Introduction: Airway remodelling in children with severe recurrent episodes of bronchial obstruction starts very early, from preschool age – a period in which the diagnosis of asthma is not yet confirmed. Assessing these early structural changes presents a challenge in clinical practice. Due to the limitations of invasive methods, reliable noninvasive markers of these changes are sought. Galectin-3 (Gal-3), a regulator of inflammatory and fibrotic processes, and Krebs von den Lungen-6 (KL-6), a marker of alveolar epithelial damage, are considered as indicators of lung remodelling. Methods: Forty-eight children were studied: 26 children under 4 years of age with recurrent episodes of wheezing (RW) and 22 with cystic fibrosis (CF). Children with RW were divided into two subgroups: those with a low frequency (≤3 episodes/year) and those with a high frequency (>6 episodes/year) of bronchoobstructive symptoms. CF patients were stratified according to genotype (ΔF508 homozygous or heterozygous), and all underwent computed tomography (HRCT). Serum Gal-3 and KL-6 levels were measured by the ELISA method. The correlation between Gal-3 and KL-6 and clinical severity in children with recurrent wheezing at preschool age, and between Gal-3 and KL-6 and radiologically confirmed structural lung changes in children with cystic fibrosis, was assessed. Results: Elevated Gal-3 levels were found in children with RW from infancy. Although the differences in median Gal-3 levels did not reach statistical significance in the two RW subgroups, children with a high frequency of wheezing were 1.76 times more likely to have elevated Gal-3 (>26 ng/mL) compared to those with a low frequency of RW (p = 0.02). In CF, Gal-3 levels were significantly higher in children with confirmed structural lung disease on HRCT compared to those without pathological changes (38.35 vs. 11.63 ng/mL, p = 0.001). The highest Gal-3 values were found in ΔF508 homozygous patients with bronchiectasis. KL-6 levels remained within the normal range for the pediatric population across all groups and did not correlate with the frequency of bronchoobstructive manifestations, genotype, or CT findings. Conclusion: Galectin-3 is a reliable biomarker for pediatric pulmonology practice, reflecting early pulmonary changes in children with frequent recurrent bronchoobstructive episodes and a risk of persistent manifestations, and it correlates with structural damage in cystic fibrosis patients. KL-6 has no diagnostic value in the early stages of pulmonary pathology.
| Published in | American Journal of Pediatrics (Volume 12, Issue 1) |
| DOI | 10.11648/j.ajp.20261201.13 |
| Page(s) | 14-19 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2026. Published by Science Publishing Group |
Galectin-3, KL-6, Recurrent Wheezing, Cystic Fibrosis, Airway Remodelling
| [1] | Saglani S, Payne DN, Zhu J, et al. Early detection of airway wall remodelling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med. 2007; 176(9): 858-864. |
| [2] | Lezmi G, Gosset P, Deschildre A, et al. Airway Remodeling in Preschool Children with Severe Recurrent Wheeze. Am J Respir Crit Care Med. 2015; 192(2): 164-171. |
| [3] | Silva TKBD, Zanon M, Altmayer S, et al. High-resolution CT pulmonary findings in children with severe asthma. J Pediatr (Rio J). 2021; 97(1): 37-43. |
| [4] | Portacci A, Iorillo I, Maselli L, et al. The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review. Curr Issues Mol Biol. 2024; 46(5): 4271-4285. Published 2024 May 3. |
| [5] | Henderson, NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009; 230(1): 160-171. |
| [6] | Zuberi RI, Hsu DK, Kalayci O, et al. Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. Am J Pathol. 2004; 165(6): 2045-2053. |
| [7] | Calver JF, Parmar NR, Harris G, et al. Defining the mechanism of galectin-3-mediated TGF-β1 activation and its role in lung fibrosis. J Biol Chem. 2024; 300(6): 107300. |
| [8] | Mauri P, Riccio AM, Rossi R, et al. Proteomics of bronchial biopsies: galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients. Immunol Lett. 2014; 162(1 Pt A): 2-10. |
| [9] | Riccio AM, Mauri P, De Ferrari L, et al. Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months. Clin Transl Allergy. 2017; 7: 6. Published 2017 Mar 9. |
| [10] | Krintus M, Kozinski M, Fabiszak T, Kubica J, Panteghini M, Sypniewska G. Establishing reference intervals for galectin-3 concentrations in serum requires careful consideration of its biological determinants. Clin Biochem. 2017; 50(10-11): 599-604. |
| [11] | Gravrand V, Lefebvre CS, Hamza F, et al. Pediatric reference values of NT-proBNP and Galectin-3 based on a French cohort. Clin Chim Acta. 2025; 564: 119925. |
| [12] | Meeusen JW, Johnson JN, Gray A, et al. Soluble ST2 and galectin-3 in pediatric patients without heart failure. Clin Biochem. 2015; 48(18): 1337-1340. |
| [13] | Wang C, Wang Q, Liu T, Zhu J, Zhang B. Krebs von den Lungen-6 (KL-6) as a diagnostic marker for pulmonary fibrosis: A systematic review and meta-analysis. Clin Biochem. 2023; 114: 30-38. |
| [14] | Imai T, Takase M, Takeda S, Kougo T. Serum KL-6 levels in pediatric patients: reference values for children and levels in pneumonia, asthma, and measles patients. Pediatr Pulmonol. 2002; 33(2): 135-141. |
| [15] | Vianello A, Guarnieri G, Achille A, et al. Serum biomarkers of remodeling in severe asthma with fixed airway obstruction and the potential role of KL-6. Clin Chem Lab Med. 2023; 61(10): 1679-1687. Published 2023 Mar 30. |
| [16] | Xu L, Yan DR, Zhu SL, et al. KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation. Eur Rev Med Pharmacol Sci. 2013; 17(22): 3073-77. |
| [17] | Gao P, Simpson JL, Zhang J, Gibson PG. Galectin-3: its role in asthma and potential as an anti-inflammatory target. Respir Res. 2013 Dec 9; 14(1): 136. |
| [18] | Ademhan Tural D, Emiralioglu N, Akin S, et al. Galectin-3 levels in children with cystic fibrosis. Eur J Pediatr. 2024; 183(5): 2333-2342. |
| [19] | Hilliard TN, Regamey N, Shute JK, et al. Airway remodelling in children with cystic fibrosis. Thorax. 2007; 62(12): 1074-1080. |
APA Style
Kostova, P., Hristova, J., Georgieva, B., Petrova, G., Mileva, S. (2026). Galectin-3 and KL-6 as Biomarkers of Airway Remodelling and Fibrosis in Children with Chronic Lung Diseases. American Journal of Pediatrics, 12(1), 14-19. https://doi.org/10.11648/j.ajp.20261201.13
ACS Style
Kostova, P.; Hristova, J.; Georgieva, B.; Petrova, G.; Mileva, S. Galectin-3 and KL-6 as Biomarkers of Airway Remodelling and Fibrosis in Children with Chronic Lung Diseases. Am. J. Pediatr. 2026, 12(1), 14-19. doi: 10.11648/j.ajp.20261201.13
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ajp.20261201.13,
author = {Polina Kostova and Julieta Hristova and Bilyana Georgieva and Gergana Petrova and Sirma Mileva},
title = {Galectin-3 and KL-6 as Biomarkers of Airway Remodelling and Fibrosis in Children with Chronic Lung Diseases},
journal = {American Journal of Pediatrics},
volume = {12},
number = {1},
pages = {14-19},
doi = {10.11648/j.ajp.20261201.13},
url = {https://doi.org/10.11648/j.ajp.20261201.13},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20261201.13},
abstract = {Introduction: Airway remodelling in children with severe recurrent episodes of bronchial obstruction starts very early, from preschool age – a period in which the diagnosis of asthma is not yet confirmed. Assessing these early structural changes presents a challenge in clinical practice. Due to the limitations of invasive methods, reliable noninvasive markers of these changes are sought. Galectin-3 (Gal-3), a regulator of inflammatory and fibrotic processes, and Krebs von den Lungen-6 (KL-6), a marker of alveolar epithelial damage, are considered as indicators of lung remodelling. Methods: Forty-eight children were studied: 26 children under 4 years of age with recurrent episodes of wheezing (RW) and 22 with cystic fibrosis (CF). Children with RW were divided into two subgroups: those with a low frequency (≤3 episodes/year) and those with a high frequency (>6 episodes/year) of bronchoobstructive symptoms. CF patients were stratified according to genotype (ΔF508 homozygous or heterozygous), and all underwent computed tomography (HRCT). Serum Gal-3 and KL-6 levels were measured by the ELISA method. The correlation between Gal-3 and KL-6 and clinical severity in children with recurrent wheezing at preschool age, and between Gal-3 and KL-6 and radiologically confirmed structural lung changes in children with cystic fibrosis, was assessed. Results: Elevated Gal-3 levels were found in children with RW from infancy. Although the differences in median Gal-3 levels did not reach statistical significance in the two RW subgroups, children with a high frequency of wheezing were 1.76 times more likely to have elevated Gal-3 (>26 ng/mL) compared to those with a low frequency of RW (p = 0.02). In CF, Gal-3 levels were significantly higher in children with confirmed structural lung disease on HRCT compared to those without pathological changes (38.35 vs. 11.63 ng/mL, p = 0.001). The highest Gal-3 values were found in ΔF508 homozygous patients with bronchiectasis. KL-6 levels remained within the normal range for the pediatric population across all groups and did not correlate with the frequency of bronchoobstructive manifestations, genotype, or CT findings. Conclusion: Galectin-3 is a reliable biomarker for pediatric pulmonology practice, reflecting early pulmonary changes in children with frequent recurrent bronchoobstructive episodes and a risk of persistent manifestations, and it correlates with structural damage in cystic fibrosis patients. KL-6 has no diagnostic value in the early stages of pulmonary pathology.},
year = {2026}
}
TY - JOUR T1 - Galectin-3 and KL-6 as Biomarkers of Airway Remodelling and Fibrosis in Children with Chronic Lung Diseases AU - Polina Kostova AU - Julieta Hristova AU - Bilyana Georgieva AU - Gergana Petrova AU - Sirma Mileva Y1 - 2026/01/30 PY - 2026 N1 - https://doi.org/10.11648/j.ajp.20261201.13 DO - 10.11648/j.ajp.20261201.13 T2 - American Journal of Pediatrics JF - American Journal of Pediatrics JO - American Journal of Pediatrics SP - 14 EP - 19 PB - Science Publishing Group SN - 2472-0909 UR - https://doi.org/10.11648/j.ajp.20261201.13 AB - Introduction: Airway remodelling in children with severe recurrent episodes of bronchial obstruction starts very early, from preschool age – a period in which the diagnosis of asthma is not yet confirmed. Assessing these early structural changes presents a challenge in clinical practice. Due to the limitations of invasive methods, reliable noninvasive markers of these changes are sought. Galectin-3 (Gal-3), a regulator of inflammatory and fibrotic processes, and Krebs von den Lungen-6 (KL-6), a marker of alveolar epithelial damage, are considered as indicators of lung remodelling. Methods: Forty-eight children were studied: 26 children under 4 years of age with recurrent episodes of wheezing (RW) and 22 with cystic fibrosis (CF). Children with RW were divided into two subgroups: those with a low frequency (≤3 episodes/year) and those with a high frequency (>6 episodes/year) of bronchoobstructive symptoms. CF patients were stratified according to genotype (ΔF508 homozygous or heterozygous), and all underwent computed tomography (HRCT). Serum Gal-3 and KL-6 levels were measured by the ELISA method. The correlation between Gal-3 and KL-6 and clinical severity in children with recurrent wheezing at preschool age, and between Gal-3 and KL-6 and radiologically confirmed structural lung changes in children with cystic fibrosis, was assessed. Results: Elevated Gal-3 levels were found in children with RW from infancy. Although the differences in median Gal-3 levels did not reach statistical significance in the two RW subgroups, children with a high frequency of wheezing were 1.76 times more likely to have elevated Gal-3 (>26 ng/mL) compared to those with a low frequency of RW (p = 0.02). In CF, Gal-3 levels were significantly higher in children with confirmed structural lung disease on HRCT compared to those without pathological changes (38.35 vs. 11.63 ng/mL, p = 0.001). The highest Gal-3 values were found in ΔF508 homozygous patients with bronchiectasis. KL-6 levels remained within the normal range for the pediatric population across all groups and did not correlate with the frequency of bronchoobstructive manifestations, genotype, or CT findings. Conclusion: Galectin-3 is a reliable biomarker for pediatric pulmonology practice, reflecting early pulmonary changes in children with frequent recurrent bronchoobstructive episodes and a risk of persistent manifestations, and it correlates with structural damage in cystic fibrosis patients. KL-6 has no diagnostic value in the early stages of pulmonary pathology. VL - 12 IS - 1 ER -
Department of Paediatrics, Medical University, Sofia, Bulgaria;Aleksandrovska Hospital, Sofia, Bulgaria
Department of Clinical Laboratory, Medical University, Sofia, Bulgaria;Aleksandrovska Hospital, Sofia, Bulgaria
Department of Paediatrics, Medical University, Sofia, Bulgaria;Aleksandrovska Hospital, Sofia, Bulgaria
Department of Paediatrics, Medical University, Sofia, Bulgaria;Aleksandrovska Hospital, Sofia, Bulgaria
Department of Paediatrics, Medical University, Sofia, Bulgaria;Aleksandrovska Hospital, Sofia, Bulgaria
Information