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Systemic inflammatory biomarkers in relation to lung function and exercise-induced bronchoconstriction in adolescents
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Physiotherapy and behavioral medicine.ORCID iD: 0000-0003-3185-3316
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Inflammation, Metabolism and Child Health Research.ORCID iD: 0000-0003-0784-0443
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.ORCID iD: 0000-0003-1308-105x
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.ORCID iD: 0000-0001-5093-6980
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2025 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 36, no 10, article id e70231Article in journal (Refereed) Published
Abstract [en]

Introduction

The forced oscillation technique (FOT) complements spirometry in assessing lung function, with higher sensitivity to small airway dysfunction. Systemic inflammation is thought to influence lung development and exercise-induced bronchoconstriction (EIB), but its relationship to circulating inflammatory proteins in adolescents is unclear.

Objective

To investigate associations between systemic inflammatory biomarkers and baseline lung function and post-exercise airway responses in adolescents.

Methods

In 143 adolescents (13–15 years) from a population-based cohort, baseline spirometry, FOT, and baseline blood samples were obtained. Participants completed an exercise challenge to assess EIB via changes in forced expiratory volume in 1 s (FEV1), resistance at 5 Hz (R5), and reactance at 5 Hz (X5). Plasma protein levels were measured using the proximity extension assay technique (Olink Target Inflammation and Immune Response panels). Associations with lung function (FEV1% predicted, R5, and X5 z-scores) and post-exercise responses (∆FEV1, ∆R5, ∆X5) were analyzed using linear regression with false discovery rate correction. Interaction with atopy was also examined.

Results

Higher plasma levels of C-C motif chemokine 19 (CCL19) were significantly associated with lower FEV1% predicted and lower X5 z-scores at baseline, indicating reduced lung function and impaired small airway function. No proteins were associated with post-exercise airway responses after correction. Five proteins showed significant interactions with atopy in relation to EIB.

Conclusion

Elevated CCL19 may reflect systemic inflammatory processes contributing to impaired lung function in early adolescence. The observed atopy-related interactions suggest the need to consider atopy in studies of systemic inflammation and airway physiology.

Place, publisher, year, edition, pages
John Wiley & Sons, 2025. Vol. 36, no 10, article id e70231
Keywords [en]
adolescents, epidemiology, exercise-induced bronchoconstriction, inflammatory biomarkers, proteomics, pulmonary function testing
National Category
Respiratory Medicine and Allergy Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-568670DOI: 10.1111/pai.70231ISI: 001599455700001PubMedID: 41132128OAI: oai:DiVA.org:uu-568670DiVA, id: diva2:2004398
Available from: 2025-10-07 Created: 2025-10-07 Last updated: 2025-12-08Bibliographically approved
In thesis
1. Airway responses to exercise in adolescents: Epidemiology, inflammation markers and pulmonary function testing
Open this publication in new window or tab >>Airway responses to exercise in adolescents: Epidemiology, inflammation markers and pulmonary function testing
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Airway disorders related to exercise are common in adolescents but remain underrecognized. This thesis investigates the prevalence, course, and characteristics of exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) in adolescent athletes as well as postexercise airway responses in athlete and nonathlete adolescents focusing on aspects of airway physiology and inflammation. 

Aim: The aim was to improve understanding of exercise-related airway responses in adolescents using epidemiological, clinical, and biomarker approaches. Objectives included assessing the prevalence and course of EIB and EILO in athletes, examining links between symptoms, fractional exhaled nitric oxide (FeNO), and postexercise airway responses in athletes and nonathletes, and exploring associations between systemic inflammation proteins, lung function, and airway responses in nonathletes.

Methods: Two adolescent groups were studied: athletes from a national sports high school (N=98) and nonathletes from the general population (N=143). All completed questionnaires, exercise challenge tests, FeNO measurement, and lung function assessment by spirometry and oscillometry; nonathletes also underwent plasma proteomic analysis. Studies I–II examined EIB and EILO prevalence and progression in athletes; Study III explored links between symptoms, FeNO, and postexercise airway responses in both groups; Study IV investigated associations between inflammatory proteins, lung function, and airway responses in nonathletes.

Results: Estimated EIB prevalence among athletes was 23% (95% confidence interval (CI) 14.5–33.8) and EILO 8% (95% CI 2.5–18.5). Self-reported exercise-induced dyspnea poorly predicted either condition. Both EIB and EILO were dynamic over two years. Ten participants had incident EIB, eight had persistent EIB, and five remitted. Reporting more asthma-like symptoms at baseline increased the risk of incident EIB (odds ratio (OR) 2.78; 95% CI: 1.16–6.58), while FeNO, aeroallergy, and sex were not associated with incident EIB. Incident EILO occurred in three and persistent EILO in two of 27 tested. Postexercise airway responses measured by spirometry and oscillometry showed modest concordance, indicating complementary insights into airway physiology by the two methods. Elevated FeNO was associated with EIB by both spirometric (adjusted OR 2.54; 95% CI: 1.05–6.12) and oscillometric criteria (adjusted OR 3.05; 95% CI: 1.18–7.9) in nonathletes, but not in athletes. Proteomic analyses identified the chemokine CCL19 as related to reduced baseline lung function, though no systemic proteins were associated with postexercise responses. 

Conclusions: Exercise-induced airway disorders like EIB and EILO are common but often overlooked in adolescent athletes. Because symptoms alone are unreliable, objective testing is essential. Differences in FeNO associations suggest distinct EIB mechanisms in athletes versus nonathletes. These results enhance understanding of exercise-related airway responses and support targeted diagnostic and management approaches. The association of CCL19 with lower baseline lung function in nonathletes also points to a possible link between immune activity and airway function in adolescents.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2205
Keywords
Adolescents, athletes, exercise-induced bronchoconstriction, exercise-induced laryngeal obstruction, epidemiology, inflammation markers, pulmonary function testing.
National Category
Respiratory Medicine and Allergy
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-568684 (URN)978-91-513-2644-3 (ISBN)
Public defence
2025-12-05, H:som Holmdahl, Uppsala University Hospital/Akademiska sjukhuset, Entrance 100, Uppsala, 09:15 (English)
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Supervisors
Available from: 2025-11-14 Created: 2025-10-19 Last updated: 2025-11-14

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Ersson, KarinAlving, KjellEmtner, MargaretaJanson, ChristerJohansson, HenrikMalinovschi, Andrei

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