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 ...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.展开更多
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 a...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.展开更多
Background:The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality.The aim of this study was to describe the clinical features and survival of patients with AE-...Background:The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality.The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT).Methods:This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016.The subjects were divided into UIP (n =86) and P-UIP group (n=21) based on chest HRCT.Continuous variables were analyzed using Student's t test or Mann-Whimey U test.Categorical variables were analyzed using x2 test.Log-rank test was used for the survival analysis.Cox proportional models evaluated the risk factors for AE occurrence and survival.Results:The male,older patients,previous N-acetylcysteine use,elevated white blood cell (WBC) counts,and microbiology infection were more common in the UIP group than the P-UIP group (X2 =13.567,P < 0.001;z =-2.936,P =0.003;X2 =5.901,P =0.015;t =2.048,P =0.043;x2 =10.297,P =0.036,respectively).The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (ⅡP) was significantly higher than P-UIP pattern (X2 =40.011,P < 0.001).Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group.The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (x2 =5.489,P =0.019) despite of the similar overall survival in the two groups.Multivariate Cox regression analysis indicated WBC count,partial pressure of oxygen in artery (PaO2)/ffactional concentration of inspired oxygen (FiOz),and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]:1.070,95% confidential interval [CI]:1.027-1.114,P=0.001;HR:0.992,95% CI:0.986-0.997,P=0.002;and HR:1.649,95% CI:1.253-2.171,P < 0.001,respectively).Conclusions:AE occurrence of UIP patients in IIP was significantly more than P-UIP cases.The short-term survival was better in the UIP group despite of the similar overall survival in the two groups.WBC count,PaO2/FiO2,and CT score were the independent predictors for survival in UIP subjects.展开更多
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 pote...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.展开更多
Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of ma...Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.展开更多
AIM: To research the natural course of idiopathic pulmonary fibrosis(IPF) with advanced non-small cell lung cancer(NSCLC) and the association between acuteMETHODS: From May 2007 through April 2011, 17 CT naive patient...AIM: To research the natural course of idiopathic pulmonary fibrosis(IPF) with advanced non-small cell lung cancer(NSCLC) and the association between acuteMETHODS: From May 2007 through April 2011, 17 CT naive patients with IPF and advanced NSCLC were enrolled. Patients were classified into best supportive care(BSC) group or CT group based on the patient's preference. Patients in the CT group received carboplatin(CBDCA)(AUC 5-6) plus paclitaxel(PTX)(175-200 mg/m2) on day 1 of each 21-d cycle as first-line therapy.RESULTS: All patients but one chose the CT group. In the CT group, the objective response rate was 38%. The most frequent toxicity ≥ grade 3 was neutropenia(88%). Two patients(12.5%) developed AE-IPF. The median progression-free survival, the median survival time and the 1-year survival rate were 4.1 mo, 8.7 mo and 35%, respectively. Second-line CT-related AE and CT-unrelated AE occurred in 2 and 3 patients(1: BSC group; 2: CT group), respectively. Seven(41%) of all patients developed AE-IPF throughout the clinical course, and 6 of 7 patients with AE-IPF died within one month.CONCLUSION: The incidence of AE-IPF was higher among IPF patients with advanced NSCLC than among those without NSCLC. CBDCA plus PTX regimen was tolerable and effective. However, AE-IPF has a fatal toxicity with or without CT in IPF patients with advanced NSCLC.展开更多
Acute exacerbations of idiopathic pulmonary fibrosis(IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns(PMX-DHP) was originally introduced ...Acute exacerbations of idiopathic pulmonary fibrosis(IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns(PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMXDHP has been applied to acute respiratory failure fromvarious causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease(ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or casecontrol analytic study needs to be conducted, preferably from more than one center or research group.展开更多
基金Supported by Beijing Natural Science Foundation,No.7202118National Natural Science Foundation of China,No.81573970and Basic Scientific Research Foundation of Beijing University of Chinese Medicine,No.2021-JYB-XJSJJ-033.
文摘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.
基金supported by the Foundation for University Youth Key Teacher of Henan Province of China[No.2019GGJS107]the Special Program for Scientific Research of Traditional Chinese Medicine from Henan Province,China in 2019[No.2019ZY2001]the construction project of the characteristic discipline of Chinese medicine in Henan Province,China[No.STS-ZYX-2019028].
文摘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.
基金This study was partially supported by the grants from the National Natural Science Foundation of China (No.81200049 and No.81670059)the Nanjing Medical Science and Technique Development Foundation (No.ORX17005).
文摘Background:The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality.The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT).Methods:This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016.The subjects were divided into UIP (n =86) and P-UIP group (n=21) based on chest HRCT.Continuous variables were analyzed using Student's t test or Mann-Whimey U test.Categorical variables were analyzed using x2 test.Log-rank test was used for the survival analysis.Cox proportional models evaluated the risk factors for AE occurrence and survival.Results:The male,older patients,previous N-acetylcysteine use,elevated white blood cell (WBC) counts,and microbiology infection were more common in the UIP group than the P-UIP group (X2 =13.567,P < 0.001;z =-2.936,P =0.003;X2 =5.901,P =0.015;t =2.048,P =0.043;x2 =10.297,P =0.036,respectively).The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (ⅡP) was significantly higher than P-UIP pattern (X2 =40.011,P < 0.001).Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group.The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (x2 =5.489,P =0.019) despite of the similar overall survival in the two groups.Multivariate Cox regression analysis indicated WBC count,partial pressure of oxygen in artery (PaO2)/ffactional concentration of inspired oxygen (FiOz),and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]:1.070,95% confidential interval [CI]:1.027-1.114,P=0.001;HR:0.992,95% CI:0.986-0.997,P=0.002;and HR:1.649,95% CI:1.253-2.171,P < 0.001,respectively).Conclusions:AE occurrence of UIP patients in IIP was significantly more than P-UIP cases.The short-term survival was better in the UIP group despite of the similar overall survival in the two groups.WBC count,PaO2/FiO2,and CT score were the independent predictors for survival in UIP subjects.
基金supported by National Natural Science Foundation of China(81402482,91313303)
文摘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.
文摘Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.
基金Supported by The Clinical Research Support Center Kyush(http://www.cres-kyushu.or.jp/)
文摘AIM: To research the natural course of idiopathic pulmonary fibrosis(IPF) with advanced non-small cell lung cancer(NSCLC) and the association between acuteMETHODS: From May 2007 through April 2011, 17 CT naive patients with IPF and advanced NSCLC were enrolled. Patients were classified into best supportive care(BSC) group or CT group based on the patient's preference. Patients in the CT group received carboplatin(CBDCA)(AUC 5-6) plus paclitaxel(PTX)(175-200 mg/m2) on day 1 of each 21-d cycle as first-line therapy.RESULTS: All patients but one chose the CT group. In the CT group, the objective response rate was 38%. The most frequent toxicity ≥ grade 3 was neutropenia(88%). Two patients(12.5%) developed AE-IPF. The median progression-free survival, the median survival time and the 1-year survival rate were 4.1 mo, 8.7 mo and 35%, respectively. Second-line CT-related AE and CT-unrelated AE occurred in 2 and 3 patients(1: BSC group; 2: CT group), respectively. Seven(41%) of all patients developed AE-IPF throughout the clinical course, and 6 of 7 patients with AE-IPF died within one month.CONCLUSION: The incidence of AE-IPF was higher among IPF patients with advanced NSCLC than among those without NSCLC. CBDCA plus PTX regimen was tolerable and effective. However, AE-IPF has a fatal toxicity with or without CT in IPF patients with advanced NSCLC.
文摘Acute exacerbations of idiopathic pulmonary fibrosis(IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns(PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMXDHP has been applied to acute respiratory failure fromvarious causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease(ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or casecontrol analytic study needs to be conducted, preferably from more than one center or research group.
