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

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) × mean airway pressure), SP-B content (+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.

Polyethylene glycol/surfactant mixtures improve lung function after HCl and endotoxin lung injuries.

Addition of nonionic polymers such as polyethylene glycol (PEG) and dextran ameliorates inactivation of Survanta by a variety of substances in vitro. Addition of polymers to Survanta also improves pulmonary function when used to treat rats with lung injury caused by instillation of human meconium. To find whether this approach is effective in lung injuries that more closely resemble adult respiratory distress syndrome (ARDS), we have compared the use of Survanta with Survanta + PEG in two additional models of lung injury caused by either lipopolysaccharide (LPS) or HCl in adult rats. Significant improvement of serial measures for arterial oxygenation and of postmortem pressure-volume measurements were found after treatment with Survanta + PEG compared with Survanta alone. PEG added to Survanta increased resistance to inactivation caused by tracheal fluid taken from animals injured with HCl. Other work suggests that PEG promotes surfactant aggregation, separates surfactant from surfactant inhibitors, and enhances access of surfactant to the gas-liquid interface. The addition of polymers to surfactants may also be useful in the treatment of lung injury where inactivation of surfactant has already occurred.

Ventilatory defect in coal workers with simple pneumoconiosis: early detection of functional abnormalities.

Airway obstruction is a prominent feature in coal workers' pneumoconiosis (CWP). However, many patients with CWP have even demonstrated a normal forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1). The purpose of this study was to evaluate the ventilatory defect by spirometry and search for parameters, other than FVC and FEV1, suitable for early detection of pulmonary impairment in CWP. A sample of 227 coal miners was selected from the medical clinics of two teaching hospitals. Maximal expiratory flow volume measurement and determination of functional residual capacity (FRC) and residual volume (RV) were carried out with an automated plethysmograph. The prevalence of airway obstruction (FEV1/FVC < 70%) in this sample of miners was 52.9% (120/227). There was a progression of functional impairment with the transition from category 0 to categories 2 and 3, no matter what the miners smoking habits. All of the 107 non-obstructed miners had a normal FVC and FEV1. However, the mean values for FEF25-75% (mean forced expiratory flow during the middle half of FVC) and Vmax50 (maximal expiratory flow rate at 50% FVC) were abnormally low, and RV was already elevated, in those non-obstructed subjects with category 1 simple pneumoconiosis. A borderline abnormally elevated FRC in the miners with radiological category 3 of CWP was also noted. We conclude that the Vmax50, FEF25-75%, and RV appeared to be the discriminative indices for detecting early ventilatory defect in non-obstructed patients with simple CWP. Further studies is still needed to clarify the cause of small airway dysfunction.

Polymer-surfactant treatment of meconium-induced acute lung injury.

Substances (for example, serum proteins or meconium) that interfere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant/polymer mixtures are more effective for treating one form of acute lung injury than is surfactant alone. Acute lung injury in adult rats was created by tracheal instillation of human meconium. Injured animals, which were anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with surfactant mixtures, remained hypoxic and required high ventilator pressures to maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured animals maintained normal values for oxygen and compliance of the respiratory system. The greatest improvement in both oxygenation (178%) and compliance (42%) occurred in animals with lung injury that were treated with Survanta and PEG (versus untreated control animals; p < 0.01), whereas little improvement was found after treatment with Survanta alone. Similar results were found when postmortem pulmonary pressure-volume curves and histology were examined. We conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics, and histologic appearance of the lungs in a rat model of acute lung injury caused by meconium.

Nonionic polymers reverse inactivation of surfactant by meconium and other substances.

A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic polymers, we added dextrans, polyethylene glycols (PEGs), or polyvinylpyrrolidones (PVPs) of various molecular weights to pulmonary surfactants. One to 3% human meconium or other inactivating substances were then added to the mixtures, which were tested in a modified pulsating bubble surfactometer. Polymers (3.3-500 kD) in 1-10% concentrations enhanced the ability of a commercial surfactant replacement (Survanta) to lower the minimum surface tension in the presence of meconium, serum, or lysophosphatidylcholine. Similar effects were seen when polymers were added after mixing of surfactant and meconium or other inhibitors, indicating that polymers are capable of reversing the inactivation. Results from rat experiments indicate that total lung capacity is increased when PEG is first added to the Survanta, then mixed with meconium and instilled into the lungs. We postulate that polymers separate meconium-surfactant complexes, permitting surfactant components better access to the air-liquid interface. Taeusch HW, Lu KW, Goerke J, Clements JA. Nonionic polymers reverse inactivation of surfactant by meconium and other substances.