Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review

Luca, Danièle De; Cogo, Paola; Zecca, Enrico; Piastra, Marco; Pietrini, Domenico; Tridente, Ascanio; Conti, Guido; Carnielli, VP

doi:10.1183/09031936.00024910

Cited by 27 publications

(24 citation statements)

References 168 publications

(167 reference statements)

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“…This meant testing BD against the most stringent conditions (i.e., the most relevant age range with distinct characteristics). This adds significantly to the relevance of the data, as these peculiarities lead to differences in terms of epidemiology, prognosis, ventilatory modalities [7], efficacy of surfactant [15,22], and ancillary therapies [23], as well.…”

Section: Discussionmentioning

confidence: 99%

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus

et al. 2013

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Section: Discussionmentioning

confidence: 99%

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus

et al. 2013

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“…Moreover, it has been shown that treatment of cold blooded lizards with leptin, a product of adipocytes, increases their body temperature [83]. These synergistic selection pressures for adipogenesis would have been further functionally enhanced by the coordinate physiologic effects of epinephrine on the heart [84], lung [85], and fat depots [86], underpinned structurally by the increased production of leptin by fat cells, which is known to promote the formation of blood vessels [80] and bone [87], accommodating the infrastructural changes necessitated by the evolution of complex physiologic traits.…”

Section: Pparγ Mediates the Evolutionary History Of The Adipocytementioning

confidence: 99%

PPARγSignaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung

Rehan

Torday

2012

PPAR Research

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Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine.

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“…7,9 This route of administration, whose paradigmatic example is surfactant, is common in neonatal critical care and ensures a total bioavailability of the drug where it is needed. 42 Because neonatal respiratory diseases are characterized mainly by local injury, the intrapulmonary delivery of varespladib might be a preferred route of administration because it will provide enzyme-and tissue-specific anti-inflammatory action at the lung. In this sense, our model should represent the situation of BALF in the diseased alveoli.…”

Section: Discussionmentioning

confidence: 99%

Varespladib Inhibits Secretory Phospholipase A2 in Bronchoalveolar Lavage of Different Types of Neonatal Lung Injury

Luca

Minucci

Trias

et al. 2012

The Journal of Clinical Pharma

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Secretory phospholipase A2 (sPLA2), which links surfactant catabolism and lung inflammation, is associated with lung stiffness, surfactant dysfunction, and degree of respiratory support in acute respiratory distress syndrome and in some forms of neonatal lung injury. Varespladib potently inhibits sPLA2 in animal models. The authors investigate varespladib ex vivo efficacy in different forms of neonatal lung injury. Bronchoalveolar lavage fluid was obtained from 40 neonates affected by hyaline membrane disease, infections, or meconium aspiration and divided in 4 aliquots added with increasing varespladib or saline. sPLA2 activity, proteins, and albumin were measured. Dilution was corrected with the urea ratio. Varespladib was also tested in vitro against pancreatic sPLA2 mixed with different albumin concentration. Varespladib was able to inhibit sPLA2 in the types of neonatal lung injury investigated. sPLA2 activity was reduced in hyaline membrane disease (P < .0001), infections (P = .003), and meconium aspiration (P = .04) using 40 µM varespladib; 10 µM was able to lower enzyme activity (P = .001), with an IC(50) of 87 µM. An inverse relationship existed between protein level and activity reduction (r = 0.5; P = .029). The activity reduction/protein ratio tended to be higher in hyaline membrane disease. Varespladib efficacy was higher in vitro than in lavage fluids obtained from neonates (P < .001).

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Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review

Cited by 27 publications

References 168 publications

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus

The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus

PPARγSignaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung

Varespladib Inhibits Secretory Phospholipase A2 in Bronchoalveolar Lavage of Different Types of Neonatal Lung Injury

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