The pharmacogenetics of asthma treatment
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Asthma and chronic obstructive pulmonary disease (COPD) are prevalent conditions, and despite recent advances and multiple available therapies and interventions, there remains a significant unmet clinical need. In recent years, it has become clear that there is both significant heterogeneity within each of these conditions and additionally significant overlap in many of the clinical and inflammatory features. In parallel, useful clinical and immunological biomarkers which inform about prognosis and response to therapy have emerged in both asthma and COPD. These biomarkers will allow both better targeting of existing treatments and the identification of those patients who will respond to novel therapies which are now becoming available. Biomarkers will also facilitate the identification of novel therapeutic targets for future development. Delivery of precision medicine in airways disease is now feasible and is a core component of a personalised healthcare delivery in asthma and COPD.
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Cardiovascular disease remains the leading global cause of death. Early intervention, with lifestyle advice alongside appropriate medical therapies, is fundamental to reduce patient mortality among high-risk individuals. For those who live with the daily challenges of cardiovascular disease, pharmacological management aims to relieve symptoms and prevent disease progression. Despite best efforts, prescription drugs are not without their adverse effects, which can cause significant patient morbidity and consequential economic burden for healthcare systems. Patients with cardiovascular diseases are often among the most vulnerable to adverse drug reactions due to multiple co-morbidities and advanced age. Examining a patient's genome to assess for variants that may alter drug efficacy and susceptibility to adverse reactions underpins pharmacogenomics. This strategy is increasingly being implemented in clinical cardiology to tailor patient therapies. The identification of specific variants associated with adverse drug effects aims to predict those at greatest risk of harm, allowing alternative therapies to be given. This review will explore current guidance available for pharmacogenomic-based prescribing as well as exploring the potential implementation of genetic risk scores to tailor treatment. The benefits of large databases and electronic health records will be discussed to help facilitate the integration of pharmacogenomics into primary care, the heartland of prescribing.
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The main drugs used for asthma include β2- adrenoceptor agonists,corticosteroids and leukotriene modifiers. Clinical and experimental studies found that there are individual differences in patient' s response to asthma drugs. The individual differences is associated with asthma- related genes,while some mutant gene loci can affect the patient's response to drug. These genes include β2- adrenergic receptor gene( ADRB2),the glucocorticoid receptor gene( NR3C1),leukotriene synthase( LTC4 S and ALOX5) genes and so on. The article will summarize asthma- related pharmacogenomics research,hoping to provide help for the future realization of personalized medicine for asthma.
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Allergic diseases such as bronchial asthma and atopic dermatitis develop by a combination of genetic and environmental factors. Several candidate causative genes of asthma and atopy have been reported as the genetic factors. The clinical features of patients and causes of diseases vary. Therefore, personalized medicine (tailor-made medicine) is necessary for the improvement of quality of life (QOL) and for asthma cure. Pharmacogenetics is very important for personalized medicine. Here, we present the genetics and pharmacogenetics of asthma in children. Finally, we show the guideline for personalized medicine for asthma, particularly in childhood, including the pharmacogenetics of anti-asthmatic drugs, preliminarily produced by the authors.
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Asthma is one of the most significant diseases worldwide and causes overwhelming costs physically and economically. The study of asthma has revealed various groups of asthma patients who share phenotypic characteristics that naturally elicit the need for personalized asthma therapy. An increasing amount of pharmacogenetics research, genotype-based trials and precision medicine trials have been conducted to investigate this problem.A systematic bibliography retrieval was performed in MEDLINE (Ovid) and PubMed for our topic and all relative records were exported and screened.We identified 377 publications and added 4 articles related to this topic artificially to reach a bigger scope, of which 36 met the inclusion criteria. Our review focuses on the three most widely used treatments for asthma management, which are β-adrenergic receptor agonists, inhaled corticosteroids (ICS) and anti-leukotriene modifiers. We summarize the existing loci reported in the literature that are potentially associated with drug responses to typically used medications.Our results suggest that a genetic test with high predictive accuracy could predict therapeutic responses, and proper management can be achieved in asthma patients. This personalized approach to curative medicine should make way for the realization of personalized preventive and predictive medicine in the coming years.
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Asthma is a chronic inflammatory lung disease that leads to significant morbidity, mortality, and economic burden. The clinical symptoms, which are a result of airway inflammation and reversible airway obstruction, have led to the mainstay of therapies for asthma: anti-inflammatory medications and bronchodilators. However, the efficacies of the various classes of medications are not equal among all patients and may be affected by asthma phenotypes, environmental exposures, and genetic differences. Similarly, the risk for developing asthma and the natural history of the disease show great inter-individual variability due to these same factors. Over the past few decades, much effort has been focused on the genetics of asthma, and investigators have identified more than one hundred potential asthma susceptibility genes, of which at least ten have been replicated in numerous independent studies. In parallel, researchers have also identified genetic factors that impact the pharmacotherapeutic responses to the major classes of asthma medications. While the results of previous studies have been promising, future investigations need to combine genetics, pharmacogenetics, accurate disease phenotyping, and environmental exposures to build the foundation for personalized and predictive medicine for the 21st century. The ultimate goal is to enable physicians to identify those at risk for asthma, intervene to prevent or attenuate the disease, and select the optimal medical regimen for each individual patient. If successful, the resulting paradigm shift in medical practice will lead to improved clinical outcomes and decreased health care expenditures.
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