Simultaneously elevated exhaled nitric oxide and serum‐eosinophil cationic protein relate to recent asthma events in asthmatics in a cross‐sectional population‐based study

Mogensen, Ida; Alving, Kjell; Bjerg, Anders; Borres, Magnus P.; Hedlin, Gunilla; Sommar, Johan Nilsson; Dahlén, Sven‐Erik; Janson, Christer; Malinovschi, Andreï

doi:10.1111/cea.12792

Cited by 28 publications

(23 citation statements)

References 38 publications

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“…28 ECP, a protein released when eosinophils are activated, may better reflect the degree of eosinophilic inflammation in the airways and is closely related to recent exacerbations. 29,30 This may explain our result that the cases had significantly higher eosinophil counts in blood but their serum ECP only showed a statistical trend to be higher than in the controls, as their airway inflammation had not yet developed into symptomatic asthma. Measurements of ECP in sputum also showed a tendency to be higher in the cases than in the controls, which is in line with another study that showed a correlation between sputum ECP and FeNO, in children with asthma.…”

Section: Feno Represents Local Inflammation In the Airways And Relatesmentioning

confidence: 75%

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Kalm-Stephens

Malinovschi

Janson

et al. 2020

Pediatric Pulmonology

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Objectives The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type‐2 inflammation in the airways. Methodology A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO100 > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO100 < 5 ppb) and without reported symptoms of asthma or allergy (n = 28), participated in a follow‐up study where FeNO50, airway responsiveness to methacholine (PD20), blood eosinophil counts, and serum neutrophil lipocalin (HNL) and myeloperoxidase (MPO) levels were measured. Questionnaire follow‐ups were performed 4 and 16 years later. Results Airway responsiveness (PD20: 6.94 [1.87, 11.39] vs 11.42 [6.33, 59.4] µmol; P < .05) and blood eosinophil counts (0.31 [0.20, 0.44] vs 0.13 [0.1, 0.22] 109/L; P < .001) (geometric mean [95% CI]) were higher among cases than controls. A significant correlation between blood eosinophils and FeNO was found (rho = 0.41; P = .005). In contrast, serum HNL and MPO were lower in cases than controls (P < .05 both), and there was a negative correlation between HNL and FeNO (r = −0.31; P = .04). At both follow‐ups, a higher proportion of subjects reported allergic symptoms compared with baseline (P = .02, P = .01). Conclusions Elevated FeNO in nonasthmatic adolescents was associated with airway hyperresponsiveness, elevated blood eosinophil counts, and lower systemic activation of neutrophils.

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Section: Feno Represents Local Inflammation In the Airways And Relatesmentioning

confidence: 75%

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Kalm-Stephens

Malinovschi

Janson

et al. 2020

Pediatric Pulmonology

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“…10 Four biomarkers known to reflect type 2 inflammation are as follows: serum periostin (S-periostin), fraction of exhaled NO (FeNO), urinary eosinophilderived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP). 23 It is important to identify whether there is a relation between fixed airflow obstruction and type 2 inflammation markers, as these markers of inflammation are regarded as treatable disease traits 24 and therefore might change the course of the disease. 12,13 Nitric oxide is produced by the airway epithelium and is increased by IL 4 and IL 13 in particular.…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22] We have previously demonstrated that a combination of type 2 biomarkers, FeNO, and S-ECP relates to more asthma attacks the preceding 3 months. 23 It is important to identify whether there is a relation between fixed airflow obstruction and type 2 inflammation markers, as these markers of inflammation are regarded as treatable disease traits 24 and therefore might change the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Mogensen

Alving

Dahlén

et al. 2018

Clin Experimental Allergy

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Background: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO. Objectives:To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.Methods: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV 1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).Results: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06(2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO. Conclusions and clinical relevance:These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO.This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

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“…Mogensen et al have shown that simultaneously elevated exhaled nitric oxide and serum‐eosinophil cationic protein are related to recent asthma events in asthmatics in a cross‐sectional population‐based study. Simultaneously elevated FeNO and ECP (controlling for current smoking) were associated with more symptoms and exacerbations of asthma with each marker contributing independently to symptoms and exacerbations respectively.…”

Section: Asthma and Rhinitismentioning

confidence: 99%

Developments in the field of allergy in 2016 through the eyes of Clinical and Experimental Allergy

Roberts

Boyle

Crane

et al. 2017

Clin Experimental Allergy

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Simultaneously elevated exhaled nitric oxide and serum‐eosinophil cationic protein relate to recent asthma events in asthmatics in a cross‐sectional population‐based study

Abstract: FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.

Cited by 28 publications

References 38 publications

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Developments in the field of allergy in 2016 through the eyes of Clinical and Experimental Allergy

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