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Am J Perinatol 2022; 39(S 01): S26-S30
DOI: 10.1055/s-0042-1758867
Review Article

Early Biomarkers of Bronchopulmonary Dysplasia: A Quick Look to the State of the Art

Luca Bonadies
1   Neonatal Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padova, Italy
2   Department of Woman's and Child's Health, Institute of Pediatric Research “Città della Speranza,” Padova, Italy
,
Laura Moschino
1   Neonatal Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padova, Italy
2   Department of Woman's and Child's Health, Institute of Pediatric Research “Città della Speranza,” Padova, Italy
,
Enrico Valerio
1   Neonatal Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padova, Italy
2   Department of Woman's and Child's Health, Institute of Pediatric Research “Città della Speranza,” Padova, Italy
,
Giuseppe Giordano
2   Department of Woman's and Child's Health, Institute of Pediatric Research “Città della Speranza,” Padova, Italy
3   Department of Woman's and Child's Health, Mass Spectrometry and Metabolomic Laboratory, University of Padova, Padova, Italy
,
Paolo Manzoni
4   Division of Pediatrics and Neonatology, Department of Maternal, Neonatal and Infant Medicine, University Hospital “Degli Infermi,” Ponderano, Italy
5   Department of Sciences of Public Health and Pediatrics, University of Turin School of Medicine, Turin, Italy
,
Eugenio Baraldi
1   Neonatal Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padova, Italy
2   Department of Woman's and Child's Health, Institute of Pediatric Research “Città della Speranza,” Padova, Italy
3   Department of Woman's and Child's Health, Mass Spectrometry and Metabolomic Laboratory, University of Padova, Padova, Italy
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Abstract

Bronchopulmonary dysplasia (BPD) is one of the most common pulmonary sequelae of extreme preterm birth, with long-lasting respiratory symptoms and reduced lung function. A reliable predictive tool of BPD development is urgent and its search remains one of the major challenges for neonatologists approaching the upcoming arrival of possible new preventive therapies. Biomarkers, identifying an ongoing pathogenetic pathway, could allow both the selection of preterm infants with an evolving disease and potentially the therapeutic targets of the indicted pathogenesis. The “omic” sciences represent well-known promising tools for this objective. In this review, we resume the current laboratoristic, metabolomic, proteomic, and microbiomic evidence in the prediction of BPD.

Key Points

  • The early prediction of BPD development would allow the targeted implementation of new preventive therapies.

  • BPD is a multifactorial disease consequently it is unlikely to find a single disease biomarker.

  • “Omic” sciences offer a promising insight in BPD pathogenesis and its development's fingerprints.

Keyword

bronchopulmonary dysplasia - biomarkers - preterm


Publikationsverlauf

Artikel online veröffentlicht:
05. Dezember 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA 2015; 314 (10) 1039-1051
    CrossrefPubMedGoogle Scholar
  • 2 Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med 2007; 357 (19) 1946-1955
    CrossrefPubMedGoogle Scholar
  • 3 Bonadies L, Papi A, Baraldi E. Is bronchopulmonary dysplasia in adult age a novel COPD endotype?. Eur Respir J 2022; 60 (03) 2200984
    CrossrefPubMedGoogle Scholar
  • 4 Crump C, Howell EA, Stroustrup A, McLaughlin MA, Sundquist J, Sundquist K. Association of preterm birth with risk of ischemic heart disease in adulthood. JAMA Pediatr 2019; 173 (08) 736-743
    CrossrefPubMedGoogle Scholar
  • 5 Bonadies L, Zaramella P, Porzionato A, Muraca M, Baraldi E. Bronchopulmonary dysplasia: what's new on the horizon?. Lancet Child Adolesc Health 2018; 2 (08) 549-551
    CrossrefPubMedGoogle Scholar
  • 6 Bonadies L, Zaramella P, Porzionato A, Perilongo G, Muraca M, Baraldi E. Present and future of bronchopulmonary dysplasia. J Clin Med 2020; 9 (05) 1539
    CrossrefPubMedGoogle Scholar
  • 7 Álvarez-Fuente M, Moreno L, Mitchell JA. et al. Preventing bronchopulmonary dysplasia: new tools for an old challenge. Pediatr Res 2019; 85 (04) 432-441
    CrossrefPubMedGoogle Scholar
  • 8 Ambalavanan N, Carlo WA, D'Angio CT. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birth weight infants. Pediatrics 2009; 123 (04) 1132-1141
    CrossrefPubMedGoogle Scholar
  • 9 Kotecha S, Wilson L, Wangoo A, Silverman M, Shaw RJ. Increase in interleukin (IL)-1 β and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. Pediatr Res 1996; 40 (02) 250-256
    CrossrefPubMedGoogle Scholar
  • 10 Jónsson B, Tullus K, Brauner A, Lu Y, Noack G. Early increase of TNF α and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77 (03) F198-F201
    CrossrefPubMedGoogle Scholar
  • 11 Baier RJ, Majid A, Parupia H, Loggins J, Kruger TE. CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. Pediatr Pulmonol 2004; 37 (02) 137-148
    CrossrefPubMedGoogle Scholar
  • 12 Bourbia A, Cruz MA, Rozycki HJ. NF-kappaB in tracheal lavage fluid from intubated premature infants: association with inflammation, oxygen, and outcome. Arch Dis Child Fetal Neonatal Ed 2006; 91 (01) F36-F39
    CrossrefPubMedGoogle Scholar
  • 13 Capoluongo E, Vento G, Lulli P. et al. Epithelial lining fluid neutrophil-gelatinase-associated lipocalin levels in premature newborns with bronchopulmonary dysplasia and patency of ductus arteriosus. Int J Immunopathol Pharmacol 2008; 21 (01) 173-179
    CrossrefPubMedGoogle Scholar
  • 14 Contreras M, Hariharan N, Lewandoski JR, Ciesielski W, Koscik R, Zimmerman JJ. Bronchoalveolar oxyradical inflammatory elements herald bronchopulmonary dysplasia. Crit Care Med 1996; 24 (1, suppl): 29-37
    CrossrefPubMedGoogle Scholar
  • 15 Gladstone Jr IM, Levine RL. Oxidation of proteins in neonatal lungs. Pediatrics 1994; 93 (05) 764-768
    CrossrefPubMedGoogle Scholar
  • 16 Collard KJ, Godeck S, Holley JE, Quinn MW. Pulmonary antioxidant concentrations and oxidative damage in ventilated premature babies. Arch Dis Child Fetal Neonatal Ed 2004; 89 (05) F412-F416
    CrossrefPubMedGoogle Scholar
  • 17 Joung KE, Kim HS, Lee J. et al. Correlation of urinary inflammatory and oxidative stress markers in very low birth weight infants with subsequent development of bronchopulmonary dysplasia. Free Radic Res 2011; 45 (09) 1024-1032
    CrossrefPubMedGoogle Scholar
  • 18 Mohamed WAW, Niyazy WH, Mahfouz AA. Angiopoietin-1 and endostatin levels in cord plasma predict the development of bronchopulmonary dysplasia in preterm infants. J Trop Pediatr 2011; 57 (05) 385-388
    CrossrefPubMedGoogle Scholar
  • 19 Janér J, Andersson S, Kajantie E, Lassus P. Endostatin concentration in cord plasma predicts the development of bronchopulmonary dysplasia in very low birth weight infants. Pediatrics 2009; 123 (04) 1142-1146
    CrossrefPubMedGoogle Scholar
  • 20 Tsao PN, Wei SC, Su YN. et al. Placenta growth factor elevation in the cord blood of premature neonates predicts poor pulmonary outcome. Pediatrics 2004; 113 (5, 5I): 1348-1351
    CrossrefPubMedGoogle Scholar
  • 21 Vento G, Capoluongo E, Matassa PG. et al. Serum levels of seven cytokines in premature ventilated newborns: correlations with old and new forms of bronchopulmonary dysplasia. Intensive Care Med 2006; 32 (05) 723-730
    CrossrefPubMedGoogle Scholar
  • 22 Hasan J, Beharry KD, Valencia AM, Strauss A, Modanlou HD. Soluble vascular endothelial growth factor receptor 1 in tracheal aspirate fluid of preterm neonates at birth may be predictive of bronchopulmonary dysplasia/chronic lung disease. Pediatrics 2009; 123 (06) 1541-1547
    CrossrefPubMedGoogle Scholar
  • 23 Ogihara T, Hirano K, Morinobu T. et al. Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia. Pediatr Res 2006; 60 (05) 613-618
    CrossrefPubMedGoogle Scholar
  • 24 Schrama AJJ, Bernard A, Poorthuis BJHM, Zwinderman AH, Berger HM, Walther FJ. Cord blood Clara cell protein CC16 predicts the development of bronchopulmonary dysplasia. Eur J Pediatr 2008; 167 (11) 1305-1312
    CrossrefPubMedGoogle Scholar
  • 25 Sarafidis K, Stathopoulou T, Diamanti E. et al. Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates. Eur J Pediatr 2008; 167 (11) 1297-1303
    CrossrefPubMedGoogle Scholar
  • 26 Ramsay PL, DeMayo FJ, Hegemier SE, Wearden ME, Smith CV, Welty SE. Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 164 (01) 155-161
    CrossrefPubMedGoogle Scholar
  • 27 Kotecha S, Wangoo A, Silverman M, Shaw RJ. Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity. J Pediatr 1996; 128 (04) 464-469
    CrossrefPubMedGoogle Scholar
  • 28 Fanos V, Pintus MC, Lussu M. et al. Urinary metabolomics of bronchopulmonary dysplasia (BPD): preliminary data at birth suggest it is a congenital disease. J Matern Fetal Neonatal Med 2014; 27 (2, suppl 2): 39-45
    CrossrefPubMedGoogle Scholar
  • 29 Baraldi E, Giordano G, Stocchero M. et al. Untargeted metabolomic analysis of amniotic fluid in the prediction of preterm delivery and bronchopulmonary dysplasia. PLoS One 2016; 11 (10) e0164211
    CrossrefPubMedGoogle Scholar
  • 30 La Frano MR, Fahrmann JF, Grapov D. et al. Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2018; 315 (05) L870-L881
    CrossrefPubMedGoogle Scholar
  • 31 Pintus MC, Lussu M, Dessì A. et al. Urinary 1H-NMR metabolomics in the first week of life can anticipate BPD diagnosis. Oxid Med Cell Longev 2018; 2018: 7620671
    CrossrefPubMedGoogle Scholar
  • 32 Piersigilli F, Lam TT, Vernocchi P. et al. Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics. Metabolomics 2019; 15 (02) 20
    CrossrefPubMedGoogle Scholar
  • 33 Rogosch T, Herrmann N, Maier RF. et al. Detection of bloodstream infections and prediction of bronchopulmonary dysplasia in preterm neonates with an electronic nose. J Pediatr 2014; 165 (03) 622-624
    CrossrefPubMedGoogle Scholar
  • 34 Charitharth Vivek Lal NA. Biomarkers, early diagnosis, and clinical predictors of BPD. Clin Perinatol 2016; 42 (04) 739-754
    PubMedGoogle Scholar
  • 35 Magagnotti C, Matassa PG, Bachi A. et al. Calcium signaling-related proteins are associated with broncho-pulmonary dysplasia progression. J Proteomics 2013; 94: 401-412
    CrossrefPubMedGoogle Scholar
  • 36 Förster K, Sass S, Ehrhardt H. et al. Early identification of bronchopulmonary dysplasia using novel biomarkers by proteomic screening. Am J Respir Crit Care Med 2017; 197 (08) 1076-1080
    CrossrefPubMedGoogle Scholar
  • 37 Zasada M, Suski M, Bokiniec R. et al. Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia. Ital J Pediatr 2019; 45 (01) 112
    CrossrefPubMedGoogle Scholar
  • 38 Arjaans S, Wagner BD, Mourani PM. et al. Early angiogenic proteins associated with high risk for bronchopulmonary dysplasia and pulmonary hypertension in preterm infants. Am J Physiol Lung Cell Mol Physiol 2020; 318 (04) L644-L654
    CrossrefPubMedGoogle Scholar
  • 39 Ballard PL, Oses-Prieto J, Chapin C, Segal MR, Ballard RA, Burlingame AL. Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome. PLoS One 2020; 15 (12) e0243168
    CrossrefPubMedGoogle Scholar
  • 40 Lal CV, Bhandari V, Ambalavanan N. Genomics, microbiomics, proteomics, and metabolomics in bronchopulmonary dysplasia. Semin Perinatol 2018; 42 (07) 425-431
    CrossrefPubMedGoogle Scholar
  • 41 Mourani PM, Harris JK, Sontag MK, Robertson CE, Abman SH. Molecular identification of bacteria in tracheal aspirate fluid from mechanically ventilated preterm infants. PLoS One 2011; 6 (10) e25959
    CrossrefPubMedGoogle Scholar
  • 42 Lohmann P, Luna RA, Hollister EB. et al. The airway microbiome of intubated premature infants: characteristics and changes that predict the development of bronchopulmonary dysplasia. Pediatr Res 2014; 76 (03) 294-301
    CrossrefPubMedGoogle Scholar
  • 43 Lal CV, Travers C, Aghai ZH. et al. The airway microbiome at birth. Sci Rep 2016; 6: 31023
    CrossrefPubMedGoogle Scholar
  • 44 Wagner BD, Sontag MK, Harris JK. et al. Airway microbial community turnover differs by BPD severity in ventilated preterm infants. PLoS One 2017; 12 (01) e0170120
    CrossrefPubMedGoogle Scholar
  • 45 Moschino L, Bonadies L, Baraldi E. Lung growth and pulmonary function after prematurity and bronchopulmonary dysplasia. Pediatr Pulmonol 2021; 56 (11) 3499-3508
    CrossrefPubMedGoogle Scholar