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Pulmonary fibrosis as a complication of COVID-19 has been widely reported. Several studies have reported prolonged respiratory symptoms in significant numbers of people lasting months after the acute episode of COVID-19 infection. Nintedanib is being explored as a potential therapeutic agent in the treatment of post-COVID-19 pulmonary fibrosis. However, the exact role of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis is not clear. Objectives of this article are to perform a scoping review of the literature on the mechanism of pulmonary fibrosis, role of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis, and emerging treatments in the treatment of post-COVID-19 pulmonary fibrosis. The United States Clinical Trials Registry and Clinical Trials Registry of India were searched to identify studies evaluating the role of nintedanib in post-COVID-19 pulmonary fibrosis. Embase and PubMed databases were searched and relevant articles were reviewed. Over all 26 article in PubMed and 67 articles in Embase were reviewed. There are several ongoing studies evaluating the safety and efficacy of nintedanib in the treatment of post-COVID-19 pulmonary fibrosis. Some studies have shown promising results for nintedanib while results from several large ongoing clinical trials are awaited. Use of nintedanib in post-COVID-19 pulmonary fibrosis is promising based on the preliminary evidence from the present studies. However, the current evidence is limited and more evidence is awaited from the ongoing randomized clinical trials evaluating the safety and efficacy of nintedanib in the management of post-COVID-19 pulmonary fibrosis.
ABSTRACT
Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.
Subject(s)
Animals , Rats , Rats, Sprague-Dawley , Paraquat , Transforming Growth Factor beta1 , Receptor, Platelet-Derived Growth Factor alpha , Vascular Endothelial Growth Factor A , Acute Lung Injury/drug therapyABSTRACT
Se presenta un estudio observacional compasivo de seguimiento de 20 pacientes portadores de Fibrosis Pulmonar Idiopática tratados con Nintedanib, que muestra que Nintedanib es un medicamento en general bien tolerado, sin efectos adversos serios, que otorga una sobrevida más prolongada que la que cabría esperar en pacientes con esta enfermedad.
A compassionate observational follow-up study of 20 patients with Idiopathic Pulmonary Fibrosis treated with Nintedanib is presented, showing that Nintedanib is a generally well-tolerated drug, with no serious adverse effects, that grants a longer survival in real-life patients.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Protein Kinase Inhibitors/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/therapeutic use , Survival Analysis , Vital Capacity , Retrospective Studies , Follow-Up Studies , Protein Kinase Inhibitors/adverse effects , Idiopathic Pulmonary Fibrosis/physiopathology , Indoles/adverse effectsABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a condition that has been described as alveolar collapse and thickening, which correlate with dysregulated surfactant production and injury to type 2 alveolar cells. As resolution of chest computed tomography has improved, especially with the development of high-resolution computed tomography (HRCT), the diagnostic measures adopted for pulmonary fibrosis has gradually shifted from biopsy to HRCT. This shift towards HRCT has aided in diagnostic evaluation and detection of the therapeutic and adverse effects of drugs for pulmonary fibrosis. Further, after the endpoint was changed to forced vital capacity, significant improvements are being observed in clinical trial outcomes. Currently active clinical trials are replacing lung biopsy with HRCT. In 2014, pirfenidone and nintedanib gained approval for tandem use in patients with IPF. These drugs were found to not only reduce the progression of pulmonary fibrosis, but also the acute exacerbation and mortality associated with the condition. These drugs showed consistent benefits regardless of the severity of patients' symptoms. Additionally, both nintedanib and pirfenidone were found to be effective in patients with advanced pulmonary fibrosis that was not classified as IPF. Nintedanib has been shown to reduce forced vital capacity in interstitial lung diseases associated with systemic sclerosis. In the next three to five years, many changes in treatment are expected, not only for IPF, but also for the entire spectrum of pulmonary fibrotic diseases. Pirfenidone and nintedanib are now considered standard treatments for IPF and few other fibrotic lung diseases. Clinicians treating patients with pulmonary fibrosis should keep themselves updated with the results of clinical trials that are currently underway.
Subject(s)
Humans , Biopsy , Idiopathic Pulmonary Fibrosis , Lung , Lung Diseases , Lung Diseases, Interstitial , Mortality , Pulmonary Fibrosis , Scleroderma, Systemic , Thorax , Vital CapacityABSTRACT
Pulmonary fibrosis is the terminal manifestation of a variety of interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of the chronic, progressive, fibrotic lung disease with high incidence and poor prognosis. Nintedanib and pirfenidone are currently marketed anti-pulmonary fibrosis drugs, and their efficacy and safety are recognized in patients with IPF. This article reviews the targets and clinical trials of the two drugs, and provides a basis for the expansion of indications for anti-pulmonary fibrosis drugs.
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The aim of this study was to determine whether the anti-fibrotic effects of pirfenidone (Pirf) and nintedanib (Nint) associated with the regulation of the alveolar epithelial type 2 cell (AEC II)-mediated lung alveolar regeneration in single- and multiple-dosage animal models of bleomycin-induced pulmonary fibrosis. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. We found that the Pirf and Nint treatment of mice decreased the lung weight index, inflammation level, and the content of hydroxyproline compared with nontreated fibrotic mice in the single dosage model. Also, Pirf and Nint increased the oxygen saturation level and improved the lung functions in fibrotic mice, indicating that both drugs have anti-fibrotic effects in this model. However, the anti-fibrotic effects of Pirf and Nint were not observed in the multiple-dosage model. Further studies showed that Pirf and Nint decreased the expression of β-catenin, Axin2, c-Myc, Cyclin D1, and inhibited the Wnt/β-catenin signaling pathway, suggesting that Pirf and Nint did not produce anti-fibrotic effects in the multiple-dosage model due to their inhibiting the Wnt/β-catenin pathway and suppressing the stemness of AEC II, namely, suppressing AEC II-mediated lung alveolar regeneration.
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La historia natural de la fibrosis pulmonar idiopática (FPI) es heterogénea e impredecible. Aunque el curso de la enfermedad, sin tratamiento, es inevitablemente progresiva y de mal pronóstico. Los tratamientos históricos han variado desde corticosteroides e inmunosupresores (azatioprina, ciclofosfamida), hasta colchicina y N-acetilcisteína. En las últimas décadas se han realizado múltiples ensayos terapéuticos fallidos. Sin embargo, desde el año 2014 en los Estados Unidos, Europa y otros países, dos drogas, denominadas terapia antifibrótica o modificadoras de la enfermedad, están aprobadas para el tratamiento de la FPI: nintedanib y pirfenidona. La terapia antifibrótica, tiene como objetivo enlentecer en hasta 50% la declinación de la función pulmonar en pacientes con FPI.
The natural history of idiopathic pulmonary fibrosis (IPF) is heterogeneous and unpredictable. The course of the disease without treatment, is inevitably progressive, with a poor prognosis. Historical treatments have varied from corticosteroids and immunosuppressants (azathioprine, cyclophosphamide), to colchicine and N-acetylcysteine. In the last decades, multiple failed therapeutic trials have been carried out. However, since 2014 in the United States, Europe and other countries, two drugs, called antifibrotic therapy or disease modifiers, are approved for the treatment of IPF: nintedanib and pirfenidone. The purpose of antifibrotic therapy is to slow down the decline in lung function in patients with IPF up to 50%.
Subject(s)
Humans , Pyridones/therapeutic use , Idiopathic Pulmonary Fibrosis/drug therapy , Immunosuppressive Agents/therapeutic use , Indoles/therapeutic useABSTRACT
OBJECTIVE: To systematically review the efficacy and safety of Nintedanib in patient with idiopathic pulmonary fibrosis.METHODS: We search systematically for randomized controlled trials and cohort study of Nintedanib for idiopathic pulmonary fibrosis patients published between January 1999 and May 2018. The literatures that met all eligibility criteria were selected. The extracted data were analyzed with RevMan 5.3. RESULTS: A total of 4 random control trials(RCT) and one cohort study were included. Nintedanib, as compared with placebo, reduced the decline in FVC and the predicted FVC% from baseline by 130 mL/yr or 3.84% of the mean value respectively. It also significantly reduced relative the risk of FVC%pred≥10% or FVE decline≥200 mL(RR 0.78, 95% confidence interval(CI) 0.67 to 0.90, P=0.0006), the hazard ratio(HR) of first acute exacerbation(HR with Nintedanib, 0.53; 95%CI 0.33-0.86;P=0.02), all-cause mortality(HR in the Nintedanib group, 0.70; 95%CI 0.45-1.08; P=0.11) and respiratory mortality(HR in the Nintedanib group, 0.63; 95%CI 0.37-1.10; P=0.11) in IPF patients. The Nintedanib group had a higher rate of gastrointestinal adverse events and a lower rate of cardiovascular events compared to the placebo group(P=0.02). CONCLUSION: Nintedanib delays disease progression in patients with IPF. Nintedanib is generally well tolerated, and the mild gastrointestinal adverse events are more common.
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Pirfenidone and nintadanib are two new anti-fibrotic drugs that have been shown to reduce the decline of lung function in patients with idiopathic pulmonary fibrosis (IPF) in multiple clinical trials,and have become first-line drugs for the treatment of IPF.However there are lack of references for how to choose between these two drugs. This article collected the latest research literatures related to pirfenidone or nintedanib,and summarized pharmacokinetics, pharmacological mechanism, clinical trials and safety profile of pirfenidone and nintedanib, so as to provide reference for clinical drug use. Evidences show both pirfenidone and nintedanib can reduce the decline of lung function and delay disease progression in mild-to-moderte IPF patients, and may have similar effects on severe IPF patients. There are large differences in pharmacological mechanisms, pharmacokinetics, and adverse events between these two new antifibrotic drugs. However, in terms of efficacy, there is no clear evidence to show which drug is better. Clinicians choosing drug should base on pharmacokinetic characteristics and adverse events between these two drugs.
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Aim To compare the mechanism of action of currently marketed pulmonary fibrosis drugs at the cellular level by evaluating the inhibitory effects of pirfenidone and nintedanib on the proliferation, migration and activation of human embryonic lung fibroblast HFL1. Methods The inhibitory effects of pirfenidone and nintedanib on TGF-β1/PDGF-induced HFL1 proliferation, migration and activation were evaluation of by MTT, scratch test,Q-PCR and Western blot. Results MTT, scratch test results showed that both pirfenidone and nintedanib could inhibit TGF-β1-induced fibroblast proliferation and migration, in which nintedanib had a higher titer than pirfenidone. In anti-activation experiments, both pirfenidone and nintedanib inhibited the expression of fibroblast activation markers mRNA and protein, and both inhibited the phosphorylation of Smad3 and inhibited the activation of TGF-β/ Smad3 signaling pathway. Nintedanib had a stronger inhibitory effect on TGF-β/Smad3 signaling pathway, which exerted 51 % inhibitory rate on Smad3 phosphorylation compared with 13% inhibitory rate of pirfenidone. Conclusions Both pirfenidone and nintedanib can inhibit the proliferation, migration and activation of myofibroblasts, where nintedanib has a higher inhibitory potency than pirfenidone does, and the inhibition of TGF-β/Smad3 signaling pathway is stronger.
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Objetivo: O objetivo do estudo foi avaliar o custo-efetividade de pirfenidona em comparação ao nintedanibe no tratamento de pacientes com fibrose pulmonar idiopática (FPI) na perspectiva do sistema suplementar de saúde. Métodos: O modelo foi realizado considerando um horizonte de tempo lifetime. O principal desfecho da análise foram os anos de vida ganhos. Os custos de aquisição de medicamentos foram obtidos por meio das listas oficiais de preço, considerando o ICMS 18%. Os demais custos relacionados ao manejo da doença, transplante de pulmão e custo de final de vida foram calculados por um microcusteio baseado em opinião de especialistas e listas de preços de procedimentos. Os dados de eficácia foram extraídos dos estudos CAPACITY 1, 2 e ASCEND, e extrapolados por meio de uma distribuição paramétrica Weibull. Os dados referentes ao nintedanibe foram extrapolados por uma comparação indireta. Resultados: Os custos totais de pirfenidona e de nintedanibe foram R$ 319.689 e R$ 522.887, respectivamente. Os anos de vida salvos resultantes foram 6,536 para pirfenidona e 5,726 para nintedanibe, resultando em um valor incremental de 0,810. Conclusão: Dessa maneira, a partir dos valores incrementais de custos e efetividade, a pirfenidona demonstrou ser uma opção terapêutica dominante quando comparada ao nintedanibe.
Objective: The objective of the study was to evaluate the cost-effectiveness of pirfenidone in comparison to nintedanib in the treatment of patients with idiopathic pulmonary fibrosis (IPF) under the Brazilian private healthcare system perspective. Methods: The model was performed considering a lifetime time horizon. The main outcome was life years (LY) gained. The drug acquisition costs were obtained from official price lists, considering taxes of 18%. The other related costs (disease management, lung transplantation and end-of-life costs) were calculated by a micro-costing based on specialists' opinion and procedures price lists, costs are presented in 2017 (R$). The efficacy data was extracted from CAPACITY 1, 2 and ASCEND studies, and extrapolated by the parametric distribution Weibull. The data related to nintedanib was extrapolated by an indirect comparison. Results: The total costs of pirfenidone and nintedanibe were R$ 319,689 and R$ 522,887, respectively. The LY results were 6.536 for pirfenidone and 5.726 for nintedanib, resulting in an incremental value of 0.810. Conclusion: Therefore, pirfenidone demonstrated to be a dominant therapeutic option when compared to nintedanib, based on incremental values of cost and effectiveness.
Subject(s)
Humans , Cost-Benefit Analysis , Supplemental Health , Idiopathic Pulmonary FibrosisABSTRACT
Introducción: La Fibrosis Pulmonar Idiopática (FPI) es una enfermedad pulmonar difusa (EPD) de etiología desconocida, crónica y progresiva. Ocurre en adultos mayores, se encuentra limitada a los pulmones y se asocia con la patente anatomopatológica y/o tomográfica de neumonía intersticial usual (NIU). El curso de la enfermedad es progresivo y se asocia con una supervivencia media a 5 años del 20%. Objetivos: Conocer las características clínicas y de función pulmonar del grupo de pacientes con FPI ingresados al programa de uso compasivo (NPU); conocer el perfil de seguridad reportado con nintedanib. Materiales y Métodos: Estudio retrospectivo descriptivo transversal en donde se incluyeron 54 pacientes ingresados al programa de NPU desde el 1 de septiembre de 2015 hasta el 10 de agosto de 2016. Los datos se recolectaron de los registros del programa de NPU. Resultados: Cincuenta y cuatro pacientes con FPI fueron incluidos en el programa de NPU, de ellos 47 recibieron nintedanib y se analizaron los datos del total de estos últimos. Treinta y siete (78.72%) eran varones, la edad media al inicio del tratamiento era 67.47 ± 7.85 años y en 9 casos (19.14%) el diagnóstico se estableció mediante biopsia pulmonar. La capacidad vital forzada (CVF) media al inicio del tratamiento era de 65.87 ± 19.23 expresada en porcentaje del valor predictivo; la capacidad de difusión de dióxido de carbono media (DLCO) expresada en porcentaje del valor predictivo era de 38.74 ± 3.09. El tiempo de evolución desde el diagnóstico de FPI hasta el inicio del tratamiento con nintedanib era de 27.17± 27.9 meses (mediana 17). La exposición de la droga promedio hasta el corte era de 9.92 semanas ± 2.15 (mediana: 10 semanas). En 7 casos (31.91%) la CVF era mayor del 80%, en 22 (46.80%) casos entre 50 y 79% y en 10 casos (21.27%) era menor de 49%. En total 7 pacientes (14.89%) presentaron eventos adversos: 5 (10.6%) pacientes presentaron descenso ponderal, 4 (8.51%) diarrea, 2 pacientes presentaron náusea, 1 (2.12%) elevación de las enzimas hepáticas y 1 (2.12%) prurito. En la mayoría de los casos los eventos adversos aparecieron durante las 2 primeras semanas del inicio del tratamiento con nintedanib. En 3 (6.38%) casos fue mandatorio la suspensión del nintedanib definitivamente por eventos adversos y en 4 (8.51%) se debió titular la dosis a 100 mg cada 12 horas. Del total, 6 (12.76%) pacientes fallecieron por progresión de su enfermedad de base. Conclusiones: Al igual que lo reportado por otros grupos, el nintedanib presenta un perfil de seguridad manejable y tolerable. En nuestra serie de 47 pacientes con FPI que recibieron al menos una dosis de nintedanib, el 14.89% presentó algún evento adverso que solo en 3 pacientes (6.38%) motivó la suspensión definitiva del fármaco.
Subject(s)
Therapeutics , Idiopathic Pulmonary FibrosisABSTRACT
Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a diffuse lung disease (DLD) of unknown etiology that is chronic and progressive. It occurs in older adults; it is restricted to the lungs and it is associated with the anatomopathological and/or tomographic pattern of Usual Interstitial Pneumonia (UIP). The evolution of the disease is progressive and it is associated with a mean 5-year survival rate of 20%. Objectives: to identify the clinical and pulmonary function characteristics in the group of patients with IPF included in the Compassionate Use Program (NPU, Named Patient Use); to identify the safety profile reported with nintedanib. Materials and methods: a retrospective, descriptive and cross-sectional study including 54 patients enrolled in the NPU program from September 1st, 2015 to August 10th, 2016. Data were collected from the NPU program records. Results: fifty-four patients with IPF were included in the NPU program, of whom 47 received nintedanib; the data from the latter were analyzed. Thirty-seven (78.72%) were males, with a mean age at the beginning of treatment of 67.47 ± 7.85 years, and in 9 cases (19.14%) the diagnosis was confirmed by lung biopsy. The mean forced vital capacity (FVC) at the beginning of treatment was 65.87±19.23 and it is presented as the percentage of the predictive value; the mean carbon dioxide diffusing capacity (DLCO) presented as the percentage of the predictive value was 38.74 ± 3.09. The time of progression from the diagnosis of IPF to the beginning of the treatment with nintedanib was 27.17± 27.9 months (median 17). Average drug exposure to cut-off point was 9.92 weeks ± 2.15 (median: 10 weeks). In 7 cases (31.91%) the FVC was over 80%, in 22 (46.80%) cases it was between 50 and 79% and in 10 cases (21.27%) it was below 49%. In total, 7 patients (14.89%) exhibited adverse events: Five (10.6%) patients exhibited weight loss, 4 (8.51%) diarrhea, 2 patients had nausea, 1 (2.12%) an increase of the liver enzymes and 1 (2.12%) pruritus. In most cases, the adverse events appeared during the first 2 weeks after beginning the treatment with nintedanib. In 3 (6.38%) cases it was imperative to suspend nintedanib permanently due to the adverse effects and in 4 (8.51%) cases the dose had to be titrated to 100 mg every 12 hours. Out of the total of patients, 6 (12.76%) passed away due to the progression of their underlying disease. Conclusions: such as it was reported by other groups, nintedanib has a manageable and tolerable safety profile. In our series of 47 patients with IPF who received at least one dose of nintedanib, 14.89% had an adverse event that led to the permanent discontinuation of the drug in only 3 patients (6.38%).
Subject(s)
Therapeutics , Idiopathic Pulmonary FibrosisABSTRACT
Objective:To develop an HPLC method for the determination of nintedanib in rabbit plasma and study the pharmacoki-netics of nintedanib in rabbits. Methods:The separation was performed on an Agilent ZORBAX SB-C18 column. A mixture of acetoni-trile-0. 1% trifluoroacetic acid-water (35∶ 20∶ 45) was used as the mobile phase at a flow rate of 1. 0 ml·min-1. The detection wavelength was set at 286 nm. Carbamazepine was used as the internal standard and nintedanib was extracted by ethyl acetate from plasma under basic condition. Totally 6 rabbits were given 20 mg·kg-1 nintedanib with intravenous administration. The blood samples were collected from the auricular vein at different time points after the administration. The concentration of nintedanib in plasma was detected by the HPLC method. The pharmacokinetics parameters were analyzed by DAS program. Results: An excellent linear rela-tionship was obtained within the range of 0. 05-10. 00 μg·ml-1(r=0. 999 8). The intra-day RSD was 5. 55%, 4. 53% and 2. 74%and inter-day RSD was 6. 15%, 5. 45% and 3. 15%, respectively for the three concentrations(0. 10, 2. 50 and 7. 50μg·ml-1), and the relative recovery was (98. 50 ± 5. 47)%, (100. 25 ± 4. 54)% and (99. 94 ± 2. 74)%, respectively. The main pharmacokinetics parameters of nintedanib were as follows: Cmaxwas (3.01 ±0.35) μg·ml-1, t1/2 was (4.38 ±1.53) h and AUC0-t was (11.67 ± 1. 71) μg·h·ml-1 . Conclusion:The method is simple, rapid and accurate, and can be used to determine the nintedanib concentra-tion in rabbit plasma and study its pharmacokinetics. Nintedanib is fitted the first-order elimination kinetics in rabbits.
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La FPI predomina en el sexo masculino, en edades avanzadas, con tos y/o disnea progresivas. Un 5% se presenta como una forma familiar. La tomografía axial computarizada de tórax, fundamental en el diagnóstico, en al menos un 50% hace innecesaria la biopsia. El diagnóstico es conjunto con clínicos, radiólogos y patólogos. La sobrevivencia media es de tres a cinco años desde el diagnóstico. La historia natural es un deterioro progresivo, pero hay formas rápidas y también pueden aparecer exacerbaciones que ensombrecen el pronóstico. Diversas comorbilidades se han descrito como la hipertensión pulmonar, la asociación con enfisema y el reflujo gastroesofágico. Sólo recientemente aparecen fármacos útiles, que son la Pirfenidona y el Nintedanib. El clásico esquema de prednisona, azatriopina y N-acetil cisteina, se ha demostrado ineficaz. Otros recursos que pueden utilizarse como complementos útiles en la enfermedad son el oxígeno, la rehabilitación, las terapias antirreflujo y el manejo sintomático de la tos.
PF appears mainly in aged males, with progressive cough and dyspnea. In 5% of the cases the disease presents as a familial form. CT scan is key in diagnosis of the disease. In no less than 50% biopsy is unnecessary but diagnosis must be made in conjunction with clinician, radiologist and pathologist. Median survival is 3 to 5 years from diagnosis. Natural history is a progressive deterioration but there are fast evolution cases and exacerbation of the disease that make worse the prognosis. Pulmonary hypertension, the association with emphysema and gastroesophageal reflux has been described as comorbidities of the disease. Last year has been published the positive results of therapeuticall trials with two new drugs, Pirfenidone and Nintedanib. The classical regime for IPF with Prednisone, Azathriopine and Acetylcysteine has been showed as useless. Oxygen, Pulmonary rehabilitation, gastroesophageal reflux and cough management are complementary treatment for the disease.