Theoretical open-loop model of respiratory mechanics in the extremely preterm infant

Non-invasive ventilation is increasingly used for respiratory support in preterm infants, and is associated with a lower risk of chronic lung disease. However, this mode is often not successful in the extremely preterm infant in part due to their markedly increased chest wall compliance that does not provide enough structure against which the forces of inhalation can generate sufficient pressure. To address the continued challenge of studying treatments in this fragile population, we developed a nonlinear lumped-parameter model of respiratory system mechanics of the extremely preterm infant that incorporates nonlinear lung and chest wall compliances and lung volume parameters tuned to this population. In particular we developed a novel empirical representation of progressive volume loss based on compensatory alveolar pressure increase resulting from collapsed alveoli. The model demonstrates increased rate of volume loss related to high chest wall compliance, and simulates laryngeal braking for elevation of end-expiratory lung volume and constant positive airway pressure (CPAP). The model predicts that low chest wall compliance (chest stiffening) in addition to laryngeal braking and CPAP enhance breathing and delay lung volume loss. These results motivate future data collection strategies and investigation into treatments for chest wall stiffening.Comment: 22 pages, 5 figure

Potential contribution of Type I lung epithelial cells to chronic neonatal lung disease

The alveolar surface is covered by large flat Type I cells (alveolar epithelial cells 1, AEC1). The normal physiological function of AEC1s involves gas exchange, based on their location in approximation to the capillary endothelium and their thinness, and in ion and water flux, as shown by the presence of solute active transport proteins, water channels, and impermeable tight junctions between cells. With the recent ability to produce relatively pure cultures of AEC1 cells, new functions have been described. These may be relevant to lung injury, repair and the abnormal development that characterizes bronchopulmonary dysplasia. To hypothesize a potential role for AEC1 in the development of lung injury and abnormal repair/development in premature lungs, evidence is presented for their presence in the developing lung, how their source may not be the Type II cell (AEC2) as has been assumed for forty years, and how the cell can be damaged by same type of stressors as those which lead to bronchopulmonary dysplasia (BPD). Recent work shows that the cells are part of the innate immune response, capable of producing pro-inflammatory mediators, which could contribute to the increase in inflammation seen in early bronchopulmonary dysplasia. One of the receptors found exclusively on AEC1 cells in the lung, called RAGE, may also have a role in increased inflammation, and to alveolar simplification. While the current evidence for AEC1 involvement in BPD is circumstantial and limited at present, the accumulating data supports several hypotheses and questions regarding potential differences in the behavior of AEC1 cells from newborn and premature lung compared with the adult lung

Covid-19 in pregnant women and babies: what pediatricians need to know.

Beginning in late 2019, a novel coronavirus labeled SARS-CoV-2 spread around the world, affecting millions. The impact of the disease on patients and on health care delivery has been unprecedented. Here, we review what is currently known about the effects of the virus and its clinical condition, Covid-19 in areas of relevance to those providing care to neonates. While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this. Viral carriage prevalence based on universal screening show that rates vary from 13% in “hot spots” such as New York City, to 3% in areas with lower cases. Vertical transmission risks are unknown but 3.1% of 311 babies born to mothers with Covid-19 were positive within a week of birth. The clinical description of 26 neonates <30 days of age showed no deaths and only one requiring intensive care. Risks for breast-feeding and for milk banks are discussed

Breath-to-breath dynamic lung compliance and tidal volume.

<p>Depicted are high and low <i>C</i>_<i>w</i> conditions, with simulated CPAP triggered in the high <i>C</i>_<i>w</i> condition when recruited fraction dropped 10%, 5%, and 3%.</p

Aggregate parameters and output states targeted during simulations.

<p>Aggregate parameters and output states targeted during simulations.</p

Initial conditions.

<p>Initial conditions.</p

Lung, chest wall, and total respiratory system compliance curves for high <i>C</i>_<i>w</i> (left) and low <i>C</i>_<i>w</i> (right).

<p>Curves are described by Eqs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198425#pone.0198425.e016" target="_blank">(9)</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198425#pone.0198425.e017" target="_blank">(10)</a> and parameterized using the procedures described in <b>Parameterization</b>. Tidal breathing loops with normal <i>R</i>_<i>u</i> (grey) and increased <i>R</i>_<i>u</i> (black) are superimposed for each condition over the lung compliance curve and larger in each inset to display hysteresis.</p