Claudia Valenzuela - Academia.edu (original) (raw)
Papers by Claudia Valenzuela
Respiratory Research
Background The objective of the present study is to describe the characteristics of interstitial ... more Background The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. Methods A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. Main outcome: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. Statistics: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR...
Advances in Therapy
Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with inte... more Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with interstitial lung disease (ILD). STARLINER aimed to characterise disease behaviour in patients with suspected ILD during the peridiagnostic period using real-time home-based assessments. Methods: STARLINER (NCT03261037) was an international, multicentre study. Patients C 50 years old with suspected ILD were followed throughout the peri-diagnostic period, consisting of a pre-diagnostic period (from enrolment to diagnosis) and a post-diagnostic period (from diagnosis to treatment initiation). Study length was variable (B 18 months). The primary endpoint was time-adjusted semi-annual forced vital capacity (FVC) change measured during the peridiagnostic period using daily home spirometry in patients with idiopathic pulmonary fibrosis
R e v i e w open access to scientific and medical research Open Access Full Text Article
ERS Handbook Respiratory Medicine, 2019
Respiratory Research, 2020
Background Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patien... more Background Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. Methods Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression. Results In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ...
Respiratory Research, 2020
The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonar... more The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases.This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and ...
Advances in Therapy, 2018
Background/Objectives: This study will aim to characterise disease behaviour during the peridiagn... more Background/Objectives: This study will aim to characterise disease behaviour during the peridiagnostic period in patients with suspected interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), using daily home spirometry and accelerometry. Additionally, this study will aim to increase collaboration between secondary and tertiary centres using a digital collaboration platform. Methods: The STARLINER study (NCT03261037) will enrol approximately 180 symptomatic patients aged 50 years or more with radiological evidence of ILD/IPF from community and tertiary centres in Canada and Europe. Approximately two-thirds of sites will be community centres. Patients will be followed during prediagnosis (inclusion to diagnosis; up to a maximum of 12 months) and post-diagnosis (diagnosis to treatment initiation; up to a maximum of 6 months). The study will be facilitated by a digital ecosystem consisting of the devices used for home-based assessments and a digital collaboration platform enabling communication between community and tertiary centres, and between clinicians and patients. Planned Outcomes: The primary endpoint will be time-adjusted semi-annual change in forced vital capacity (FVC; in millilitres) during the peri-diagnostic period. Physical functional capacity and patient-reported outcomes (PROs) will also be assessed. FVC and physical functional capacity will be measured using daily home spirometry and accelerometry, and at site visits using spirometry and the 6-min walk test. PROs will be assessed prior to, or during, site visits and will always be completed in the same order. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.7358393.
The European respiratory journal, Jan 24, 2018
Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more tha... more Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more than 60 countries, including the USA [1]. In the two phase III INPULSIS trials, nintedanib reduced disease progression by reducing decline in forced vital capacity [2]. Most patients were able to manage the side-effects of nintedanib, with 19.3% of patients treated with nintedanib versus 13.0% treated with placebo permanently discontinuing the study medication due to adverse events. The most frequent adverse events were gastrointestinal, particularly diarrhoea. The proportion of patients who had one or more serious adverse events was similar between nintedanib and placebo (30.4% versus 30.0%). Following the launch of nintedanib as a treatment for IPF, information on its safety and tolerability in the real-world setting has been collected via post-marketing surveillance. Here, we report an analysis of data collected in the USA between the launch of nintedanib on October 15, 2014, and October 31, 2015. Data on adverse events in patients with IPF treated with nintedanib, irrespective of causality, were collected via proactive communications with specialty pharmacies and a spontaneous reporting system. In addition, reports of adverse events were collected via direct contact with patients and caregivers as part of a patient support programme (OPEN DOORS). Adverse events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Based on the mechanism of action of nintedanib and data from the INPULSIS trials, adverse events of interest in the post-marketing surveillance data were defined as diarrhoea, bleeding, hepatic disorders, arterial hypertension, major adverse cardiovascular events (MACE), myocardial infarction and stroke. For the purposes of this post-marketing safety analysis, the rates of these adverse events were assessed using the same definitions as used in the INPULSIS trials. Epidemiological data on the incidence of diarrhoea (in the general population) and other adverse events of interest (in unmatched patients with IPF) were obtained from the literature [3-9] and from a proprietary research database of patients representative of the commercially insured population of the USA (data on file, Optum Research Database). Our post-marketing surveillance data came from 6758 patients with IPF treated with nintedanib. Median duration of exposure was 113 days (range 6-390 days). Estimated cumulative exposure was 2715 patient-years. Diarrhoea (2858 events, not individuals reporting at least one event), nausea (1476 events) and vomiting (705 events) were the most frequent adverse events. Most (95.0%) adverse events were not serious. A total of 4062 adverse events defined as of interest in the post-marketing surveillance data were reported. Of these, 322 had a fatal outcome, including 27 cases of MACE, eight of myocardial infarction, three of stroke and two of bleeding. In 123 cases, the cause of death was not reported. The most frequent causes of death that were reported were progression of IPF (81 cases), respiratory failure (27 cases) and pulmonary fibrosis (18 cases). The incidence of diarrhoea in the post-marketing surveillance data was 1053 per 1000 patient-years. Understanding that diarrhoea is a very common side-effect of nintedanib therapy, this was lower than the rate reported in INPULSIS (1331 per 1000 patient-years) and similar to the rate in epidemiological data from the general population (980 per 1000 patient-years) [5, 8] (figure 1a). Based on its inhibition of the vascular endothelial growth factor receptor, nintedanib may increase the risk of bleeding. Patients at known risk of bleeding, including those treated with full-dose anticoagulants or @ERSpublications The safety and tolerability profile of nintedanib in patients with IPF in the clinical setting is consistent with the product label http://ow.ly/Nulb30jPAld
Reumatología Clínica (English Edition)
Current Medical Research and Opinion, 2019
Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary f... more Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims.
ERJ Open Research, 2021
Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the ... more Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the potential to be challenging. The variable course and poor prognosis of IPF complicate discussions around life expectancy but should not prevent clinicians from having meaningful conversations about patients’ fears and needs, while acknowledging uncertainties. Patients want information about the course of their disease and management options, but the provision of information needs to be individualised to the needs and preferences of the patient. Communication from clinicians should be empathetic and take account of the patient's perceptions and concerns. Models, tools and protocols are available that can help clinicians to improve their interactions with patients. In this article, we consider the difficulties inherent in discussions with patients with IPF and their loved ones, and how clinicians might communicate with patients more effectively, from breaking the news about the diagnos...
Journal of Clinical Medicine, 2021
There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results fro... more There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic patients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma who later developed SS led us to review the previous tumors of patients with SS. The aim of the study is to see whether granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of whom had previously had a tumor. We were able to review 29 cases, 12 of which showed tumor-associated granulomas (TAGs) (41.4%). This ratio is much higher than that of the normal population (4.4–13.8). We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we observed an increased number of TAGs in patients who later developed SS. This finding reinforces a ...
Chest, 2019
BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) path... more BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF. METHODS: All patients randomized to placebo (n ¼ 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of $ 10% absolute decline in % predicted FVC, $ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52 weeks. RESULTS: At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95% CI, 0.4-0.9]; P ¼ .026), but not ARB (HR, 0.9 [95% CI, 0.6-1.2]; P ¼ .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95% CI, 0.5-2.9]; P ¼ .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6% vs 3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95% CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial. CONCLUSIONS: Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF.
The European respiratory journal, 2018
]. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) greater or eq... more ]. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) greater or equal to 25 mmHg, and is a frequent complication in patients with idiopathic pulmonary fibrosis (IPF) [1], especially at an advanced stage of the disease, or when emphysema is associated, as in the syndrome of combined pulmonary fibrosis and emphysema [2]. At diagnosis, 8% to 15% of patients with IPF may already have precapillary PH [3], a proportion which rises up to 30% to 50% of patients at the time of evaluation for lung transplantation [4-7]. The frequency of PH further increases with comorbidities such as obstructive sleep apnoea, thromboembolism or cardiac diastolic dysfunction [8]. PH, when present, is associated with dramatic worsening of shortness of breath, greater oxygen requirements, more severe limitation to exercise capacity and increased mortality [4, 8-10]. PH in IPF (group 3 of the World Health Organization pulmonary hypertension classification [11]) is usually of mild or moderate haemodynamic severity, although 2-10% of patients have a mean PAP greater than 35-40 mmHg [3-5].
![Research paper thumbnail of Erratum to “Guidelines for the medical treatment of idiopathic pulmonary fibrosis” <[Arch. Bronconeumol. 53 (2017) 263–269]>](https://attachments.academia-assets.com/92898564/thumbnails/1.jpg)
](Archivos de Bronconeumología (English Edition), 2017
Erratum Erratum to "Guidelines for the medical treatment of idiopathic pulmonary fibrosis" <[Arch... more Erratum Erratum to "Guidelines for the medical treatment of idiopathic pulmonary fibrosis" <[Arch. Bronconeumol. 53 (2017) 263-269]> ଝ Fe de errores de «Normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática» <[Arch Bronconeumol. 53 (2017) 263-9]>
Archivos de Bronconeumología, 2017
La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con... more La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con mal pronóstico. Su incidencia ha aumentado en los últimos años, probablemente por la optimización de los métodos diagnósticos y el aumento en la esperanza de vida. En 2013 se publicó la normativa SEPAR sobre el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Desde entonces, se han publicado los resultados de ensayos clínicos y metaanálisis que han supuesto, con base en la evidencia científica, la introducción de pirfenidona y nintedanib en el tratamiento de la enfermedad. En 2015 se ha actualizado el consenso internacional de 2011, en el que se describen los cambios en las recomendaciones terapéuticas. Debido a ello cabía actualizar el apartado de la normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática. No se tratarán aspectos diagnósticos ni el tratamiento no farmacológico, ya que no se han producido cambios relevantes desde la normativa de 2013.
Sarcoidosis Vasculitis and Diffuse Lung Disease, Sep 1, 2013
A number of pharmacological agents have been the focus of clinical trials over the past years. Al... more A number of pharmacological agents have been the focus of clinical trials over the past years. Although no single pharmacological agent is recommended by current guidelines, preliminary negative findings regarding the safety of a triple therapy regimen consisting of prednisone, azathioprine and N-acetylcysteine have raised the question of whether it is no longer a treatment option. More recent data have resulted in the approval of pirfenidone in Europe. Pirfenidone shows a favourable risk-benefit profile and a beneficial effect in reducing the decline in lung function in patients with IPF. This case study describes the diagnosis and initial treatment of a patient with IPF with triple therapy of prednisone, azathioprine and N-acetylcysteine (NAC) followed by inclusion into a double-blind, randomised, placebo-controlled study and subsequent open-label extension trial of pirfenidone in IPF.
Enfermedades Infecciosas y Microbiología Clínica, 2016
Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of ... more Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism.
Revista de Patología Respiratoria, 2011
Therapeutics and Clinical Risk Management, 2015
Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane con... more 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.
Respiratory Research
Background The objective of the present study is to describe the characteristics of interstitial ... more Background The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. Methods A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. Main outcome: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. Statistics: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR...
Advances in Therapy
Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with inte... more Introduction: Disease behaviour may guide diagnosis and treatment decisions in patients with interstitial lung disease (ILD). STARLINER aimed to characterise disease behaviour in patients with suspected ILD during the peridiagnostic period using real-time home-based assessments. Methods: STARLINER (NCT03261037) was an international, multicentre study. Patients C 50 years old with suspected ILD were followed throughout the peri-diagnostic period, consisting of a pre-diagnostic period (from enrolment to diagnosis) and a post-diagnostic period (from diagnosis to treatment initiation). Study length was variable (B 18 months). The primary endpoint was time-adjusted semi-annual forced vital capacity (FVC) change measured during the peridiagnostic period using daily home spirometry in patients with idiopathic pulmonary fibrosis
R e v i e w open access to scientific and medical research Open Access Full Text Article
ERS Handbook Respiratory Medicine, 2019
Respiratory Research, 2020
Background Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patien... more Background Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. Methods Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression. Results In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ...
Respiratory Research, 2020
The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonar... more The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases.This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and ...
Advances in Therapy, 2018
Background/Objectives: This study will aim to characterise disease behaviour during the peridiagn... more Background/Objectives: This study will aim to characterise disease behaviour during the peridiagnostic period in patients with suspected interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), using daily home spirometry and accelerometry. Additionally, this study will aim to increase collaboration between secondary and tertiary centres using a digital collaboration platform. Methods: The STARLINER study (NCT03261037) will enrol approximately 180 symptomatic patients aged 50 years or more with radiological evidence of ILD/IPF from community and tertiary centres in Canada and Europe. Approximately two-thirds of sites will be community centres. Patients will be followed during prediagnosis (inclusion to diagnosis; up to a maximum of 12 months) and post-diagnosis (diagnosis to treatment initiation; up to a maximum of 6 months). The study will be facilitated by a digital ecosystem consisting of the devices used for home-based assessments and a digital collaboration platform enabling communication between community and tertiary centres, and between clinicians and patients. Planned Outcomes: The primary endpoint will be time-adjusted semi-annual change in forced vital capacity (FVC; in millilitres) during the peri-diagnostic period. Physical functional capacity and patient-reported outcomes (PROs) will also be assessed. FVC and physical functional capacity will be measured using daily home spirometry and accelerometry, and at site visits using spirometry and the 6-min walk test. PROs will be assessed prior to, or during, site visits and will always be completed in the same order. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.7358393.
The European respiratory journal, Jan 24, 2018
Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more tha... more Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in more than 60 countries, including the USA [1]. In the two phase III INPULSIS trials, nintedanib reduced disease progression by reducing decline in forced vital capacity [2]. Most patients were able to manage the side-effects of nintedanib, with 19.3% of patients treated with nintedanib versus 13.0% treated with placebo permanently discontinuing the study medication due to adverse events. The most frequent adverse events were gastrointestinal, particularly diarrhoea. The proportion of patients who had one or more serious adverse events was similar between nintedanib and placebo (30.4% versus 30.0%). Following the launch of nintedanib as a treatment for IPF, information on its safety and tolerability in the real-world setting has been collected via post-marketing surveillance. Here, we report an analysis of data collected in the USA between the launch of nintedanib on October 15, 2014, and October 31, 2015. Data on adverse events in patients with IPF treated with nintedanib, irrespective of causality, were collected via proactive communications with specialty pharmacies and a spontaneous reporting system. In addition, reports of adverse events were collected via direct contact with patients and caregivers as part of a patient support programme (OPEN DOORS). Adverse events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Based on the mechanism of action of nintedanib and data from the INPULSIS trials, adverse events of interest in the post-marketing surveillance data were defined as diarrhoea, bleeding, hepatic disorders, arterial hypertension, major adverse cardiovascular events (MACE), myocardial infarction and stroke. For the purposes of this post-marketing safety analysis, the rates of these adverse events were assessed using the same definitions as used in the INPULSIS trials. Epidemiological data on the incidence of diarrhoea (in the general population) and other adverse events of interest (in unmatched patients with IPF) were obtained from the literature [3-9] and from a proprietary research database of patients representative of the commercially insured population of the USA (data on file, Optum Research Database). Our post-marketing surveillance data came from 6758 patients with IPF treated with nintedanib. Median duration of exposure was 113 days (range 6-390 days). Estimated cumulative exposure was 2715 patient-years. Diarrhoea (2858 events, not individuals reporting at least one event), nausea (1476 events) and vomiting (705 events) were the most frequent adverse events. Most (95.0%) adverse events were not serious. A total of 4062 adverse events defined as of interest in the post-marketing surveillance data were reported. Of these, 322 had a fatal outcome, including 27 cases of MACE, eight of myocardial infarction, three of stroke and two of bleeding. In 123 cases, the cause of death was not reported. The most frequent causes of death that were reported were progression of IPF (81 cases), respiratory failure (27 cases) and pulmonary fibrosis (18 cases). The incidence of diarrhoea in the post-marketing surveillance data was 1053 per 1000 patient-years. Understanding that diarrhoea is a very common side-effect of nintedanib therapy, this was lower than the rate reported in INPULSIS (1331 per 1000 patient-years) and similar to the rate in epidemiological data from the general population (980 per 1000 patient-years) [5, 8] (figure 1a). Based on its inhibition of the vascular endothelial growth factor receptor, nintedanib may increase the risk of bleeding. Patients at known risk of bleeding, including those treated with full-dose anticoagulants or @ERSpublications The safety and tolerability profile of nintedanib in patients with IPF in the clinical setting is consistent with the product label http://ow.ly/Nulb30jPAld
Reumatología Clínica (English Edition)
Current Medical Research and Opinion, 2019
Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary f... more Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims.
ERJ Open Research, 2021
Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the ... more Communications between clinicians and patients with idiopathic pulmonary fibrosis (IPF) have the potential to be challenging. The variable course and poor prognosis of IPF complicate discussions around life expectancy but should not prevent clinicians from having meaningful conversations about patients’ fears and needs, while acknowledging uncertainties. Patients want information about the course of their disease and management options, but the provision of information needs to be individualised to the needs and preferences of the patient. Communication from clinicians should be empathetic and take account of the patient's perceptions and concerns. Models, tools and protocols are available that can help clinicians to improve their interactions with patients. In this article, we consider the difficulties inherent in discussions with patients with IPF and their loved ones, and how clinicians might communicate with patients more effectively, from breaking the news about the diagnos...
Journal of Clinical Medicine, 2021
There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results fro... more There is a relationship between systemic sarcoidosis (SS) and malignancy. Sarcoidosis results from an exaggerated immune response in genetically susceptible individuals. In oncologic patients with sarcoidosis, tumoral antigens and antineoplastic treatment are considered potential triggering factors. The observation of a patient with granulomas in a parotid carcinoma who later developed SS led us to review the previous tumors of patients with SS. The aim of the study is to see whether granulomas were already present in the tumors that preceded sarcoidosis. We identified 196 sarcoidosis patients, 47 of whom had previously had a tumor. We were able to review 29 cases, 12 of which showed tumor-associated granulomas (TAGs) (41.4%). This ratio is much higher than that of the normal population (4.4–13.8). We analyzed five control patients without sarcoidosis for each tumor. In conclusion, we observed an increased number of TAGs in patients who later developed SS. This finding reinforces a ...
Chest, 2019
BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) path... more BACKGROUND: Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF. METHODS: All patients randomized to placebo (n ¼ 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of $ 10% absolute decline in % predicted FVC, $ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52 weeks. RESULTS: At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95% CI, 0.4-0.9]; P ¼ .026), but not ARB (HR, 0.9 [95% CI, 0.6-1.2]; P ¼ .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95% CI, 0.5-2.9]; P ¼ .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6% vs 3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95% CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial. CONCLUSIONS: Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF.
The European respiratory journal, 2018
]. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) greater or eq... more ]. Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (PAP) greater or equal to 25 mmHg, and is a frequent complication in patients with idiopathic pulmonary fibrosis (IPF) [1], especially at an advanced stage of the disease, or when emphysema is associated, as in the syndrome of combined pulmonary fibrosis and emphysema [2]. At diagnosis, 8% to 15% of patients with IPF may already have precapillary PH [3], a proportion which rises up to 30% to 50% of patients at the time of evaluation for lung transplantation [4-7]. The frequency of PH further increases with comorbidities such as obstructive sleep apnoea, thromboembolism or cardiac diastolic dysfunction [8]. PH, when present, is associated with dramatic worsening of shortness of breath, greater oxygen requirements, more severe limitation to exercise capacity and increased mortality [4, 8-10]. PH in IPF (group 3 of the World Health Organization pulmonary hypertension classification [11]) is usually of mild or moderate haemodynamic severity, although 2-10% of patients have a mean PAP greater than 35-40 mmHg [3-5].
Archivos de Bronconeumología (English Edition), 2017
Erratum Erratum to "Guidelines for the medical treatment of idiopathic pulmonary fibrosis" <[Arch... more Erratum Erratum to "Guidelines for the medical treatment of idiopathic pulmonary fibrosis" <[Arch. Bronconeumol. 53 (2017) 263-269]> ଝ Fe de errores de «Normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática» <[Arch Bronconeumol. 53 (2017) 263-9]>
Archivos de Bronconeumología, 2017
La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con... more La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con mal pronóstico. Su incidencia ha aumentado en los últimos años, probablemente por la optimización de los métodos diagnósticos y el aumento en la esperanza de vida. En 2013 se publicó la normativa SEPAR sobre el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Desde entonces, se han publicado los resultados de ensayos clínicos y metaanálisis que han supuesto, con base en la evidencia científica, la introducción de pirfenidona y nintedanib en el tratamiento de la enfermedad. En 2015 se ha actualizado el consenso internacional de 2011, en el que se describen los cambios en las recomendaciones terapéuticas. Debido a ello cabía actualizar el apartado de la normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática. No se tratarán aspectos diagnósticos ni el tratamiento no farmacológico, ya que no se han producido cambios relevantes desde la normativa de 2013.
Sarcoidosis Vasculitis and Diffuse Lung Disease, Sep 1, 2013
A number of pharmacological agents have been the focus of clinical trials over the past years. Al... more A number of pharmacological agents have been the focus of clinical trials over the past years. Although no single pharmacological agent is recommended by current guidelines, preliminary negative findings regarding the safety of a triple therapy regimen consisting of prednisone, azathioprine and N-acetylcysteine have raised the question of whether it is no longer a treatment option. More recent data have resulted in the approval of pirfenidone in Europe. Pirfenidone shows a favourable risk-benefit profile and a beneficial effect in reducing the decline in lung function in patients with IPF. This case study describes the diagnosis and initial treatment of a patient with IPF with triple therapy of prednisone, azathioprine and N-acetylcysteine (NAC) followed by inclusion into a double-blind, randomised, placebo-controlled study and subsequent open-label extension trial of pirfenidone in IPF.
Enfermedades Infecciosas y Microbiología Clínica, 2016
Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of ... more Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism.
Revista de Patología Respiratoria, 2011
Therapeutics and Clinical Risk Management, 2015
Cystic fibrosis (CF) is a fatal inherited disease caused by mutations in the CF transmembrane con... more 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.