An Unsettled Promise: The Newborn Piglet Model of Neonatal Acute Respiratory Distress Syndrome (NARDS). Physiologic Data and Systematic Review

Abstract

Despite great advances in mechanical ventilation and surfactant administration for the newborn infant with life-threatening respiratory failure no specific therapies are currently established to tackle major pro-inflammatory pathways. The susceptibility of the newborn infant with neonatal acute respiratory distress syndrome (NARDS) to exogenous surfactant is linked with a suppression of most of the immunologic responses by the innate immune system, however, additional corticosteroids applied in any severe pediatric lung disease with inflammatory background do not reduce morbidity or mortality and may even cause harm. Thus, the neonatal piglet model of acute lung injury serves as an excellent model to study respiratory failure and is the preferred animal model for reasons of availability, body size, similarities of porcine and human lung, robustness, and costs. In addition, similarities to the human toll-like receptor 4, the existence of intraalveolar macrophages, the sensitivity to lipopolysaccharide, and the production of nitric oxide make the piglet indispensable in anti-inflammatory research. Here we present the physiologic and immunologic data of newborn piglets from three trials involving acute lung injury secondary to repeated airway lavage (and others), mechanical ventilation, and a specific anti-inflammatory intervention via the intratracheal route using surfactant as a carrier substance. The physiologic data from many organ systems of the newborn piglet—but with preference on the lung—are presented here differentiating between baseline data from the uninjured piglet, the impact of acute lung injury on various parameters (24 h), and the follow up data after 72 h of mechanical ventilation. Data from the control group and the intervention groups are listed separately or combined. A systematic review of the newborn piglet meconium aspiration model and the repeated airway lavage model is finally presented. While many studies assessed lung injury scores, leukocyte infiltration, and protein/cytokine concentrations in bronchoalveolar fluid, a systematic approach to tackle major upstream pro-inflammatory pathways of the innate immune system is still in the fledgling stages. For the sake of newborn infants with life-threatening NARDS the newborn piglet model still is an unsettled promise offering many options to conquer neonatal physiology/immunology and to establish potent treatment modalities.

Changes in the live birth profile in Henan, China: A hospital registry‐based study

“…47 Pneumonia may be transmitted vertically from the mother or acquired from the postnatal environment, and the resultant inflammatory response leads to cellular injury that impairs gas exchange, alters pulmonary circulation, interferes with normal respiratory mechanics, denudates alveolar surfaces, and interferes with surfactant function, which results in respiratory failure leading to morbidity and mortality in newborn infants regardless of gestational age. 48 Respiratory distress syndrome primarily affects preterm infants, but RDS was also one of the leading causes in death of term infants in our study. It has been reported that the incidence of RDS increases in term infants with elective cesarean births, 49 and the reason for increased RDS in these infants is delayed removal of lung fluid and a lack of cortisol response associated with spontaneous labor.…”

Organic vs. Inorganic Tracheobronchial Airway Foreign Body Aspiration: Does Type/Duration Matter?

“…Swine tracheobronchical anatomy closely resembles humans grossly and histologically, making them ideal airway models 16–19 . We sought to determine the impact of a prolonged airway foreign body in the swine airway.…”

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

“…This could, however, be an advantage for neurodevelopment studies, since behavioral assessments can be performed from birth onward, in contrast to other models such as rats and dogs [ 28 ]. Regarding the respiratory system, there are some maturational differences ( Table 1 ), although respiratory disease models (meconium aspiration and lavage models, further discussed later in this review) have been developed in neonatal pigs [ 54 ]. Moreover, it is possible to reach the required degree of immaturity of the respiratory system in a pig model by using preterm or IUGR pigs.…”

“…Characteristics of lung function, immune response, hemodynamic during ventilation and renal function were described. The newborn pig has many similarities to the human newborn including lung development, the presence of lung macrophages, NO production, the response to lipopolysaccharides and the hypervariable region of toll like receptor 4 [ 54 , 68 , 181 ]. The latter neonatal acute lung injury model was also used for nonclinical studies of high frequency oscillatory ventilation and (partial) liquid ventilation using perfluorocarbons [ 182 , 183 ].…”