The move from animal to human surfactant isn't analogous to the move from animal to human insulin.
Archimedes..you got me to put on my critical care thinking cap<g>Thanks!..I'm not on the front lines right now and this is SO my thing!...I thrived on the challenge of taking care of these babes but in lower volumes since I spent most of my time in the PICU where ARDS was our nemesis[edit: ONE of them <g>..we nurses/doc's floated between both units at Childrens' to help when staffing/patient census was uneven<vbg>..
My statement may have been too broad and open to different interpretations..I submit that immunogenicity risk is low(premies and and term infants have immature immune systems until about 3 months post term(40 weeks gestation my reference point)..that said...I don't know of a single neonatologist that would prefer an animal based surfactant over an engineered humanized form..the recent issues with mad cow disease amplify this concern, the manufacturing issues(costly, chemicals used in extraction process are also a problem). And my opinion(without cheat sheets from physician colleagues)..because of the cascade of physiologic procesess, many of which remain elusive to our understanding of premies during the early post-natal period, I can't accept that bovine or porcine based products are as good as we can expect, and I think unacceptable if alternatives exist...imo, even if Surfaxin just shows non-inferiority to Survanta(by proxy it did although I too would rather have seen a direct head to head).
We get a flavor of it in DSCO's European trial of porcine Curosurf(the most widely used surfactant replacement in Europe), in which non-inferiority was found. Another issue: cost of Survanta makes it difficult/limiting its use in poorer countries outside the US/Europe..a synthetic like Surfaxin with its large scale/better margin production incentivises industry and offers help to babies/societies who now do not have access to it on the broad scale we enjoy here...
<<proteins b, c that support claims that animal derived surfactant is superior.>>
Surfaxin in contrast to Exosurf has the physiologic proportions of proteins B and C..preclinicals from different groups seem to conclude that the B protein is the most important aspect of surfactant replacement compounds
Here are some abstracts I dug up..
Certainly open to debate and discussion as I do have a professional/financial interest...
Zeta
A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants.
Am J Perinatol 2004 Apr;21(3):109-19 (ISSN: 0735-1631)
Ramanathan R; Rasmussen MR; Gerstmann DR; Finer N; Sekar K
Department of Pediatrics, Division of Neonatal Medicine, Women's and Children's Hospital and Good Samaritan Hospital, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. ramanath@usc.edu; Collective Name: North American Study Group.
We compared the onset of clinical response and safety of two surfactants, poractant alfa (Curosurf, Chiesi Pharmaceuticals, Parma, Italy) and beractant (Survanta, Ross Laboratories, Columbus, OH), for treatment of respiratory distress syndrome (RDS) in preterm infants weighing 750 to 1750 g at birth and <35 weeks gestation. The study was performed as a 20-center prospective, randomized, masked comparison trial. Preterm infants (n = 293) with RDS were randomized to receive an initial dose of either 100 (n = 96) or 200 (n = 99) mg/kg of poractant alfa or 100 ( n = 98) mg/kg of beractant. All repeat dosing was given at 100 mg/kg. The onset of clinical response after the first dose was studied by comparing changes in the fraction of inspired oxygen (F IO(2)) between 0 and 6 hours measured using the area under the curve (F IO(2) AUC (0-6)); other outcomes were assessed for the entire cohort at 28 days and for infants born at < or = 32 weeks gestation at 36 weeks postconceptional age. We found that the mean F IO(2) AUC (0-6) values for the 100 and 200 mg/kg poractant alfa groups were both significantly lower than the mean F IO(2) AUC (0-6) values for the beractant group ( p < 0.005) but were not different from each other. Other outcomes were not different among the three groups for the entire cohort, but in infants born at < or = 32 weeks gestation, mortality up to 36 weeks postconceptional age was significantly less in the 200 mg/kg poractant alfa group than in either the beractant group (3% versus 11%; p = 0.034) or in the 100 mg/kg poractant alfa group (3% versus 11%; p = 0.046). Need for more than one dose of surfactant was significantly lower in infants treated with an initial dose of 200 mg/kg poractant alfa in comparison to the beractant-treated group ( p < 0.002). Treatment with poractant alfa (200 mg/kg initial dose) resulted in rapid reduction in supplemental oxygen with fewer additional doses of surfactant versus treatment with beractant in infants <35 weeks gestation with RDS, and significantly reduced mortality ( p <0.05) than either beractant or poractant alfa (100 mg/kg dosing) in infants < or =32 weeks gestation with RDS.
Comment In: Comment In: RefSource:Am J Perinatol. 2004 Jul; 21(5):307-9/PMID:15232767
Alveofact and Survanta..the latter did better..Kuwait
Randomized clinical trial comparing two natural surfactant preparations to treat respiratory distress syndrome.
J Matern Fetal Neonatal Med 2004 Mar;15(3):167-75 (ISSN: 1476-7058)
Hammoud M; Al-Kazmi N; Alshemmiri M; Thalib L; Ranjani VT; Devarajan LV; Elsori H
Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait.
OBJECTIVES: Natural surfactant preparations have been shown to reduce the severity and mortality of respiratory distress syndrome (RDS) in preterm infants. The objective of this study was to compare the efficacy of two natural surfactants, namely SF-RI 1 (Alveofact) and barectant (Survanta), on the incidence of chronic lung disease (CLD) and other associated complications of RDS in preterm infants. METHODS: Preterm infants with RDS requiring artificial ventilation were randomly selected to receive an initial dose of either Alveofact or Survanta. The two treatment groups were tested for variation in gas exchange, ventilatory settings and neonatal complications such as CLD and mortality. RESULTS: After 5 days the Survanta-treated infants had a lower fraction of inspired oxygen (FiO2) compared with the Alveofact-treated infants. There were no differences in the ventilatory settings. More infants in the Survanta group were extubated at 3 days and fewer required the use of postnatal steroids. Less CLD and duration of oxygenation were experienced by the Survanta-treated group. CONCLUSIONS: Improved oxygenation and reduced ventilatory requirements were greater with Survanta compared to Alveofact, which in turn was associated with a trend towards a lower incidence of serious pulmonary complications.
Surfactant reduces pro-inflammatory cytokine production..first to demonstrate this
Am J Respir Cell Mol Biol 2004 Feb;30(2):228-32 (ISSN: 1044-1549)
Raychaudhuri B; Abraham S; Bonfield TL; Malur A; Deb A; Di Donato JA; Kavuru MS; Thomassen MJ
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Surfactant plays an important role in lung homeostasis and is also involved in maintaining innate immunity within the lung. Lipopolysaccharide (LPS) from gram-negative bacteria is known to elicit acute proinflammatory responses in lung diseases such as acute respiratory distress syndrome and pneumonia, among others. Our previous studies demonstrated that the clinically used, natural surfactant product Survanta inhibited proinflammatory cytokine secretion from LPS-stimulated human alveolar macrophages. Here we investigated the effect of Survanta on mitogen-activated protein (MAP) and IkappaB kinases. Survanta blocked LPS-induced activation of nuclear factor-kappaB, a key regulatory transcription factor involved in cytokine production, by preventing phosphorylation of IkappaBalpha, and its subsequent degradation. IkappaB is phosphorylated by specific kinases (IKK) before degradation. Survanta inhibited activity of both alpha and beta subunits of IKK, thereby delaying the phosphorylation of IkappaB. Interestingly, IKK-alpha is predominant in alveolar macrophages, whereas IKK-beta predominates in monocytes. Survanta also inhibited extracellular signal-regulated kinase and p38 MAP kinase activity induced by LPS. Data are the first to show that surfactant may regulate lung homeostasis in part by inhibiting proinflammatory cytokine production through reduction of IKK and MAP kinase activity.
Survanta and addition of SP-B
Eur J Med Res 2000 Jul 19;5(7):277-82 (ISSN: 0949-2321)
Friedrich W; Schmalisch G; Stevens PA; Wauer RR
Clinic of Neonatology (Charite), Humboldt University Berlin, Berlin, Germany.
In addition to the primary surfactant deficiency in newborns with respiratory distress syndrome (RDS), in the later course of RDS substantial protein leakage into the alveolar spaces can occur by damage to the alveolocapillary membrane. Acute lung injury results in surfactant dysfunction due in part to inhibition by serum proteins. The aim of this study was to investigate the influence of SP-B on the inhibitory effects of albumin (alb) and fibrinogen (fib) on the surface activity of pulmonary surfactant, using a) surface tension measurement with the pulsating bubble surfactometer in suspensions and b) in surfactant films applying the hypophase exchanger. After hypophase exchange a preformed film of Survanta is very resistant to the inhibitory activity of alb or fib. The surface tensions of suspensions are significantly higher (p <0.001) than the surface tensions of preformed surfactant films if alb or fib were added, e.g., 42 (41 to 43) mN/m vs. 21 (19 to 22) mN/m for Survanta with 20 mg alb/ml. After additional supplementation of Survanta with SP-B the surface activity of Survanta/1% SP-B films did not show inhibition by fib (2 mg/ml), (surface tension 8 (4 to 13) mN/m). These results indicate that SP-B can play an important role to protect the pulmonary surfactant film from inactivation by serum proteins.
Major Subject Heading(s) Minor Subject Heading(s) CA
Another demonstrating Survanta with not enough SP-B protein
Notter RH; Wang Z; Egan EA; Holm BA
Department of Pediatrics (Neonatology, Box 777), University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Composition, surface activity and effects on pressure-volume (P-V) mechanics are examined for lavaged calf lung surfactant (LS) and the clinical exogenous surfactants Infasurf and Survanta. Lavaged LS and Infasurf had closely-matching compositions of phospholipids and neutral lipids. Survanta had higher levels of free fatty acids and triglycerides consistent with its content of added synthetic palmitic acid and tripalmitin. Infasurf and Survanta both contained less total protein than LS because of extraction with hydrophobic solvents, but the total protein content relative to phospholipid in Survanta was about 45% lower than in Infasurf. This difference was primarily due to surfactant protein (SP)-B, which was present by ELISA at a mean weight percent relative to phospholipid of 1.04% in LS, 0.90% in Infasurf, and 0.044% in Survanta. Studies on component fractions separated by gel permeation chromatography showed that SP-B was a major contributor to the adsorption, dynamic surface activity, and P-V mechanical effects of Infasurf, which approached whole LS in magnitude. Survanta had lower adsorption, higher minimum surface tension, and a smaller effect on surfactant-deficient P-V mechanics consistent with minimal contributions from SP-B. Addition of 0.05% by weight of purified bovine SP-B to Survanta did not improve surface or physiological activity, but added 0.7% SP-B improved adsorption, dynamic surface tension lowering, and P-V activity to levels similar to Infasurf. The SP-B content of lung surfactants appears to be a crucial factor in their surface activity and efficacy in improving surfactant-deficient pulmonary P-V mechanics.
This one done in Oman..Exosurf/Survanta..latter better #'s in first 24h but overall the same..recommend the synthetic because of theoretical and and easier storage and transport
Comparative trial of artificial and natural surfactants in the treatment of respiratory distress syndrome of prematurity: experiences in a developing country.
Pediatr Pulmonol 1999 May;27(5):312-7 (ISSN: 8755-6863)
da Costa DE; Pai MG; Al Khusaiby SM
Division of Neonatology, Royal Hospital, Sultanate of Oman.
We conducted a randomized clinical trial to compare the effects of a synthetic (Exosurf) and natural (Survanta) surfactant in infants with neonatal respiratory distress syndrome. Eighty-nine patients were randomly allocated to receive one of the two surfactants. Primary outcome variables were the acute and long-term effects of the surfactant preparations, i.e., ventilatory requirements at 24 h of age as judged by the oxygenation index (OI), and the combined incidence of chronic lung disease or death at 28 days. The OIs in the Exosurf and Survanta groups at 24 h were the same (10.1 and 7, respectively; P > 0.05). The magnitude and rapidity of response, however, were greater for Survanta than for Exosurf. When arterial/alveolar oxygen tension ratios (a/A) were compared, the Exosurf group had a significantly worse a/A ratio at 24 h than the Survanta group (0.21 Exosurf vs. 0.37 Survanta; P < 0.05). The long-term outcome as judged by the combined incidence of death or chronic lung disease was not different in the two groups (18.6% Exosurf vs. 15.2% Survanta; P > 0.05). When the complications of prematurity were compared, there were no statistically significant differences between the two groups. We conclude that both preparations are reasonable choices for the treatment of respiratory distress syndrome of prematurity.
Other Abstract: This study compares the effects of synthetic (Exosurf) and natural (Survanta) surfactants on infants with neonatal respiratory distress syndrome in Oman. Subjects included 89 patients, randomly allocated to receive one of the two surfactants. Results suggest that 43 and 46 of the total infants enrolled in the study were randomized to the Exosurf and Survanta groups, respectively. The oxygenation index in the Exosurf and Survanta groups at 24 hours were the same (10.1 and 7, respectively; P 0.05). The magnitude and rapidity of response, however, were greater for Survanta than for Exosurf. Moreover, when arterial/alveolar oxygen tension ratios (a/A) were compared, the Exosurf group had a significantly worse a/A ratio at 24 hours than the Survanta group. There were no statistically significant differences between the two groups when the complications of prematurity were compared. In conclusion, both preparations offer reasonable choices in the treatment of the respiratory distress syndrome. However, this should be weighed against the minor theoretical risks of transmission of infectious agents in a natural preparation, and the easier storage and transport of the synthetic surfactant.
Comment In: Comment In: RefSourcd:Pediatr Pulmonol. 1999 May; 27(5):303-4/PMID:10344707; |
