Pulmonary Outcomes in Bronchopulmonary Dysplasia

doi:10.1053/j.semperi.2006.05.009

Seminars in Perinatology

Volume 30, Issue 4, August 2006, Pages 219-226

https://doi.org/10.1053/j.semperi.2006.05.009 Get rights and content

The incidence of bronchopulmonary dysplasia (BPD), defined as oxygen need at 36 weeks of postmenstrual age, is about 30% for infants with birth weights <1000 g. BPD is associated with persistent structural changes in the lung that result in significant effects on lung mechanics, gas exchange, and pulmonary vasculature. Up to 50% of infants with BPD require readmission to the hospital for lower respiratory tract illness in the first year of life. Long-term measurements of lung function in BPD include normalization of pulmonary mechanics and some lung volumes over time as somatic and lung growth occur, whereas abnormality of small airway function persists. The majority of data reveals no long-term decrease in exercise capacity. Mild to moderate radiological abnormalities persist. BPD is a result of dynamic processes involving inflammation, injury, repair, and maturation. Infants with BPD have significant pulmonary sequelae during childhood and adolescence, and continued surveillance of young adults with BPD is critical.

Section snippets

Pulmonary Pathology

Pathology of the BPD lung from the presurfactant era was remarkable for the presence of central and peripheral airway injury, airway inflammation, and parenchymal fibrosis. Rosan described four pathological stages of BPD.¹¹ This most commonly represented the effects of oxygen toxicity and barotrauma from positive pressure ventilation on lungs at the saccular phase of development (28-34 weeks gestation) recovering from RDS.

Pathological findings in the lungs of infants with “new” BPD are

Respiratory Morbidity

It is difficult to find uniform agreement from published studies about the clinical outcomes of children with BPD because different definitions of BPD are used, reported patient populations and their comparison groups are disparate, and there is patient attrition from original cohorts in most studies (Table 1). Many studies do not distinguish those children who developed BPD from others who were very low birth weight (VLBW) but who did not develop chronic lung disease in infancy. Only one study

Pulmonary Function

Measurement of lung mechanics, flows, and volumes from birth through adulthood in subjects born prematurely with and without BPD can lend insight into the normal growth process of the lung, and also help to distinguish the effects of early injury on subsequent airway and parenchymal repair from the effects of prematurity alone. Furthermore, longitudinal studies can help determine if and when in the repair process normalization of function occurs. Comparison of lung function measurements between

Airway Disease

Although pulmonary function measurements in BPD survivors reflect abnormalities primarily of the small airways, large airway disease occurs commonly in this patient population during infancy. Tracheomalacia and bronchomalacia secondary to endotracheal intubation and prolonged mechanical ventilation are well known.68, 69, 70 An increase in central airway compliance can result in “BPD spells” which are acute cyanotic events most commonly seen in older BPD infants.69, 71 The natural history of

Exercise Testing

Although the majority of survivors of BPD participate in play, exercise, and other physical activities without symptoms, there is concern over their respiratory reserve given their, often stormy, perinatal course. Most studies, however, show no reduction in exercise capacity in children with BPD when compared with children who were healthy term infants or preterm babies without lung disease.28, 48, 53, 59, 76 Only one study of 12 children between the ages of 6 to 12 years with mild BPD found a

Radiological Findings

There have been few follow-up studies that looked at the long-term effects of BPD radiologically. In 10 patients with BPD studied at 6 to 9 years, Hakulinen and coworkers found only minor fibrotic changes on chest radiographs in 40% of the BPD children.⁵⁰ No hyperinflation was evident, even though the RV/TLC ratio was elevated. Andreasson and coworkers found chest radiographic abnormalities in 8 of 10 children with BPD studied at 8 to 10 years.⁴⁸ All demonstrated generalized hyperinflation, and

Conclusions

BPD is the result of dynamic processes involving inflammation, injury, repair, and maturation. Outcomes of BPD are difficult to assess given the lack of a uniform definition, and changing modalities of management. Infants with BPD continue to have significant pulmonary sequelae during childhood and adolescence. Neonates with chronic lung disease are more immature today than those studied in the past, and so the prognosis for this population may be different from that reported thus far. There is

Acknowledgments

The authors would like to thank D.J. Weiner, MD, and J.L. Allen, MD, for their critical review of the manuscript.

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Bronchopulmonary dysplasia (BPD) is a prevalent and critical complication among premature infants, with potentially long-lasting adverse effetcs. The present study aimed to establish a nomogram model to predict the risk of BPD in premature infants born at <32 weeks gestational age.
A retrospective single-center study was conducted on premature infants admitted to the neonatal intensive care unit (NICU) of the Children's Hospital of Nanjing Medical University from January 2018 to December 2020. Data were collected from clinical medical records, including the perinatal data and the critical information after birth. Clinical parameters and features were analyzed using univariate and multivariate logistic regression. A nomogram based on clinical data was established and validated using bootstrapping samples. The specificity and sensitivity of the nomogram were estimated using the receiver operating characteristic (ROC) based area under the curve (AUC).
A total of 542 premature babies were included, and 152 infants (28.04%) were diagnosed with BPD. Birth weight, cesarean delivery, invasive/non-invasive ventilation at day 7 and 14 were identified as significant factors (p < 0.05) using univariate and the multivariate logistic regression analysis, and were entered into a nomogram. The calibration curve for BPD probability demonstrated a favorable concurrence between actual probability and predicted ability of the BPD nomogram. The nomogram showed potential differentiation, with an AUC of 0.925, 89.90% sensitivity, 76.71% specificity, and 86.35% accuracy.
The nomogram developed in this study provides a straightforward tool to predict the probability of BPD and assist clinicians in optimizing treatment regimens for premature infants born at <32 weeks gestational age. This study highlights the importance of identifying and monitoring significant clinical factors associated with BPD in premature infants to improve clinical outcomes.
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Premature infants who require oxygen therapy for respiratory distress syndrome often develop bronchopulmonary dysplasia, a chronic lung disease characterized by interrupted alveologenesis. Disrupted angiogenesis inhibits alveologenesis; however, the mechanisms through which disrupted angiogenesis affects lung development are poorly understood. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple oxygen-sensitive genes, including those encoding for vascular endothelial growth factor (VEGF). However, the HIF modulation of angiogenesis in hyperoxia-induced lung injury is not fully understood. Therefore, we explored the effects of roxadustat, an HIF stabilizer that has been shown to promote angiogenesis, in regulating pulmonary angiogenesis on hyperoxia exposure.
C57BL6 mice pups reared in room air and 85% O₂ were injected with phosphate-buffered saline or 5 mg/kg or 10 mg/kg roxadustat. Their daily body weight and survival rate were recorded. Their lungs were excised for histology and angiogenic factor expression analyses on postnatal Day 7.
Exposure to neonatal hyperoxia reduced body weight; survival rate; and expressions of von Willebrand factor, HIF-1α, phosphor mammalian target of rapamycin, VEGF, and endothelial nitric oxide synthase and increased the mean linear intercept values in the pups. Roxadustat administration reversed these effects.
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To investigate, in infants born preterm with or without bronchopulmonary dysplasia (BPD), the trajectory of tidal breathing flow-volume (TBFV) parameters in the first 2 years of life; the association between TBFV parameters and perinatal risk factors; and the predictive value of TBFV parameters for rehospitalizations due to respiratory infections and wheeze.
We retrospectively analyzed TBFV measurements performed at 0-6, 6-12, and 12-24 months of corrected age in 97 infants <32 weeks of gestation and <1500 g. We assessed the association between TBFV parameters and perinatal risk-factors using linear regressions and the predictive capacity for subsequent respiratory morbidity using logistic regressions. We used the area under the curve and likelihood ratio test (LRT) to compare nested models.
Time to peak tidal expiratory flow/expiratory time ratio (tPTEF/tE) was lower than normal for the first 2 years of corrected age. Longer duration of oxygen supplementation, intubation, and respiratory support were associated with reduced tPTEF/tE at all time points. For each z-score increase in tPTEF/tE, the OR for rehospitalizations decreased by 0.70. tPTEF/tE added significantly to BPD classifications alone in predicting rehospitalizations (area under the receiver operating characteristic curve = 0.81 vs 0.76, P value for LRT = .0012), and wheeze (area under the receiver operating characteristic curve = 0.76 vs 0.71, P value for LRT <.001).
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Citation Excerpt :
In fact, at 24 months CA, significantly worst Z-scores for all auxological parameters and a significantly negative variation of ΔW Z-score between 24 months and birth were found in Moderate and Severe BPD groups, if compared to controls. As already reported by different authors who evaluated the clinical evolution of pediatric patients with BPD, up to 50% of infants with BPD (in particular if Moderate or Severe) require readmission to the hospital for respiratory illness in first years of life [53]. We confirmed this trend in all infants with BPD, when compared to infants without BPD, but we found that also infants with mild forms required more readmissions than controls during follow-up.
Bronchopulmonary dysplasia is a chronic respiratory disease that still affects preterm neonates; its association with neurodevelopmental (ND) impairment is already known. Different studies investigated neurodevelopmental outcomes in infants with BPD, often using the old dichotomous definition (BPD vs Non-BPD). This retrospective study aims to evaluate the role of different BPD severity grades on ND outcomes at 24 months of corrected age (CA).
All preterm infants born between 2011 and 2015 in the study hospital with a gestational age (GA) ≤ 30 weeks and discharged from our NICU were included and were divided in infants with and without BPD. Infants with BPD were divided into three severity groups as defined by NICHD/NHLBI Workshop in 2001, and were compared to their Non-BPD peers, matching them according to the same GA and year of birth. At 24 months postmenstrual age, we assessed general outcomes (growth and hospital readmissions) and neurodevelopmental outcomes (motor, developmental and sensory outcomes) with a standardized assessment.
We enrolled 89 patients affected by BPD of different grades of severity and a control group of 89 preterm infants without BPD.
Infants with Moderate and Severe BPD showed a significantly higher corrected odds ratio (OR) for cognitive impairment compared to controls. Within the group of infants without severe disability (regarding Griffiths' scales), infants with Moderate and Severe BPD as well as infants with Mild BPD showed a significantly higher risk of a lower total Developmental Quotient (DQ) score, even after correction for confounding factors.
Our study evidenced that not only Severe BPD infants, but also Moderate ones showed a higher risk of overall cognitive impairment at 24 months CA. Within the group of infants without severe disability, also those with Mild BPD had lower Griffiths DQ scores than those without. This would suggest that infants with BPD, regardless of severity, warrant neurodevelopmental follow-up.

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