Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. A major breakthrough in treatment came when, after decades of clinical trials which failed to identify an ...efficacious treatment regimen, two therapies were successful in Phase-III trials. The advent of these therapies, nintedanib and pirfenidone, meant that for the first time IPF patients had two treatment options that could reduce disease progression. This review summarises the key lessons to be obtained from the clinical trials that led to the current international clinical practice guidelines for the treatment of IPF and provides insights for the design of future clinical trials that are needed if we are to improve outcomes that are clinically meaningful to IPF patients.
Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation of RA being lung involvement. While essentially any of the lung compartments can be ...affected and manifest as interstitial lung disease (ILD), pleural effusion, cricoarytenoiditis, constrictive or follicular bronchiolitis, bronchiectasis, pulmonary vasculitis, and pulmonary hypertension, RA-ILD is a leading cause of death in patients with RA and is associated with significant morbidity and mortality. In this review, we focus on the common pulmonary manifestations of RA, RA-ILD and airway disease, and discuss evolving concepts in the pathogenesis of RA-associated pulmonary fibrosis, as well as therapeutic strategies, and have revised our previous review on the topic. A rational clinical approach for the diagnosis and management of RA-ILD, as well as an approach to patients with clinical worsening in the setting of treatment with disease-modifying agents, is included. Future directions for research and areas of unmet need in the realm of RA-associated lung disease are raised.
Over the past two and a half decades, many clinical trials have been designed to determine the safety and efficacy of pharmacotherapy for patients with idiopathic pulmonary fibrosis (IPF). However, ...so far, only two drugs (pirfenidone and nintedanib) have been found to have an impact on disease progression as defined by reducing the rate of decline in forced vital capacity over a year among IPF patients with mild to moderate impairment in lung function. These two drugs have been approved for treatment of IPF by regulatory agencies and are currently in clinical use worldwide. This article summarises the current landscape of pharmacotherapy for IPF and highlights the prospects and potential of new therapies that are currently being pursued in clinical trials.
Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are ...to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF. In addition to pharmacological therapy, optimal management of IPF includes treatment of comorbidities, symptom relief, pulmonary rehabilitation, and palliative care. Patient education is important to enable patients to make decisions about their care and to help them manage their disease and the side-effects of anti-fibrotic drugs. Research continues into new treatments and combinations of treatments that may improve outcomes for patients with this devastating disease.
The oxygen evolution reaction (OER) is the primary challenge in renewable energy storage technologies, specifically electrochemical water splitting for hydrogen generation. The development of ...affordable, robust, and efficient OER electrocatalysts plays a prominent role in water splitting by lowering the reaction kinetics barrier and boosting the performance of the process. This review discusses the recent progress in probing the electronic structure of catalytically active materials and its relevance to OER activity. We have aimed to emphasize state-of-the-art engineering strategies for modulating the electronic structure to exhibit ideal OER performance, including doping, alloying, generation of oxygen vacancies, heterostructure realization, and strain engineering. Finally, we summarize the existing challenges and opportunities in electronic structure modulation for future electrocatalyst development.
Strategies for regulating the electronic structure of transition-metal-based electrocatalysts through doping, heterostructure, oxygen vacancies, alloy, and strain engineering are investigated.
(C) Innate immune response: 1) antigen recognition with pattern recognition receptors; 2) phagocytosis; 3) antigen processing, MHC I and II pathways; MHC I pathway: after phagocytosis, soluble forms ...of antigens are formed and escape from phagosomes to cytosol; in cytosol, antigens are connected to TAP and transported to the endosome, where they are connected with MHC I molecules; MHC II pathway: foreign peptides degrade in the proteasome to antigens that are bound to MHC II molecules; and 4) antigen expression: expression of the complex of peptide and MHC I (presented to CD8+ cells) or MHC II (presented to CD4+ T cells) at the surface of antigen-presenting cells (APCs). Reported Genetic Factors in Hypersensitivity Pneumonitis Genes and Genetic Variants Population Race or Nationality First Author (Year) (Reference) MHC II polymorphisms HLA-DR3 White Rittner (1983) (63) HLA-DR7 Mexican Selman (1987) (64) HLA-DQ3 Japanese Ando (1989) (65) HLA-DRB1*04 Mexican Falfán-Valencia (2014) (66) MHC II haplotypes Increased DRB1*1305-DQB1*0301; decreased DRB1*0802-DQB1*0402 Mexican Camarena (2001) (67) Proteasome and transporter polymorphisms PSMB8 KQ Mexican Camarena (2010) (68) TAP1 637, 661 Mexican Aquino-Galvez (2008) (69) Mucin polymorphisms MUC5B rs35705950 White Ley (2017) (70) Telomere length and mutations Telomere length <10th percentile White Ley (2017) (70) Telomere-related gene mutations White Newton (2016) (71) Antiprotease polymorphisms TIMP-3-915 TIMP-3-1296 (protective role) White Hill (2004) (72) Definition of abbreviations: MHC = major histocompatibility complex; TAP = transporter for antigen presentation; TIMP = tissue inhibitor of metalloproteinase. To date, there is only one study revealing gene mutations (telomerase components) in patients with HP, and we have very little evidence of common variants of candidate genes increasing the risk of developing the disease (50). ...the relatives of patients with HP are not screened for genetic background, yet we can anticipate that, in the near future, the individuals at genetic risk of HP will be offered counseling to avoid exposure that might trigger the disease (Figures 1A and 1B). Martina Vasakova 1, Moises Selman 2, Ferran Morell 3, 4, Martina Sterclova 1, Maria Molina-Molina 5, 6, and Ganesh Raghu 7 1Department of Respiratory Medicine, First Faculty of Medicine of Charles University, Thomayer Hospital Prague, Prague, Czech Republic 2Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas,” Mexico City, Mexico 3Vall d’Hebron Institut de Recerca, Servei de Pneumologiía, Hospital Universitari Vall d’Hebron, Barcelona, Spain 4Department de Medicina UAB, Consorcio Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratoria, Barcelona, Spain 5Hospital Universitario de Bellvitge, Instituto de Investigaciones Biomédicas de Bellvitge, Universidad de Barcelona, Hospitalet de Llobregat, Barcelona, Spain 6CIBER de Enfermedades Respiratorias, Barcelona, Spain; and 7Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, Washington Corresponding Author: Ganesh Raghu
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown origin that is associated with high morbidity and mortality. In this perspective, we briefly review the current ...understanding of the pathophysiology of IPF and the importance of environmental triggers as a precipitant of disease. We discuss occult intrinsic and extrinsic environmental factors that affect the lung microenvironment and may contribute to the development and progression of disease. The clinical implications of this framework need to be further elucidated, because prompt identification and elimination of occult exposures may represent a novel treatment modality.
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