Sökning: WFRF:(Marcus C.) > Validated and longi...
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001 | oai:DiVA.org:kth-280494 | |
003 | SwePub | |
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024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2804942 URI |
024 | 7 | a https://doi.org/10.1186/s12931-016-0482-92 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1348433882 URI |
040 | a (SwePub)kthd (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
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100 | 1 | a Loza, M. J.4 aut |
245 | 1 0 | a Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study |
264 | c 2016-12-15 | |
264 | 1 | b Springer Nature,c 2016 |
338 | a print2 rdacarrier | |
500 | a QC 20200910 | |
520 | a Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Lungmedicin och allergi0 (SwePub)302192 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Respiratory Medicine and Allergy0 (SwePub)302192 hsv//eng |
653 | a Biological markers | |
653 | a Cluster analysis | |
653 | a Observational study | |
653 | a biological marker | |
653 | a interleukin 13 | |
653 | a interleukin 4 | |
653 | a autacoid | |
653 | a IL4 protein | |
653 | a human | |
653 | a interleukin-13 | |
653 | a human | |
653 | a adult | |
653 | a airway obstruction | |
653 | a Article | |
653 | a asthma | |
653 | a bronchus biopsy | |
653 | a controlled study | |
653 | a disease classification | |
653 | a disease severity | |
653 | a female | |
653 | a gene expression | |
653 | a human | |
653 | a lung function | |
653 | a major clinical study | |
653 | a male | |
653 | a phenotype | |
653 | a respiratory tract disease assessment | |
653 | a Th2 cell | |
653 | a classification | |
653 | a cross-sectional study | |
653 | a forced expiratory volume | |
653 | a fuzzy logic | |
653 | a gene expression regulation | |
653 | a genetics | |
653 | a genotype | |
653 | a immunology | |
653 | a longitudinal study | |
653 | a lung | |
653 | a pathophysiology | |
653 | a predictive value | |
653 | a prognosis | |
653 | a reproducibility | |
653 | a severity of illness index | |
653 | a time factor | |
653 | a validation study | |
653 | a vital capacity | |
653 | a Cross-Sectional Studies | |
653 | a Humans | |
653 | a Inflammation Mediators | |
653 | a Interleukin-13 | |
653 | a Interleukin-4 | |
653 | a Longitudinal Studies | |
653 | a Predictive Value of Tests | |
653 | a Reproducibility of Results | |
653 | a Th2 Cells | |
653 | a Time Factors | |
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700 | 1 | a Mikus, Mariau KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik4 aut0 (Swepub:kth)u1qjoszn |
700 | 1 | a Nilsson, Peteru KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik4 aut0 (Swepub:kth)u1ws88sk |
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700 | 1 | a Therapeutics), For the ADEPT (Airways Disease Endotyping for Personalized4 aut |
700 | 1 | a investigators, U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome Consortium)4 aut |
710 | 2 | a KTHb Science for Life Laboratory, SciLifeLab4 org |
773 | 0 | t Respiratory Researchd : Springer Natureg 17:1q 17:1x 1465-9921x 1465-993X |
856 | 4 | u https://doi.org/10.1186/s12931-016-0482-9y Fulltext |
856 | 4 | u https://respiratory-research.biomedcentral.com/track/pdf/10.1186/s12931-016-0482-9 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-280494 |
856 | 4 8 | u https://doi.org/10.1186/s12931-016-0482-9 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:134843388 |
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