Tracheal Lavage Research Articles

Breath Condensate Hydrogen Peroxide Correlates with Both Airway Cytology and Epithelial Lining Fluid Ascorbic Acid Concentration in the Horse

The relationship between hydrogen peroxide (H2O2) concentration in expired breath condensate (EBC) and cytology of the respiratory tract obtained from tracheal wash (TW) or bronchoalveolar lavage (BAL), and epithelial lining fluid (ELF) antioxidant status is unknown. To examine this we analysed the concentration of H2O2 in breath condensate from healthy horses and horses affected by recurrent airway obstruction (RAO), a condition considered to be an animal model of human asthma. The degree of airway inflammation was determined by assessing TW inflammation as mucus, cell density and neutrophil scores, and by BAL cytology. ELF antioxidant status was determined by measurement of ascorbic acid, dehydroascorbate, reduced and oxidised glutathione, uric acid and α-tocopherol concentrations. RAO-affected horses with marked airway inflammation had significantly higher concentrations of breath condensate H2O2 than control horses and RAO-affected horses in the absence of inflammation (2.0±0.5 μmol/l, 0.4±0.2 μmol/l and 0.9±0.2 μmol/l H2O2, respectively; p<0.0001). The concentration of breath condensate H2O2 was related inversely to the concentration of ascorbic acid in ELF (r=-0.80; p<0.0001) and correlated positively with TW inflammation score (r=0.76, p<0.0001) and BAL neutrophil count (r=0.80, p<0.0001). We conclude that the concentration of H2O2 in breath condensate influences the ELF ascorbic acid concentration and provides a non-invasive diagnostic indicator of the severity of neutrophilic airway inflammation.

Demographic, clinical, and radiographic features of bronchiectasis in dogs: 316 cases (1988-2000).

To determine demographic, clinical, and radiographic features of bronchiectasis in dogs. Retrospective study. 289 dogs identified through the Veterinary Medical Database (VMDB) and 27 dogs examined at the North Carolina State University Veterinary Teaching Hospital. Demographic characteristics of dogs identified through the VMDB were compared with characteristics of the entire population of dogs entered in the VMDB. Medical records of dogs examined at the teaching hospital were reviewed; the diagnosis was confirmed through review of thoracic radiographs. Analysis of data from the VMDB indicated that American Cocker Spaniels, West Highland White Terriers, Miniature Poodles, Siberian Huskies, English Springer Spaniels, and dogs > 10 years old had an increased risk of bronchiectasis. Among dogs examined at the teaching hospital, coughing was the most common clinical sign. There was evidence for excessive airway mucus but not hemorrhage. A variety of bacterial organisms were isolated from tracheal wash and bronchoalveolar lavage samples. On thoracic radiographs, cylindrical bronchiectasis, generalized disease, and right cranial lung lobe involvement were most common. Seven of 14 dogs for which follow-up radiographs were available did not have any progression of radiographic lesions. Median duration of clinical signs prior to diagnosis of bronchiectasis was 9 months (range, 1 day to 10 years). Median survival time was 16 months (range, 2 days to 72 months). Results suggest that despite substantial clinical abnormalities, dogs with bronchiectasis may survive for years. Certain purebred dogs and older dogs may have an increased risk of developing bronchiectasis.

Quantitative tracheal lavage versus bronchoscopic protected specimen brush for the diagnosis of nosocomial pneumonia in mechanically ventilated patients

Background No gold standard method exists for the diagnosis of ventilator-associated pneumonia despite the availability of multiple techniques. Methods A prospective, crossover study was performed on mechanically ventilated patients meeting with suspected pneumonia. Eighteen paired samples were obtained on 15 patients, comparing the results of quantitative tracheal lavage (QTL) to bronchoscopic protected brush specimen (PSB) by quantitative culture and gram stain examination. Results The sensitivity, specificity, positive and negative predictive values, and accuracy are affected by the growth density threshold selected, and whether the same organisms are expected by both methods. There is a significant relationship between QTL and PSB ( P = 0.0048; R = 0.632), gram stain and PSB ( P <0.001; R = 0.791), and gram stain and QTL ( P = 0.0125; R = 0.575), by Spearman rank order correlation. Conclusions QTL may have a role for diagnosing and directing treatment of ventilator-associated pneumonia, allowing reservation of bronchoscopic PSB for secondary, high risk and refractory cases.

Hydrogen peroxide-scavenging properties of normal human airway secretions.

To examine the antioxidant capacity of normal human airway secretions and to characterize its molecular components, tracheal lavages were obtained from eight patients intubated for elective surgery and free of lung disease. These samples (20 microl, approximately 6.8 microg of protein) scavenged 0.57 +/- 0.09 nmol of added 0.96 nmol hydrogen peroxide (H2O2) within 10 minutes at room temperature (n = 8). The scavenging activity was inhibited 60 +/- 4% by azide (an inhibitor of heme-containing peroxidases and catalase) and 42 +/- 9% by dapsone (an inhibitor of lactoperoxidase). Mercaptosuccinic acid (an inhibitor of glutathione peroxidase) did not significantly inhibit H2O2 scavenging by these secretions. Fourfold diluted secretions showed only nonenzymatic scavenging activity, but the addition of thiocyanate to these samples (0.4 mM; substrate for lactoperoxidase) restored their ability to scavenge H2O2. The addition of reduced glutathione (8 microM) only enhanced nonenzymatic scavenging activity. These data provide evidence that multiple enzymatic and nonenzymatic systems coexist in human airway secretions that contribute to H2O2 scavenging. It appears, however, that H2O2 is mainly consumed by the lactoperoxidase system.

Evaluation of a Mucoactive Herbal Drug, Radix Ophiopogonis, in a Pathogenic Quail Model

We investigated the effect of Radix Ophiopogonis on airway mucociliary clearance and mucus secretion in anesthetized quails. The oral administration of 10 g/kg of Radix Ophiopogonis significantly increased tracheal mucociliary transport velocity (MTV). Moreover, either 10 g/kg or 3 g/kg of Radix Ophiopogonis markedly attenuated the human neutrophil elastase (HNE)-induced decrease in MTV. Furthermore, we found that 10 g/kg of Radix Ophiopogonis significantly abolished the HNE-induced increases in fucose and protein contents of tracheal lavage, whereas Radix Ophiopogonis at the same dose only significantly decreased the protein content in the control group. These results suggest that Radix Ophiopogonis improves airway mucociliary clearance and that the improvement may, at least in part, be ascribed to the amelioration of airway mucus secretion.

Inhibiting effect of ammonia on citric acid-induced cough in pigs: a possible involvement of substance P.

The effect of ammonia on the cough response to citric acid and on substance P release from C-fibers involved in this reflex was assessed. For a period from one to four days, piglets were exposed, in an inhalation chamber, to ammonia at a concentration of 15 or 30 ppm. During exposure, cough induction tests were done every two days. Recovery of the cough reflex after ammonia exposure was also determined. In a separate group of piglets exposed for 2 days to 30 ppm ammonia, substance P content was determined in bronchial and tracheal lavage fluids and in the tracheal and bronchial mucosa. Ammonia (30 ppm) was found to inhibit coughing significantly (the cough frequency was reduced by 64%) after a two-day exposure. In animals exposed for 4 days to this ammonia concentration, the recovery ranged from 3 to 7 days (mean: 5 days). The same ammonia concentration also caused the substance P content to increase significantly in bronchoalveolar lavage fluid (to 432% of its initial value) and tracheal lavage fluid (to 149%) and to decrease significantly in the tracheal mucosa (-58%), however the content in bronchial mucosa was not significantly affected (-43%). Exposure to 15 ppm ammonia had no effect on the frequency of citric acid-induced coughing. In conclusion, ammonia inhibits citric acid-induced coughing in pigs at concentrations that can be detected in piggeries. This inhibitory effect may be related to substance-P depletion in C-fiber endings.

Role of substance P and tachykinin receptor antagonists in citric acid-induced cough in pigs

The purpose of this work was to investigate the role of tachykinins in cough induced by citric acid (0.8 M) in pigs. With this object, we have studied the effect of citric acid on substance P content in the tracheo-bronchial tree and the effects of substance P and of tachykinin receptor antagonists on citric acid-induced cough. Citric acid exposure significantly increased substance P concentration in both broncho-alveolar and tracheal lavage fluids, while it decreased significantly the substance P content in tracheal mucosa. Substance P did not elicit cough, but significantly potentiated the citric acid-induced cough frequency. Tachykinin NK 1, NK 2 or NK 3 receptor antagonists, SR 140333 (nolpitantium), SR 48968 (saredutant) and SR 142801 (osanetant), respectively, significantly inhibited citric acid-induced cough. The same inhibitory effect of tachykinin receptor antagonists was observed, when substance P was nebulised before citric acid challenge. We conclude that citric acid induces in pigs a release of substance P in the tracheo-bronchial tree, which plays a sensitising role on the cough reflex. The involvement of tachykinin NK 1, NK 2, NK 3 receptors are also demonstrated in this reflex.

Iron Disequilibrium in the Rat Lung After Instilled Blood

The extravasation of erythrocytes into the human lung occurs in a myriad of pulmonary disorders. Metal that is initially included in hemoglobin has been postulated to precipitate a disequilibrium in iron metabolism, to present an oxidative stress, and to contribute to tissue injury in several lung diseases. The objective of this study is to test the hypothesis that the tracheal instillation of blood in an animal model would have significant effects on iron equilibrium and would be associated with an injury to the lower respiratory tract. Rats were intratracheally instilled with either 1.0 mL saline solution (n = 36) or 1.0 mL blood (n = 36). Biochemical end points and histochemistry were obtained at times between 20 min and 14 days after the exposure to saline solution or blood. Total and nonheme iron concentrations in tracheal lavage fluid increased after the instillation of the blood. The percentage of neutrophils in the lavage fluid was elevated 1 day after the instillation of blood and remained at that level for at least 4 days following exposure, while protein concentrations were significantly increased at 1 day and 2 days only. Erythrocytes in the lung tissue were stained for hemoglobin immediately after exposure, but by 4 days after exposure, there was none. Ferritin was elevated between 1 day and 4 days after exposure, but by 7 days after exposure, the expression of this storage protein had returned to baseline values. We conclude that intratracheal instillation of whole blood in the rat can induce a neutrophilic lung injury that is associated with a disruption of normal iron metabolism. This disruption of the iron equilibrium is made evident by quantifying iron and staining for hemoglobin and ferritin. All indexes of biological effect had corrected by 7 days after exposure.

Absence of Lamellar Bodies with Accumulation of Dense Bodies Characterizes a Novel Form of Congenital Surfactant Defect

Two female sibling full-term newborns developed respiratory distress shortly after birth, which progressed to respiratory failure. Tracheal lavage demonstrated presence of surfactant protein A (SP-A), but little surfactant protein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung biopsy performed in both infants, prominent type II pneumocyte hyperplasia was evident. Through ultrastructural examination an absence of normally formed lamellar bodies was determined, with numerous irregular electron dense bodies within the type II pneumocytes. These electron dense bodies could also be identified in the alveolar spaces and alveolar macrophages. No alveolar tubular myelin was present. Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and proSP-C was demonstrated by light microscopy. Presence of incompletely processed immunopositive proSP-B, but not proSP-C was observed in the alveolar lumina. No mutations in either the SP-B or SP-C gene were identified by sequence analysis of amplified cDNA. We conclude that these siblings exhibit an inherited surfactant deficiency characterized by abnormal accumulations of surfactant proteins within the pneumocytes. This abnormal accumulation may be due to a primary secretory defect, a defect in surfactant phospholipids, or an abnormal interaction between the phospholipids and surfactant proteins.

Links between early adrenal function and respiratory outcome in preterm infants: airway inflammation and patent ductus arteriosus.

To investigate the relationship of cortisol concentrations during the first week of life to patent ductus arteriosus (PDA), markers of lung inflammation, and respiratory outcome in very low birth weight infants. Newborns <1,500 g birth weight were prospectively enrolled at 2 centers. Serum cortisol was measured 3 times during days 2 to 7 of life. Tracheal lavage was performed on intubated infants and analyzed for interleukin-1beta, -6, and -8, and for total protein, albumin, and alpha-1 protease inhibitor. Infants receiving prenatal glucocorticoids were excluded. We obtained 337 cortisol values from 125 infants. Infants treated for PDA had lower cortisol values after day 2. One hundred thirty-three tracheal fluid samples were obtained on matching days from 71 intubated infants. Cortisol correlated inversely with tracheal interleukins and proteins. Lower cortisol values during the second half of the week correlated with longer duration of supplemental oxygen therapy and with subsequent development of chronic lung disease at 28 days and at 36 weeks. Infants with lower cortisol values in the first week of life had an increased incidence of PDA, increased lung inflammation, and an increased incidence of chronic lung disease. These findings suggest that early adrenal insufficiency may underlie the previously observed association of increased lung inflammation and PDA with adverse respiratory outcome in this population.

INHALED ATP CAUSES MUCIN RELEASE FROM GOBLET CELLS OF INTACT RATS

Secretion of mucins from airway epithelial cells has been studied almost exclusively using in vitro cell culture systems. Our understanding of in vivo secretion is greatly limited due to the unavailability of both suitable model systems and adequate assays. It has been reported that ATP induces mucin release from the cultured primary tracheal surface epithelial cell, but there is no clear demonstration of the effect of ATP on mucin release in vivo, which is important to understand the mechanism of mucin release in vivo and also to devise means for regulation of mucin release. The objective of this experiment was to see if inhaled ATP could stimulate airway mucin release in intact rats using both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. The results were: (1) a new monoclonal antibody (mAbRT03) developed against purified rat mucins specifically recognized high-molecular-mass mucins; (2) ELISA results with conventional gel-filtration assay results are virtually superimposable; (3) inhalation of ATP in intact rats resulted in a dose-independent increase in the amount of mucins in the tracheal lavage fluid with a concomitant decrease in the number of mucin-positive cells in the trachea. We conclude that extracellular ATP can stimulate mucin release from the airway in vivo, and the present rat inhalation system combined with ELISA of the airway secretions should serve a useful model for studying the pharmacology of airway mucin secretion in vivo.

Measuring Serial Levels of Interleukin-6 (IL-6) and Interleukin-1B (IL-1B) in Tracheal Lavage Fluid of Premature Infants with Respiratory Distress Syndrome (RDS) Does Not Help in Determining the Optimal Timing for the Administration of Steroids in the Prevention of Bronchopulmonary Dysplasia (BPD)

Measuring Serial Levels of Interleukin-6 (IL-6) and Interleukin-1B (IL-1B) in Tracheal Lavage Fluid of Premature Infants with Respiratory Distress Syndrome (RDS) Does Not Help in Determining the Optimal Timing for the Administration of Steroids in the Prevention of Bronchopulmonary Dysplasia (BPD)

The live attenuated subgroup B respiratory syncytial virus vaccine candidate RSV 2B33F is attenuated and immunogenic in chimpanzees, but exhibits partial loss of the ts phenotype following replication in vivo

The cold-adapted ( ca), temperature-sensitive ( ts) respiratory syncytial virus (RSV) subgroup B vaccine candidate, designated RSV 2B33F, was found previously to be restricted in replication, immunogenic, and protective against wild-type ( wt) virus challenge in rodents and African green monkeys. We sought to investigate the level of attenuation, immunogenicity and genetic stability of this vaccine candidate in seronegative chimpanzees. The 2B33F vaccine candidate was attenuated in chimpanzees and manifested a ten- and 1000-fold restriction in replication in the upper and lower respiratory tracts respectively, compared with its wt RSV 2B parent virus. Despite this attenuation, chimpanzees immunized with RSV 2B33F were completely resistant to respiratory tract disease and virus replication upon challenge with wt virus. The ts phenotype of the RSV 2B33F mutant exhibited some alteration during replication in vivo in three of four chimpanzees tested. Virus present in nasopharyngeal swab or tracheal lavage secretions of these three chimpanzees was biologically cloned by plaque passage in Vero cells at permissive temperature. The plaque progeny retained the ts phenotype, but uniformly produced plaques at 39 and 40°C to a level intermediate between that of the 2B33F input virus and the 2B wt parent virus, indicating that partial loss of the level of temperature sensitivity occurred following replication in vivo. The implications of these findings for RSV vaccine development are discussed.

Association between inflammation and epithelial damage‐restitution processes in allergic airways in vivo

Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The distribution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.

OZONE-INDUCED DNA STRAND BREAKS IN GUINEA PIG TRACHEOBRONCHIAL EPITHELIAL CELLS

Ozone (O3), the major oxidant of photochemical smog, is thought to be genotoxic and a potential respiratory carcinogen or promoter of carcinogenic processes. Because of oxidative reactions with the mucus in the upper airway, O3 reaction products are able to penetrate into the tracheobronchial epithelial (TE) cells. The carcinogenic effects of O3 on the TE cells are especially of interest since most previous studies have focused on the morphology or permeability changes of tracheas only. Therefore, the objective of this study was to examine the potential O3 genotoxicity in TE cells after an in vivo exposure, using DNA strand breaks as an index. Two-month-old male Dunkin-Hartley guinea pigs, specific pathogen free, 4 in each group, were exposed to 1.0 ppm 03 for 0, 12, 24, 48, 72, or 96 h. Animals exposed to filtered air without 03 exposure were used as controls. After O3 exposure, the trachea with two main bronchi was removed from each animal, and TE cells were isolated and employed for determination of DNA strand breaks by fluorometric analysis of DNA unwinding (FADU). The statistical significance level was set at a=.05. Compared with controls, ozone exposure did not alter the TE cell yield or viability, but caused an increase in protein content in tracheal lavage and an increase in DNA strand breaks. The amount of DNA left in the alkali lysate of TE cells found at 72 h exposure was significantly decreased from controls for 3 different alkali incubation times. An increase of the double-stranded DNA left in the alkali lysate of TE cells was observed at 96 h of exposure and approached the value of 24 h of exposure. The same pattern was seen with all 3 different alkali incubation times at 15°C. One Qd unit was estimated to correspond to 100 strand breaks per cell. The Qd was also used as an indicator for 03 damage. Compared to controls, the Qd increases significantly after 1 ppm 03 exposure for 72 h, regardless of the alkali incubation time at 15°C.

Effects of thermal environment on response to acute peripheral lipopolysaccharide challenge exposure in neonatal pigs

Abstract Objective To evaluate effects of thermal environment on response to acute peripheral lipopolysaccharide (LPS) challenge exposure in neonatal pigs. Animals 26 neonatal pigs. Procedure Pigs were assigned to the following treatment groups: 1 warm environment/LPS; 2 warm environment/saline solution; 3 cool environment/LPS; and 4 cool environment/saline solution. For each pig given LPS. 1 littermate of the same sex was given saline solution. Sows with baby pigs were housed in a warm (32 C) or cool (21 C) thermal environment. At 28 days of age, pigs were given 150 µg/kg of body weight of Escherichia coli LPS or saline solution intraperitoneally as a control. Rectal temperature and signs of sickness were monitored for 3 hours after LPS administration, when pigs were euthanatized and blood samples were collected to determine serum concentrations of tumor necrosis factor (TNF) α and cortisol. To determine in vitro production of TNFα, alveolar macrophages were collected by tracheal lavage and incubated for 24 hours at 37 or 41 C, with or without LPS (10 µg/ml). Results Thermal environment had a significant (P = 0.0004) effect on rectal temperature; LPS administration induced a febrile response (P = 0.0007) only in pigs in the warm environment. All LPS-injected pigs developed signs of endotoxemia; serum TNFα and cortisol concentrations were significantly increased (TNFα, P = 0.003; cortisol, P = 0.0001); there was no significant in vivo thermal effect on serum TNFα and cortisol concentrations. LPS-stimulated alveolar macrophages produced significantly less (P = 0.0086) TNFα when incubated at 41 C. Conclusions Thermal environment can have a significant impact on the response of neonatal pigs exposed to bacterial endotoxins. (Am J Vet Res 1997; 58:364-369)

Immunoelectron Microscopy of Protein Kinase C in Resting and Phagocytosing Macrophages.

We report here the intracellular dynamics of protein kinase C (PKC) in rabbit alveolar macrophages during phagocytosis using immunoelectron microscopy. Pulmonary alveolar macrophages were obtained by tracheal lavage from rabbits. The harvested cells were exposed to latex beads (1 pm in diameter) for 20 min at 25°C, and then fixed for 1 hr in 4% formaldehyde and 0.1% glutaraldehyde. Ultrathin frozen sections were processed for immunolabelling with anti-PKC monoclonal antibodies (mAbs) against rabbit Type 1 (γ), 2 (β) and 3 (α) PKC. Specific immunostaining was observed in macrophages incubated with anti-Type 2 or 3 mAb, and no apparent staining was observed with anti-Type 1 mAb. Type 2 and 3 mAbs labelling revealed a diffuse cytosolic distribution of the PKC in resting macrophages (without phagocytic pulse using latex beads). In phagocytosing macrophages, the most striking feature was an immunolabelling on the plasma membrane binding to latex beads and the phagosomal membrane. These results demonstrate that binding of latex beads causes a rapid translocation of cytosolic Type 2 and 3 PKC to the latex bead-attached plasma membrane, and imply that these isozymes have a crucial role in phagocytosis of foreign particles.

Effect of Human Neutrophil Elastase on Tracheal Mucociliary Transport in Anesthetized Quails

We investigated the effect of human neutrophil elastase (HNE) on tracheal mucociliary transport in anesthetized quails. Topical application of HNE (30-300/μg/kg) to tracheal mucosa dose-dependently decreased mucociliary transport velocity (MCTV). The HNE (300 μg/kg)-induced decrease in MCTV was blocked by ONO-5046 · Na (sodium N-[2-[4-(2,2-dimethylpropionyloxy)phenyl-sulfonylamino]-benzoyl]aminoacetate tetrahydrate) (3-30mg/kg, i.m.), a specific neutrophil elastase inhibitor. Furthermore, we found that HNE increased DNA, fucose and protein contents of tracheal lavages, and the increases were also reverted by ONO-5046·Na. These results indicated that HNE decreased tracheal mucociliary transport, and the decrease may be, at least in part, ascribed to the deterioration of tracheal secretions.

Altered platelet-activating factor levels and acetylhydrolase activities are associated with increasing severity of bronchopulmonary dysplasia.

Lipid inflammatory mediators are thought to play an important role in the pathogenesis of neonatal lung injury and bronchopulmonary dysplasia (BPD). Because preliminary studies from the intensive care nursery of the University of Tennessee Medical Center, Knoxville, revealed linear increased in blood platelet-activating factor (PAF) levels in very low birthweight infants developing chronic lung disease and lower cord blood PAF acetylhydrolase activities in premature infants, it was theorized that altered platelet-activating factor levels and PAF acetylhydrolase activities are associated with increasing severity of BPD. Platelet-activating factor levels (blood and tracheal lavage) and PAF acetylhydrolase activities (blood and tracheal lavage) were measured over days 1 to 2, 3 to 5 and 6 to 7 in 16 ventilated infants and weekly in 9 infants with bronchopulmonary dysplasia. Platelet-activating factor values were normalized per nanogram of lavage blood urea nitrogen. Severity of bronchopulmonary dysplasia was estimated using the scoring system developed by Toce. Mean blood and lavage PAF levels and PAF acetylhydrolase activities were compared in infants developing bronchopulmonary dysplasia with those without the disease over the first seven days of life. Infants developing chronic lung disease were significantly smaller and of younger gestational age. In infants with bronchopulmonary dysplasia, higher PAF levels in blood were seen on days 3 to 5, along with increased lavage acetylhydrolase activities on days 1 to 2. Increased levels of PAF in lavage on days 3 to 5 were associated with increasing severity of bronchopulmonary dysplasia. Altered blood and lavage platelet-activating factor levels and PAF acetylhydrolase activities appear to be associated with the pathogenesis and severity of bronchopulmonary dysplasia.

Altered Platelet-Activating Factor Levels and Acetylhydrolase Activities Are Associated With Increasing Severity of Bronchopulmonary Dysplasia

<h2>ABSTRACT:</h2> Lipid inflammatory mediators are thought to play an important role in the pathogenesis of neonatal lung injury and bronchopulmonary dysplasia (BPD). Because preliminary studies from the intensive care nursery of the University of Tennessee Medical Center, Knoxville, revealed linear increases in blood platelet-activating factor (PAF) levels in very low birth-weight infants developing chronic lung disease and lower cord blood PAF acetylhydrolase activities in premature infants, it was theorized that altered platelet-activating factor levels and PAF acetylhydrolase activities are associated with increasing severity of BPD. Platelet-activating factor levels (blood and tracheal lavage) and PAF acetylhydrolase activities (blood and tracheal lavage) were measured over days 1 to 2, 3 to 5 and 6 to 7 in 16 ventilated infants and weekly in 9 infants with bronchopulmonary dysplasia. Platelet-activating factor values were normalized per nanogram of lavage blood urea nitrogen. Severity of bronchopulmonary dysplasia was estimated using the scoring system developed by Toce. Mean blood and lavage PAF levels and PAF acetylhydrolase activities were compared in infants developing bronchopulmonary dysplasia with those without the disease over the first seven days of life. Infants developing chronic lung disease were significantly smaller and of younger gestational age. In infants with bronchopulmonary dysplasia, higher PAF levels in blood were seen on days 3 to 5, along with increased lavage acetylhydrolase activities on days 1 to 2. Increased levels of PAF in lavage on days 3 to 5 were associated with increasing severity of bronchopulmonary dysplasia. Altered blood and lavage platelet-activating factor levels and PAF acetylhydrolase activities appear to be associated with the pathogenesis and severity of bronchopulmonary dysplasia.