RESUMEN
Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Fibrosis Pulmonar Idiopática , Neoplasias Pulmonares , Humanos , Femenino , Masculino , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/diagnóstico , Programas Nacionales de Salud , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung fibrosis of unknown aetiology. Epidemiological studies have suggested that IPF progression may negatively affect nutritional status. Weight loss during antifibrotic therapy is also frequently encountered. The association of nutritional status and outcome has not been fully evaluated in IPF patients. METHODS: This retrospective multicohort study assessed nutritional status of 301 IPF patients receiving antifibrotic therapy (Hamamatsu cohort, n = 151; Seirei cohort, n = 150). Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). The GNRI was calculated based on body mass index and serum albumin. The relationship between nutritional status and tolerability of antifibrotic therapy as well as mortality was explored. RESULTS: Of 301 patients, 113 (37.5%) had malnutrition-related risk (GNRI < 98). Patients with malnutrition-related risk were older, had increased exacerbations and worse pulmonary function than those without a GNRI status <98. Malnutrition-related risk was associated with a higher incidence of discontinuation of antifibrotic therapy, particulary due to gastrointestinal disturbances. IPF patients with malnutrition-related risk (GNRI < 98) had shorter survival than those without such risk (median survival: 25.9 vs. 41.1 months, p < 0.001). In multivariate analysis, malnutrition-related risk was a prognostic indicator of antifibrotic therapy discontinuation and mortality, independent of age, sex, forced vital capacity, or gender-age-physiology index. CONCLUSION: Nutritional status has significant effects on the treatment and outcome in patients with IPF. Assessment of nutritional status may provide important information for managing patients with IPF.
Asunto(s)
Fibrosis Pulmonar Idiopática , Desnutrición , Humanos , Anciano , Evaluación Nutricional , Estudios Retrospectivos , Estado Nutricional , Desnutrición/complicaciones , Desnutrición/epidemiología , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Evaluación Geriátrica , Factores de RiesgoRESUMEN
INTRODUCTION: With dissatisfaction of western medicine, traditional Chinese medicine becomes alternative treatment for idiopathic pulmonary fibrosis patients. The common syndrome of idiopathic pulmonary fibrosis (IPF) is qi and yin deficiency syndrome. The prescription, Modified Maimendong Decoction (MMD), is usually used for IPF patients with qi and yin deficiency syndrome. However, there is no convinced evidence for the efficacy and safety of MMD to treat IPF. METHODS: A double-blind, placebo-controlled, randomized clinical trial was put forward by us. After a 1-day run-in period, 60 eligible patients will be included in the study. These subjects will be allocated to the experiment group or control group in a 1:1 ratio. Patients in the experiment group will take MMD plus Pirfenidone capsule. At the same time, patients in the control group will receive a matched placebo plus Pirfenidone capsule. All subjects will receive 24 weeks of treatment and follow-up period. The primary outcomes are the mean change from the baseline in forced vital capacity and times of acute exacerbations at week 4, 12, 24. Secondary outcomes are the mean change from baseline in the St. George's respiratory questionnaire total score, forced expiratory volume in 1 second percentage/forced vital capacity, diffusing capacity of Carbon monoxide, brain natriuretic peptide, and curative effect of traditional Chinese medicine syndrome at week 4, 12, and 24. Any side effects of the treatment will be recorded. DISCUSSION: The results of this trial will provide the evidence for the effect of MMD in patients with idiopathic pulmonary fibrosis.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Qi , Deficiencia Yin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacos , Deficiencia Yin/etiología , Adulto JovenRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and hidden onset, which causes major health problems worldwide. Cough is a typical manifestation of IPF, which is usually characterized by cough without phlegm, and seriously affects the quality of life (QOL) of patients. At present, the treatment of IPF is mainly focused on prolonging survival time and improving lung function, such as pirfenidone, nintedanib, and N-acetylcysteine (NAC), but lack of effective measures to improve the QOL. Chinese herbal medicines (CHMs) is widely used in the clinical treatment of IPF. The adjuvant treatment of CHMs can effectively reduce the clinical symptoms of patients. Therefore, we designed this study to evaluate the role of CHMs in the treatment of cough in IPF. METHOD: This systematic review and meta-analysis will extract all randomized controlled trials (RCTs) related to the treatment of IPF from the following electronic database without date or language restrictions: PubMed, EMBASE, Cochrane CENTRAL, CNKI, VIP, CBM, and Wanfang database. The primary outcomes will be cough frequency and QOL, while secondary outcomes will include safety events. The methodologic quality of RCTs will be assessed using the Cochrane risk assessment tool. The I test will be used to identify the extent of heterogeneity, and funnel plot analysis will be used to test the publication deviation (the number of studies included >10). We will use RevMan5.3 software for data synthesis and analysis. RESULT: This review evaluates the efficacy and safety of CHMs in combination therapy on cough frequency, the quality of life, adverse reactions and safety incidents in patients with IPF. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of CHMs in combination with conventional therapy in treatment of cough in IPF. OSF REGISTRATION DOI: 10.17605/OSF.IO/JKQYV.
Asunto(s)
Tos/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Tos/etiología , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Resultado del Tratamiento , Metaanálisis como AsuntoRESUMEN
OBJECTIVE: To investigate the therapeutic effect of combined application of Wuweizi (Schisandrae Chinensis Fructus) and dexamethasone in rats with idiopathic pulmonary fibrosis (IPF) and the possible protective effect of Wuweizi against dexamethasone-induced glucocorticoid osteoporosis (GIOP). METHODS: There were five groups in this study, including the sham operation group, model group, Wuweizi group, dexamethasone group, and the combination group. A rat IPF model was made by the endotracheal injection of bleomycin. After modeling, rats were given drug interventions for 7 and 28 days. Rats were sacrificed for pathological morphology examination of the bone and lung and quantitative determination of biochemical markers of bone metabolism and angiogenesis-related cytokine to observe therapeutic efficacy on the 7th and 28th day. ELISA was used for the quantitative determination of tartrate-resistant acid phosphatase (TRACP), bone alkaline phosphatase (BALP), hypoxia-inducible factor (HIF-1α), platelet-derived growth factor (PDGF), pigment epithelium-derived factor (PEDF), and endostatin in serum. The concentrations of calcium (Ca) and phosphorus (P) were detected with the automatic biochemical analyzer. RESULTS: After drug interventions for 7 and 28 days, alveolitis and pulmonary fibrosis in treatment groups showed significant improvement compared with those in the model group (P < 0.05). Bone histopathological figures showed severely damaged trabecular bone and bone marrow cavity in the dexamethasone group, but it was significantly alleviated in the combination group. The concentrations of BALP and Ca in the combination group were significantly higher than those in the dexamethasone group after treatment, while the concentrations of TRACP and P were lower than those in the dexamethasone group (P < 0.05). Bone histopathological figures showed severely damaged trabecular bone and bone marrow cavity in the dexamethasone group, but it was significantly alleviated in the combination group. The concentrations of BALP and Ca in the combination group were significantly higher than those in the dexamethasone group after treatment, while the concentrations of TRACP and P were lower than those in the dexamethasone group (α), platelet-derived growth factor (PDGF), pigment epithelium-derived factor (PEDF), and endostatin in serum. The concentrations of calcium (Ca) and phosphorus (P) were detected with the automatic biochemical analyzer. P < 0.05). Bone histopathological figures showed severely damaged trabecular bone and bone marrow cavity in the dexamethasone group, but it was significantly alleviated in the combination group. The concentrations of BALP and Ca in the combination group were significantly higher than those in the dexamethasone group after treatment, while the concentrations of TRACP and P were lower than those in the dexamethasone group (P < 0.05). Bone histopathological figures showed severely damaged trabecular bone and bone marrow cavity in the dexamethasone group, but it was significantly alleviated in the combination group. The concentrations of BALP and Ca in the combination group were significantly higher than those in the dexamethasone group after treatment, while the concentrations of TRACP and P were lower than those in the dexamethasone group (α), platelet-derived growth factor (PDGF), pigment epithelium-derived factor (PEDF), and endostatin in serum. The concentrations of calcium (Ca) and phosphorus (P) were detected with the automatic biochemical analyzer. CONCLUSIONS: The combination therapy of Wuweizi and dexamethasone effectively treated IPF rats by regulating angiogenesis, meanwhile distinctly alleviating dexamethasone-induced GIOP.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Glucocorticoides/uso terapéutico , Fibrosis Pulmonar Idiopática/complicaciones , Osteoporosis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Schisandra/química , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Bleomicina/efectos adversos , Médula Ósea/metabolismo , Médula Ósea/patología , Huesos/patología , Hueso Esponjoso/patología , Dexametasona , Modelos Animales de Enfermedad , Endostatinas/metabolismo , Proteínas del Ojo/metabolismo , Fibrosis Pulmonar Idiopática/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Factores de Crecimiento Nervioso/metabolismo , Osteoporosis/inducido químicamente , Osteoporosis/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratas , Ratas Wistar , Serpinas/metabolismo , Fosfatasa Ácida TartratorresistenteRESUMEN
Scleroderma-associated pulmonary fibrosis (SSc-PF) and idiopathic pulmonary fibrosis (IPF) are two of many chronic fibroproliferative diseases that are responsible for nearly 45% of all deaths in developed countries. While sharing several pathobiological characteristics, they also have very distinct features. Currently no effective anti-fibrotic treatments exist that can halt the progression of PF or reverse it. Our goal is to uncover potential gene targets for the development of anti-fibrotic therapies efficacious in both diseases, and those specific to SSc-PF, by identifying universal pathways and molecules driving fibrosis in SSc-PF and IPF tissues as well as those unique to SSc-PF. Using DNA microarray data, a meta-analysis of the differentially expressed (DE) genes in SSc-PF and IPF lung tissues (diseased vs. normal) was performed followed by a full systems level analysis of the common and unique transcriptomic signatures obtained. Protein-protein interaction networks were generated to identify hub proteins and explore the data using the centrality principle. Our results suggest that therapeutic strategies targeting IL6 trans-signaling, IGFBP2, IGFL2, and the coagulation cascade may be efficacious in both SSc-PF and IPF. Further, our data suggest that the expression of matrikine-producing collagens is also perturbed in PF. Lastly, an overall perturbation of bioenergetics, specifically between glycolysis and fatty acid metabolism, was uncovered in SSc-PF. Our findings provide insights into potential targets for the development of anti-fibrotic therapies that could be effective in both IPF and SSc-PF.
Asunto(s)
Basidiomycota/inmunología , Fibrosis Pulmonar Idiopática/inmunología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interleucina-6/metabolismo , Pulmón/inmunología , Micosis/inmunología , Progresión de la Enfermedad , Metabolismo Energético , Homeostasis , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Micosis/complicaciones , Análisis de Secuencia por Matrices de Oligonucleótidos , Transducción de Señal , Receptores Toll-Like/metabolismo , TranscriptomaRESUMEN
No disponible
Asunto(s)
Humanos , Trastornos Nutricionales , Enfermedades Musculares/complicaciones , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico , Estrés Oxidativo , Neumonía/complicaciones , Estado Nutricional , Anabolizantes , Suplementos DietéticosRESUMEN
INTRODUCTION: There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF. Areas covered: We advance the hypothesis that modulation of vitamin K-dependent MGP activation in IPF patients by either vitamin K antagonism or administration may result in acceleration and deceleration of fibrosis progression, respectively. Furthermore, shortfall in vitamin K could be suspected in IPF based on the high prevalence of certain co-morbidities, such as vascular calcification and lung cancer. Expert commentary: We hypothesize that vitamin K status is reduced in IPF patients. This, in combination with studies suggesting that vitamin K may play a role in lung fibrosis pathogenesis, would provide a rationale for conducting a clinical trial assessing the potential mitigating effects of vitamin K administration on progression of lung fibrosis, prevention of co-morbidities and mortality in IPF.
Asunto(s)
Antifibrinolíticos/farmacología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Vitamina K/farmacología , Proteínas de Unión al Calcio/efectos de los fármacos , Suplementos Dietéticos , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/efectos de los fármacos , Fibrosis , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/patología , Neoplasias Pulmonares/epidemiología , Calcificación Vascular/epidemiología , Proteína Gla de la MatrizRESUMEN
RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.
Asunto(s)
Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/sangre , Dermatomiositis/complicaciones , Fibrosis Pulmonar Idiopática/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Miositis/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/mortalidad , Dermatomiositis/inmunología , Dermatomiositis/mortalidad , Femenino , Humanos , Oxigenoterapia Hiperbárica/métodos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Mortalidad , Miositis/mortalidad , Estudios Observacionales como Asunto , Evaluación de Resultado en la Atención de Salud , Pronóstico , ARN/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often suffer from progressive worsening of dyspnea and lung function. Although 2 drugs are now available for IPF treatment, many gaps are still to be filled. Evidences suggest that there may be some beneficial effect of acupuncture on pulmonary diseases. This review aims to systematically determine the efficacy and safety of acupuncture for treating IPF. METHODS: The following 8 databases will be searched from their inception to March 20, 2017: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Data. Randomized controlled trials (RCTs) of acupuncture for IPF without restriction of publication status will be included. Two review authors will independently undertake study selection, extraction of data, and assessment of study quality. Meta-analysis will be conducted after screening of studies if possible. Dichotomous data will be analyzed using odds ratio (OR), and continuous data mean difference (MD). Statistical analysis will be conducted using Review Manager (RevMan) software. RESULTS: This systematic review will provide a detailed summary of the current evidences related to the efficacy and safety of acupuncture in improving breathlessness, exercise limitation, health status impairment of patients with IPF. CONCLUSION: This evidence may be useful to clinicians, patients, and health policy-makers with regard to the use of acupuncture in IPF treatment. ETHICS AND DISSEMINATION: This systematic review will provide up-to-date information on acupuncture for IPF. This review does not require ethical approval and will be disseminated electronically through a peer-reviewed publication or conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO 2017:CRD42017059848.