Ventilatory control in infants, children, and adults with bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD), or chronic lung disease of prematurity, occurs in ~30% of preterm infants (15,000 per year) and is associated with a clinical history of mechanical ventilation and/or high inspired oxygen at birth. Here, we describe changes in ventilatory control that exist in patients with BPD, including alterations in chemoreceptor function, respiratory muscle function, and suprapontine control. Because dysfunction in ventilatory control frequently revealed when O2 supply and CO2 elimination are challenged, we provide this information in the context of four important metabolic stressors: stresses: exercise, sleep, hypoxia, and lung disease, with a primary focus on studies of human infants, children, and adults. As a secondary goal, we also identify three key areas of future research and describe the benefits and challenges of longitudinal human studies using well-defined patient cohorts.

Keywords: Bronchopulmonary dysplasia; Exercise; Hypoxia; Premature infant; Sleep; Ventilatory control.

Copyright © 2013 Elsevier B.V. All rights reserved.

Figures

Figure 1

Change in minute ventilation during a five minute eucapnic, 12% O2 challenge in a 20 year old woman with BPD (Beshish et al. 2012). This individual was clinically unremarkable, with normal spirometric function and exercise capacity. In the comparable term-born participant, minute ventilation increases within the first 30 seconds of hypoxic gas breathing, increasing 65% by the end of five minutes. In the participant with BPD, minute ventilation fails to increase.

Figure 2

Change in arterial CO2 (PaCO2) in a 27 year old man with BPD performing incremental exercise to volitional exhaustion. Note that in a comparable term-born participant, PaCO2 falls with high intensity exercise as is characteristic of the typical hyperpneic response. In the participant with BPD, PaCO2 remains constant, indicating the lack of a hyperpneic response. This individual had previously experienced high altitude pulmonary edema and had compromised spirometric function (see (Lovering et al. 2007) for the complete case report).

Figure 3

Mechanical ventilator duration (ventilator hours ± SD) and intubation frequency of very- and extremely-low birth weight infants at seven NICUs in Wisconsin and Iowa between 1988 and 1991 (n=675 infants). Note the high variability in both parameters. Given this high degree of inter-center variability, we might expect similarly high variability in response from individuals born at different centers. Understanding and quantifying this variability is important in future clinical studies.