Novel insights in bronchopulmonary dysplasia : an innovative, translational approach to diagnosis, follow-up and treatment
Bronchopulmonary dysplasia (BPD) remains the most common respiratory complication of preterm birth. The development of BPD is based on incomplete lung development after preterm birth and involves multiple pre-, peri- and postnatal exposures (maternal infection, pre-eclampsia, genetic and iatrogenic factors) with a crucial role for inflammation and oxidative stress. Children with BPD present with more frequent respiratory infections in infancy and impaired lung function that tracks into adulthood. While several supportive measures exist, there is currently no curative treatment for BPD. In this thesis, we provide novel insights into the diagnosis, follow-up and treatment of BPD. Concerning the diagnosis of BPD, we investigated the use of exhaled breath VOCs as pathophysiological markers for BPD that directly reflect inflammation, oxidative stress and consequent lipid peroxidation local to the lungs. In this study, we showed the feasibility of exhaled VOCs sampling in preterm infants with or without BPD as well as in a preterm lamb model, during invasive and non-invasive ventilation. We found that BPD patients can be discriminated from preterm controls based on exhaled VOCs. Furthermore, exhaled breath VOCs seem to change in response to invasive and non-invasive ventilation respectively. Importantly, our ovine experiments provided evidence that exhaled breath VOCs significantly correlate with local inflammation and oxidative stress in the lungs. Regarding the follow-up of BPD, we explored – for the first time – the use of functional respiratory imaging as a combined structural and functional assessment of the sequelae of BPD into adolescence. FRI allowed to identify increased air trapping in the BPD group, and significantly higher distal airway resistance that was not present on classic lung function testing – yet very relevant given the pathophysiology of BPD. FRI holds promise as an integrated imaging technique that can be used in clinical as well as translational settings. Then, we studied the effects of rhIGF-1/IGBP-3 treatment on lung development in a late preterm piglet model. We showed marked preterm-term differences, but no effect of rhIGF-1/rhIGBP-3 on structural lung development nor the expression of inflammatory cytokines or mucins. This is likely due to the relative maturity of the model. Finally, we identified priorities for research and clinical care in the BPD field. These include: (i) efforts towards a pathophysiological approach to BPD diagnosis; (ii) a continued search for targeted therapies and the advancement of already available compounds; and (iii) the development of adequate, standardised follow-up programs that span from the neonatal period into adulthood.
Antwerp : University of Antwerp, Faculty of Medicine and Health Sciences , 2023
324 p.
Supervisor: Verhulst, Stijn [Supervisor]
Supervisor: Mulder, Antonius [Supervisor]
Supervisor: De Winter, Benedicte [Supervisor]
Supervisor: Lamote, Kevin [Supervisor]
Supervisor: van Hoorenbeeck, Kim [Supervisor]
Supervisor: van Eyck, Annelies [Supervisor]
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The publisher created published version Available from 19.12.2024
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Creation 12.12.2023
Last edited 04.03.2024
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