The Human Phenotype Ontology in 2017 Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark ...
Nucleic acids research,
11/2016, Letnik:
45, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three ...components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.
Background Guidelines recommend that for patients uncontrolled on inhaled corticosteroids (ICSs), step-up options include an increase in ICS dosage or addition of a long-acting β-agonist (LABA). ...Controversy persists about the best option in routine practice. Objective To compare asthma outcomes in patients whose first step-up from ICS monotherapy was by addition of LABA (LABA cohort) or increase in ICS dosage or formulation (ICS cohort). Methods Observational study using the General Practice Research Database, comparing outcomes in the following 12 months with regression modeling allowing for baseline cohort differences: age, sex, socioeconomic status, body mass index, comorbidity (rhinitis, heart disease), smoking status, short-acting β-agonist (SABA) use, oral corticosteroid use, and use of asthma complicating medication. Results We found 46,930 patients in the ICS and 17,418 in the LABA cohort. In adjusted analysis, the odds ratio (95% CI) of successful treatment (no hospitalization, no oral corticosteroid use, average daily SABA use <1 dose/d) was lower in the ICS cohort (0.75; 0.72-0.79). The adjusted odds ratio of needing rescue SABA prescriptions was higher in the ICS cohort (1.67; 1.59-1.76). However, the adjusted odds of using any oral corticosteroids were lower (0.75; 0.71-0.78), particularly of using 3 or more courses (0.50, 0.46-0.55), and the adjusted odds of respiratory hospitalization were lower (0.69; 0.59-0.81). Conclusion Although symptomatic control and rescue bronchodilator use may be improved by the addition of a LABA to ICS, there may be a lower risk of severe exacerbations and hospitalizations from ICS dose increase.
While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin ...pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.
We therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.
We show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.
In conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted.
Reply Price, David; Martin, Richard J; Barnes, Neil ...
Journal of allergy and clinical immunology,
03/2011, Letnik:
127, Številka:
3
Journal Article
Recenzirano
...more than two thirds of patients had at least 1 asthma consultation and one fifth an asthma exacerbation during the baseline year. Furthermore, we used composite measures based on European ...Respiratory Society/American Thoracic Society definitions of severe exacerbations and clinically relevant markers of disease severity. ...we believe our data to be complementary to those from previous classical randomized controlled trials.
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