What is eosinophilic pneumonia?
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Acute Disease↗
Biomedical subjects
W B Davis
Publications and source records attributed to W B Davis.
Black-white differences in blood pressure among participants in NHANES II: the contribution of blood lead.
Separate studies using data from the second National Health and Nutrition Examination Survey, 1976-1980 (NHANES II) have shown that blacks in the United States have higher blood lead levels than whites and that blood lead is positively related to blood pressure. Based on these reports, we examined data from NHANES II to determine the extent to which race differences in blood pressure were explained by elevated blood lead levels in blacks. Regression analyses, with race as an indicator variable, were used to estimate the contribution of blood lead to black-white differences in blood pressure. The overall effect of blood lead on race differences in blood pressure was small, reflecting, in part, the magnitude of race differences in blood lead and in the association of blood lead and blood pressure. Nevertheless, a pronounced and consistent effect of lead on race differences in blood pressure was found among the poor, particularly women.
Adolescent↗
Inhibition of hypochlorous acid by lidocaine and native components of alveolar epithelial lining fluid.
Alveolar epithelial lining fluid (ELF) contains several antioxidant substances that may provide in vivo protection. We studied the ability of ELF and ELF components to inhibit the neutrophil oxidant hypochlorous acid (HOCI). Normal bronchoalveolar lavage fluid containing ELF was incubated with physiologically relevant concentrations of HOCI (0.04 mM). After incubation, residual HOCI activity was titered by the iodide method. The inhibitory activity of lavage fluid was unexpectedly strong. For example, lavage fluid diluted 20-fold in the assay system quenched 49% of starting HOCI. We initially postulated that ELF total protein and glutathione would account for most of the inhibition of HOCI. However, several experimental approaches demonstrated that the total protein and glutathione concentrations in diluted lavage fluid were too low to explain the observed inhibition. Instead, the majority of HOCI inhibition was due to the lidocaine used for upper airway anesthesia. Reagent lidocaine exhibited strong reactivity in the HOCI assay system. Furthermore, the lavage fluid lidocaine concentration (32.4 +/- 6.9 micrograms/ml) was sufficient to explain most of the observed quenching activity. Additional experiments explored the hypothetical quenching activity of ELF components devoid of lidocaine. These findings demonstrate the technical problems posed by lidocaine in antioxidant studies involving lavage fluid or ELF.
Adult↗
Tumor necrosis factor infusions in humans prime neutrophils for hypochlorous acid production.
Five cancer patients undergoing intravenous infusions of human recombinant tumor necrosis factor (TNF)alpha were evaluated for the effects these infusions had on the priming of circulating neutrophils for hypochlorous acid (HOCl) production. These patients were also studied for changes in temperature, circulating white blood cell counts, blood pressure, and spontaneous monocyte interleukin 1 beta (IL-1 beta) and TNF production. As predicted by previous in vitro studies, patient neutrophils increased their HOCl production to unopsonized zymosan from a baseline of 29.2 +/- 5.9 nmol I- oxidized/4 x 10(6) cells to a peak of 64.2 +/- 9.8 nmol I- oxidized/4 x 10(6) cells at 4 h after TNF infusion (P less than 0.01). Similar increases were also seen at 4 h with phorbol myristic acetate and opsonized zymosan as the stimuli. The priming effect could be reproduced in neutrophils from a normal individual by incubating them with the 30-min serum samples from the infused patients. The ability of this serum to prime neutrophils was completely blocked by a monoclonal anti-TNF alpha-antibody but not by an anti-IL-1 beta antibody. In addition to the priming of their neutrophils, patients also experienced fever, marked hypotension, and an initial fall, followed by rebound to an elevation, in circulating white blood cell counts. The TNF infusions did not produce detectable circulating IL-1 beta nor did they induce significant production of TNF or IL-1 beta by circulating blood monocytes. These studies confirm the role of TNF in producing the signs of sepsis such as hypotension, fever, and leukopenia followed by leukocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Diagnostic significance of increased bronchoalveolar lavage fluid eosinophils.
We determined the incidence of increased bronchoalveolar lavage (BAL) fluid eosinophil percentages in 1,059 consecutive patients undergoing bronchoscopy with BAL over a 33-month period. Forty-eight (48) patients were found to have 5% or more BAL eosinophils. The most common causes for increased BAL eosinophils were interstitial lung diseases (40% of patients), acquired immunodeficiency syndrome (AIDS)-associated pneumonia (17% of patients), idiopathic eosinophilic pneumonia (15% of patients), and drug-induced lung disease (12% of patients). Together, these four diagnoses accounted for 84% of all patients. In contrast, eosinophils were uncommon in the BAL of patients with the adult respiratory distress syndrome, lung cancer, community-acquired pneumonia, or immunocompromising diseases other than AIDS. The finding of increased BAL eosinophils was most helpful in patients presenting with unexplained pulmonary infiltrates. In these patients, this finding was often an important clue to the final diagnosis. We conclude that although the finding of an increased percentage of BAL eosinophils is uncommon, when present it is relatively specific for a limited number of diseases.
Adolescent↗
Failure of high-dose vitamin E to correct ceruloplasmin ferroxidase deficiency in cigarette smokers.
Cigarette smokers have a biochemical defect in the ferroxidase activity of their serum ceruloplasmin. Ceruloplasmin is one of the main serum antioxidants, and this defect in ferroxidase activity most likely accounts for the previously observed decrease in smoker serum antioxidant activity. This defect may be related to oxidation of ceruloplasmin in the lung. We hypothesized that vitamin E might be able to reverse the decrease in smoker ferroxidase activity and thus restore serum antioxidant activity. To test this hypothesis, we administered high-dose vitamin E to a group of young asymptomatic cigarette smokers (n = 8). Although serum levels of vitamin E significantly increased (8.7 +/- 0.8 to 20.6 +/- 3.1 micrograms/ml, p = 0.01), the ferroxidase activity of smoker serum (0.139 +/- 0.02 (0.139 +/- 0.02 to 0.144 +/- 0.03 U/ml, p = 0.824), and the antioxidant activity of serum (45.8 +/- 7.2 to 51.6 +/- 8.4%, p = 0.587) remained unchanged. Thus, at the current dose and duration of supplementation, vitamin E was unable to reverse the defect in smoker serum ferroxidase activity and thus unable to augment the antioxidant capacity of the serum.
Adult↗
Effects of oxidized low density lipoproteins on arachidonic acid metabolism in smooth muscle cells.
The role of oxidized plasma lipoproteins in modifying arachidonic acid (AA) metabolism was studied in smooth muscle cells (SMC). Very low density lipoproteins (VLDL), unoxidized low density lipoproteins (LDLBHT) isolated with butylated hydroxytoluene (BHT), and oxidized LDL (LDLOXID) were separated from human serum. Thiobarbituric acid reactant (TBAR) levels were adjusted by saline incubations. Prostanoids in guinea pig SMC cultures were measured either by radioimmunoassay (RIA) or the isolation by high performance liquid chromatography (HPLC) of labeled prostanoids from SMC prelabeled with [14C]AA. Cell morphology and viability were studied by staining with Giemsa, nile red, and propidium iodide. VLDL and LDLBHT had little effect on prostanoid synthesis. Low-TBAR-LDLOXID enhanced total prostanoid levels and diminished the release of labeled prostanoids. Similar effects were found with exogenous free AA (unlabeled). Low-TBAR-LDLOXID did not affect the release of endogenous phospholipid AA as free AA. Synergism occurred between LDLOXID and exogenous free AA in prostanoid synthesis. Low-TBAR-LDLOXID evidently enhanced prostanoid levels in SMC both by supplying AA and by stimulating cyclooxygenase. High-TBAR-LDLOXID blocked prostanoid synthesis and enhanced cell death but time and pulse-recovery experiments showed that these effects were unrelated. High-TBAR-LDLOXID stimulated prostanoid synthesis when BHT was added to the incubation media. High-TBAR-LDLOXID also caused massive free AA release and the formation of many nonprostanoid derivatives. High-TBAR-LDLOXID evidently diminished overall prostanoid levels in SMC by inhibiting cyclooxygenase and at the same time stimulating AA release and the formation of other AA derivatives.
6-Ketoprostaglandin F1 alpha↗
Hydroxylation of salicylate by activated neutrophils.
Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 x 10(6) cells) produced 55 +/- 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.
Amitrole↗
Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure.
Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well characterized. We describe the clinical features, results of bronchoalveolar lavage, and follow-up studies of four patients with acute eosinophilic pneumonia. The patients presented with an acute febrile illness, severe hypoxemia (partial pressure of arterial oxygen less than 60 mm Hg), diffuse pulmonary infiltrates, an increased number of eosinophils (mean +/- SEM, 42 +/- 4.8 percent) in bronchoalveolar-lavage fluid, and an absence of infection and previous atopic illness. The illness resolved rapidly after treatment with erythromycin and corticosteroids. The patients received doses of oral prednisone that were tapered over 10 days to 12 weeks, and none have relapsed since the steroids were discontinued. After a minimum follow-up period of five months, clinical evaluation, chest radiography, and pulmonary-function tests have shown no residual abnormalities attributable to the acute eosinophilic pneumonia. Follow-up bronchoalveolar lavage has demonstrated less than or equal to 1 percent eosinophils in all patients. We believe that we are describing an acute form of eosinophilic lung disease distinct from previously described syndromes. It can be diagnosed by bronchoalveolar lavage and seems to respond to treatment with corticosteroids.
Acute Disease↗
Activation and deactivation of guinea pig peritoneal eosinophils during chronic polymyxin B stimulation.
Eosinophils exhibit different levels of oxidative metabolism depending on their site of origin and various host factors that may influence metabolism. The present study examined the time course of eosinophil oxidative metabolism in animals undergoing chronic peritoneal stimulation. Eosinophils were purified from the peritoneal exudates of guinea pigs stimulated with weekly polymyxin B and saline peritoneal lavage. 14C-1- and 14C-6-glucose oxidation and H2O2 production were measured at week 0 and at various time points throughout 43 weeks of stimulation. Baseline oxidative metabolism of eosinophils was relatively high throughout the time course, but then declined sharply after 32 weeks. These "deactivated" cells that were recovered after 32 weeks also failed to respond to phorbol myristate acetate (PMA) or opsonized zymosan. Electron microscopy did not reveal significant differences between deactivated eosinophils and cells from earlier time points. These findings document the time course of eosinophil activation and deactivation in this model and suggest that metabolic heterogeneity of eosinophils can occur over time in response to a chronic stimulus.
Animals↗
Mechanisms for the stimulation of prostanoid synthesis by cyclosporine and bacterial lipopolysaccharide.
Both cyclosporine and bacterial lipopolysaccharide enhance prostanoid synthesis and regulate the immune response. This study was designed to establish whether these agents affect prostanoid synthesis by common or different mechanisms. CsA and LPS stimulate prostanoid synthesis both in human monocytes and smooth muscle cells from guinea pig aorta. Only LPS stimulates synthesis in the presence of exogenous arachidonic acid. Dexamethasone totally blocks CsA but only partially inhibits LPS. CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid, but indomethacin only blocks the effect of LPS. CsA and the releasing agent calcium ionophore (A23187) both increase PGE2 and PGI2 synthesis without changing their relative concentrations, cause the release of free arachidonic acid, and lead to the formation of new metabolites that are not products of cyclooxygenase activity. Preincubation with either CsA or A23187 and a subsequent wash deplete the arachidonic acid pool available for prostanoid synthesis. Thus, A23187 and CsA have very similar effects on arachidonic acid metabolism. In contrast, LPS increases PGE2 and PGI2 synthesis and alters their relative concentrations, diminishes the relative concentration of free arachidonic acid, and enhances the formation of new metabolites that are products of cyclooxygenase activity. These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release, and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.
Animals↗
Tumor necrosis factor primes neutrophils for hypochlorous acid production.
Tumor necrosis factor (TNF) has a weak direct effect on neutrophil oxidative metabolism and primes neutrophils for oxidant release in response to other stimuli. We examined the effect of recombinant human TNF alpha (rTNF alpha) on production of hypochlorous acid (HOCl) by human neutrophils. TNF alone, even at concentrations of 1,000 U/ml, did not stimulate HOCl production. In contrast, rTNF alpha, in a dose-dependent manner, primed neutrophils for HOCl production in response to the weak agent unopsonized zymosan. rTNF alpha concentrations as low as 10 U/ml resulted in a fivefold increase in HOCl in this system. rTNF alpha-primed cells also exhibited increased phagocytosis. Priming in this model system occurred regardless of whether cells were preincubated with rTNF alpha before addition of zymosan or coincubated with both rTNF alpha and zymosan. rTNF alpha priming for HOCl production could not be washed away and required a lag period of approximately 10 min. rTNF alpha priming was not dependent on extracellular Ca2+ and Mg2+. Preincubation experiments demonstrated that rTNF alpha priming was not inhibited by the microfilament blocker cytochalasin B. Although the mechanism remains unclear, these findings demonstrate that rTNF alpha has an important priming effect on the neutrophil myeloperoxidase pathway.
Calcium↗
Effect of dimethylthiourea on the neutrophil myeloperoxidase pathway.
The sulfur-centered compound dimethylthiourea (DMTU) affords antioxidant protection in animal models of acute lung injury, an effect that has been attributed to its OH. scavenging properties. Although DMTU can also react with H2O2 in certain experimental systems, the effect of DMTU on the neutrophil myeloperoxidase (MPO) pathway has not been studied. DMTU (1-10 mM) completely blocked stable oxidants and hypochlorous acid formation by phorbol myristate acetate- and zymosan-stimulated neutrophils. DMTU also provided complete inhibition when incubated with cell-free supernatants after the formation of the MPO products. DMTU prevented the oxidative inactivation of alpha 1-antitrypsin by neutrophil-stable oxidants. Evidence that DMTU was oxidized by the MPO products was obtained by titration of oxidized DMTU with reduced glutathione. Surprisingly, supernatants from cells incubated with DMTU (10 mM) consumed two- to threefold higher amounts of reduced glutathione than supernatants from cells incubated with taurine (15 mM). Metabolic studies with stimulated neutrophils and experiments with the MPO enzyme system in a cell-free system suggested that DMTU acts by scavenging the products of the MPO pathway rather than by blocking H2O2 production in the intact cell. These findings demonstrate that DMTU blocks the neutrophil MPO pathway in addition to its known ability to scavenge other reactive O2 species. The capacity of DMTU to scavenge MPO products may explain some of its protective effects in acute lung injury.
Glutathione↗
Bronchiolitis in adults. A reversible cause of airway obstruction associated with airway neutrophils and neutrophil products.
In the past 4 yr, 16 adult patients were identified who had accelerated onset of a severe respiratory disorder (usually obstructive in nature) that was clinically distinct from the more commonly encountered chronic obstructive disorders (e.g., chronic bronchitis, emphysema, asthma, bronchiectasis, cystic fibrosis, and alpha 1-antitrypsin deficiency). These patients, termed patients with "bronchiolitis," underwent pulmonary function testing, bronchoscopy with bronchoalveolar lavage (BAL), and open lung biopsy. Although lung biopsy findings varied somewhat among the patients, each biopsy contained a prominent component of bronchiolitis. Pulmonary function testing and BAL were also repeated after 3 months of treatment with oral prednisone (1 mg/kg/day). Initial BAL neutrophil percentages were significantly higher in the bronchiolitis group (54 +/- 10%) than in smokers with chronic bronchitis (3.9 +/- 1.0%) or in normal nonsmoking volunteers (0.8 +/- 0.5%) (p less than 0.01, both comparisons). Eleven of 15 patients with bronchiolitis had significant improvement (greater than or equal to 15% increase in FEV1) in their lung function after prednisone treatment. Furthermore, this "responder" subgroup had a significant reduction in BAL neutrophil percentages after treatment with prednisone (46 +/- 15% to 6 +/- 3%, p less than 0.05). Finally, the neutrophil products collagenase and myeloperoxidase were detected in the BAL fluid of patients with bronchiolitis. These findings suggest a central role for the neutrophil in the pathogenesis of bronchiolitis and emphasize the utility of BAL in the identification of these patients.
Adolescent↗
Validity of bronchoalveolar lavage in acute lung injury: recovered cells accurately reflect changes in the lung parenchyma.
Bronchoalveolar lavage (BAL) has come into widespread use as a tool to diagnose and manage various lung diseases. However, the usefulness of BAL is based on the assumption that the cells recovered in BAL fluid accurately reflect cellular populations in the lung parenchyma. To test this hypothesis, random source (n = 16) dogs were given intravenous phorbol myristate acetate (PMA) to produce acute, diffuse lung inflammation. Dogs were divided into three groups. Group I animals (n = 2) underwent BAL and open lung biopsy at time zero. Group II (n = 7) animals underwent hourly BAL after PMA with open lung biopsy at 3 h. Group III (n = 7) animals underwent hourly BAL after PMA with open lung biopsy at 6 h. When BAL cell populations were compared with the corresponding biopsies, there was a direct correlation (r = 0.67) between BAL neutrophil percentages and neutrophils present in histologic sections. These findings suggest BAL accurately reflects changes in the lung parenchyma in acute lung disease.
Acute Disease↗
Studies on oxidized low density lipoproteins. Controlled oxidation and a prostaglandin artifact.
Low density lipoproteins (LDL), isolated by ultracentrifugal flotation, were oxidized (LDLOXID) slowly during dialysis against 0.15 M NaCl and subsequent incubation in 96% air-4% CO2 at 37 degrees C. Butylated hydroxytoluene prevented LDL oxidation. LDL preparations from different sera were oxidized at different rates and the degree of lipid peroxidation was controlled by varying the incubation time. Mild oxidation did not alter the electrophoretic mobility of the LDLOXID preparations. LDLOXID contained lipid peroxides in neutral lipids, had increased amounts of lysophosphatidylcholine, and contained a number of complex oxidation products that were generated from the oxidation of free fatty acids. These oxidation products included large amounts of soluble material that cross-reacted with antibodies to PGE2 but not 6-keto-PGF1 alpha. The amount of cross-reacting material was proportional to the degree of lipid peroxidation. Cross-reacting material in LDLOXID preparations was evidently formed from the oxidation of free fatty acids released from LDL, since cross-reacting material was also formed when a synthetic fat emulsion was oxidized in the presence of free arachidonic acid.
Arachidonic Acids↗
Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid.
Lung epithelial lining fluid (ELF) is a thin layer of plasma ultrafiltrate and locally secreted substances that may provide antioxidant protection and serve as a "front-line" defense for the lower respiratory tract epithelium. To characterize the antioxidant properties of ELF, young, healthy, nonsmoking volunteers underwent bronchoalveolar lavage with determination of ELF volumes and ELF proteins. ELF (greater than 0.4 ml) is a potent inhibitor of lipid peroxidation as measured by malondialdehyde (MDA) production in an in vitro iron-dependent assay system. Two serum proteins, transferrin and ceruloplasmin, were quantitated in ELF and found to be potent inhibitors of lipid peroxidation. Other ELF components, including vitamin E, vitamin C, and albumin, did not function as antioxidants in this system. Several experimental observations suggest that ELF transferrin was more important than ceruloplasmin in inhibiting lipid peroxidation: 1) ELF concentrations of transferrin were 20-fold higher than those for ceruloplasmin; 2) ELF antioxidant activity was abolished by preincubation with Fe3+; 3) ELF antioxidant activity was minimally affected by sodium azide, which is known to inhibit ceruloplasmin ferroxidase activity; and 4) ELF ceruloplasmin ferroxidase activity was virtually nondetectable. ELF possesses a significant antioxidant activity that may be important in vivo in protecting the lung from oxidant injury.
Antioxidants↗
Effect of O2 partial pressure on the myeloperoxidase pathway of neutrophils.
Neutrophils recruited to different tissues undergo respiratory burst activity at widely different PO2 levels. The present study investigated the in vitro effects of PO2 on neutrophil oxidative metabolism. When neutrophils were stimulated with either zymosan or phorbol myristate acetate (PMA) under different PO2's (0-700 Torr), hexose monophosphate shunt activity, H2O2, and hydroxyl radical (OH.) production were directly related to the level of PO2. Neutrophils functioned surprisingly well at PO2's as low as 10 Torr, where metabolic burst activity was prolonged and usually exceeded 50% of maximal values. The production of neutrophil stable oxidants and hypochlorous acid (HOCl) by zymosan-stimulated neutrophils was also directly related to PO2. In contrast, the production of stable oxidants and HOCl by PMA-stimulated neutrophils was significantly higher at 10 Torr compared with 700 Torr. The decrease in stable oxidant production by PMA-stimulated neutrophils at elevated PO2's was explained by both increased destruction of stable oxidant products and by decreased availability of the precursor HOCl. Superoxide dismutase and the OH. scavenger benzoate partially prevented the fall in stable oxidants at elevated PO2's. Measurements of stable oxidants in PMA-stimulated supernates generated at 10 and 700 Torr correlated with the ability of these supernates to decrease the elastase inhibitory capacity of the serum antiprotease alpha 1-antitrypsin. These findings suggest that different PO2's alter the magnitude and pattern of neutrophil oxidative metabolism.
Humans↗