0000000000249599
AUTHOR
María Mercedes Navarro-garcía
Evaluation of the quality of publications on randomized clinical trials using the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines in a Spanish tertiary hospital.
The main reason for conducting a clinical trial (CT) is to test the effect of a drug or medical procedure to improve treatment of a disease. CTs contribute most when they are rigorously conducted and the results are published adequately. The aim of this study is to assess, using the CONSORT statement guidelines, the quality of reporting of completed CTs conducted at a tertiary hospital to determine which sections of the articles should be improved. CTs published between 2002 and 2008 were identified by searching the MEDLINE and Cochrane Library. Forty of 127 completed CTs were published. There was a marked increase in the number of articles and the quality of the journals that published the…
LSC Abstract – Increased oxidative stress leads to telomere shortening in children with alpha-1 antitrypsin deficiency
Background: Oxidative stress (OS) is involved in the pathophysiology of AATD (Escribano A. et al. Thorax 2015; 70:82-3). In addition, it has been shown that OS accelerates telomere shortening which is associated to higher emphysema risk in COPD patients. Rationale and aims: Since AATD is characterised by chronic OS, we hypothesise that telomere shortening would be accelerated in AATD patients and would be associated with higher risk of developing lung disease. This study is aimed to assess the OS profile, the enzymatic antioxidant defence mechanisms and telomere length (TL) in children with AATD and to study its association with AAT phenotypes. Methods: OS parameters, the activity of the ma…
New Laboratory Protocol to Determine the Oxidative Stress Profile of Human Nasal Epithelial Cells Using Flow Cytometry
Several studies have shown the importance of oxidative stress (OS) in respiratory disease pathogenesis. It has been reported that the nasal epithelium may act as a surrogate for the bronchial epithelium in several respiratory diseases involving OS. However, the sample yields obtained from nasal biopsies are modest, limiting the number of parameters that can be determined. Flow cytometry has been widely used to evaluate cellular OS profiles. It has the advantage that analyses can be performed using a small amount of sample. Therefore, we aimed to set up a new method based on flow cytometry to assess the oxidative profile of human nasal epithelial cells which could be used in research on resp…
Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?
Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…
Knowledge of Rare Respiratory Diseases among Paediatricians and Medical School Students.
Alpha-1-antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD) are underdiagnosed rare diseases showing a median diagnostic delay of five to ten years, which has negative effects on patient prognosis. Lack of awareness and education among healthcare professionals involved in the management of these patients have been suggested as possible causes. Our aim was to assess knowledge of these diseases among paediatricians and medical school students to determine which knowledge areas are most deficient. A survey was designed with questions testing fundamental aspects of the diagnosis and treatment of AATD and PCD. A score equal to or greater than 50% of the maximum score was set as th…
Oxidative Stress in COPD.
Numerous studies over the years have shown that oxidative stress plays a major role in the development of the disease. Oxidative stress involvement in COPD opens up the possibility of using antioxidant therapies in the treatment of the disease. However, so far, these therapies have shown no clinical benefit indicating that more basic research efforts are needed to understand the underlying mechanisms by which oxidative stress leads to the development of COPD.
Alpha-1 antitrypsin deficiency: outstanding questions and future directions
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. METHODS: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical and…
Anti-angiogenic therapies in prostate cancer.
Prostate cancer (PCa) is the second most common type of cancer among men in Western societies. Once in the castrate-resistant metastatic setting therapeutic options are limited. The importance of angiogenesis in the progression of PCa has been widely reported providing a rationale to test anti-angiogenic compounds for PCa treatment in clinical trials (CTs). However, in spite of the promising results shown in preclinical models and some anti-tumor activity observed in CTs, to date, no angiogenic inhibitor has been approved for use in PCa. This editorial outlines the latest clinical evidence regarding anti-angiogenic therapies in PCa treatment.
Hypoxia induces proinflammatory cytokines production in alpha-1 antitrypsin deficiency patients
Introduction: Alpha-1 antitrypsin deficiency (AATD) is a rare respiratory condition characterized by abnormal inflammation, where neutrophils play a key role. Excessive neutrophil activation leads to an increase in the oxygen (O2) intake, causing local hypoxia and increased tissue-injury capacity. Tissue hypoxia is part of the inflammatory process so neutrophils can function effectively under these conditions. However, the mechanisms by which neutrophils mediate tissue damage under hypoxia remain unclear. The study aimed to determine whether hypoxia modifies the cytokine profile in AATD patients. Methods: Neutrophils from 22 AATD patients (6 MZ; 9 SZ; 7 ZZ) and 7 controls (MM) were exposed …
Plasma circulating miRNAs as diagnostic and prognostic biomarkers in alpha-1 antitrypsin deficiency
Introduction: Alpha-1 antitrypsin (AATD) deficiency is an inherited condition that leads to decreased circulating AAT levels, significantly increasing the risk of lung and liver disease. AATD is underdiagnosed. Severity of symptoms in AATD patients are highly variable and neither protein levels nor phenotype are sufficient to identify which patients will develop lung and/or liver disease. Therefore, new strategies and biomarkers for early diagnosis and prognosis of the disease are needed. Rationale and Aims: MicroRNAs (miRNAs) regulate gene expression and have been associated with the pathogenesis of various lung and liver diseases. Circulating miRNAs may serve as diagnostic and prognostic …
LSC Abstract – Oxidative stress in nasal epithelial cells from patients with primary ciliary dyskinesia
Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive inheritance disorder characterized by dysfunction of respiratory cilia and impaired mucociliary clearance, leading to respiratory problems appearing in childhood, decreased fertility and situs inversus in 50% of the cases. The deficient ciliary movement causes stasis of secretions in the airways leading to recurrent airway infection and chronic inflammation. Rationale and aims: Chronic inflammation has been associated to oxidative stress (OS). Moreover, evidence of increased OS in the airways of stable children with PCD has been shown (Zihlif, N. et al . Pediatr Pulmonol 2006; 41:509-14.). Therefore, we hypothesize t…