Research

Cardiopulmonary consequences of preterm birth and bronchopulmonary dysplasia (BPD)

One area of research in the lab is to better understand cardiopulmonary function in adult survivors of preterm birth and BPD. Being born preterm (8 or more weeks) results in underdeveloped lungs. For those premies that survive the critical neonatal period, there is, presumably, normal lung development until early adolescents, but they never 'catch-up' to those individuals that were born at full term (40 weeks gestation). Those that develop BPD received supplemental oxygen therapy during the neonatal period (>28 days), which gives those infants a better chance at surviving, but results in worse cardiopulmonary outcomes. Individuals born premature with and without BPD have lung function and aerobic exercise capacity that is 20-30% lower than what would be expected for individuals of the same age born at full term. Research in the lab is focused upon looking at the physiologic mechanisms limiting pulmonary function and exercise capacity in this population.

Figures:

(Left). The alveolar-to-arterial difference in PO₂ (A-aDO₂) in adults born preterm (PRET) and full term (CONT) at rest and during exercise breathing hypoxic (12% O₂) gas. There is no difference in the A-aDO₂ between groups at any time point (Duke et al. J Appl Physiol 2014). (Right). A flow-volume loop (FVL) for a subject with BPD at rest and during exercise. Note the significant expiratory flow limitation during moderate intensity exercise (Lovering et al. Ann Am Thoc Soc 2014).

*** This research is currently funded by the National Institutes of Health (R15HL148850) ***

Publications in this area:

• Lovering, AT and Duke, JW. Reduced aerobic exercise capacity in adults born very low birth weight - no small matter (invited editorial)! Am J Respir Crit Care Med. 205: 8-10, 2022.

• Duke, JW, Lewandowski, AJ, Abman, SH, and Lovering, AT. Physiologic aspects of cardiopulmonary dysanapsis on exercise in adults born preterm. J Physiol. 600: 463-482, 2022.

• Duke, JW and Lovering AT. Respiratory and cardiopulmonary limitations to aerobic exercise capacity in adults born preterm. J Appl Physiol. 129: 718-724, 2020.

• Duke, JW, Lovering, AT, and Goss, KN. Premature aging and cardiopulmonary disease after extreme preterm birth: getting to the heart (and lungs) of the matter (invited editorial). Am J Respir Crit Care Med. 202: 319-320, 2020.

• Molgat-Seon, Y, Dominelli, PB, Peters, CM, Sheel, AW, Gladstone, IM, Lovering, AT, and Duke, JW. Analysis of maximal expiratory flow volume curves in adult survivors of preterm birth. Am J Physiol Regul Integr Comp Physiol. 317: R588-296, 2019.

• Duke, JW, Zidron, AM, Gladstone, IM, and Lovering, AT. Alleviating mechanical constraints to ventilation with helix improves exercise endurance in adult survivors of very preterm birth. Thorax, 74: 302-304, 2019.

Basic and applied respiratory mechanics

One area of research in the lab is/are basic and applied respiratory mechanics. We are particularly interested in sex based differences in respiratory mechanics including: thoracic gas compression, evolution of respiratory muscle pressure generation, responses to respiratory muscle fatigue, etc. Likewise, we are interested in methodologies associated with quantifying the mechanical work of breathing. We have recently demonstrated that measuring chest wall compliance significantly impacts the measured work of breathing, but not to a physiologically meaningful extent. Likewise, we have demonstrated that the method of quantifying the work of breathing impacts the magnitude of the work of breathing and the information that can be extrapolated from the data. Our ongoing work is examining potential sex differences in the work, power, and mechanical cost of breathing during exercise, as well as how the varying balloon-catheter positioning methods impact static and dynamic respiratory mechanics data.

Recent publications in this area:

• Cross, TK, Gideon, EA, Morris, SJ, Coriell, CL, Hubbard, CD, and Duke, JW. A comparison of methods used to quantify the work of breathing during exercise. J Appl Physiol. 131: 1123-1133, 2021.

• *Gideon, EA, *Cross, TJ, Coriell, CL, and Duke, JW. The effect of estimating chest wall compliance on the work of breathing during exercise as determined via the modified Campbell diagram. Am J Physiol Regul Integr Comp Physiol. 320: R268-R275, 2021.

• Gideon, EA, Cross, TJ, Cayo, BE, Betts, AW, Merrell, DS, Coriell, CL, Hays, LE, and Duke, JW. Thoracic gas compression during forced expiration is greater in men than women. Physiol Rep. 8: e14404, 2020.

Respiratory muscle function and fatigue

Another focus of the lab is the impact of respiratory muscle fatigue on muscle function and exercise performance. Specifically, we are currently investigating the presence and magnitude of coactivation of the respiratory muscles at the point of fatigue, i.e., do the expiratory muscles become fatigued during inspiratory muscle pressure-threshold loading.