Julio Ancochea

Universidad Autónoma de Madrid, Madrid, Madrid, Spain

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Publications (144)433.78 Total impact

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    ABSTRACT: Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P.aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.
    No preview · Article · Nov 2015 · Expert Review of Anti-infective Therapy
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    ABSTRACT: Problem: In 2008, the prevalence of paediatric asthma in Zambia was unknown and the national treatment guideline was outdated. Approach: We created an international partnership between Zambian clinicians, the Zambian Government and a pharmaceutical company to address shortcomings in asthma treatment. We did two studies, one to estimate prevalence in the capital of Lusaka and one to assess attitudes and practices of patients. Based on the information obtained, we educated health workers and the public. The information from the studies was also used to modernize government policy for paediatric asthma management. Local setting: The health-care system in Zambia is primarily focused on acute care delivery with a focus on infectious diseases. Comprehensive services for noncommunicable diseases are lacking. Asthma management relies on treatment of acute exacerbations instead of disease control. Relevant changes: Seven percent of children surveyed had asthma (255/3911). Of the 120 patients interviewed, most (82/120, 68%) used oral short-acting β2-agonists for symptom control; almost half (59/120, 49%) did not think the symptoms were preventable and 43% (52/120) thought inhalers were addictive. These misconceptions informed broad-based educational programmes. We used a train-the-trainer model to educate health-care workers and ran public awareness campaigns. Access to inhalers was increased and the Zambian standard treatment guideline for paediatric asthma was revised to include steroid inhalers as a control treatment. Lessons learnt: Joint activities were required to change paediatric asthma care in Zambia. Success will depend on local sustainability, and it may be necessary to shift resources to mirror the disease burden.
    Preview · Article · Oct 2015 · Bulletin of the World Health Organisation

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: COPD is a frequent condition ranking within the top three causes of mortality in the Global Burden of Disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations. We analyzed representative samples of adults aged ≥40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Post-BD FEV1/FVC<LLN was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had post-BD FEV1/FVC<LLN but were not previously diagnosed with COPD. Among 30,874 participants with a mean age of 56 yrs, 55.8% were female, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia to 19.0% in Cape Town, SA. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, while 9.7% had post-BD FEV1/FVC<LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, US (50.0%). In multivariate analysis, a greater probability of being underdiagnosed with COPD was associated with male gender, younger age, never and current smoking, lower education, no previous spirometry and less severe airflow limitation. Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Since effective management strategies are available for COPD, spirometry can help to diagnose COPD at a stage when treatment will lead to better outcomes and improved quality of life.
    No preview · Article · May 2015 · Chest
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    ABSTRACT: Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene whose mortality is conditioned by a progressive decline in lung function. Bacterial infections play a key role in this decline. Chronic bacterial infection in CF patients varies over time and the presence of Pseudomonas aeruginosa in sputum is a marker of poor prognosis. P. aeruginosa is eradicated from the airways using inhaled antibiotics administered in various formulations and devices. Antipseudomonal antibiotics have extended the survival of CF patients to 40 years. Tobramycin is a bactericidal aminoglycoside antibiotic with demonstrated activity against gram-negative microorganisms. Initially, the drug was administered as an inhaled parenteral solution. Subsequently, a specific tobramycin inhalation solution was developed. PulmoSphere™ technology enables dry tobramycin powder to be formulated for inhalation (tobramycin inhalation powder) using a small and portable capsule-based breath-activated device (T-326). Chronic colonization by P. aeruginosa is the main indication for aerosol antibiotic therapy. The American Cystic Fibrosis Foundation, European guidelines, and Spanish consensus guidelines provide different recommendations for eradication.
    Preview · Article · Mar 2015 · Therapeutics and Clinical Risk Management
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    ABSTRACT: Introduction: Bronchiectasis (BQ) are the final consequence of many diseases, including asthma is, however this has been inconsiderate. The main objective was to evaluate the presence of BQ by high resolution computerized tomography (HRCT) in a subgroup of patients with asthma using a modified Bhalla score. We compared also whether there were clinical differences between asthmatics who presented or not BQ and clinical variables were associated with modified Bhalla scores. Material and methods: Pulmonary HRCT was performed in patients with asthma during a recruitment period of 2 years, who had the following conditions: three or more respiratory exacerbations per year history of coughing or hemoptysis usual on occasion, asthma longstanding and images suggestive of BQ in the chest radiograph. The HRCT were evaluated by 2 radiologists according to the modified Bhalla score. Results: We observed 48 patients with BQ in 65 studies, 88[%] were cylindrical and bilateral in 62[%]. The more affected were the lower and middle lobes. All patients suffering from gastroesophageal reflux had evident BQ. Patients with BQ showed worse FEV1 (p = 0.04), FVC (p=0.05) and rhinitis more often. The total modified Bhalla score was related to the average percentage of FEV1/FVC value (p=0.01), the number of exacerbations (p = 0.01), and the presence of bacterial colonization (p = 0.01). Conclusions: A high proportion of patients with difficult asthma clinic have BQ. Usually these BQ are bilateral and cylindrical and the patients with BQ present worse respiratory functional state. Bhalla total score correlated with the presence of bacterial colonization and the number of exacerbations.
    No preview · Article · Jan 2015
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    ABSTRACT: Late prognosis of Community-Acquired Pneumonia (CAP) patients is related to cardiovascular events. Persistence of inflammation-related markers, defined by high circulatory levels of interleukin 6 and 10 (IL-6/IL-10), is associated with a higher post-event mortality rate for CAP patients. However, association between these markers and other components of the immune response, and the risk of cardiovascular events, has not been adequately explored. The main objectives of this study are: 1) to quantify the incidence of cardiovascular disease, in the year post-dating their hospital admittance due to CAP and, 2) to describe the distribution patterns of a wide spectrum of inflammatory markers upon admittance to and release from hospital, and to determine their relationship with the incidence of cardiovascular disease.Methods/design: A cohort prospective study. All patients diagnosed and hospitalized with CAP will be candidates for inclusion. The study will take place in the Universitary Hospital "La Princesa", Spain, during two years. Two samples of blood will be taken from each patient: the first upon admittance and the second one prior to release, in order to analyse various immune agents. The main determinants are: pro-adrenomedullin, copeptin, IL-1, IL-6, TNF-alpha, IL-17, IFN-gamma, IL-10 and TGF-beta, E-Selectin, ICAM-1, VCAM-1 and subpopulations of peripheral T lymphocytes (T regulator, Th1 and Th17), together with other clinical and analytical variables. Follow up will start at admittance and finish a year after discharge, registering incidence of death and cardiovascular events. The main objective is to establish the predictive power of different inflammatory markers in the prognosis of CAP, in the short and long term, and their relationship with cardiovascular disease. The level of some inflammatory markers (IL-6/IL-10) has been proposed as a means to differentiate the degree of severity of CAP, but their association with cardiovascular risk is not well established. In this study we aim to define new inflammatory markers associated with cardiovascular disease that could be helpful for the prognosis of CAP patients, by describing the distribution of a wide spectrum of inflammatory mediators and analyzing their association with the incidence of cardiovascular disease and mortality one year after release from hospital.
    Full-text · Article · Dec 2014 · BMC Pulmonary Medicine
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    ABSTRACT: Background Pulmonary exacerbation is one of the main risk factors for death in patients with cystic fibrosis. Several biomarkers have proven useful in the diagnosis and treatment of pulmonary exacerbations, although none has been associated with severity. The objective of the present study was to investigate whether C-reactive protein (CRP) level was associated with the severity of pulmonary exacerbation requiring admission to hospital in patients with cystic fibrosis. Methods We designed a severity index for exacerbations based on 4 clinical parameters and determined whether there was an association between CRP levels and severity of the exacerbation. We also investigated the association between CRP and baseline functional and clinical variables. Results Twenty-seven patients with cystic fibrosis required 62 admissions to hospital. CRP levels were not significantly associated with the severity index, although they were associated with specific patient characteristics: colonization by Pseudomonas aeruginosa, allergic bronchopulmonary aspergillosis, treatment with oral corticosteroids, and number of severe exacerbations treated with intravenous antibiotics during the previous year. Conclusions CRP level is not associated with the severity of pulmonary exacerbations, but it is associated with specific clinical characteristics. This simple scoring system (severity index) could prove very useful for evaluating the severity of exacerbations.
    Preview · Article · Sep 2014 · BMC Pulmonary Medicine
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    ABSTRACT: Aims To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity. Methods A population-based sample of 3,797 subjects aged 40–80 years from the EPI-SCAN study was selected. Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) or obese (BMI≥30.0 kg/m2). Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests. Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded. Results The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8–33.9% vs. 24.3, 95%CI 22.9–25.8; and 44.7%, 95%CI 39.7–49.6% vs. 43.0%, 95%CI 41.3–44.6, respectively; p = 0.020). In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status. Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806–12.736, p = 0.002). Conclusions In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation. Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity.
    Full-text · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: BACKGROUND: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. RESULTS: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.
    Full-text · Article · May 2014 · New England Journal of Medicine
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    ABSTRACT: BACKGROUND: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period. RESULTS: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was -114.7 ml with nintedanib versus -239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and -113.6 ml with nintedanib versus -207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.
    Full-text · Article · May 2014 · New England Journal of Medicine
  • J Ancochea · A Xaubet

    No preview · Article · Apr 2014 · SEMERGEN - Medicina de Familia

  • No preview · Article · Apr 2014 · SEMERGEN - Medicina de Familia
  • J. Ancochea · A. Xaubet

    No preview · Article · Apr 2014 · SEMERGEN - Medicina de Familia

  • No preview · Article · Mar 2014 · SEMERGEN - Medicina de Familia
  • Adolfo Villar · Julio Ancochea · Antonio Xaubet
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    ABSTRACT: Pulmonary Hypertension Posters IISESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: The prevalence of PAH in patients with IPF is not well known. There has been no prospective study to date. The purpose of our study was to know the prevalence of PAH in patients with IPF at any stage of severity IPF patients diagnosed by clinical-radiological or pathological criteria were included. All patients underwent echocardiography. If the systolic pulmonary arterial pressure was greater than 40 mmHg, right heart catheterization was performed. A mean pulmonary artery pressure greater than or equal to 25 mmHg with a wedge pressure less than 16 mmHg was considered diagnostic of PAH. 60 patients (18 women, age at diagnosis 64 years) were included and 56 completed the study protocol. Patient characteristics: FVC 64%, DLCO 41%, 6MWT 357 meters, systolic pulmonary arterial pressure 46 mmHg. 17 patients showed a systolic pulmonary artery pressure greater than 40 mmHg and in 14 of them PAH was confirmed by right heart catheterization with a mean pulmonary arterial pressure of 28.6 mmHg. When comparing various clinical and functional parameters between patients with and without PAH significant differences were seen in FVC, FEV1, DLCO, 6MWT and Functional Class. In a multivariate analysis DLCO was associated with the presence of PAHCONCLUSIONS: PAH is not infrequent in patients with IPF (around 26%).Patients with more severe disease are more likely to develop PAH. A marked decrease in DLCO is independently associated with the presence of PAHCLINICAL IMPLICATIONS: PAH is a devastating disease with prognostic and therapeutic implications in patients with IPF. To know the prevalence and associated factors in very important for a better management of this patients because we now have effective treatments in PAHDISCLOSURE: The following authors have nothing to disclose: Adolfo Villar, Julio Ancochea, Antonio XaubetNo Product/Research Disclosure Information.
    No preview · Article · Mar 2014 · Chest
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    ABSTRACT: COPD Epidemiology & Physiology PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: The aim of our study was to evaluated the capacity of NT-proBNP to identify high risk patients with COPD exacerbations. Pilot observational prospective study. We did the present study at the Hospital Universitario La Princesa (Madrid) in the period between 2012 may and 2013 may. We included 41 patients with COPD exacerbation and respiratory acidosis (pH<7,35 and PaCO2>45 mmHg) and needed of non-invasive mechanical ventilation. We did the following mesurements: 1.Clinical dates: spirometric values, previous COPD exacerbations, chronic oxygen therapy, comorbidities. 2.Laboratorie test. 3.NT-proBNP in the first 24th hours at the admission. 4.Complications during the income. 5.Death during the income. We classificated the patients into four groups according to the values of NT-proBNP: <500 pg/ml, 500-1.000 pg/ml, 1.000-5.000 pg/ml and >5.000 pg/ml. 56% were men with about 76 years old. 25 patients had almost 2 exacerbations in the previous year. Patients with NT-proBNP>500 pg/ml had more probability of clinical complications during the income (more frequency cardiovascular one), more time of hospitalizations (13,3 vs 8,1 days), more death (7 vs 2), lower pH levels (7,26 vs 7,29) and higer PaCO2 levels (83,4 vs 70,6 mmHg). NT-proBNP was a good biomarker in patients with COPD exacerbation and could difference a high risk group. 1. Pre-selected a patients with poor prognostic. 2. Evaluated the implications of right ventricular function in the pathogenesis of the COPD exacerbation. 3. Evaluated news biomarkers in the COPD exacerbations. The following authors have nothing to disclose: Elena Garcia Castillo, Tamara Alonso Pérez, Gonzalo Segrelles Calvo, Olga Rajas Naranjo, Enrique Zamora García, Julio AncocheaNo Product/Research Disclosure Information.
    No preview · Article · Mar 2014 · Chest
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    Full-text · Article · Feb 2014 · Archivos de Bronconeumología
  • Antoni Xaubet · Anna Serrano-Mollar · Julio Ancochea
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    ABSTRACT: Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal fibrosing interstitial pneumonia. The median survival from the onset of the symptoms is 2.8 - 4.2 years and the 5-year survival rate is 20%. Its poor prognosis, combined with the scarcity of treatment options, provides a strong rationale for the development of novel therapeutic strategies. During the past decade there has been a huge rise in clinical trials with anti-fibrotic drugs, although only pirfenidone (Esbriet) has shown a beneficial effect. Areas covered: This article reviews the medical literature on the effectiveness and safety of pirfenidone in IPF, by means of a PubMed search from 1995 to present, completed with some data on file from the manufacturer. Expert opinion: Pirfenidone is the only anti-fibrotic drug approved for the treatment of IPF. Pirfenidone provides a meaningful clinical effect on reductions in the decrease in forced vital capacity (FVC), six-minute walk test (6MWT) distance and mortality, and it improves the progression-free survival in IPF patients with mild-to-moderate disease. Pirfenidone is well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. Pirfenidone has a favorable benefit-risk profile and represents a suitable treatment option for patients with mild-to-moderate IPF.
    No preview · Article · Dec 2013 · Expert Opinion on Pharmacotherapy

Publication Stats

3k Citations
433.78 Total Impact Points

Institutions

  • 2005-2015
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 1991-2015
    • Hospital Universitario de La Princesa
      • Servicio de Neumología
      Madrid, Madrid, Spain
  • 2011
    • Instituto de Investigación Sanitaria
      Madrid, Madrid, Spain
  • 2010
    • Fundación Caubet-Cimera Centro Internacional de Medicina Respiratoria Avanzada
      Bunyola, Balearic Islands, Spain
  • 2004
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 2003
    • Hospital de la Santa Creu i Sant Pau
      Barcino, Catalonia, Spain
  • 1997-2003
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain