Pharmacogenomics of chronic obstructive pulmonary disease.

Pharmacogenomics of chronic obstructive pulmonary disease. Expert Rev Respir Med. 2019 Mar 29;: Authors: Hersh CP Abstract INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, which presents the opportunity for precision therapy based on genetics or other biomarkers. Areas covered: Alpha-1 antitrypsin deficiency, a genetic form of emphysema, provides an example of this precision approach to diagnosis and therapy. To date, research in COPD pharmacogenomics has been limited by small sample sizes, lack of accessible target tissue, failure to consider COPD subtypes, and different outcomes relevant for various medications. There have been several published genome-wide association studies and other omics studies in COPD pharmacogenomics; however, clinical implementation remains far away. There is a growing evidence base for precision prescription of inhaled corticosteroids in COPD, based on clinical phenotypes and blood biomarkers, but not yet based on pharmacogenomics. Expert opinion: At this time, there is insufficient evidence for clinical implementation of COPD pharmacogenomics. Additional genome-wide studies will be required to discover predictors of drug response and to identify genomic biomarkers of COPD subtypes, which could be targeted with subtype-directed therapies. PMID: 30925849 [PubMed - as supplied by publisher]
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research

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Rationale: Alpha-1 Antitrypsin Deficiency (AATD) is a rare genetic disease that can lead to the emphysema. Evidence suggests that small airways (SA) disease precedes emphysema. We compared traditional lung function and SA tests to CT evidence of emphysema in AATD subjects with mild or no COPD.Methods: 70 non-smokers with severe (PiZZ) AATD underwent lung function testing and high resolution CT (HRCT) scan. They were categorised based on HRCT data (Gevenois, P.A., et al. ERJ 1995; 5: 843–848); No emphysema (PD15> -910HU, n=16), microscopic emphysema (PD15 -950 to -910HU, n=48) and macroscopic emphysema (PD15
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory function technologists/scient. Source Type: research
α1-Antitrypsin deficiency (AATD) is a genetic disorder that predisposes to the development of early pulmonary emphysema, especially in smokers. Episodes of exacerbations are frequent in patients with emphysema due to AATD and are associated with a deficient antiprotease screen in the airways compared with that of non-deficient COPD patients [1]. As a consequence, exacerbations have great impact on the evolution of the lung disease in AATD, measured in terms of decline in gas transfer [2], in health status [2, 3], and in lung function over time [4, 5].
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Editorials Source Type: research
This study included 9,053 Japanese participants (male 2,962; female 6,091), in whom 7,525 (male 2,397; female 5,128) were included in the longitudinal analysis. The change in FEV1 was calculated by dividing the difference between the baseline and follow-up by follow-up periods (years). The change in FEV1 was categorized into two groups: rapid decline (change in FEV1
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Clinical Problems Source Type: research
We report on the 6 &12-month results of the AATD arm of the EMPROVE study.20 AATD subjects on optimal medical management with hyperinflation, severe dyspnea were treated with SVS valves at 12 centers. Target lobe selection was done using high resolution computed tomography. Targeted lobe was a lower lobe in 85% and an upper lobe in 15% of patients.A mean of 4.4 valves per patient were used to isolate the target lobe, with an average procedure time of 20 minutes. Results are presented as baseline and mean changes in FEV1, Target Lobe Volume (TLV), disease specific quality of life measures – St. George’s Resp...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Interventional pulmonology Source Type: research
Abstract Although chronic obstructive pulmonary disease (COPD) risk is strongly influenced by cigarette smoking, genetic factors are also important determinants of COPD. In addition to Mendelian syndromes such as alpha-1 antitrypsin deficiency, many genomic regions that influence COPD susceptibility have been identified in genome-wide association studies. Similarly, multiple genomic regions associated with COPD-related phenotypes, such as quantitative emphysema measures, have been found. Identifying the functional variants and key genes within these association regions remains a major challenge. However, newly ide...
Source: Annual Review of Physiology - Category: Physiology Authors: Tags: Annu Rev Physiol Source Type: research
Conclusion: Serum concentration and alleleic conformation of SFTPD has a significantly high predictive value for COPD and AECOPD. Thus, these can be tested further and could be applied as a predictive or prognostic marker. Introduction Chronic Obstructive Pulmonary Disease (COPD) affects lungs and exhibits irreversible airflow conditions that leads to improper respiratory function (Carolan et al., 2014). COPD is a global disease burden which accounts for ~3 million deaths annually (Zemans et al., 2017) and is responsible for the increase in worldwide mortality and morbidity (Dickens et al., 2011). Chronic Obstructi...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 15 April 2019Source: The Lancet Respiratory MedicineAuthor(s): Yohan Bossé, Maxime Lamontagne, Nathalie Gaudreault, Christine Racine, Marie-Hélène Levesque, Benjamin M Smith, Dominique Auger, Alisson Clemenceau, Marie-Ève Paré, Louis Laviolette, Victor Tremblay, Bruno Maranda, Mathieu C Morissette, François MaltaisSummaryBackgroundInherited mutations in SERPINA1 coding for the alpha-1 antitrypsin (A1AT) protein is the only well established cause of hereditary emphysema. We aimed to identify the genetic ecause of early-onset emphysema in a five-gen...
Source: The Lancet Respiratory Medicine - Category: Respiratory Medicine Source Type: research
Abstract Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors. For many years, knowledge of the genetic basis of COPD was limited to Mendelian syndromes, such as alpha-1 antitrypsin deficiency and cutis laxa, caused by rare genetic variants. Fortunately, over the past decade, the proliferation of genome-wide association studies (GWAS), the accessibility of whole genome sequencing, and the development of novel methods for analyzing genetic variation data have led to a substantial increase in our understanding of genetic variant...
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research
In conclusion, serum level of OxyA1AT would be potentially good biomarker for the assessment of harmful effect of smoking to the onset and severity of COPD. Also, clinical significance of OxyA1AT as prognostic biomarker could be useful in assessing the effectiveness of antioxidant therapy for COPD and emphysema. Suitable and inexpensive laboratory method for determination of OxyA1AT is additional benefit for the introduction of OxyA1AT into routine clinical practice for diagnosis and monitoring of COPD. PMID: 30822244 [PubMed - in process]
Source: COPD: Journal of Chronic Obstructive Pulmonary Disease - Category: Respiratory Medicine Tags: COPD Source Type: research
Authors: Janssen R, Piscaer I, Franssen FM, Wouters EF Abstract INTRODUCTION: Distinct pathologies can cause chronic obstructive pulmonary disease (COPD). Emphysema is a COPD-phenotype characterized by destruction of lung parenchyma. Alpha-1 antitrypsin deficiency (AATD) is a genetic cause of emphysema, whereas smoking is the most important risk factor of non-AATD emphysema. A general underappreciation of non-AATD emphysema has hampered progress in the field, and clinical guidelines have prohibited the use of emphysema as a diagnosis. Non-AATD emphysema, however, is far from irrelevant as it associates with dyspnea...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research
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