Early perfluorodecalin lung distension in infants with congenital diaphragmatic hernia

Walker, Gregor; Kasem, K.F.; O’Toole, Stuart; Watt, Arleen; Skeoch, C; Davis, Carl

doi:10.1053/jpsu.2003.50002

Cited by 28 publications

(15 citation statements)

References 9 publications

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“…Several lines of basic research have approached clinical application, such as exogenous retinoic acid for patients with emphysema (480) and perfluorocarbon lung distention for neonates with CDH (481)(482)(483). Other applications yet to be explored include inducing compensatory lung growth in children who survive BPD beyond the injury-repair stage or those who survive repair of CDH but are left with small lungs and marginal gas exchange capacity.…”

Section: Future Directionsmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

140

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Abnormal DevelopmentClinical syndromes. Syndromes that alter expression of growth factors, cytokines, transcription factors, or extracellular matrix (ECM) proteins provide models to explore mechanisms that control alveolar development. Signals that regulate the saccularto-alveolar morphologic transition are poorly understood, but disrupting lung septation during this transition impairs alveolar formation, resulting in a loss of alveolar surface area (20, 21). There are several syndromes of abnormal lung alveolarization in humans. Trisomy 21 (Down syndrome) is associated with reduced lung volumes, alveolar surface area, fewer alveoli, defective elastin deposition, and vascular abnormalities (22, 23). Leprechaunism, caused by a defect of the insulin/insulin-like growth factor-I receptor, is associated with reduced lung surface areas as well as fewer and larger alveoli (24). Oligohydramnios (25), congenital diaphragmatic hernia (CDH) (26), and intrathoracic mass lesions are all associated with pulmonary hypoplasia caused by the lack of interplay between thoracic expansion and stretch imposed on the lung. Lung hypoplasia in CDH is not just a consequence of mechanical lung compression caused by a hole in the diaphragm but also involves primary developmental defects (27). Prenatal tracheal occlusion markedly increases lung size in some fetuses with severe CDH; however, survival remains poor because of respiratory insufficiency and prematurity (28). After CDH repair, significant postnatal alveolar growth and vascular remodeling are seen (26); long-term survivors show lower lung volumes but normal airway function and exercise tolerance (29), suggesting the occurrence of "catch-up" lung growth once the underlying abnormalities are corrected.By far the most common cause of abnormal postnatal human lung development is bronchopulmonary dysplasia (BPD). Classically, BPD occurs in the preterm infant lung exposed to hyperoxia and mechanical ventilation (30-32), resulting in extensive alveolar fibroproliferation, bronchovascular smooth muscle hyperplasia, and inhibition of distal lung formation leading to longterm pulmonary dysfunction persisting into adolescence and adulthood. The advent of antenatal steroids, postnatal surfactant replacement, and improved intensive care has ushered in the "new BPD," which lacks the severe bronchovascular lesions and interstitial fibrosis but is characterized by abnormal lung development with simplified acinar structure, poorly formed secondary crests, dysmorphic alveolar capillaries, and blunted expression of angiogenic growth factors and their receptors (33-36). There is little information on the pathology of "new BPD" in infants who survive; it remains to be seen whether long-term "catch-up" lung growth occurs in these survivors.

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Section: Future Directionsmentioning

confidence: 99%

Mechanisms and Limits of Induced Postnatal Lung Growth

2004

Am J Respir Crit Care Med

140

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“…Although lung growth does occur naturally in these patients, it is usually too slow to enable long-term survival. Fauza et al [9] and Walker et al [10] demonstrated significantly increased lung volumes according to serial radiographic measurements after 3 to 10 days of PFC distension in neonates with CDH on ECMO. In a prospective, randomized trial comparing neonates with CDH on ECMO with or without PFC distension, survival was also increased (75% vs 40%, P = NS) [11].…”

Section: Discussionmentioning

confidence: 97%

“…When used as a respiratory medium during liquid ventilation in animals/neonates with CDH, PFC has resulted in some improvements in gas exchange and compliance but does not accelerate lung growth or increase survival [12][13][14]. In contrast, selective PFC distension, which has been performed in both sheep and human neonates, appears promising with respect to increasing postnatal lung growth [8][9][10]15] and survival [11]. To our knowledge, no one has examined the short-term effects of PFC distension on lung growth in healthy neonatal piglets.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, selective pulmonary distension using PFC liquid has been used in neonates with CDH on ECMO [9][10][11]. Although lung growth does occur naturally in these patients, it is usually too slow to enable long-term survival.…”

Section: Discussionmentioning

confidence: 99%

“…In cases of severe lung hypoplasia, these modalities remain ineffective [5,6]. Liquid distension using perfluorocarbon (PFC) liquid is hypothesized to accelerate postnatal lung growth via stretch-induced mechanisms [7][8][9][10][11]. For neonates with CDH, increased lung growth could translate into decreased time spent on ECMO with subsequent decreases in associated morbidity and mortality [11].…”

mentioning

confidence: 99%

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