Elsevier

Early Human Development

Volume 105, February 2017, Pages 35-39
Early Human Development

Cellular and humoral biomarkers of Bronchopulmonary Dysplasia

https://doi.org/10.1016/j.earlhumdev.2016.12.003Get rights and content

Abstract

The pathogenesis of Bronchopulmonary Dysplasia (BPD) is multifactorial and the clinical phenotype of BPD is extremely variable. Predicting BPD is difficult, as it is a disease with a clinical operational definition but many clinical phenotypes and endotypes. Most biomarkers studied over the years have low predictive accuracy, and none are currently used in routine clinical care or shown to be useful for predicting longer-term respiratory outcome. Targeted cellular and humoral biomarkers and novel systems biology ‘omic’ based approaches including genomic and microbiomic analyses are described in this review.

Section snippets

Targeted cellular biomarkers of Bronchopulmonary Dysplasia

Abnormalities in the number and function of multiple cell types, primarily those related to inflammation and lung repair, have been shown in human BPD as well as in animal models of BPD (e.g. hyperoxia-exposed newborn rodent models). Early in the course of respiratory distress syndrome in human preterm infants, there is evidence of early systemic activation and transendothelial migration of neutrophils [15], with increased neutrophils in the tracheal aspirate of preterm infants who go on to

Targeted humoral biomarkers of Bronchopulmonary Dysplasia

Humoral biomarkers refer to biomarkers present in body fluids (called “humors”) which were categorized in ancient literature as blood, yellow bile, black bile, and phlegm. In this review, we will focus primarily on blood and airway secretions (phlegm). Biomarker measurements in blood have been studied due to easy accessibility, but they may not accurately reflect the lung concentrations of the respective mediator. Tracheal aspirates also have limitations, as they are available only in intubated

Unbiased “omic” biomarkers of BPD

Advances in molecular genetics and next-generation sequencing (NGS) technology have enabled the examination of BPD at an unbiased molecular ‘omic’ level. In this review, we will focus on biomarkers in the genome, transcriptome, and microbiome.

Future steps

Better phenotyping of BPD and more detailed data collection of clinical variables, in addition to careful determination of unbiased, specific, temporal, systems biology based ‘omic’ biomarkers are needed [58], [59]. Strategies that supplement or expand upon genomic, proteomic, metabolomic and microbiomic approaches need to be studied. With the discovery of the presence and role of the neonatal airway microbiome in BPD [53], the study of environmental pathogens and host response has become of

Disclosures

The authors have no conflict of interest to disclose.

References (59)

  • B.J. Stoll et al.

    Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network

    Pediatrics

    (2010)
  • A.H. Jobe et al.

    Bronchopulmonary dysplasia

    Am. J. Respir. Crit. Care Med.

    (2001)
  • M.C. Walsh et al.

    Impact of a physiologic definition on bronchopulmonary dysplasia rates

    Pediatrics

    (2004)
  • N. Ambalavanan et al.

    Integrated genomic analyses in bronchopulmonary dysplasia

    J. Pediatr.

    (2015)
  • R. Bhat et al.

    Prospective analysis of pulmonary hypertension in extremely low birth weight infants

    Pediatrics

    (2012)
  • I.J. Doull et al.

    Tracheobronchomalacia in preterm infants with chronic lung disease

    Arch. Dis. Child. Fetal Neonatal Ed.

    (1997)
  • J. Woodcock

    Chutes and ladders on the critical path: comparative effectiveness, product value, and the use of biomarkers in drug development

    Clin. Pharmacol. Ther.

    (2009)
  • Biomarkers Definitions Working G

    Biomarkers and surrogate endpoints: preferred definitions and conceptual framework

    Clin. Pharmacol. Ther.

    (2001)
  • K. Sarafidis et al.

    Evidence of early systemic activation and transendothelial migration of neutrophils in neonates with severe respiratory distress syndrome

    Pediatr. Pulmonol.

    (2001)
  • B.I. Kim et al.

    Increase in cord blood soluble E-selectin and tracheal aspirate neutrophils at birth and the development of new bronchopulmonary dysplasia

    J. Perinat. Med.

    (2004)
  • R.L. Auten et al.

    Anti-neutrophil chemokine preserves alveolar development in hyperoxia-exposed newborn rats

    Am. J. Phys. Lung Cell. Mol. Phys.

    (2001)
  • R.L. Auten et al.

    Nonpeptide CXCR2 antagonist prevents neutrophil accumulation in hyperoxia-exposed newborn rats

    J. Pharmacol. Exp. Ther.

    (2001)
  • P. Ballabh et al.

    Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids

    Arch. Dis. Child. Fetal Neonatal Ed.

    (2004)
  • P. Ballabh et al.

    Lymphocyte subpopulations in bronchopulmonary dysplasia

    Am. J. Perinatol.

    (2003)
  • E.B. Brostrom et al.

    Eosinophil activation in preterm infants with lung disease

    Acta Paediatr.

    (2007)
  • J. Kandasamy et al.

    Serum eotaxin-1 is increased in extremely-low-birth-weight infants with bronchopulmonary dysplasia or death

    Pediatr. Res.

    (2015)
  • D.E. Johnson et al.

    Pulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia

    Anat. Rec.

    (1993)
  • J.E. Gillan et al.

    Abnormal pulmonary bombesin immunoreactive cells in Wilson-Mikity syndrome (pulmonary dysmaturity) and bronchopulmonary dysplasia

    Pediatr. Pathol.

    (1993)
  • M.E. Sunday et al.

    Bombesin-like peptide mediates lung injury in a baboon model of bronchopulmonary dysplasia

    J. Clin. Invest.

    (1998)
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