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Airway responses to exercise in adolescents: Epidemiology, inflammation markers and pulmonary function testing
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0003-3185-3316
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
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 [en]
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: urn:nbn:se:uu:diva-568684ISBN: 978-91-513-2644-3 (print)OAI: oai:DiVA.org:uu-568684DiVA, id: diva2:2007387
Public defence
2025-12-05, H:som Holmdahl, Uppsala University Hospital/Akademiska sjukhuset, Entrance 100, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2025-11-14 Created: 2025-10-19 Last updated: 2025-11-14
List of papers
1. Prevalence of exercise-induced bronchoconstriction and laryngeal obstruction in adolescent athletes
Open this publication in new window or tab >>Prevalence of exercise-induced bronchoconstriction and laryngeal obstruction in adolescent athletes
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2020 (English)In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 55, no 12, p. 3509-3516Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To study the prevalence of exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) in adolescent athletes.

METHODS: All adolescents (n = 549) attending first year at a sports high school in 2016 and 2017, were invited to answer a questionnaire on respiratory symptoms. The 367 responding participants were divided into two groups based on whether they reported exercise-induced dyspnea (dyspnea group) or not (non-dyspnea group). Randomly selected participants in each group were invited to undergo two standardized exercise tests, an EIB test and a continuous laryngoscopy exercise (CLE) test, to investigate EILO.

RESULTS: In total, 98 participants completed an EIB test, 75 of whom also completed a CLE test. Positive EIB tests: eight of 41 in the dyspnea group and 16 of 57 in the non-dyspnea group. Positive CLE tests: five of 34 in the dyspnea group and three of 41 in the non-dyspnea group. The estimated prevalence of EIB was 23.1 % (95 % CI 14.5 - 33.8) and of EILO 8.1 % (95 % CI 2.5 - 18.5) in the whole study population. No differences in prevalence of EIB or EILO were found between the dyspnea and the non-dyspnea groups.

CONCLUSION: EIB was highly prevalent in this cohort of adolescent athletes. EILO was less prevalent, but represents an important differential diagnosis to EIB. Self-reported exercise-induced dyspnea is a weak indicator for both EIB and EILO and standardized testing should be provided.

Keywords
adolescents, dyspnea, exercise tests, high school athletes
National Category
Respiratory Medicine and Allergy Physiotherapy
Identifiers
urn:nbn:se:uu:diva-421187 (URN)10.1002/ppul.25104 (DOI)000579553600001 ()33002318 (PubMedID)
Funder
Swedish Asthma and Allergy Association, F2017-0010
Available from: 2020-10-06 Created: 2020-10-06 Last updated: 2025-10-19Bibliographically approved
2. A longitudinal study of exercise-induced bronchoconstriction and laryngeal obstruction in high school athletes
Open this publication in new window or tab >>A longitudinal study of exercise-induced bronchoconstriction and laryngeal obstruction in high school athletes
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2023 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 33, no 8, p. 1509-1518Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are common in elite athletes. Knowledge of which factors are related to incident EIB and EILO is limited. The aim of this study was to explore the course of EIB and EILO in adolescent athletes over a 2 years period and baseline characteristics related to incident EIB.

METHODS: Questionnaire data on respiratory symptoms, asthma, and aeroallergy and results of objective EIB and EILO tests were collected from 58 participants (27 tested for EILO) at baseline and after 2 years (follow-up). Associations between incident EIB and baseline asthma-like symptoms, exercise-induced symptoms, fractional exhaled nitric oxide (FeNO), aeroallergy, and sex were assessed using logistic regression models.

RESULTS: Ten participants had incident EIB, and eight participants had persistent EIB. Five were EIB positive at baseline but negative at follow-up, while 35 participants were EIB negative at both time points. Having incident EIB was associated with reporting waking up with chest tightness (OR = 4.38; 95% CI: 1.06, 22.09). Reporting an increased number of asthma-like symptoms increased the likelihood of incident EIB (OR = 2.78; 95% CI: 1.16, 6.58). No associations were found between exercise-induced symptoms, FeNO, aeroallergy, or sex and incident EIB. Incident EILO was found in three and persistent EILO in two of the 27 participants tested.

CONCLUSION: Two in nine had incident EIB and one eighth had incident EILO, suggesting that recurrent testing for EIB and EILO may be relevant in young athletes. Particularly, EIB-negative athletes reporting multiple asthma-like symptoms could benefit from recurrent EIB testing.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
adolescent, athletes, bronchoconstriction, cohort, epidemiology, exercise-induced, laryngeal obstruction
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Physiology
Identifiers
urn:nbn:se:uu:diva-501281 (URN)10.1111/sms.14373 (DOI)000975583000001 ()37082779 (PubMedID)
Funder
Swedish Asthma and Allergy Association, F2017-0010Bror Hjerpstedts stiftelseGillbergska stiftelsen
Available from: 2023-05-04 Created: 2023-05-04 Last updated: 2025-10-19Bibliographically approved
3. Postexercise Airway Responses by Spirometry and Oscillometry in Nonathlete and Athlete Adolescents
Open this publication in new window or tab >>Postexercise Airway Responses by Spirometry and Oscillometry in Nonathlete and Athlete Adolescents
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2025 (English)In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 60, no 9, article id e71296Article in journal (Refereed) Published
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-568051 (URN)10.1002/ppul.71296 (DOI)
Available from: 2025-09-25 Created: 2025-09-25 Last updated: 2025-10-19
4. Systemic inflammatory biomarkers in relation to lung function and exercise-induced bronchoconstriction in adolescents
Open this publication in new window or tab >>Systemic inflammatory biomarkers in relation to lung function and exercise-induced bronchoconstriction in adolescents
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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
Keywords
adolescents, epidemiology, exercise-induced bronchoconstriction, inflammatory biomarkers, proteomics, pulmonary function testing
National Category
Respiratory Medicine and Allergy Pediatrics
Identifiers
urn:nbn:se:uu:diva-568670 (URN)10.1111/pai.70231 (DOI)001599455700001 ()41132128 (PubMedID)
Available from: 2025-10-07 Created: 2025-10-07 Last updated: 2025-12-08Bibliographically approved

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