0000000000307148
AUTHOR
Lucía Bañuls
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…
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…
Methodologies for the Determination of Blood Alpha1 Antitrypsin Levels: A Systematic Review
Background: The study of hematic concentrations of alpha1 antitrypsin (AAT) is currently one step in the diagnosis of AAT deficiency. To try to clarify the relevance of the laboratory techniques, we carried out a systematic review of the literature. Methods: Studies evaluating the quantification of AAT in peripheral blood were searched in PubMed in July 2021. The selection criteria included (1) any type of study design that included a quantification of AAT in peripheral blood; (2) studies written in English or Spanish; (3) studies evaluating human beings; and (4) studies involving adults. Results: Out of 207 studies, the most frequently used techniques were nephelometry (43.9%), followed by…
Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases
Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review.
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 …