Updates on Functional Characterization of Bronchopulmonary Dysplasia – The Contribution of Lung Function Testing

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that predominantly affects prematurely born infants. Initially, BPD was described in infants who had suffered severe respiratory failure and required high pressure, mechanical ventilation with high concentrations of supplementary oxygen. Now, it also occurs in very prematurely born infants who initially had minimal or even no signs of lung disease. These differences impact the nature of the lung function abnormalities suffered by “BPD” infants, which are also influenced by the criteria used to diagnose BPD and the oxygen saturation level used to determine the supplementary oxygen requirement. Key also to interpreting lung function data in this population is whether appropriate lung function tests have been used and in an adequately sized population to make meaningful conclusions. It should also be emphasized that BPD is a poor predictor of long-term respiratory morbidity. Bearing in mind those caveats, studies have consistently demonstrated that infants who develop BPD have low compliance and functional residual capacities and raised resistances in the neonatal period. There is, however, no agreement with regard to which early lung function measurement predicts the development of BPD, likely reflecting different techniques were used in different populations in often underpowered studies. During infancy, lung function generally improves, but importantly airflow limitation persists and small airway function appears to decline. Improvements in lung function following administration of diuretics or bronchodilators have not translated into long-term improvements in respiratory outcomes. By contrast, early differences in lung function related to different ventilation modes have led to investigation and demonstration that prophylactic, neonatal high-frequency oscillation appears to protect small airway function.

Imbalance of Ly-6Chi and Ly-6Clo Monocytes/Macrophages Worsens Hyperoxia-Induced Lung Injury and Is Rescued by IFN-γ

“…Neonatal clinical practice has progressed to limit supplemental oxygen exposure after delivery with subsequent improvements in respiratory morbidity (52), but the most premature infants are necessarily exposed to significant supplemental oxygen. Previous studies have described long-lasting effects of hyperoxia on airway injury in mouse models (53) and development of airway obstruction in BPD survivors (4,(54)(55)(56). The precise inflammatory mechanisms of HILI are incompletely understood but have been thought to include roles for monocytes/macrophages and neutrophils (17,53,57).…”

N-methyl-D-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats

“…Low pulmonary compliance indicates a stiff lung and can be thought of as a thick balloon; this parameter has been widely used in the evaluation of lung development in neonatal patients with CLD [ 28 – 31 ]. To determine the functional impact of our histological findings, we further performed dynamic lung compliance testing.…”

Elevated lung volumes in neonates with bronchopulmonary dysplasia measured via MRI

“…Functional residual capacity (FRC), or the amount of gas remaining in the lungs after tidal expiration, has been demonstrated to be an important quantitative physiologic measure for further understanding of BPD . Plethysmography requires sedation, and while it is a noninvasive method for producing measurements of FRC that can reflect hyperinflation and gas trapping, the equipment cannot be used for bedside assessment required in small and sick infants like those with BPD . Additionally, accuracy of plethysmography in patients with airway obstruction has been debated, often resulting in overestimation of FRC .…”

“…21,22 Plethysmography requires sedation, and while it is a noninvasive method for producing measurements of FRC that can reflect hyperinflation and gas trapping, the equipment cannot be used for bedside assessment required in small and sick infants like those with BPD. 22,23 Additionally, accuracy of plethysmography in patients with airway obstruction has been debated, often resulting in overestimation of FRC. 22,24 Conversely, gas dilution techniques can be used in sick and ventilated infants (provided that they remain in quiet sleep for at least 10 minutes), but they may frequently underestimate FRC when sufficient time for gas equilibration is not allowed.…”