Suneela Zaigham, Nils Oskar Jõgi, Robert Movérare, Anders Sjölander, Niclas Rydell, Magnus Molin, Christer Janson, Andrei Malinovschi
<p>Eosinophilic inflammation in asthma is related to disease severity, lung function decline, disease control and response to corticosteroids during exacerbations [<span>1-3</span>]. Eosinophil activation leads to the release of cytokines, lipid mediators, chemotactic polypeptides and cytotoxic proteins that promote a pro-inflammatory host response and neutralises pathogens [<span>4</span>]. One of the cytotoxic granule proteins released during degranulation of activated eosinophils is the eosinophil-derived neurotoxin (EDN). Serum EDN is emerging as a novel marker of eosinophilic inflammation in patients with asthma [<span>4</span>]. In order to implement serum EDN as a marker in clinical practice, determinants and reference ranges for EDN need to be clearly established. Recently, EDN reference values were defined in early childhood [<span>5</span>]; however, further large studies defining values in older adults are needed. We aimed to study determinants of EDN using the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population study of middle-aged adults and propose reference values for EDN, including the lower (LLN) and upper limit of normal (ULN), in a healthy sub-population.</p><p>The Swedish CArdioPulmonary bioImage Study is a national, multicentred, population-based study of randomly selected men and women aged 50–64 years. Nationally, 30,154 men and women participated and from the Uppsala cohort 5036 subjects [<span>6</span>]. Serum EDN was an add-on measurement in the Uppsala cohort of SCAPIS (<i>n</i> = 4916) and was measured using an ImmunoCAP EDN research assay as described elsewhere [<span>7</span>]. EDN values were log-transformed for analysis. Univariate analyses were carried out to assess determinants of EDN, including age, sex, lifestyle, clinical conditions (assessed via questionnaire) and laboratory data. Independent sample <i>t</i>-tests were used to obtain mean values of EDN by each potential determining factor. The <i>p</i>-values were adjusted for false discovery rate (FDR) using the Benjamini–Hochberg method. Multiple linear regression models were used to assess the effect of determining factors on EDN. To define normal values of EDN, we selected a healthy population based on subjects free from EDN-modifying conditions. In this healthy sub-cohort, we used the 5<sup>th</sup> (LLN), 50<sup>th</sup> (median), 75<sup>th</sup>, 90<sup>th</sup> and 95<sup>th</sup> (ULN) percentiles to determine reference levels for serum EDN.</p><p>Male sex, body mass index (BMI) > 25, current smoking, presence of atopy, ever asthma, allergic rhinitis, angina pectoris, heart failure, hypertension, diabetes and impaired kidney function were all associated with higher mean EDN levels. Both pre-bronchodilatory FEV<sub>1</sub> < LLN and a post-bronchodilatory FEV<sub>1</sub>/FVC ratio < 0.70 were associated with higher mean EDN levels. After adjusting the <i>p</i>-values for FDR, these determining factors remained significantly
{"title":"Eosinophil-Derived Neurotoxin Determinants and Reference Values in a Swedish Middle-Aged General Population","authors":"Suneela Zaigham, Nils Oskar Jõgi, Robert Movérare, Anders Sjölander, Niclas Rydell, Magnus Molin, Christer Janson, Andrei Malinovschi","doi":"10.1111/cea.14579","DOIUrl":"10.1111/cea.14579","url":null,"abstract":"<p>Eosinophilic inflammation in asthma is related to disease severity, lung function decline, disease control and response to corticosteroids during exacerbations [<span>1-3</span>]. Eosinophil activation leads to the release of cytokines, lipid mediators, chemotactic polypeptides and cytotoxic proteins that promote a pro-inflammatory host response and neutralises pathogens [<span>4</span>]. One of the cytotoxic granule proteins released during degranulation of activated eosinophils is the eosinophil-derived neurotoxin (EDN). Serum EDN is emerging as a novel marker of eosinophilic inflammation in patients with asthma [<span>4</span>]. In order to implement serum EDN as a marker in clinical practice, determinants and reference ranges for EDN need to be clearly established. Recently, EDN reference values were defined in early childhood [<span>5</span>]; however, further large studies defining values in older adults are needed. We aimed to study determinants of EDN using the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population study of middle-aged adults and propose reference values for EDN, including the lower (LLN) and upper limit of normal (ULN), in a healthy sub-population.</p><p>The Swedish CArdioPulmonary bioImage Study is a national, multicentred, population-based study of randomly selected men and women aged 50–64 years. Nationally, 30,154 men and women participated and from the Uppsala cohort 5036 subjects [<span>6</span>]. Serum EDN was an add-on measurement in the Uppsala cohort of SCAPIS (<i>n</i> = 4916) and was measured using an ImmunoCAP EDN research assay as described elsewhere [<span>7</span>]. EDN values were log-transformed for analysis. Univariate analyses were carried out to assess determinants of EDN, including age, sex, lifestyle, clinical conditions (assessed via questionnaire) and laboratory data. Independent sample <i>t</i>-tests were used to obtain mean values of EDN by each potential determining factor. The <i>p</i>-values were adjusted for false discovery rate (FDR) using the Benjamini–Hochberg method. Multiple linear regression models were used to assess the effect of determining factors on EDN. To define normal values of EDN, we selected a healthy population based on subjects free from EDN-modifying conditions. In this healthy sub-cohort, we used the 5<sup>th</sup> (LLN), 50<sup>th</sup> (median), 75<sup>th</sup>, 90<sup>th</sup> and 95<sup>th</sup> (ULN) percentiles to determine reference levels for serum EDN.</p><p>Male sex, body mass index (BMI) > 25, current smoking, presence of atopy, ever asthma, allergic rhinitis, angina pectoris, heart failure, hypertension, diabetes and impaired kidney function were all associated with higher mean EDN levels. Both pre-bronchodilatory FEV<sub>1</sub> < LLN and a post-bronchodilatory FEV<sub>1</sub>/FVC ratio < 0.70 were associated with higher mean EDN levels. After adjusting the <i>p</i>-values for FDR, these determining factors remained significantly ","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 1","pages":"91-93"},"PeriodicalIF":6.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}