Pilot trial of late booster doses of surfactant for ventilated premature infants

Abstract

Objective: Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant.Study Design: A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period.Result: For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO 2 Â mean airway pressure), SP-B content ( þ 75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment.Conclusion: Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B

“…We examined the association between Max, tMax, and ½Max and SP-B content (range: 0.02–1.02% PL) in surfactant samples of premature infants (1,14). There were nonsignificant negative correlations of SP-B/PL content with Max (Figure 3a) and tMax (Figure 3c), and a highly significant ( P < 0.0001) negative correlation with ½Max (Figure 3b).…”

“…To further analyze the influence of SP-B, we added SP-B to a pooled tracheal aspirate (TA) sample with low endogenous SP-B content (0.05% PL) from the same source (1,14). Max values were not altered by SP-B up to 5% PL (Figure 4a), while ½Max (Figure 4b) and tMax (Figure 4c) were strikingly reduced in a dose-dependent manner with a maximal effect reached around physiological concentrations (0.8% PL for ½Max, >1.3% for tMax).…”

“…We used TA samples obtained in a previous study from preterm infants intubated for persisting respiratory failure and randomized for late surfactant administration (day 7–21) (1,14). Written, informed consent was obtained from the families of all the participating infants, and all research activities were overseen by the University of California San Francisco Committee of Human Research.…”

Gestational Exposure of Mice to Secondhand Cigarette Smoke Causes Bronchopulmonary Dysplasia Blocked by the Nicotinic Receptor Antagonist Mecamylamine

“…Down-regulation of secretory proteins contributes to the pathology of several airway diseases, including BPD, and many premature infants are given a mixture of surfactant proteins to improve lung function (Kinsella et al 2006; Merrill et al 2011). To determine whether gestational SS broadly affected the airway secretory functions, we examined airway Clara and goblet cells in FA- and SS-exposed mouse lung sections at PD7 by staining for CCSP and SP-B (Clara cell markers) and SPDEF (goblet cell marker).…”

“…CCSP modulates immune responses, reduces lung injury in animal models, up-regulates the expression of surfactant proteins and VEGF in the lung, and ameliorates BPD (Ramsay et al 2001). SP-B lowers surface tension and prevents atelectasis and protects epithelial cells (Abdel-Latif and Osborn 2011), and its administration may improve lung functions in BPD (Logan and Moya 2009; Merrill et al 2011). The expression of CCSP, SP-B, and SP-C is significantly down-regulated in the gestationally SS-exposed PD7 lungs.…”