Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study

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Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study

Kolmert, Johan (author): Karolinska Institutet

Gomez, Cristina (author): Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, Biomed Quarter 9A, S-17177 Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.

Balgoma, David (author): Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, Biomed Quarter 9A, S-17177 Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.

Sjodin, Marcus (author): Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, Biomed Quarter 9A, S-17177 Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.

Bood, Johan (author): Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.;Karolinska Inst, Dept Med, Huddinge Campus, Stockholm, Sweden.

Konradsen, Jon R. (author): Karolinska Institutet

Ericsson, Magnus (author): Karolinska Institutet

Thorngren, John-Olof (author): Karolinska Inst, Dept Clin Pharmacol, Huddinge Campus, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.

James, Anna (author): Karolinska Institutet

Mikus, Maria (author): Karolinska Institutet

Sousa, Ana R. (author): GlaxoSmithKline, London, England.

Riley, John H. (author): GlaxoSmithKline, London, England.

Bates, Stewart (author): GlaxoSmithKline, London, England.

Bakke, Per S. (author): Univ Bergen, Inst Med, Bergen, Norway.

Pandis, Ioannis (author): Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll London, Dept Comp, London, England.;Imperial Coll London, Data Sci Inst, London, England.

Caruso, Massimo (author): Univ Catania, Dept Clin & Expt Med, Catania, Italy.;Univ Catania, Dept Biomed & Biotechnol Sci, Catania, Italy.

Chanez, Pascal (author): Aix Marseille Univ, AP HM, Clin Bronches Allergies & Sommeil, Marseille, France.

Fowler, Stephen J. (author): Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Infect Immun & Resp Med, Manchester, Lancs, England.;Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.;Manchester Univ Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, Manchester, Lancs, England.

Geiser, Thomas (author): Univ Hosp Bern, Dept Pulm Med, Bern, Switzerland.

Howarth, Peter (author): Southampton Univ, Fac Med, Southampton, Hants, England.;Univ Hosp Southampton, Biomed Res Ctr, Natl Inst Hlth Res, Southampton Resp Biomed Res Ctr, Southampton, Hants, England.

Horvath, Ildiko (author): Semmelweis Univ, Dept Pulmonol, Budapest, Hungary.

Krug, Norbert (author): Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany.

Montuschi, Paolo (author): Univ Cattolica Sacro Cuore, Dept Pharmacol, Rome, Italy.;IRCCS, Agostino Gemelli Univ Hosp Fdn, Rome, Italy.

Sanak, Marek (author): Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.

Behndig, Annelie F., 1963- (author): Umeå universitet,Avdelningen för medicin,Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.

Shaw, Dominick E. (author): Univ Nottingham, Nottingham Natl Inst Hlth Res, Biomed Res Ctr, Nottingham, England.

Knowles, Richard G. (author): Knowles Consulting, Stevenage Biosci Catalyst, Stevenage, Herts, England.

Holweg, Cecile T. J. (author): Genentech Inc, S San Fransisco, CA USA.

Wheelock, Asa M. (author)

Dahlen, Barbro (author): Karolinska Institutet

Nordlund, Bjorn (author): Karolinska Institutet

Alving, Kjell, 1959- (author): Uppsala universitet,Pediatrisk inflammations- och metabolismforskning samt barnhälsa

Hedlin, Gunilla (author): Karolinska Institutet

Chung, Kian Fan (author): Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll London, Dept Comp, London, England.;Imperial Coll London, Data Sci Inst, London, England.

Adcock, Ian M. (author)

Sterk, Peter J. (author): Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Resp Med, Amsterdam, Netherlands.

Djukanovic, Ratko (author): Southampton Univ, Fac Med, Southampton, Hants, England.;Univ Hosp Southampton, Biomed Res Ctr, Natl Inst Hlth Res, Southampton Resp Biomed Res Ctr, Southampton, Hants, England.

Dahlen, Sven-Erik (author): Karolinska Institutet

Wheelock, Craig E. (author): Karolinska Institutet

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Karolinska Institutet Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Karolinska Inst, Div Physiol Chem 2, Dept Med Biochem & Biophys, Biomed Quarter 9A, S-17177 Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden. (creator_code:org_t)

NEW YORK, USA : AMER THORACIC SOC, 2021
2021
English.
In: American Journal of Respiratory and Critical Care Medicine. - NEW YORK, USA : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 203:1, s. 37-53

Related links:: https://umu.diva-por... (primary) (Raw object); show more...; https://doi.org/10.1...; https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE(2) pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE(2) metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE4 and the PGD(2) metabolite 2,3-dinor-11 beta-PGF(2 alpha). High concentrations of LTE4 and PGD(2) metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOARED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Respiratory Medi ...

Articles in the publication: American Journal ...

By the university: Umeå University; Uppsala University; Karolinska Institutet

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Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study

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