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At least 181 records · Page 10Linked to original sources
PubMed2000

Lavage administration of dilute recombinant surfactant in acute lung injury in piglets.

In an acute lung injury model, we previously observed reversal of pulmonary dysfunction with natural surfactant administered by lavage (dose = 18 mg/kg phospholipid). The present study questioned whether a lower dose of phospholipid would be effective if a recombinant preparation rather than natural surfactant were used. Acute lung injury was induced by repeated saline lung lavage in ventilated, sedated, and paralyzed piglets. Three concentrations of recombinant surfactant were studied (low phospholipid, 1 mg/mL; medium phospholipid, 4 mg/mL; high phospholipid, 13.5 mg/mL). Control piglets received no surfactant. Thirty-five milliliters per kilogram of surfactant was administered by gravity, followed by passive drainage of excess fluid. All treatment groups retained similar volumes (4.7+/-0.3 mL/ kg), corresponding to phospholipid doses of 4+/-0.4, 22+/-3, and 67+/-4 mg/kg in low, medium, and high-dose groups, respectively. Treatment groups showed significant improvement in Pao2 compared with controls. Other parameters different from controls were found in only the medium and high-dose groups. All surfactant-treated groups showed improvement over time in Pao2, Paco2, lung resistance mean airway pressure, functional residual capacity, and dynamic compliance. These data support the statement that whereas there is a dose response to exogenous surfactant, the effective dose of recombinant surfactant in acute lung injury may be as low as 4 mg/kg phospholipid when administered by lavage.

Animals↗
PubMed2004

Hyperoxia exposure impairs surfactant function and metabolism.

OBJECTIVE: To evaluate the effects of hyperoxia exposure on lung function and the endogenous surfactant system in spontaneously breathing adult rats. DESIGN: Analysis of the pulmonary surfactant system isolated from adult rats following exposure to > 90% oxygen or room air for 48 or 72 hrs. SETTING: A basic science research laboratory in a university setting. SUBJECTS: Sixty pathogen-free Sprague-Dawley rats. INTERVENTIONS: Exposure to > 90% oxygen for 72 hrs. MEASUREMENTS AND MAIN RESULTS: Exposure to > 90% oxygen for 72 hrs resulted in significant lung dysfunction and an increase in neutrophils and total protein concentrations within the airspace compared with animals exposed to room air or 48 hrs of 90% oxygen exposure. Total alveolar surfactant and large aggregate pool sizes were increased after 72 hrs of hyperoxia compared with the other groups, and there was evidence of lipid peroxidation within these large aggregate subtractions. The biophysical function of large aggregate isolated from 72-hr hyperoxia-exposed animals was also impaired and converted into small aggregate forms faster than large aggregate from normoxia-exposed animals when assessed using in vitro surface area cycling techniques. CONCLUSIONS: Oxidative stress on the endogenous surfactant system may represent an important mechanism contributing to the surfactant dysfunction and abnormal surfactant metabolism associated with hyperoxia-induced lung injury.

Acute Disease↗
PubMed1999

Exogenous surfactant improves survival and surfactant function in ischaemia-reperfusion injury in minipigs.

Reperfusion injury is the major cause of early morbidity and mortality after lung transplantation. This complication has been experimentally linked to dysfunction of pulmonary surfactant. Therefore, the hypothesis that reperfusion injury might be preventable by exogenous surfactant treatment was tested. Left lungs of minipigs were exposed to 120 min of ischaemia, and the lungs were then reperfused for up to 7 h. Animals were divided into a control group and a surfactant group (n=5 each). The surfactant group received 50 mg x kg(-1) Alveofact intrabronchially via a bronchoscope at the beginning of the ischaemic period. Bronchoalveolar lavage was performed at baseline before ischaemia and 90 min after reperfusion. Surfactant treatment significantly improved short-term survival. Pulmonary vascular resistance increased markedly in control animals leading to right heart failure and death within 3 h after reperfusion whereas the surfactant-treated animals survived the 7 h observation period. After reperfusion, alveolar accumulation of neutrophils and exuded proteins was present in both groups to the same extent. Surfactant activity after reperfusion deteriorated markedly in the control group but was preserved in the surfactant group. In conclusion, early surfactant treatment alleviates the deterioration of surfactant function and improves survival in this minipig model of ischaemia-reperfusion injury.

Animals↗
PubMed2005

Surfactant composition and function in a primate model of infant chronic lung disease: effects of inhaled nitric oxide.

Bronchopulmonary dysplasia, or chronic lung disease (CLD), of premature infants involves injury from hyperoxia and mechanical ventilation to an immature lung. We examined surfactant and nitric oxide (NO), which are developmentally deficient in premature infants, in the baboon model of developing CLD. Fetuses were delivered at 125 d gestation and were managed for 14 d with ventilation and oxygen prn without (controls) or with inhaled NO at 5 ppm. Compared with term infants, premature control infants had reduced maximal lung volume, decreased tissue content of surfactant proteins SP-A, -B, and -C, abnormal lavage surfactant as assessed by pulsating bubble surfactometer, and a low concentration of SP-B/phospholipid. NO treatment significantly increased maximal lung volume and tissue SP-A and SP-C, reduced recovery of lavage surfactant by 33%, decreased the total protein:phospholipid ratio of surfactant by 50%, and had no effect on phospholipid composition or SP content except for SP-C (50%). In both treatment groups, levels of SP-B and SP-C in surfactant were negatively correlated with STmin, with a 5-fold greater SP efficiency for NO versus control animals. By contrast, lung volume and compliance were not correlated with surfactant function. We conclude that surfactant is often dysfunctional in developing CLD secondary to SP-B deficiency. NO treatment improves the apparent ability of hydrophobic SP to promote low surface tension, perhaps secondary to less protein inactivation of surfactant, and improves lung volume by a process unrelated to surfactant function.

Administration, Inhalation↗
PubMed2001

Surfactant proteins: role in lung physiology and disease in early life.

Pulmonary surfactant is an amalgam of proteins and phospholipids which serves to maintain a low surface tension within the alveolar regions of the lungs during changes in lung volume. Recently, two of the surfactant proteins--A and D--have been characterised within the collectin family and found to play important roles in the non-specific host defence of the lung. The field of surfactant biology has attracted the attention of physiologists, biochemists, molecular biologists and clinical scientists in an effort to describe the nature and role of pulmonary surfactant in health and disease. This paper will review the history and content of discoveries in the field of surfactant biology together with pulmonary diseases related to surfactant deficiency or dysfunction.

Child↗
PubMed2004

Surfactant function in children with chronic airway inflammation.

Pulmonary surfactant is necessary to keep the terminal conducting airways patent. It is unknown whether mild to moderate airway inflammation may influence surfactant function and thus contribute to the pathogenesis of chronic airway inflammation in children. To answer this question, 21 children with chronic obstructive bronchitis and 19 asymptomatic children with long-term tracheostomy and increased numbers of neutrophils in their airways were compared with 15 healthy controls. Bronchoalveolar lavage fluid was separated into large surfactant aggregates (LA) and a supernatant containing inhibitory constituents. Surfactant function of LA, recombinations of LA and supernatant, and recombinations of a defined bovine surfactant and supernatant was assessed in a capillary surfactometer. Compared with controls, the function of the LA surfactant was reduced and there was no difference between children with tracheostomy and chronic obstructive bronchitis. The function of LA-supernatant recombinations was poor in all subjects. This may be explained by the well-known protein influx during the lavage procedure. The activity of bovine surfactant-supernatant reconstitutions was impaired in children with tracheostomy. In all surfactant mixtures assessed, surfactant function was inversely correlated to the number of neutrophils in the lavage fluid. Chronic lower airway inflammation with mild or no clinical symptoms is associated with impaired surfactant function. The dysfunction may contribute to airflow restrictions frequently observed in these children.

Bronchitis, Chronic↗
PubMed1999

Comparison of two methods of diagnostic lung lavage in ventilated infants with lung disease.

The methods of nonbronchoscopic lung lavage used for collection of samples of epithelial lining fluid (ELF) in intubated patients are poorly standardized and incompletely validated. In infants with lung disease requiring ventilatory support, we evaluated two techniques of small volume saline lavage for the collection of a specimen suitable for pulmonary surfactant analysis. We aimed to compare apparent origin of the return fluid obtained by each method, equivalence and agreement of the estimates of measured pulmonary surfactant concentration, and the relative strength of association between surfactant indices and lung dysfunction. Fifty-three contemporaneous paired samples of lung lavage fluid suitable for surfactant analysis were collected from 31 infants using tracheal aspirate (TA, 4 x 0.5 ml saline), and then nonbronchoscopic bronchoalveolar lavage (NB-BAL, 3 x 1 ml/kg). Return fluid from TA had higher mean ELF concentration of total protein and IgA secretory component (SC), and a lower surfactant protein A (SP-A) concentration than NB-BAL, indicating that the TA lavage was sampling ELF more proximally in the tracheobronchial tree (protein: TA 7.7 versus NB-BAL 4.7 mg/ml; SC: 21 versus 1.8 microgram/ml; SP-A: 9.8 versus 19 microgram/ml; all p < 0.01). Mean concentration of surfactant indices in ELF differed only for SP-A, but for all indices, paired values showed poor agreement on Bland-Altman analysis, highlighting the potential imprecision associated with small volume lung lavage. TA return fluid yielded estimates of surfactant indices which were at least equivalent to NB-BAL in prediction of the severity of lung dysfunction. We conclude that NB-BAL return fluid has more distal origin, but analysis of TA fluid may have equal validity in the estimation of indices of pulmonary surfactant. The results of individual estimates of ELF constituents in a single sample of lavage fluid should be interpreted with caution, even when standardized sampling techniques are employed.

Bronchoalveolar Lavage↗
PubMed2004

Evaluation of surfactant function at birth determined by the stable microbubble test in term and near term infants with respiratory distress.

UNLABELLED: Surfactant function using the stable microbubble test (SMT) was investigated in term or near term infants with respiratory distress. Newborn infants > or = 34 weeks gestation with an initial clinical hypothesis of transient tachypnoea of the newborn (TTN) needing supplemental oxygen and controls were included. Gastric aspirates were collected immediately after birth for SMT. The first chest X-ray films were examined by three independent radiologists and according to their interpretation the babies were divided into a TTN, a respiratory distress syndrome of the newborn (RDS), or a poorly-defined X-ray group. A total of 32 infants with respiratory distress and 32 controls with similar gestational age and birth weight were studied. The median and interquartile range (IQR) of the stable microbubble (SMB) count was significantly lower (P < 0.001) for the respiratory distress group than for the control group (17; range 6-33 versus 120; range 79-275). The proportion of babies with less than 35 stable microbubbles/mm2 (SMB/mm2) was significantly different for the whole respiratory distress group (24/32-75%) and for the TTN (9/13-69%), the RDS (5/5-100%), and the poorly-defined (10/12-83%) groups as compared with the controls (2/32-6%; P < 0.05). A total of 24/26 babies (92%) who needed oxygen for > or = 24 h but only 1/6 (17%) of them who needed < 24 h had a bubble count of less than 35 SMB/mm2 (P < 0.05). CONCLUSION: the results suggest that deficiency or dysfunction of the surfactant system is involved in the majority of cases of respiratory distress in near term and possibly term babies. The stable microbubble test can enable clinicians to take an earlier decision to give surfactant to term or near term infants with more severe and progressive respiratory distress.

Case-Control Studies↗
PubMed2000

Acute inhalation toxicity of polymeric diphenyl-methane 4,4'-diisocyanate in rats: time course of changes in bronchoalveolar lavage.

The early acute pulmonary response of Wistar rats exposed nose-only to respirable polymeric diphenylmethane 4,4'-diisocyanate (MDI) aerosol was examined. This study investigated the time course of the relationship between acute pulmonary irritation and ensuing disturbances of the air/blood barrier in rats exposed to concentrations of 0.7, 2.4, 8, or 20 mg MDI/m3. The duration of exposure was 6 h. The time-response relationship of MDI-induced acute lung injury was examined 0 h (directly after cessation of exposure), 3 h, 1 day, 3 days, and 7 days after exposure. Bronchoalveolar lavage (BAL) fluid was analyzed for markers indicative of injury of the bronchoalveolar region, i.e., angiotensin-converting enzyme, protein, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and sialic acid. Phosphatidylcholine and acid phosphatase were determined in BAL fluid and cells. Glutathione was determined in BAL fluid and lung tissue. This analysis revealed no latent period of effects except a transiently delayed influx of cells and increased lung weights on postexposure days 1 and 3. Markedly loaded BAL cells with phosphatidylcholine were observed on day 1 only. In most instances, changes returned to the level of the air exposed control on day 7, except increased glutathione in lung tissue. The findings suggest that the most sensitive markers of dysfunction of the air/blood barrier are angiotensin-converting enzyme and protein, including alkaline phosphatase. The statistically significant increase in intracellular phosphatidylcholine and decreased intracellular acid phosphatase on the exposure day suggest that increased amounts of phospholipids are phagocytized by alveolar macrophages, associated with protracted lysosomal catabolism. Partially glutathione-depleted rats exposed to 20 mg/m3 experienced a more pronounced increase in BAL protein than normal rats. In summary, this study suggests that respirable polymeric MDI aerosol interacts directly with the air/blood barrier causing increased extravasation of plasma constituents as a result of increased permeability of capillary endothelial cells. Overall, a transient dysfunction of the pulmonary epithelial barrier occurred at level as low as 0.7 mg/m3 and appears to be related a dysfunction of pulmonary surfactant. Nonprotein sulfhydryl constituents appear to play a role as portal-of-entry specific modifying factors.

Acid Phosphatase↗
PubMed2002

Pulmonary preservation with Bretscheider's HTK and Celsior solution in minipigs.

BACKGROUND: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. METHODS: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. RESULTS: Animals in the EC group survived 3.7+/-1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO(2)/FiO(2) ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. CONCLUSIONS: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.

Animals↗
PubMed1999

Surfactant replacement therapy for respiratory distress syndrome. American Academy of Pediatrics. Committee on Fetus and Newborn.

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in low birth weight immature infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. The statement summarizes the indications for surfactant replacement therapy. Because respiratory insufficiency may be a component of multiorgan dysfunction in sick infants, surfactant should be administered only at institutions with qualified personnel and facilities for the comprehensive care of sick infants.

Humans↗
PubMed1983

Fluid balance in the air filled alveolar space.

Studies in vitro and in vivo of the alveolar epithelial membrane, which show it can normally be characterized as having a "pore radius" of 0.5 to 1.5 nm, have been presented frequently over 20 years in a number of species (2, 3, 6, 8, 12). The alveolar epithelium appears to share these permeability properties with other epithelia. The changes that can be produced in the solute permeability of the alveolar epithelium by inflation are profound and point to its fragility (table; see text) in experimental situations that are not closely controlled. It is likely that experimental results unable to demonstrate molecular sieving bear the burden of proving that this property has not been altered by the experimental procedure. The inflation changes in epithelial permeability appear restricted to situations in which only a fraction of the lung expands in response to high pressures, such as in the clinical situation of respiratory failure where much of the air space is fluid filled or atelectatic, and large distending pressures are used to ventilate a small fraction of the total alveoli. Inflation-induced permeability changes, particularly to protein, may be important in alveolar water balance or in protein-induced dysfunctions of lung surfactant in such clinical situations.

Animals↗
PubMed2002

Glutathione replacement preserves the functional surfactant phospholipid pool size and decreases sepsis-mediated lung dysfunction in ethanol-fed rats.

BACKGROUND: Alcohol abuse increases the incidence of acute respiratory distress syndrome (ARDS). Previous evidence from our laboratory links ethanol-mediated glutathione depletion to impaired surfactant production by alveolar epithelial cells in vitro and to endotoxin-mediated edematous injury in isolated lungs ex vivo. ARDS patients have an imbalance between the inactive small aggregate (SA) and the bioactive large aggregate (LA) forms of surfactant phospholipid (as reflected by increased SA/LA ratios). Therefore, we hypothesized that ethanol ingestion, via glutathione depletion, could alter surfactant phospholipid distribution between LA and SA forms and thereby exacerbate sepsis-mediated lung dysfunction in vivo. METHODS: Rats fed an isocaloric diet with or without ethanol (36% total calories) for 6 weeks were made septic via cecal ligation and perforation. Some ethanol-fed rats had their diets supplemented with the glutathione precursor procysteine (>L-2-oxothiaxolidine-4-carboxylate). Sepsis physiology was assessed by determining respiratory rates, arterial blood pressures, and plasma lactate levels, and lung dysfunction was assessed by determining lung lavage fluid protein levels (index of alveolar endothelial/epithelial barrier disruption), arterial hypoxemia (index of impaired gas exchange) and surfactant phospholipid SA and LA fractions (index of the alveolar epithelium's ability to maintain a functional surfactant pool during sepsis). RESULTS: Ethanol ingestion decreased (p< 0.05) lung lavage fluid glutathione levels, and this defect was prevented by procysteine. Although ethanol ingestion had no effect (p< 0.05) on any of the indices of sepsis, it increased (p< 0.05) lung lavage fluid protein levels, worsened hypoxemia, and decreased the functional (LA) surfactant phospholipid pool after sepsis, all of which was prevented by procysteine. CONCLUSIONS: Ethanol ingestion, via glutathione depletion, increased sepsis-mediated lung dysfunction, and these effects could contribute to the increased risk of ARDS seen in alcoholic patients.

Animals↗
PubMed2006

Exogenous surfactant therapy for ARDS.

Regardless of the cause, a common pathophysiological feature of patients with acute respiratory distress syndrome is a dysfunction of the endogenous surfactant system. Although exogenous surfactant therapy has proven to be an effective treatment for neonatal respiratory distress syndrome, no similar current effective therapy exists for patients with acute respiratory distress syndrome. This is mainly due to the complexity of the lung injury that is involved with this disorder. Results from clinical trials, to date, have failed to show an improvement in patient survival after administration of exogenous surfactant; however, ongoing and future research efforts suggest that this therapy may eventually be feasible.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice.

The pathogenesis of Pneumocystis carinii pneumonia (PCP) suggests an important role for dysfunction of the pulmonary surfactant system in the hypoxemic respiratory insufficiency associated with this infection. Surfactant protein B (SP-B) is a hydrophobic protein shown to be essential for normal surfactant function in vivo. Therefore, we hypothesized that the inhibition of SP-B expression occurs during PCP, and we tested this hypothesis in two immunodeficient animal models. PCP was induced in C.B-17 scid/scid mice by intratracheal inoculation of P. carinii organisms. Infected lung homogenates, obtained at time points up to 6 weeks after inoculation, were analyzed for SP-B and mRNA content. When a comparison was made with uninfected scid controls, the densitometric quantitation of Western blots of lung homogenates demonstrated significant reductions in 8 kd SP-B in mice infected with P. carinii 4 weeks after inoculation (16% of the control value). Northern blot analysis showed a concomitant decrease in SP-B mRNA to 24% of the control level. The decrease in SP-B and mRNA levels in lung homogenates of infected mice was reflected in lower SP-B levels in the surfactant. An enzyme-linked immunosorbent assay for the SP-B level in surfactant prepared from bronchoalveolar lavage samples of infected scid mice demonstrated a significant reduction in alveolar SP-B content (45% of the control value). In contrast to the results with SP-B, neither the SP-A protein content nor the mRNA level was significantly altered by PCP infection. To confirm these observations, SP-B expression was studied in an additional animal model of PCP. The SP-B content of lung homogenates from BALB/c mice depleted of CD4+ T cells and infected with P. carinii was also reduced (51% of the control value). We conclude that P. carinii induces selective inhibition of the expression of SP-B in two mouse models of PCP and that this down-regulation is mediated at the level of mRNA expression. Therefore, an acquired deficiency of SP-B is likely to be an important contributor to the pathogenesis of hypoxemic respiratory failure that is observed in patients with PCP.

Animals↗
PubMed1997

Effect of thyroid hormone (T3)-responsive changes in surfactant apoproteins on surfactant function during sepsis.

BACKGROUND: Long surfactant phospholipids are altered during sepsis; the role of surfactant apoproteins is unknown. This study investigates the effect of cecal ligation and puncture (CLP) on surfactant functional effectiveness and apoprotein transcriptional activity with or without T3 replacement. METHODS: Male Sprague Dawley rats underwent sham laparotomy or CLP with or without T3 replacement. Lung compliance, surfactant adsorption, and surface tension were measured with a surfactometer. Surfactant apoproteins A, B, and C (SP-A, SP-B, SP-C) mRNA was quantified by Northern blot analysis. RESULTS: Lung compliance was significantly decreased by sepsis; initial surface tension and adsorption values in CLP animals reflected apoprotein dysfunction. Sepsis decreased SP-A mRNA levels and increased SP-B mRNA; SP-C mRNA were unchanged. T3 treatment improved compliance, adsorption, and ST isotherms in septic animals. CONCLUSION: T3 attenuated sepsis-induced surfactant dysfunction and SP-A and SP-B transcriptional changes during sepsis. This suggests an interaction between the thyroid, surfactant apoproteins, and lung surfactant functional effectiveness and requires further study.

Animals↗
PubMed2003

Role of exogenous surfactant in acute lung injury.

OBJECTIVES: To outline both the preclinical and clinical data demonstrating surfactant alterations in acute lung injury, which provide the rationale for testing exogenous surfactant administration in this setting. We also review the results of the randomized, controlled clinical trials conducted to date that have evaluated this therapy in patients with acute respiratory distress syndrome, and we review the various factors that may have affected the outcomes of these trials. Future areas for surfactant research will also be addressed. DATA SYNTHESIS AND EXTRACTION: A review of the literature utilizing a MEDLINE search was performed using the key words: surfactant, surfactant administration, acute respiratory distress syndrome, and lung injury. Personal views are presented and references to unpublished clinical data are made based on the authors' access to this data. CONCLUSIONS: Exogenous surfactant administration has proven inconsistent as a therapeutic modality for patients with acute respiratory distress syndrome. This is because of the severity of the injury at the time of treatment and because of the variable surfactant preparations, dosing regimes, and delivery methods used in the different trials. Future research efforts will focus on determining the optimal timing of surfactant administration in patients at risk of developing acute respiratory distress syndrome with the aim of preventing progressive lung dysfunction and determining whether surfactant treatments need to be tailored to the specific patient in question. Moreover, with the recognition that surfactant also plays an important role in host defense, the future for surfactant therapy is exciting.

Clinical Trials as Topic↗