| Idiopathic pulmonary fibrosis(IPF)is a type of chronic fibrous lung disease,with insidious onset and rapid progression,leading to respiratory failure and death.Several retrospective longitudinal studies suggest that the median survival time of patients with idiopathic pulmonary fibrosis is 2-3 years from diagnosis to death.The etiology of IPF is unclear,and its pathogenesis may be related to predisposing genes,aging,tobacco exposure,environmental factors,virus,immune imbalance,and chronic gastrointestinal acid or non acid reflux and inhalation or other factors.At present,there is a hypothesis that individuals with susceptible tendency,especially in the elderly,who are repeatedly chronically inhaled,caused abnormal alveolar epithelial cell injury and repair,causes lung fibroblasts proliferation and activation,collagen deposition and formation of pulmonary fibrosis.IPF combined with high incidence of gastroesophageal reflux provides the basis for the hypothesis.Over the past ten years,many clinical trials have been conducted in the Department of respiration to explore a variety of treatments.However,the results of clinical trials are disappointing and can not improve the survival rate of patients with IPF,which means that there is no effective treatment for IPF.Previous studies have shown that therapeutic agents may not block the dynamic damage of alveolar epithelial cells,as well as the consequent inflammatory and fibrotic processes in the lung.Clinically,there is an urgent need to find effective treatment options,treatment should be changed into preventive strategies,treatment for possible causes,so as to improve the prognosis of patients with IPF.More and more studies have shown that IPF is associated with a high incidence of gastroesophageal reflux.Increased pepsin was detected in bronchoalveolar lavage fluid in patients with partial acute exacerbations of IPF,which provided direct evidence for the presence of gastric juice into the lower respiratory tract,suggesting that chronic micro inhalation may play a role in acute exacerbation of IPF.Drug or surgical treatment of gastroesophageal reflux can make the pulmonary function of patients with IPF remain stable,anti gastroesophageal reflux provides a new target for the treatment of IPF.In this study,104 patients with IPF were studied.The prognostic factors of IPF were analyzed,especially the effect of anti reflux therapy on the survival of patients.ObjectiveChronic micro-aspiration secondary to gastroesoPHageal reflux(GER)may play a role in the pathogenesis and natural history of idiopathic pulmonary fibrosis(IPF).Our goal was to investigate the relationship between chronic anti-reflux therapy and survival time in patients with IPF.MethodsCase reports comprising data involving gastroesoPHageal reflux diagnosis and treatment were analyzed to investigate the relationship between GER-related variables and survival time in an identified cohort of patients with IPF from Weihai Municipal Hospital.Among the 104 patients,51 received chronic anti-reflux therapy:16 patients were treated with a combination of antacid and gastrointestinal motility drugs,18 patients were treated with antacid therapy alone and 17 patients were treated with gastrointestinal motility drugs.SPSS 17statistical software was used for data processing and analysis.Descriptive statistics are presented as mean and standard deviation(SD)or median(25th percentile,75th percentile).Cases surviving until the last follow-up day,missing and dead cases involving non-IPF disease were managed by censoring statistical data.Survival time(in days)was reported as median(25th percentile,75th percentile).Unadjusted and adjusted Cox proportional hazards regression analyses were performed.The survival curves were plotted by Kaplan-Meier method,and the differences were tested using the log rank test.The adjusted Cox regression modeling was performed using all the significant predictors in unadjusted analysis and also using stepwise selection.All tests were two-sided and were performed at a significance level of 0.05.Result1.Study PopulationThe study cohort consisted of 104 patients.Patients were primarily males(67%)with a mean age of 68.Most patients were overweight,with a mean body mass index(BMI)of 27.The majority of patients were current or former smokers(73%).Mean baseline forced vital capacity(FVC)was 71%predicted and diffusing capacity of the lung for carbon monoxide(DLCO)was 52%predicted.Symptoms of GER were present in 35%of patients.At the time of diagnosis,49%of patients reported current treatment with anti-reflux therapy(antacids and/or gastrointestinal motility drugs).Most patients(67%)used PPI as routine antacid therapy.2.Survival AnalysisResults of univariate Cox proportional regression analysis showed no significant difference in sex,Velcro,GERD,RV%,macroPHage%,and ground-glass shaking scores on survival of IPF patients was not statistically significant(p>0.05).Age,BMI,dyspnea score,smoking history,presence of GERD,TLC%,PAP,long-term use of oxygen,anti-reflux therapy,FVC%,DLCO%,PaO2(mmHg),SaO2,PA-aO2(mmHg),L%,E%,grid shadow score,cell lung score,is the main factor affecting the prognosis of patients with IPF(P<0.05).Kaplan-Meier survival analysis between groups reported there were no significant differences in gender,GERD,PAP(mmHg),the long-term use of oxygen,PaO2(mmHg),SaO2%(mmHg),lymPHocytes%between patients with and without reported anti-reflux therapy(log-rank were 0.34,3.65,3.12,1.22,2.45,2.69,0.11,P>0.05).The following parameters survival rate between different groups were statistically significant,BMI(Cutoff = 26.45,log rank = 50.11,p = 0.000),dyspnea score(Cutoff = 6.30,log rank = 10.12,p=0.002),anti-reflux treatment(Cutoff = 6 months,log rank=47.43,p=0.000),TLC%(Cutoff=62.84,log rank=,55.00,p=0.000),FVC%(Cutoff=67.00,log rank =9.67,p=0.040),DLCO%(Cutoff = 55.00,p = 0.000),N%(Cutoff = 10.00,log rank = 14.22,p = 0.000),PA-a02(mmHg)(Cutoff = 39.90,log rank = 6.45,p = 0.010)(Cutoff = 41.00,log rank = 47.78,p = 0.000),the cellular lung score(Cutoff = 32,log rank = 52.19),and Grid scorescore(cutoff = 41.00,log rank =,P = 0.000).3.Comparison of Anti-reflux Therapy UsageThere were no significant differences in age,BMI,history of smoking,gender,long-term oxygen use,or pulmonary PHysiology between patients with and without reported anti-reflux therapy.Anti-reflux therapy was associated with a median survival time of 929-days-compared with a median survival time of 685 days in patients without such therapy.Patients undergoing anti-reflux therapy survived significantly longer than the patients without anti-reflux therapy(Log Rank = 5.936,P=0.015).After further stratification analysis,it was found that in patients with or without GERD,anti-reflux treatment resulted in longer survival than in patients without anti-reflux treatment.The difference was far more significant in patients with GERD(Log Rank = 7.263,P = 0.007).In patients with a reported presence of GER symptoms,there was no significant difference in survival time following anti-reflux therapy compared with patients without anti-reflux therapy(Log Rank = 0.592,P =0.441).However,in patients reporting absence of GER symptoms,survival with anti-reflux therapy was significantly longer than in untreated patients(Log Rank =7.148,P = 0.007).In patients undergoing anti-reflux therapy with the combination of anti-acid and gastrointestinal motility drugs,the survival was significantly longer than in those treated with antacids alone(Log Rank = 12.103,P = 0.001).4.Effects of anti-reflux therapy on IPF risk factors and serum markersCompared with the control group,the indexes DLCO(%)and PaO2(mmHg)in the anti-acid drug treatment group were significantly higher than those in the control group(p<0.05),the parameters TCL(%),DLCO(%)(P<0.05),and the scores of dyspnea were significantly decreased(p<0.05),and the scores of PaO2(mmHg)were significantly increased(p<0.05).Compared with the control group,the index grid score of the anti-acid drug treatment group was significantly lower,the difference was statistically significant(p<0.05),the parameters of the treatment group of neutroPHils(%),acid granulocytes(%Both the mesh score and the cellular lung score were significantly lower,with statistical differences(p<0.05).Compared with the control group,the serum index of MMP-7 in the anti-acid drug treatment group was significantly lower than that in the control group(p<0.05).The serum levels of TGF-β1 and MMP-7 in the combination group were significantly lower than those in the control group Differences(p<0.05).ConclusionsChronic use of anti-reflux therapy is an independent predictor of longer survival time in patients with IPF. |
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