2.Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial.
Jian-Sheng LI ; Hai-Long ZHANG ; Wen GUO ; Lu WANG ; Dong ZHANG ; Li-Min ZHAO ; Miao ZHOU
Journal of Integrative Medicine 2023;21(6):543-549
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:
We designed 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 group compared 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-cause mortality 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.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.
Humans
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Double-Blind Method
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Drugs, Chinese Herbal/therapeutic use*
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Idiopathic Pulmonary Fibrosis/drug therapy*
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Treatment Outcome
3.Spontaneous Regression of Non-Small Cell Lung Cancer in a Patient with Idiopathic Pulmonary Fibrosis: A Case Report.
Eu Dong HWANG ; Young Jae KIM ; Ah Young LEEM ; Ah Young JI ; Younjeong CHOI ; Ji Ye JUNG ; Se Kyu KIM ; Joon CHANG ; Ji Hye PARK ; Seon Cheol PARK
Tuberculosis and Respiratory Diseases 2013;75(5):214-217
Treatment of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is difficult because the mortality rate after surgery or chemotherapy is high for these patients. Spontaneous regression of cancer is rare, especially in lung cancer. A 62-year-old man, previously diagnosed with IPF, presented with stage IIIC (T2N3M0) non-small cell lung cancer. About 4 months later, spontaneous regression of the primary tumor was observed without treatment. To the best of our knowledge, this is the first report of spontaneous regression of lung cancer in a patient with IPF.
Carcinoma, Non-Small-Cell Lung*
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Drug Therapy
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Fibrosis
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Humans
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Idiopathic Pulmonary Fibrosis*
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Lung Neoplasms
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Middle Aged
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Mortality
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Neoplasm Regression, Spontaneous
4.Research Progress on Pathogenic Mechanism and Potential Therapeutic Drugs of Idiopathic Pulmonary Fibrosis Complicated with Non-small Cell Lung Cancer.
Ting XIAO ; Jiali BAO ; Xiangning LIU ; Hui HUANG ; Honggang ZHOU
Chinese Journal of Lung Cancer 2022;25(10):756-763
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrous interstitial lung disease of unknown etiology. IPF is also considered to be among the independent risk factors for lung cancer, increasing the risk of lung cancer by 7% and 20%. The incidence of IPF complicated with lung cancer, especially non-small cell lung cancer (NSCLC), is increasing gradually, but there is no consensus on unified management and treatment. IPF and NSCLC have similar pathological features. Both appear in the surrounding area of the lung. In pathients with IPF complicated with NSCLC, NSCLC often develops from the honeycomb region of IPF, but the mechanism of NSCLC induced by IPF remains unclear. In addition, IPF and NSCLC have similar genetic, molecular and cellular processes and common signal transduction pathways. The universal signal pathways targeting IPF and NSCLC will become potential therapeutic drugs for IPF complicated with NSCLC. This article examines the main molecular mechanisms involved in IPF and NSCLC and the research progress of drugs under development targeting these signal pathways.
.
Humans
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Carcinoma, Non-Small-Cell Lung/genetics*
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Idiopathic Pulmonary Fibrosis/drug therapy*
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Lung Neoplasms/genetics*
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Lung/pathology*
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Signal Transduction
5.Advances in understanding of idiopathic pulmonary fibrosis.
Chinese Medical Journal 2009;122(7):844-857
Adrenal Cortex Hormones
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therapeutic use
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Animals
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Anticoagulants
;
therapeutic use
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Antioxidants
;
therapeutic use
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Humans
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Idiopathic Pulmonary Fibrosis
;
diagnosis
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drug therapy
;
pathology
;
therapy
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Immunologic Factors
;
therapeutic use
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Lung Transplantation
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Pyridones
;
therapeutic use
6.Study on treatment effect and mechanism of Hirsutella sinensis mycelium in idiopathic pulmonary fibrosis in rats.
Qi-Yang SHOU ; Hui-Ying FU ; Li-Zong ZHANG ; Yue-Qin CAI ; Fang-Ming CHEN ; Min-Li CHEN
China Journal of Chinese Materia Medica 2012;37(23):3618-3623
OBJECTIVETo study and discuss the effect and mechanism of Hirsutella sinensis mycelium (HSM) on idiopathic pulmonary fibrosis in rats.
METHODForty Wistar rats were divided into five groups: the normal control group, the model control group, the high-dose group (1.0 g x kg(-1) HSM), the low-dose group (0.5 g x kg(-1) HSM), and the positive control group (10 mg x kg(-1) hydrocortisone). In addition to rats in the normal control group, the pulmonary fibrosis model was established by injecting 5 mg x kg(-1) bleomycin into rat tracheas for consecutively 28 days, in order to observe their lung function, lung tissue hydroxyproline, cytokines and pathology.
RESULTAfter rats were administered with HSM, 0.5 g x kg(-1) and 1.0 g x kg(-1) HSM could significantly decrease lung index and hydroxyproline content (P<0.01), while notably improving pulmonary function, alveolus inflammation and fibrosis degree (P<0.05, P<0.01); 1.0 g x kg(-1) HSM could decrease significantly protein expressions of TNF-alpha, IL-1beta and TGF-beta1 in lung tissues, while increasing significantly protein expressions of IFN-gamma (P<0.05).
CONCLUSIONHSM have better effect in treating idiopathic pulmonary fibrosis in rats. Its treatment effect and mechanism are related to the regulation of TNF-alpha, IL-1beta and TGF-beta1 and IFN-gamma imbalance.
Animals ; Disease Models, Animal ; Humans ; Hypocreales ; chemistry ; growth & development ; Idiopathic Pulmonary Fibrosis ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Mycelium ; chemistry ; growth & development ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; genetics ; metabolism
7.Effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis in rats and its mechanism.
Sheng TIAN ; Wen Fu CAO ; Yong Yue ZHANG ; Qing WU
Chinese Journal of Applied Physiology 2019;35(2):101-106
OBJECTIVE:
To investigate the effects of Yiqi Huayu Hutan decoction on pulmonary fibrosis of rats which induced by bleomycin.
METHODS:
The rat model of pulmonary fibrosis was induced by intratracheal injection of bleomycin hydrochloride (5 mg/kg). Sixty SD rats were randomly divided into the normal group (group N), the model group (group M), the positive control group (group Y), group of low concentration (group LC), group of medium concentration (group MC) and group of high concentration of Yiqi Huayu Hutan decoction (group HC). After 4 weeks, the experimental groups were treated with low concentration decoction, medium concentration decoction and high concentration decoction respectively, and the Y group was treated with hydrocortisone acetate, the Group N and group M were treated with saline by intragastric administration. Twelve weeks later, rats were killed and the pathomorphism of pulmonary tissues of each group was observed by HE staining and Masson staining. Further, the expressions of transforming growth factor-β1(TGF-β1), Snail1, E-cadherin and Fibronectin in pulmonary tissues of each group were detected by qTR-PCR and Western blot.
RESULTS:
Compared with the model group, the collagen sediment in the interstitial was reduced in the experimental groups, especially in the group of medium concentration, which was observed by HE staining and Masson staining .Compared with the model group, the expressions of TGF-β1, Snail1 and Fibronectin protein in pulmonary tissues of the treatment groups were decreased in the experimental group, especially in the group of medium concentration, which were detected by qRT-PCR and Western blot.
CONCLUSION
Yiqi Huayu Hutan decoction can significantly improve the pulmonary fibrosis which is induced by bleomycin, and the mechanism is related to the inhibition of the expression of TGF-β/Snail pathway of transcription TGF-β1.
Animals
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Bleomycin
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Cadherins
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metabolism
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Drugs, Chinese Herbal
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pharmacology
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Fibronectins
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metabolism
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Idiopathic Pulmonary Fibrosis
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chemically induced
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drug therapy
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Lung
;
metabolism
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pathology
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Snail Family Transcription Factors
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metabolism
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Transforming Growth Factor beta1
;
metabolism
8.Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study.
Yiwen ZHANG ; Kongsheng SHENG ; Feifeng SONG ; Zongfu PAN ; Xiaozhou ZOU ; Yujia LIU ; Ping HUANG
Journal of Zhejiang University. Medical sciences 2022;51(1):53-61
To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Animals
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Bleomycin/pharmacology*
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Cytokines
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Drugs, Chinese Herbal
;
Glutathione
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Idiopathic Pulmonary Fibrosis/drug therapy*
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Inflammation
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Lung/pathology*
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Male
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Network Pharmacology
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Rats
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Rats, Sprague-Dawley
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Superoxide Dismutase/metabolism*
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Transforming Growth Factor beta/pharmacology*
9.Mycobacterial Pulmonary Infections in Patients with Idiopathic Pulmonary Fibrosis.
Sung Woo PARK ; Jin Woo SONG ; Tae Sun SHIM ; Moo Suk PARK ; Hong Lyeol LEE ; Soo Taek UH ; Choon Sik PARK ; Dong Soon KIM
Journal of Korean Medical Science 2012;27(8):896-900
Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.
Aged
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Cohort Studies
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Female
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Follow-Up Studies
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Hospitals, University
;
Humans
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Idiopathic Pulmonary Fibrosis/complications/*diagnosis/pathology
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Immunosuppressive Agents/therapeutic use
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Male
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Middle Aged
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Mycobacterium Infections/complications/*diagnosis/drug therapy
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Mycobacterium Infections, Nontuberculous/*diagnosis/drug therapy/pathology
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Retrospective Studies
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Tuberculosis, Pulmonary/complications/*diagnosis/pathology