Lung inflammation and pulmonary function in meconium aspiration syndrome

Meconium aspiration syndrome (MAS) occurs in 2-6% of newborns (often leading to a requirement for particular medical care). Moreover, MAS is a major cause of respiratory failure and a common diagnosis in term infants referred for extracorporeal membrane oxygenation (ECMO) therapy.

The pathophysiology of MAS is very complex. Acute lung injury after perinatal aspiration of meconium is characterized by obstruction of the airways, ventilation/perfusion mismatch, inflammation, hypoxemia and acidosis. In addition, alveolar exudation, surfactant dysfunction and pulmonary hypertension complicate the clinical course and treatment of MAS. In particular, inflammation is recognized as playing an important role in the pathogenesis of MAS, as shown by in vitro and preclinical studies.

In humans, pro-inflammatory cytokines have been found in the tracheal aspirates of term infants with MAS. Moreover, analysis of the tracheal aspirate fluid (TAF) from term infants with MAS suggested that lung inflammation, as evidenced by the presence of elevated cell counts and pro-inflammatory cytokines, can be present as early as the first 6 hr of life. However, the sequential inflammatory and physiologic changes that occur in the first 96 hr of life in newborns with MAS have not been well defined. Further, in human MAS, the relationship between pro-inflammatory cytokines and how they affect pulmonary function, an important physiological parameter of outcome, remains unknown.

On these basis, an American group has evaluated the relationship between inflammation and pulmonary function, by quantifying changes in inflammatory cellular profile, pro-inflammatory cytokines, and pulmonary function in intubated neonates with MAS.

In total, TAF from sixteen term infants, obtained within the first 6, 24, 48, and 96 hr of life were used for measurements of: cellular profile changes, and mRNA and protein levels for pro-inflammatory cytokines, such as IL-1b, IL-6 and IL-8. Pulmonary function was monitored at the same time points, measuring mean airway pressure, oxygenation index (OI), alveolar-arterial oxygen gradient, and arterial/alveolar oxygen ratio.

Results showed that mean airway pressure and OI significantly decreased from the first 6-96 hr of age (P=0.01, P=0.027). Cell counts were elevated in the first 6 hr compared to 96 hr (17.4×106/ml vs 1.5×106/ml, P<0.05). Overall, pro-inflammatory cytokines decreased from the first 6-96 hr: IL-1b (187 vs 37 pg/ml, P<0.05); IL-6 (3,469 vs 150 pg/ml, P<0.05); IL-8 (16,230 vs 6,334 pg/ml, P=0.01).

In conclusion, this study suggests that MAS may be associated with an inflammatory response characterized by the presence of elevated cell count and pro-inflammatory cytokines which significantly decrease by 96 hr of life. This reduction in lung inflammation has a positive correlation with corresponding decreases in mean airway pressure and oxygenation index, two parameters associated with improved pulmonary function.

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