific signaling pathways.Conclusions These findings suggest that IPF is associated with increased lung cancer risk.It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients.

Clinical features and outcomes of 210 patients with idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis （IPF） is a lethal chronic interstitial lung disease （ILD） of unknown cause and having a variable and unpredictable course.This study aimed to summarize the clinical features and follow-up outcomes and to identify potential factors useful for the assessment of prognosis in IPF.Methods Two hundred and ten patients hospitalized and diagnosed as IPF in our unit from January 1999 to June 2007 were enrolled into this study.The baseline demographic,clinical,radiologic and physiologic characteristics were summarized.Clinical follow-up data until February 2010 were collected,and the median survival time and 1-,2-,and 5-year survival rates,as well as the influences of the summarized baseline variables on the prognosis were analyzed.Results The age at diagnosis as IPF was （64±10） years,the duration before diagnosis of 106 patients （50％） was shorter than 2 years,and 73％ were males.One hundred and forty-five patients （69％） had a history of smoking with a median pack-year of 18.Eighty-nine patients （42％） had emphysema and 62 patients （29％） pulmonary arterial hypertension （PAH）.One hundred and twenty-four patients were followed up,of which 99 patients died from various causes including respiratory failure related to IPF （93％）.The follow-up period was （21±23） months.The median survival time was 38months.The 1-,2-,and 5-year survival rates were 61％,52％,and 39％,respectively.Multivariate analysis showed clubbing,PAH,duration from initial onset to diagnosis,and forced expiratory volume in 1 second （FEV1）/forced vital capacity （FVC） were independent prognostic indicators of IPF.Conclusion IPF patients who have clubbing,PAH,a higher FEVJFVC,and a short duration from initial onset to diagnosis have a poorer outcome.

Cigarette smoking contributes to idiopathic pulmonary fibrosis associated with emphysema

Background Combined emphysema and pulmonary fibrosis,including idiopathic pulmonary fibrosis （IPF）,is a distinct disorder described with upper-lobe emphysema and lower-lobe fibrosis on chest computed tomography.Smoking appears to be the predominant risk factor for this disorder.We aimed to compare clinical features,smoking history,physiological and radiological findings between IPF with and without emphysema.Methods A sample of 125 IPF patients over a period of 48 months were evaluated.High resolution CT scans were reviewed blinded to clinical data.The IPF patients with or without emphysema were classified accordingly.Results The prevalence of emphysema in this IPF sample was 70/125.IPF with emphysema was significantly associated with smoking status （OR 63; 95％ CI 4.4 to 915; P=0.002） and smoking pack year （OR 1.1; 95％ CI 1.05 to 1.13; P=-0.000）.The patients with IPF and emphysema had a higher decrease in carbon monoxide diffusing capacity adjusted for alveolar volume （（58±19）％ pred vs.（66：±：21）％ pred; P=-0.021） and a higher prevalence of pulmonary hypertension （24/70 vs.7/55; P=0.006）.The two groups of patients had similar forced and residual volumes.No significant differences were found in cell differentials of bronchoalveolar lavage or the scores of fibrosis on chest CT.Survival of the patients with emphysema was significantly less than that of patients with IPF alone.Conclusions Cigarette smoking induces IPF combined with emphysema.Emphysema further impairs physiological function and increases the prevalence of pulmonary hypertension that leads to poor prognosis.The inclusion of the patients with combined pulmonary fibrosis and emphysema in IPF clinical trials may lead to under evaluation of the effect of treatment in patients.