Biomarkers, Early Diagnosis, and Clinical Predictors of Bronchopulmonary Dysplasia

Lal, Charitharth Vivek; Ambalavanan, Namasivayam

doi:10.1016/j.clp.2015.08.004

Cited by 75 publications

(63 citation statements)

References 100 publications

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“…Findings of the current study suggest that infants developing BPD may have a distinct metabolic profile and VOC profiling may have potential as an early diagnostic biomarker for BPD development. Early prediction of BPD is needed to initiate preventive strategies in a selected population of highrisk infants and to avoid potential hazardous treatments in those not at risk for BPD development (7,38,39). Although VOC analyses showed a fair discriminative power for severe BPD, this finding needs to be confirmed or refuted in a larger and more heterogeneous population.…”

Section: Discussionmentioning

confidence: 99%

Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds

et al. 2017

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BackgroundThe aim of this study was to evaluate the potential of fecal volatile organic compounds (VOCs), obtained by means of an electronic nose device (Cyranose 320), as early non-invasive biomarker for BPD.MethodsIn this nested case-control study performed at three Neonatal Intensive Care Units, fecal samples obtained at postnatal age of 7, 14, 21, and 28 days from preterm infants with severe bronchopulmonary dysplasia (BPD) were compared with fecal VOC profiles from matched controls. Microbiota analysis was performed by means of IS-pro technique on fecal samples collected at 28 days postnatally.ResultsVOC profiles of infants developing severe BPD (n=15) could be discriminated from matched controls (n=15) at postnatal age of 14 days (area under the curve (±95% confidence interval), P-value, sensitivity, specificity; 0.72 (0.54-0.90), 0.040, 60.0%, 73.3%), 21 days (0.71 (0.52-0.90), 0.049, 66.7%, 73.3%) and 28 days (0.77 (0.59-0.96), 0.017, 69.2%, 69.2%) but not at 7 days. Intestinal microbiota did not differ between BPD subjects and controls.ConclusionFecal VOC profiles of infants developing BPD could be differentiated from controls at postnatal day 14, 21, and 28. VOC differences could not be directed to intestinal microbiota alterations but presumably reflect local and systemic metabolic and inflammatory pathways associated with BPD.

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Section: Discussionmentioning

confidence: 99%

Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds

et al. 2017

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“…As the pathogenesis of BPD is multifactorial, disease prediction based solely on clinical parameters is not very accurate. Currently, there are few biomarkers that can provide early identification of risk for developing BPD, as well as determine disease severity, progression, and resolution (6). Such a biomarker would be useful for optimal management and risk stratification, as well as targeted enrollment of high-risk infants into randomized trials featuring potentially novel treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Lal

Olave²,

Travers³

et al. 2018

JCI Insight

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Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product-induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

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“…A recent review highlighted the need for BPD predictors, and discussed the challenge of searching for a reliable predictor. Most clinical predictors have shown moderate predictive accuracy, and, despite various laboratory biomarkers being under investigation, none is currently used in clinical practice (22). …”

Section: Discussionmentioning

confidence: 99%

Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

Madoglio

Rugolo

Kurokawa

et al. 2016

Braz J Med Biol Res

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Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks’ gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

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Biomarkers, Early Diagnosis, and Clinical Predictors of Bronchopulmonary Dysplasia

Cited by 75 publications

References 100 publications

Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds

Development of severe bronchopulmonary dysplasia is associated with alterations in fecal volatile organic compounds

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants

Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

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