Pharmacogenomic associations of adverse drug reactions in asthma:systematic review and research prioritisation

We would like to thank the NIHR Collaboration for Leadership in Applied Health Research and Care North West Coast (CLAHRC) for funding Amanda McKenna’s internship, and Charlotte Kings MPhil, and the members of the PiCA consortia for their help in completing the survey. U. Potočnik, K. Repnik and V. Berce were supported by SysPharmPedia grant, co-financed by Ministry of Education, Science and Sport of the Republic of Slovenia Author information These authors contributed equally: Charlotte King, Amanda McKenna These authors jointly supervised this work: Ian Sinha, Daniel B. HawcuttPeer reviewedPublisher PD

The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs.

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation

Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy

Toward composite molecular signatures in the phenotyping of asthma

The complex biology of respiratory diseases such as asthma is feeding the discovery of various disease phenotypes. Although the clinical management of asthma phenotypes by using a single biomarker (e.g., sputum eosinophils) is successful, emerging evidence shows the requirement of multiscale, high-dimensional biological and clinical measurements to capture the complexity of various asthma phenotypes. High-throughput "omics" technologies, including transcriptomics, proteomics, lipidomics, and metabolomics, are increasingly standardized for biomarker discovery in asthma. The leading principle is obeying available guidelines on omics analysis, thereby strictly limiting false discovery. In this review we address the concept of transcriptomics using microarrays or next-generation RNA sequencing and their applications in asthma, highlighting the strengths and limitations of both techniques, and review metabolomics in exhaled air (breathomics) as a noninvasive alternative for sampling the airways directly. These developments will inevitably lead to the integration of molecular signatures in the phenotyping of asthma and other disease

Targeted breath analysis: exogenous volatile organic compounds (EVOC) as metabolic pathway-specific probes

Breath research has almost invariably focussed on the identification of endogenous volatile organic compounds (VOCs) as disease biomarkers. After five decades, a very limited number of breath tests measuring endogenous VOCs is applied to the clinic. In this perspective article, we explore some of the factors that may have contributed to the current lack of clinical applications of breath endogenous VOCs. We discuss potential pitfalls of experimental design, analytical challenges, as well as considerations regarding the biochemical pathways that may impinge on the application of endogenous VOCs as specific disease biomarkers. We point towards several lines of evidence showing that breath analysis based on administration of exogenous compounds has been a more successful strategy, with several tests currently applied to the clinic, compared to measurement of endogenous VOCs. Finally, we propose a novel approach, based on the use of exogenous VOC (EVOC) probes as potential strategy to measure the activity of metabolic enzymes in vivo, as well as the function of organs, through breath analysis. We present longitudinal data showing the potential of EVOC probe strategies in breath analysis. We also gathered important data showing that administration of EVOC probes induces significant changes compared to previous exposures to the same compounds. EVOC strategies could herald a new wave of substrate-based breath tests, potentially bridging the gap between research tools and clinical applications

Article Electronic Nose Breathprints Are Independent of Acute Changes in Airway Caliber in Asthma

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