Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE

Abstract Background The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels. Methods We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0–5, 6–18, ≥ 18 years) of standardized log 10 -transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes. Results Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56–3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years ( R = 0.19, p = 0.007 ). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01–1.87), and in adult asthmatics with impaired lung function ( R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50–0.85) but higher levels in adults (OR 1.99, 95% CI 1.02–4.09). Conclusions HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring. Trial registration ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.

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Journal
Respiratory Research
Published
2026-07-27
DOI
https://doi.org/10.1186/s12931-026-03840-x
Primary Topic
Asthma and respiratory diseases
Type
article
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article

Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE

Vera Veith, Esther Zeitlmann, Wasifa Nurieva, Thomas Bahmer et al.
Respiratory Research
Asthma and respiratory diseases
article

Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE

Vera Veith, Esther Zeitlmann, Wasifa Nurieva, Thomas Bahmer, Silvia Gschwendtner, Clemens Thölken, Svenja Foth, Tobias Trojan, Folke Brinkmann, Matthias Kopp, CB Schmidt-Weber, Markus Ege, Wiebke Hagedorn, Ruth Grychtol, Inke Regina König, Svenja Gaedcke, Klaus F. Rabe, Nicole Maison, Anna‐Maria Dittrich, Frauke Pedersen, Francesco Foppiano, Erika von Mutius, Kristina Laubhahn, Harald Renz, Benjamin Waschki, Bianca Schaub, Sabina Illi, Markus Weckmann, Jan-Christoph Thomassen, Silke van Koningsbruggen‐Rietschel, Gesine Hansen, Jimmy Omony, Lennart Riemann, Heike Biller, Mustafa Abdo, Inga Jerrentrup, Adan Chari Jirmo, Anika Habener, Lea Louisa Kronziel, Mifflin-Rae Calvero, Gyde Nissen, Isabell Ricklefs, Lena Ullemeyer, Miguel A Alejandre Alcázar, A Hose, Christopher Wirks, Chrysanthi Skevaki, Constanze Jakwerth, Ernst Rietschel, Mira Bürk, Karoline I. Gaede, Silke Szymczak, Lena Lagally, Henrik Watz, Lena Keufken, Nikolas Jacobs, Bin Liu, Anne-Marie Kirsten, ALLIANCE Study Group, Michael Schloter, Constantin Blanke-Roeser, Marie Bickes, David S. DeLuca, Loana Penner, Christine Happle, Sybille Contento, Stefanie Weber
article en

Abstract

Abstract Background The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels. Methods We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0–5, 6–18, ≥ 18 years) of standardized log 10 -transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes. Results Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56–3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years ( R = 0.19, p = 0.007 ). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01–1.87), and in adult asthmatics with impaired lung function ( R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50–0.85) but higher levels in adults (OR 1.99, 95% CI 1.02–4.09). Conclusions HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring. Trial registration ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.

Respiratory ResearchVol. 27(1)
University of Bern (CH), Harvard University (US), Philipps University of Marburg (DE), Zimmer Biomet (Netherlands) (NL), University of Cologne (DE), Academy of Athens (GR), Heidelberg University (DE), University Hospital of Bern (CH), University Hospital Heidelberg (DE), Helmholtz Zentrum München (DE), LMU Klinikum (DE), Medizinische Hochschule Hannover (DE), University Hospital Schleswig-Holstein (DE), University Children’s Hospital Bern (CH), Research Center Borstel - Leibniz Lung Center (DE), German Center for Lung Research (DE), LungenClinic Grosshansdorf (DE), Loewe Center for Synthetic Microbiology (DE), University Hospital Cologne (DE), Ludwig-Maximilians-Universität München (DE), University of Lübeck (DE)
Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, European Respiratory Society, Philipps-Universität Marburg, Fondazione Internazionale Premio Balzan, McMaster University, Deutsche Forschungsgemeinschaft, Karolinska Institutet, Gottfried Wilhelm Leibniz Universität Hannover, Latvijas Zinātnes Padome, Medizinischen Hochschule Hannover, Technische Universität München, Universität Zürich, Universität zu Köln, Fondazione Internazionale Menarini, Deutsches Zentrum für Lungenforschung, European Academy of Allergy and Clinical Immunology, Universitätsklinikum Köln, Novartis Pharma, Leibniz-Gemeinschaft
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