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Aerosolized lung surfactant appears to be beneficial in patients with chronic bronchitis. Bronchitis is characterized partly by increased mucus production and the inability to clear it. Lung surfactant can help clear mucus and reduce airway inflammation. Of 87 patients with bronchitis, 66 inhaled an artificial surfactant called Exosurf through a nebulizer 3 times a day for 14 days and 21 inhaled a saline placebo. Surfactant increased lung function 11% as measured by forced expiratory volume in one second. It also increased mucus clearance by cilia in the respiratory tract., Context.--Chronic bronchitis, estimated to affect more than 13 million adults in the United States, is characterized in part by retention of airway secretions, but no approved or effective therapy for airway mucus retention in patients with chronic bronchitis has been established. Surfactant reduces sputum adhesiveness, which contributes to difficulty in clearing secretions, but surfactant has not been tested in patients with chronic bronchitis. Objective.--To examine the effects of exogenous surfactant on sputum clearance and pulmonary function in patients with stable chronic bronchitis. Design.--A prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled comparison of the effects of 2 weeks of treatment with 3 doses of aerosolized surfactant (palmitoylphosphadidylcholine [DPPC]) or saline (placebo). Setting.--Four US teaching hospitals. Participants.--A total of 87 adult patients with the diagnosis of stable chronic bronchitis. Main Outcome Measures.--Pulmonary function, respiratory symptoms, and sputum properties before treatment (day 0), after 2 weeks of treatment (day 14), and 7 days after stopping treatment (day 21). Results.--A total of 66 patients were randomized to surfactant treatment and 21 to saline treatment. Patient demographic characteristics between groups were similar at baseline. In patients who received a DPPC dose of 607.5 mg/d for 2 weeks, prebronchodilator forced expiratory volume in 1 second ([FEV.sub.1]) increased from 1.22 L (SEM, 0.08 L) at day 0 to 1.33 L (SEM, 0.09 L) at day 21 (P=.05), an improvement of 1 1.4%; postbronchodilator [FEV.sub.1] improved 10.4% by days 14 and 21 (P=.02); and the ratio of residual volume to total lung capacity, a measure of thoracic gas trapping, decreased 6.2% by day 21 (P=.009). In the surfactant groups, there was a dose-dependent increase in the ability of sputum to be transported by cilia in vitro. Conclusion.--Aerosolized surfactant improved pulmonary function and resulted in a dose-related improvement in sputum transport by cilia in patients with stable chronic bronchitis. JAMA. 1997,278:1426-1431

Infasurf appears to be more effective than Exosurf in treating respiratory distress syndrome (RDS) in newborn infants but may cause severe complications. Infasurf and Exosurf are both lung surfactants, which are necessary for proper lung function. Researchers randomly gave Infasurf or Exosurf to 846 premature infants who were at risk of RDS. Infasurf reduced the incidence of RDS by 62% and the death rate from RDS by 70% compared to Exosurf. It also increased certain measures of lung function. However, Infasurf infants were more likely to develop brain hemorrhage., Objective. To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). Design and Setting. Ten-center randomized masked comparison trial. Patients. Premature infants (n = 871) [is less than] 29 weeks gestational age by best obstetric estimate. Interventions. Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A P[O.sub.2], ratios [is less than or equal to] .10) persisted after three doses of the randomized surfactant. Primary Outcome Measures. Three primary outcome measures of efficacy [the incidence of RDS; the incidence of RDS death; and the incidence of survival without bronchopulmonary dysplasia at 28 days after birth] were compared using linear regression techniques. Results. Of 871 randomized infants, 18 infants did not receive treatment with a study surfactant, and 25 infants did not meet all eligibility criteria. The primary analysis of efficacy was performed in the 846 eligible infants and analysis of safety outcomes in the 853 infants who received study surfactant. Demographic characteristics did not differ between the two treatment groups. Compared with Exosurf, Infasurf treatment resulted in a 62% decrease in the incidence of RDS (Infasurf, 16% vs Exosurf, 42%) and a 70% decrease in RDS death (Infasurf, 1.7% vs Exosurf, 5.4%) but did not increase the incidence of survival without bronchopulmonary dysplasia at 28 days. Treatment with infasurf resulted in significant improvement in several secondary outcome measures. Infasurf-treated infants had lower average FI[O.sub.2] (Infasurf, .33 [SEM] vs Exosurf, .42; difference .08; 95% confidence interval [CI], .06 to .11) and average mean airway pressure (Infasurf, 6.0 cm [H.sub.2]O vs Exosurf, 7.1 cm [H.sub.2]O; difference 1.1 cm [H.sub.2]O; 95% CI, .7 to 1.6 cm [H.sub.2]O) for the first 72 hours of life. Crossover surfactant treatment was significantly less frequent in the Infasurf compared with the Exosurf group (Infasurf, 1% vs Exosurf, 6%). Complications (bradycardia, clinical airway obstruction, and transcutaneous arterial desaturation) associated with second and third, but not initial, surfactant treatments were observed more frequently in the Infasurf treatment group. Infasurf-treated infants had significantly less air leak ([is less than or equal to] 7 days) (Infasurf, 8% vs Exosurf, 14%; adjusted relative risk [ARR] .55; 95% CI, .37 to .81). Severe intraventricular hemorrhage (IVH) (grade 3 and 4) did not differ between the two groups (Infasurf, 11.8% vs Exosurf, 8.3%; ARR 1.41; 95% CI, .94 to 2.09) but total IVH occurred more frequently in Infasurf-treated infants (Infasurf, 39.0% vs Exosurf, 29.9%; ARR, 1.30; 95% CI, 1.08 to 1.57). Conclusion. Significant reductions in the incidence of RDS, the severity of early respiratory disease, the incidence of pulmonary air leaks associated with RDS, and the mortality attributable to RDS suggest that Infasurf is a more effective surfactant preparation than Exosurf Neonatal in the prophylaxis of RDS. However, Infasurf prophylaxis as used in this study was also associated with a greater risk of total but not severe IVH. Pediatrics 1997; 100:39-50; newborn, pulmonary surfactant, randomized clinical trial, respiratory distress syndrome., Randomized placebo-controlled trials have convincingly shown that the intratracheal instillation of different surfactant preparations, administered for the prevention or the treatment of neonatal respiratory distress syndrome (RDS), reduces the severity [...]

Infasurf appears to last longer than Survanta, which may allow doctors to use fewer doses when treating newborn infants with respiratory distress syndrome (RDS). RDS is an inflammatory lung disease. Researchers randomly gave Infasurf or Survanta to 608 infants with RDS and 374 infants with risk factors for RDS. Infasurf and Survanta are both lung surfactants, which are necessary for proper lung function. Infasurf appeared to have a modest benefit over Survanta in infants with RDS and it lasted longer., Objective. To compare the relative safety and efficacy of Infasurf (calf lung surfactant extract; ONY, Inc, Amherst, NY, IND #27169) versus Survanta (Beractant, Ross Laboratories, Columbus, OH) in reducing the acute severity of respiratory distress syndrome (RDS) when given at birth and to infants with established RDS. Design. A prospective, randomized, double-blind, multicenter clinical trial. Setting. Thirteen neonatal intensive care units participated in the treatment arm: seven of these concurrently participated in the prevention arm. Patients. The treatment arm enrolled infants of [less than or equal to] 2000 g birth weight with established RDS, and the prevention arm enrolled infants of [less than or equal to] 29 weeks' gestation with birth weights [less than or equal to] 1250 g. Intervention. Infants were randomly assigned to receive Infasurf (n = 303, treatment arm; n = 180, prevention arm) or Survanta (n = 305, treatment arm; n = 194, prevention arm) in accordance with the Survanta package insert instructions. Outcome Measures. We projected a 25% reduction between groups in the need for a third dose of surfactant for infants with established RDS, and a 25% reduction in the need for a second dose of surfactant for infants who received prophylactic surfactant. Secondary outcomes included the severity of RDS measured by inspired oxygen concentrations and mean airway pressure, air leaks, complications associated with surfactant administration, and survival to 36 weeks' postmenstrual age without the need for oxygen supplementation. Results. In the treatment arm, there was no difference between groups in the number of infants requiring more than two doses of surfactant. The interval between doses was significantly longer for Infasurf, suggesting an increased duration of treatment effect. The inspired oxygen concentration and mean airway pressure were lower in the Infasurf infants during the first 48 hours in the treatment arm. In the prevention arm, there were no differences with respect to the number of surfactant doses. The dosing intervals were longer for Infasurf infants after the second dose. No difference in inspired oxygen or mean airway pressure was noted during the first 72 hours. There were no significant differences in the incidence of air leaks, complications associated with dosing, complications of prematurity, mortality, or survival without chronic lung disease in the prevention or treatment arm. Conclusions. Infants treated with Infasurf have a modest benefit in the acute phase of RDS. Infasurf seems to produce a longer duration of effect than Survanta. Pediatrics 1997;100:31-38; respiratory distress syndrome, surfactant, Infasurf, Survanta., Clinical trials with natural surfactant preparations have documented reductions in acute respiratory disease, air leaks, bronchopulmonary dysplasia, and mortality in preterm infants.[1-9] Variations in patient selection criteria, total dose, timing [...]

The addition of dexamethasone to surfactant therapy appears to further reduce the number of lung problems in very-low-birth-weight infants. Doctors treated 70 very-low-birth-weight infants in respiratory distress with surfactant and either dexamethasone or placebo within 12 hours of birth. The frequency of bronchopulmonary dysplasia was lower at 28 days and absent at 36 days in the dexamethasone group compared to the placebo group. More infants in the dexamethasone group were breathing on their own at 14 days than the placebo group., Background. Surfactant therapy now has a well-established role in the treatment of neonates with respiratory distress syndrome but has failed to reduce the incidence of bronchopulmonary dysplasia (BPD). We conducted a double-blind, placebo-controlled trial to test the hypothesis that dexamethasone therapy given during the first 12 days of life to very low birth weight infants would be synergistic to surfactant in preventing BPD. Methods. Seventy surfactant-pretreated infants (700-1500 g) who had severe respiratory distress syndrome (a/A ratio, 0.18 [+ or -] 0.10; mean airway pressure, 11.1 [+ or -] 1.9 cm H2O; fraction of inspired oxygen, 0.81 [+ or -] 0.22) were enrolled to receive a 12-day course of dexamethasone (n = 36) or saline placebo (n = 34) starting within the first 12 hours after birth. The starting dose of dexamethasone was 0.5 mg/kg per day, and it was tapered progressively. Results. Ventilator variables at 5 to 14 days were significantly improved in those infants who received dexamethasone compared with those who received the placebo. The effect seem to be more marked in infants weighing less than 1250 g at birth. Significantly more infants could be extubated by 14 days of age in the dexamethasone group (26 of 32 vs 14 of 32). Dexamethasone therapy reduced the incidence of BPD at 28 days (odds ratio, 0.1; 95% confidence interval, 0.03 to 0.3) and eliminated BPD at 36 weeks' postconceptional age. Dexamethasone-treated infants had greater weight loss at 14 days (12.9 [+ or -] 6.4% vs 3.7 [+ or -] 8.6%, respectively) and higher blood pressures from days 3 to 10. However, no differences were seen in time to regain birth weight, hypertension (1 infant in each group), or incidence of intraventricular hemorrhage. Conclusions. We found an additive effect between dexamethasone and surfactant in improving pulmonary status and reducing the incidence of BPD. Compared with the placebo, dexamethasone therapy was more effective in reducing the incidence of BPD in surfactant-pretreated very low birth weight infants. Pediatrics 1996; 98:204-210; prevention of bronchopulmonary dysplasia, very low birth weight, respiratory distress syndrome, dexamethasone., ABBREVIATIONS. RDS, respiratory distress syndrome; BPD, bronchopulmonary dysplasia; [FIO.sub.2], fraction of inspired oxygen; MAP, mean airway pressure; NICU, neonatal intensive care unit; IVH, intraventricular hemorrhage; IMV, intermittent mandatory ventilation; PDA, [...]

Premature white babies appear to have benefitted more from surfactant therapy than premature black babies. Surfactant therapy was approved in 1990 to treat very-low-birth-weight babies with respiratory distress syndrome. After 1990, the mortality rate among these babies dropped 17%. However, the mortality rate among black babies remained the same while the rate in white babies dropped 41%. Black babies were just as likely to receive surfactant as white babies but they may have less need for it, since their lungs mature faster.

Artificial lung surfactant may not improve the survival rates of people with acute respiratory distress syndrome (ARDS). ARDS can be a complication of sepsis, which is a serious bacterial infection of the blood. Researchers used a nebulizer to administer a synthetic lung surfactant called Exosurf to 268 patients hospitalized with ARDS. A control group of 257 people with ARDS received a placebo. All participants were treated for five days. At 30 days, there was no difference in mortality rates, use of oxygen therapy, number of days in the intensive care unit and the amount of ventilation required between the two groups. Exosurf also did not improve oxygenation or peak airway pressure. There were also no differences in outcome among subgroups such as those with severe ARDS or those who had ARDS for longer periods of time. It is possible that the lungs received an insufficient dose of the surfactant.

Surfactant in aerosol form seems to be a safe treatment that may be useful for mechanically-ventilated patients with acute respiratory distress syndrome (ARDS) caused by sepsis. Researchers studied 51 patients who were in the initial 18 hours of sepsis-induced ARDS to evaluate the effects of surfactant. During a five day period, seventeen patients received 12 hours of aerosolized surfactant per day, seventeen were treated with 24 hours of aerosolized surfactant per day, and 17 received an aerosolized placebo for either 12 or 24 hours per day. Results revealed no consistent negative changes in physiologic measurements, blood chemistry or physical condition in the surfactant-treated patients or placebo-treated patients. Adverse effects from surfactant treatment were rare. Fewest patient deaths were recorded in the 24-hour surfactant group while the greatest number of deaths occurred in the placebo recipients. Differences in mortality rates among patients in the three treatment groups, however, were not statistically significant., Objective.--To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). Design.--A prospective, double-blind, placebo-controlled, randomized, parallel, mutlicenter pilot clinical trial. Patients.--A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. Intervention.--Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. Main Outcome Measures.--Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. Results.--Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameter between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. Conclusions.--Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS.

The effectiveness of surfactant in the treatment of premature infants may be influenced by practices in neonatal intensive care units (NICUs). Surfactants reduce the severity of respiratory distress syndrome in low-birth weight, premature infants, reduce deaths and increase survival without bronchopulmonary dysplasia (BPD). The efficacy of surfactant treatment was studied in 108 infants at one NICU and in 92 infants at another. Overall, there was no significant difference in the rates of survival without BPD between the two NICUs. Among 79 infants treated at one NICU, treatment with surfactant was associated with lower death rates and increased survival without BPD. Among 78 infants treated at the other NICU, treatment with surfactant had no effect on survival. Two aspects of neonatal care were associated with efficacy of surfactant therapy. Infants who had a low fluid and colloid intake and who were treated with a high mean airway pressure relative to the inspired oxygen concentration were more likely to respond to surfactant therapy., The purpose of this study was to analyze the impact of neonatal care practices on the efficacy of exogenous human surfactant. Two hundred newborns (gestational age 24.0 to 29.9 weeks, lecithin-sphingomyelin ratio less than 2 or absent phosphatidylglycerol, and requirement of mechanical ventilation at birth) participated in a randomized bicenter trial of human surfactant substitution. In only one of the two sites (site 2) surfactant substitution decreased the severity of respiratory failure and increased neonatal survival without bronchopulmonary dysplasia. For analysis of three-way association, continuous variables describing patient characteristics and treatment were dichotomized at the median. The following variables were significantly associated with good outcome in site 1 and 2 and with surfactant substitution in site 2: low oxygen requirement during first three neonatal days, low mean airway pressure during second and third day, low [Paco.sub.2] during first two neonatal days, and no ligation of ductus arteriosus. Low fluid intake during the first three days and low colloid intake during the first two days of life were associated with good outcome in both sites. The ratio between mean airway pressure and the oxygen requirement was higher in site 2 than in site 1 during the first day of life. Fluid intake and ventilatory management may influence the efficacy of exogenous surfactant. Pediatrics 1993; 91:552-560; respiratory distress syndrome, pulmonary surfactant, intensive care, neonate.

Survanta appears to be safe in the prevention and treatment of respiratory distress syndrome (RDS) among premature infants. Survanta is a synthetic lung surfactant that reduces surface tension and improves the elasticity of the lungs. Of 8,168 premature infants, 2,670 were given Survanta for the prevention of RDS, and 5,498 were given Survanta for the treatment of RDS. Overall, 56.8% of the infants required more than one dose, and 23% received the maximum four doses. There were problems with the administration of Survanta at least once in 30.4% of the infants. Adverse events occurred in 0.5% of the infants, but only one event was attributed to Survanta treatment. The overall survival rate was 84.4%., From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250g (prevention strategy). Neonates weighing 600 to 1750g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials. Pediatrics 1993; 91:546-551; Treatment Investigational New Drug, pulmonary surfactant, bovine surfactant, respiratory distress syndrome, hyaline membrane disease, prematurity, neonatal mortality.

Infants born prematurely have an increased risk of respiratory distress syndrome, a lung disorder, because the lungs are still immature and do not produce adequate quantities of a substance called surfactant. This condition can be fatal. Studies have shown that a natural surfactant derived from other species given once at birth to these infants can reduce the severity of respiratory distress syndrome, but survival rates have not been shown to increase. This study examined whether giving multiple doses of a natural surfactant derived from cows (bovine surfactant) to these infants could increase their chances of surviving respiratory distress syndrome. Infants born at 23 to 29 weeks gestation weighing between 600 and 1,250 grams (1.3 to 2.8 pounds) were included in the study. A total of 430 infants participated, with 210 assigned to the treatment group and 220 to the control group. The treatment group received the surfactant at birth and again when needed (delivered into the trachea, or windpipe), while the control group received a dose of air, which functioned as a placebo. Results showed that in the first 28 days after birth, 1.9 percent of the treated and 15.6 percent of the untreated infants died from respiratory problems, a significant difference. Respiratory distress syndrome developed in 28 percent of the treated and in 56.9 percent of the control infants. The treated infants also had lower rates of developing pulmonary interstitial emphysema, at 23.3 percent versus 36.9 percent for the control group. These results indicate that multiple treatments with a natural surfactant at birth and again when needed can reduce the rates of illness and death from respiratory problems in infants born prematurely. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infants born prematurely often suffer from lung problems such as respiratory distress syndrome that increase their risk of illness and death above that of full-term infants. Premature infants lack a substance called surfactant in the lungs which is essential for respiratory function. In the past decade, it was found that a surfactant derived from cows (bovine surfactant) could be given to these infants, and that this decreased the need for oxygen and ventilation (use of a breathing machine). Further studies found that a single dose given at birth reduced the severity of the symptoms of respiratory distress syndrome, but did not necessarily increase survival rates. This study examined if giving more than a single dose of the surfactant when disease persisted would increase survival rates in these infants. The study involved 798 infants born prematurely weighing between 600 and 1,750 grams (1.3 and 3.9 pounds) that developed respiratory distress syndrome within six hours after birth. The infants were randomly assigned to one of two groups; one was the control group (396 infants) and the other received an initial dose of the surfactant with repeated doses if needed (402 infants). Results showed that in the first 28 days after birth, 36 treated infants (9 percent) and 80 untreated infants (20 percent) died from respiratory distress syndrome. Deaths from all causes during this period were 74 (18 percent) in the treated group and 108 (27 percent) in the untreated group. Mean airway pressure and oxygenation values, measures of respiratory function, during the first 72 hours of life were significantly better in the treated than in the untreated infants. The treated infants also developed significantly fewer cases of pulmonary interstitial emphysema and of pulmonary air leaks than the untreated infants. These results indicate that multiple doses of bovine surfactant given to premature infants with respiratory distress syndrome can reduce the incidence of illness and death. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infants born prematurely often suffer from hyaline membrane disease, also known as respiratory distress syndrome, in which the lungs are unable to function properly because they are immature. A substance called surfactant is lacking in the infant's lungs. Previous studies have shown that protein-containing lung surfactants from other species can be processed and given to infants with the disease to lessen its severity and increase survival. The protein portion helps in absorption of the surfactant, but increases the risk for infection or immunologic rejection and is difficult to produce on a large scale. This study examined the effectiveness of a new synthetic surfactant, EXOSURF, that does not contain proteins, for treating infants with hyaline membrane disease. The drug was given through the trachea (windpipe) to two sets of infants soon after birth. There were 74 high-risk infants weighing between 700 and 1,350 grams (1.5 to 3 pounds) who were given the drug or a placebo at birth as a preventive measure (prophylactic trial), and 104 infants with the disease weighing more than 650 grams (1.4 pounds), who were given EXOSURF as a treatment or were given a placebo (rescue trial). In the prophylactic trial, 36 received the drug and 38 received the placebo. Within the first three days after birth, six infants given placebo died of respiratory failure while none of the prophylactically treated infants died until one died at age 34 days. In the rescue trial, 53 infants received the surfactant and 51 received a placebo. Complication and death rates were not significantly different between the treated group and the placebo group. In both trials, the treated group did have significantly greater improvements in respiratory function than the placebo group. These results indicate that EXOSURF, a synthetic surfactant, is as effective as surfactants derived from animals in treating hyaline membrane disease, with the added benefit that the former does not contain proteins. (Consumer Summary produced by Reliance Medical Information, Inc.)