&lt;p&gt;Pharmacogenetics of Pediatric Asthma: Current Perspectives&lt;/p&gt;

Pérez-García, Javier; Espuela‐Ortiz, Antonio; Lorenzo-Díaz, Fabián; Pino-Yanes, María

doi:10.2147/pgpm.s201276

Cited by 17 publications

(18 citation statements)

References 97 publications

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“…Asthma is a high prevalence chronic inflammatory pulmonary disease, the respiratory symptoms of which include cough, wheezing, shortness of breath, and chest tightness which leads to elevated morbidity, mortality, and disease social and economic costs (1)(2)(3). Pulmonary inflammation is the hallmark of asthma, which is driven by a Th2 immune reponse to inhaled allergens, and associated with infiltration of the bronchial mucosa with eosinophils, CD4+ T cells, macrophages and, in exacerbations and severe cases, neutrophils (4,5).…”

Section: Introductionmentioning

confidence: 99%

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

et al. 2020

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Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE2 and the cyclopentenone prostaglandin15-Deoxy-Delta-12,14-PGJ2 (15d-PGJ2) while from LOXs are the LXA4 and LXB4. In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblasts in vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotype in vitro and in vivo. Although PGE2 and LXA4 showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2 caused side effects, while LXA4 presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.

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Section: Introductionmentioning

confidence: 99%

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

et al. 2020

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“…To date, there have been no published head-to-head studies, although the results of ongoing trials are awaited. Pharmacogenetic/epigenetics may indicate genes and/or epigenetic modifications associated with treatment response in asthma [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

Biologicals in childhood severe asthma: the European PERMEABLE survey on thestatus quo

et al. 2021

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IntroductionSevere asthma is a rare disease in children, for which three biologicals –anti-IgE, anti-IL-5 and anti-IL-4RA antibodies– are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe.MethodsStructured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data.ResultsWe interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma and only a few restrict therapy to specialised centres. We observed significant variation in the timepoint when treatment success is assessed, in therapy duration, and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals.ConclusionSubstantial differences exist in the management of childhood severe asthma across Europe and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.

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“…Regarding the genetics of asthma, adulthood and childhood asthma phenotypes have a similar but not identical genetic basis [ 38 ]. Moreover, although several genetic variants associated with asthma-related traits, such as treatment response, have demonstrated similar effects both in adults and children, many of them are not shared and aging has a mitigating effect [ 12 ]. Nevertheless, the overlap between polymorphisms related to asthma exacerbations in adults and children has been scarcely investigated [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, genome-wide association studies (GWAS) allow for assessing genetic variation throughout the whole genome without any prior hypothesis of the processes involved in, unlike candidate-gene studies that focus on targeted genes with a previous relationship with the disease [ 10 ]. While the genetic variation of asthma and other related phenotypes, such as treatment response, have been explored by GWAS, the genetic basis of severe asthma exacerbations has been scarcely investigated through candidate-gene approaches analyzing genes involved in asthma susceptibility [ 9 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Genomics and Metagenomics of Asthma Severity (GEMAS) Study: Rationale and Design

Pérez-García

Pérez

González‐Pérez

et al. 2020

JPM

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Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables (p > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls (p < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.

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<p>Pharmacogenetics of Pediatric Asthma: Current Perspectives</p>

Cited by 17 publications

References 97 publications

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

Biologicals in childhood severe asthma: the European PERMEABLE survey on thestatus quo

The Genomics and Metagenomics of Asthma Severity (GEMAS) Study: Rationale and Design

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