Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Natural surfactant (Surfactant TA, Survanta, CLSE, SF-RI 1, Curosurf and human surfactant obtained from amniotic fluid) therapy for RDS in very premature infants has been evaluated in 17 controlled clinical trials. Uniformly intratracheal surfactant administration caused a decreased intensity of mechanical ventilation during the first hours (reduced inspiratory pressure, reduced oxygen requirements) as an immediate effect of surfactant administration. Metanalysis reveals barotraumatic pulmonary complications mainly, pneumothorax and pulmonary interstitial emphysema to occur less frequently in surfactant-treated infants in virtually all trials; an increased incidence of survival without bronchopulmonary dysplasia following surfactant treatment was observed in 10 controlled clinical trials. The incidence of other complications of prematurity (intracranial hemorrhage, patent ductus arteriosus and necrotizing enterocolitis) was unchanged following natural surfactant treatment. Dosing of natural surfactant is still under investigation, however recent data indicate that the initial dose should not be less than 100 mg/kg b.w. and retreatment should be given to infants with unsatisfactory response (i.e. fraction of inspired oxygen (FiO2) > 40%). Timing of surfactant treatment still remains controversial. Prophylactic treatment shortly following birth has been compared with rescue-treatment, i.e. surfactant administration to infants suffering from manifest RDS in most studies 4-8 h after birth. Conflicting data from 5 controlled trials may be interpreted as follows: prophylactic treatment seems to be favourable for extremely premature infants (GA < or = 26 weeks) and rescue treatment seems to be adequate for infants of 27-30 weeks of gestation. Intratracheal surfactant instillation in very premature infants did not result in an improved lung function for 24 h to 48 h in all patients. Ten--25% of study infants were reported to be "non-responders", i.e. infants without sustained decrease in oxygen requirements (i.e. FiO2 > 40%). Various factors may be operative including congenital bacterial infections (sepsis or pneumonia), lung hypoplasia and cardiac failure. Inactivation of surface properties of natural surfactant caused by a leakage of proteins across the alveolar-capillary membrane was observed in experimental and clinical studies. Current investigations focus on a combination of postnatal steroids and surfactant treatment to improve lung function and outcome in "non-responders". As long as any controlled clinical studies are being published, this approach remains experimental. Up to now, any controlled clinical trials have been performed to assess different modes of artificial ventilation (e.g. high frequency oscillating ventilation versus conventional ventilation) combined with surfactant therapy. Data obtained from premature animals given natural surfactant indicate any advantage with respect to gas exchange and lung histology to result from high frequency ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Natural surfactant for neonatal respiratory distress syndrome in very premature infants: a 1992 update. 129 66

We report two cases of adult respiratory distress syndrome (ARDS) treated successfully with repeated doses of a bovine natural surfactant (Survanta). Two former premature infants developed severe respiratory failure as a consequence of a chlamydial pneumonia at the age of 3 or 12 weeks, respectively. As both patients were threatened by hypoxia in spite of mechanical ventilation with maximal pressures using 100% O2 and as the X-rays were compatible with the diagnosis of ARDS, we decided to perform rescue surfactant treatment. Following surfactant instillation, marked improvement in oxygenation and ventilatory requirements was observed. Within 2 h after surfactant replacement, the PaO2/FiO2 ratio increased from 52 to 84 (case 1) and from 35 to 94 (case 2), and the peak inspiratory pressure could be reduced from 47 to 40 cm H2O and from 35 to 28 cm H2O, respectively. Both infants received a second surfactant dose about 10 h after the initial treatment and survived without developing chronic lung disease.
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PMID:Successful surfactant replacement therapy in two infants with ARDS due to chlamydial pneumonia. 782 16

Several lines of evidence suggest that surfactant and surfactant proteins may have direct effects on inhaled bacteria and are able to interact with lung defence mechanisms in many ways. We examined the effect of three different surfactant preparations (Alveofact, Survanta and Exosurf) approved for treatment of the infant respiratory distress syndrome on different strains of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae which are important neonatal pathogens and on Legionella pneumophila serogroup I as a frequent cause of pneumonia in adults. Addition of Survanta to saline seemed to delay the reduction of viable bacteria in sterile saline and induced a considerably accelerated growth of all examined E. coli strains. As opposed to this, addition of surfactant did not influence the kinetics of bacterial growth in brain-heart infusion or buffered yeast extract both with the exception of Exosurf which exerted an inhibitory effect on the multiplication of group B streptococci. Though the exact mechanisms underlying these effects remain to be determined, the influence of surfactant therapy on the growth of bacteria within the respiratory tract should be taken into account.
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PMID:Effects of different surfactant preparations on bacterial growth in vitro. 886 32

Connatal bacterial pneumonia is common in neonates. Animal studies and initial clinical reports indicate that surfactant dysfunction is involved in the pathophysiology of severe neonatal pneumonia. Since respiratory distress syndrome and connatal pneumonia may be difficult to differentiate in the first hours of life, neonates with respiratory failure due to bacterial infections might receive surfactant. Under such conditions surfactant components might be catabolized by bacteria and promote bacterial growth. We therefore investigated the influence of three modified natural (Curosurf, Alveofact, and Survanta) and two synthetic (Exosurf and Pumactant) surfactant preparations on the growth of bacteria frequently cultured from blood or tracheal aspirate fluid in the first days of life. Group B streptococci (GBS), Staphyloccocus aureus, and Escherichia coli were incubated in a nutrient-free medium (normal saline) for 5 h at 37 degrees C, together with different surfactants at concentrations of 0, 1, 10, and 20 mg/ml. With the exception of E. coli, incubation in saline alone led to a variable decrease in CFU. In the presence of Alveofact, Exosurf, and Pumactant the decline in bacterial numbers was less marked than in saline alone. Curosurf was bactericidal in a dose-dependent fashion for GBS and had a strong negative impact on the growth of a GBS subtype that lacked the polysaccharide capsule. In contrast, Survanta (10 and 20 mg/ml) significantly promoted the growth of E. coli, indicating that surfactant components may actually serve as nutrients. We conclude that bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. Further studies are necessary to elucidate the mechanisms behind our findings and to evaluate the effects of surfactant on bacterial growth in vivo.
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PMID:Influence of modified natural or synthetic surfactant preparations on growth of bacteria causing infections in the neonatal period. 1097 61

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.
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PMID:Surfactant blocks lipopolysaccharide signaling by inhibiting both mitogen-activated protein and IkappaB kinases in human alveolar macrophages. 1292 56