Respiratory medicine · 2026
Association of proteins involved in fetal lung development with respiratory outcomes in infancy.
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Künstle Noëmi, Gorlanova Olga, Da Silva Sena Carla Rebeca, Wyler Florian, Marten Andrea, Müller Loretta, Rüttimann Céline, Gwerder Malena, Steinberg Ruth, Sharma Pawan, Röösli Martin, Sinues Pablo, Stoecklin Benjamin, Usemann Jakob, Schär Primo, Schürmann David, Schulzke Sven, Latzin Philipp, Frey Urs, BILD study group
Аннотация
OBJECTIVE: We aimed to assess whether proteins which are involved in fetal lung development but also have an additional role in tissue or airway remodeling and oxidative stress response are associated with lung function and respiratory symptoms in infants.
STUDY DESIGN: We performed hierarchical clustering to determine distinct profiles of nine cord blood proteins (growth factors, metalloproteinases, and autophagy markers) in 369 healthy infants born to non-asthmatic mothers from the Basel-Bern Infant Lung Development cohort (BILD). Using linear and negative binomial regression analysis, we examined the association of these profiles with lung function at 4-6 weeks and respiratory symptoms in the first year of life.
RESULTS: Four protein profiles were identified, showing patterns of high growth factor, balanced protein (reference profile), low VEGF-A, and low growth factor, metalloproteinase, and autophagy marker levels. In comparison to the reference profile, the low VEGF-A levels profile was associated with reduced time to peak tidal expiratory flow to expiratory time (tPTEF/tE, -4.11, 95% confidence interval -8.04; -0.18, p = 0.041, padj = 0.123). No association was found between protein profiles and respiratory symptoms.
CONCLUSION: In healthy infants, we found no clear association between the identified protein profiles and respiratory outcomes. However, we observed a trend for reduced tPTEF/tE in the low VEGF-A levels profile, which could indicate that some protein profiles may be associated with an increased risk of impaired lung function in infancy. This might be relevant in populations with additional risk factors such as prematurity or maternal asthma.
STUDY DESIGN: We performed hierarchical clustering to determine distinct profiles of nine cord blood proteins (growth factors, metalloproteinases, and autophagy markers) in 369 healthy infants born to non-asthmatic mothers from the Basel-Bern Infant Lung Development cohort (BILD). Using linear and negative binomial regression analysis, we examined the association of these profiles with lung function at 4-6 weeks and respiratory symptoms in the first year of life.
RESULTS: Four protein profiles were identified, showing patterns of high growth factor, balanced protein (reference profile), low VEGF-A, and low growth factor, metalloproteinase, and autophagy marker levels. In comparison to the reference profile, the low VEGF-A levels profile was associated with reduced time to peak tidal expiratory flow to expiratory time (tPTEF/tE, -4.11, 95% confidence interval -8.04; -0.18, p = 0.041, padj = 0.123). No association was found between protein profiles and respiratory symptoms.
CONCLUSION: In healthy infants, we found no clear association between the identified protein profiles and respiratory outcomes. However, we observed a trend for reduced tPTEF/tE in the low VEGF-A levels profile, which could indicate that some protein profiles may be associated with an increased risk of impaired lung function in infancy. This might be relevant in populations with additional risk factors such as prematurity or maternal asthma.