Management of progressive pulmonary fibrosis associated with connective tissue disease

Altres ajuts: Roche; Boehringer Ingelheim; Pfizer.Introduction: Fibrotic interstitial lung disease (ILD) is a frequent and severe complication of connective tissue disease (CTD). Areas covered: In this narrative review, we update the most relevant differential characteristics of fibrotic ILD associated with CTD (CTD-ILD) and propose a diagnostic and therapeutic approach based on a review of the articles published between 2002 and 2022 through PubMed. Expert opinion: The subset of ILD, mainly the radiological/histological pattern and the degree of fibrotic component, usually determines the prognosis and therapeutic strategy for these patients. Some patients with CTD-ILD can develop progressive pulmonary fibrosis (PPF) with severe deterioration of lung function, rapid progression to chronic respiratory failure, and high mortality. PPF has been described in many CTDs, mainly in systemic sclerosis and rheumatoid arthritis, and requires a multidisciplinary diagnostic and therapeutic approach to improve patient outcomes

Management of progressive pulmonary fibrosis associated with connective tissue disease

Introduction: Fibrotic interstitial lung disease (ILD) is a frequent and severe complication of connective tissue disease (CTD). Areas covered: In this narrative review, we update the most relevant differential characteristics of fibrotic ILD associated with CTD (CTD-ILD) and propose a diagnostic and therapeutic approach based on a review of the articles published between 2002 and 2022 through PubMed. Expert opinion: The subset of ILD, mainly the radiological/histological pattern and the degree of fibrotic component, usually determines the prognosis and therapeutic strategy for these patients. Some patients with CTD-ILD can develop progressive pulmonary fibrosis (PPF) with severe deterioration of lung function, rapid progression to chronic respiratory failure, and high mortality. PPF has been described in many CTDs, mainly in systemic sclerosis and rheumatoid arthritis, and requires a multidisciplinary diagnostic and therapeutic approach to improve patient outcomes

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial

[Background] Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT.[Methods] This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms.[Results] Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices.[Conclusions] This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs.This study has been funded by SEPAR 2017 (Fellowship) and Rio Hortega; ISCIII (Project and fellowship).Peer reviewe

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue

Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood. By integrating complementary gene and protein LAM signatures, and single-cell and bulk tissue transcriptome profiles, we show sources of disease heterogeneity, and how they correspond to cancer molecular portraits. Subsets of LAM diseased cells differ with respect to gene expression profiles related to hormones, metabolism, proliferation, and stemness. Phenotypic diseased cell differences are identified by evaluating lumican (LUM) proteoglycan and YB1 transcription factor expression in LAM lung lesions. The RUNX1 and IRF1 transcription factors are predicted to regulate LAM cell signatures, and both regulators are expressed in LAM lung lesions, with differences between spindle-like and epithelioid LAM cells. The cancer single-cell transcriptome profiles most similar to those of LAM cells include a breast cancer mesenchymal cell model and lines derived from pleural mesotheliomas. Heterogeneity is also found in LAM lung tissue, where it is mainly determined by immune system factors. Variable expression of the multifunctional innate immunity protein LCN2 is linked to disease heterogeneity. This protein is found to be more abundant in blood plasma from LAM patients than from healthy women.This research was partially supported by AELAM (ICO-IDIBELL agreement, to M.A. Pujana), The LAM Foundation Seed Grant 2019, to M.A. Pujana, Carlos III Institute of Health grant PI18/01029, to M.A. Pujana and ICI19/00047 to M. Molina-Molina [co-funded by European Regional Development Fund (ERDF), a way to build Europe], Generalitat de Catalunya SGR grant 2017-449, to M.A. Pujana, the CERCA Program for IDIBELL institutional support, and ZonMW-TopZorg grant 842002003, to C.H.M. van Moorsel. M. Plass was supported by a “Ramón y Cajal” contract of the Spanish Ministry of Science and Innovation (RYC2018-024564-I) and J. Moss was supported by the Intramural Research Program of NIH/NHLBI

Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain: the SEPAR National Registry

BackgroundLittle is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR).MethodsThis is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries.ResultsUpon inclusion, meanSD predicted forced vital capacity was 77.6%+/- 19.4, diffusing capacity for carbon monoxide was 48.5%+/- 17.7, and the 6-min walk distance was 423.5m +/- 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile.Conclusions The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts

Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update.

Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable tolerability profile. This article reviews new available evidence on the long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis. Data from extension trials indicate that nintedanib continues to slow disease progression for up to 3 years and is similarly effective in patients with mild and severe impairment of lung function. Treatment with nintedanib reduces the risk of acute exacerbations, and a combined analysis of data from clinical trials of nintedanib shows a trend towards a reduction in mortality. Nintedanib is well tolerated and has been shown to be safe for up to 51 months. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Currently available data confirm its safety profile in real-life clinical settings, with no new safety concerns identified in patients with comorbidities

Prevalencia de asma y factores relacionados con la misma en la ciudad de Sevilla

Parece evidente que existe un incremento en las tasas de incidencia y mortalidad por asma en diferentes países. A pesar de contar con más y mejores recursos terapéuticos, esta enfermedad ha ido creciendo, al contrario de lo que ocurre con otras enfermedades. Planteamos la hipótesis de que estas tendencias son debidas probablemente a un aumento en la prevalencia del asma. No existen datos en nuestra zona sobre la prevalencia de enfermedades respiratorias. Por otra parte, siempre existen dificultades a la hora de comparar resultados con los obtenidos por otros grupos de trabajo. Por ello se diseñó el Estudio Europeo del Asma (ECRHS-European Comunity Respiratory Health Survey); se trata de un estudio multicéntrico transversal realizado sobre población general en 48 áreas de 22 países diferentes que pretende determinar las variaciones en la prevalencia y factores de riesgo de asma en Europa en base a un mismo protocolo de trabajo y la misma metodología en el estudio. Esto tiene la ventaja de que los datos de cada centro pueden ser comparables con los datos de los otros centros, lo que puede hacer posible una mejor valoración de los resultados. Además se usan métodos estandarizados de investigación en diferentes zonas. Nuestro centro forma parte de este trabajo, con la misión concreta de analizar la prevalencia de Asma en la zona de Sevilla, donde no existen datos al respecto. Objetivos: 1. Determinar la prevalencia de Asma, sintomatología respiratoria y labilidad bronquial en nuestra población. 2. Estimar la exposición a alérgenos, nivel de sensibilización en la población y su relación con el asma. 3. Analizar la influencia de posibles factores de riesgo con la presencia de síntomas/hiperreactividad bronquial o con sensibilidad cutánea/IgE sérica. Estos factores incluirán condiciones de la vivienda, trabajo, tener animales domésticos, uso de medicación antiasmática e historia de infecciones

MIDAS: a new integrated flood early warning system for the Miño river

Early warning systems have become an essential tool to mitigate the impact of river floods, whose frequency and magnitude have increased during the last few decades as a consequence of climate change. In this context, the Miño River Flood Alert System (MIDAS) early warning system has been developed for the Miño River (Galicia, NW Spain), whose flood events have historically caused severe damage in urban areas and are expected to increase in intensity in the next decades. MIDAS is integrated by a hydrologic (HEC-HMS) and a hydraulic (Iber+) model using precipitation forecast as input data. The system runs automatically and is governed by a set of Python scripts. When any hazard is detected, an alert is issued by the system, including detailed hazards maps, to help decision makers to take precise and effective mitigation measures. Statistical analysis supports the accuracy of hydrologic and hydraulic modules implemented to forecast river flow and flooded critical areas during the analyzed period of time, including some of the most extreme events registered in the Miño River. In fact, MIDAS has proven to be capable of predicting most of the alert situations occurred during the study period, showing its capability to anticipate risk situations.Interreg | Ref. 0034_RISC_ML_6_EXunta de Galicia | Ref. ED431C 2017/64-GR