Plasma cell mucositis of the distal airways.
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Bronchitis↗
Biomedical subjects
J N Allen
Publications and source records attributed to J N Allen.
Bedside tracheostomy in the intensive care unit: a prospective randomized trial comparing open surgical tracheostomy with endoscopically guided percutaneous dilational tracheotomy.
OBJECTIVES: Objectives of the study were 1) to analyze the complication incidence and resource utilization of two methods of bedside tracheostomy and 2) to define selection criteria for bedside tracheostomy. STUDY DESIGN: Prospective randomized trial in the setting of a tertiary care center at a university hospital. METHODS: One hundred sixty-four consecutive intubated patients selected for elective tracheostomy were enrolled. One hundred patients met selection criteria for bedside tracheostomy and were randomly assigned to either open surgical tracheostomy (50) or endoscopically guided percutaneous dilational tracheotomy(50). The remaining 64 patients received open surgical tracheostomies in the operating room. Main outcome measures were 1) perioperative and postoperative complication incidence and 2) resource utilization. RESULTS: Patients meeting our selection criteria for bedside tracheostomy had a significantly reduced perioperative complication rate compared with those who failed to meet these criteria, and subsequently underwent tracheostomy placement in the operating room (5% vs. 20%, P less than or equal to.01). No statistically significant difference was found in the perioperative complication incidence between the two methods of bedside tracheostomy. However, percutaneous tracheostomy placement at the bedside resulted in a significant increase in postoperative complication incidence (16% vs. 2%, P <.05) and incurred an additional patient charge of $436 per bedside procedure. CONCLUSIONS: This investigation prospectively confirms the safety of bedside tracheostomy placement in properly selected patients. Complication incidence and resource utilization are defined for two methods of bedside tracheostomy. The results of this study confirm that open surgical tracheostomy represents the standard of care in bedside tracheostomy placement by providing a more secure airway at a markedly reduced patient charge. These findings will aid in the development of protocols and pathways for surgical airway management in critically ill patients to maximize cost-effective, high-quality care.
Adult↗
Churg-Strauss syndrome associated with zafirlukast.
The leukotriene receptor antagonist zafirlukast (Accolate; Zeneca Pharmaceuticals; Wilmington, Del) recently was approved for use as maintenance therapy for persistent asthma. This new product has been well received due to convenient dosing and relatively few side effects. Based on initial success with this product, it is likely that similar compounds will be available for use in the near future. In this report, a case is described of a 47-year-old white man with moderate persistent asthma in whom Churg-Strauss syndrome developed while he was receiving zafirlukast therapy. Acute respiratory insufficiency, arthralgia, and prominent rash developed which required hospitalization. The patient's symptoms rapidly reversed following discontinuation of zafirlukast therapy and administration of systemic corticosteroids. Although the incidence of Churg-Strauss syndrome associated with zafirlukast therapy is rare, this case report illustrates steps that may be taken to diagnose quickly and treat this life-threatening condition should it occur.
Anti-Asthmatic Agents↗
The use of expandable metal stents to facilitate extubation in patients with large airway obstruction.
OBJECTIVE: To determine the clinical utility of placing airway stents to facilitate weaning in ventilator-dependent patients with large airway obstruction. METHODS: A chart review of mechanically ventilated patients who received expandable metal airway stents to attempt a facilitation of weaning. RESULTS: Eight patients, 3 women and 5 men, ranging in age from 37 to 82 years, had respiratory failure associated with large airway obstruction and underwent flexible bronchofluoroscopic placement of 12 expandable metal stents (7 Wallstents [Schneider; Minneapolis, MN], 2 Palmaz [Johnson & Johnson; Warren, NJ], and 3 Ultraflex [Microinvasive; Natick, MA]). Six had respiratory failure that was secondary to malignant airway disease, and two had benign airway disease. Seven patients with tracheal or mainstem bronchial obstruction were weaned from the ventilator within 0 to 11 days of stent placement after having previously required mechanical ventilation from 2 to 52 days. There were no associated complications. Following prolonged attempts at weaning, one patient with lobar bronchus obstruction died after mechanical ventilation was withdrawn. CONCLUSIONS: Expandable metal airway stents may be safely deployed in mechanically ventilated patients and can facilitate weaning from the mechanical ventilator. Mechanically ventilated patients with tracheal and mainstem bronchus obstruction are the best candidates for deployment of expandable airway stents to facilitate weaning.
Adult↗
Questions and answers regarding veterinarians in disaster response.
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Animals↗
Acute eosinophilic pneumonia: radiologic and clinical features.
PURPOSE: To determine the radiographic and computed tomographic (CT) characteristics of acute eosinophilic pneumonia. MATERIALS AND METHODS: Twelve consecutive patients with acute eosinophilic pneumonia were included in the study. The diagnosis was based on clinical symptoms and results of bronchoalveolar lavage. Plain chest radiographs were obtained in all patients; CT scans were obtained in three patients. Two thoracic radiologists reviewed the radiographs and CT scans. RESULTS: Ten patients had bilateral areas of air-space opacity on images obtained at presentation; in seven of these patients, interstitial areas of opacity were also present. Two patients had bilateral interstitial areas of opacity and no areas of air-space opacity. Interlobular septal thickening and ground-glass attenuation were present on CT scans in two patients; patchy bilateral consolidation was present on CT scans in one patient. Pleural effusion was present on radiographs in seven patients (58%) and was bilateral in five. Pleural effusion was present at some point during the course of disease in all patients. In all patients, air-space disease markedly improved within 3 days of initiation of treatment with corticosteroids. CONCLUSION: Acute eosinophilic pneumonia should be considered as a possible diagnosis when a previously healthy person presents with acute respiratory failure of unknown origin.
Acute Disease↗
Changes in mononuclear phagocyte microtubules after endotoxin stimulation. I. Changes in microtubule stability.
Microtubules are in a dynamic equilibrium of polymerization and depolymerization. In monocytes and macrophages, microtubules bind endotoxin and partly regulate inflammatory events such as cytokine production. To characterize the morphologic differences between alveolar macrophage and blood monocyte microtubules after LPS stimulation, cells were examined by immunofluorescent microscopy and laser confocal microscopy. Fresh monocytes contained an average of 26 microtubules per cell which significantly increased to 31 microtubules per cell following a 30-min exposure to LPS (P < 0.001). Using a nocodazole-based assay of microtubule dynamic instability, the half-life of fresh unstimulated human monocyte microtubules was approximately 18 s and extended to 26 s following a 30-min exposure to LPS. In vitro maturation of monocytes for 18 h increased microtubule stability but not number. Compared to monocytes, alveolar macrophage microtubules were longer, more numerous, and much more stable. These results suggest that alveolar macrophage microtubules are more numerous and stable than blood monocyte microtubules and that LPS causes an increase in monocyte microtubule number and stability.
Female↗
Changes in mononuclear phagocyte microtubules after endotoxin stimulation. II. Changes in microtubule composition.
Microtubules are integral components of the cytoskeleton of human cells and are composed of alpha- and beta-tubulin as well as a variable number of microtubule-associated proteins. In monocytes and macrophages, microtubules bind endotoxin and partly regulate endotoxin-induced inflammatory events such as cytokine production. Endotoxin causes a rapid alteration in monocyte microtubule stability. To characterize the effect of endotoxin on mononuclear phagocyte microtubule composition, Western blots and flow cytometry were performed on human monocytes and the monocyte/macrophage-like cell line THP-1. Compared to unstimulated monocytes, monocytes stimulated with endotoxin for 18 h had increased quantities of alpha-, beta-, and tyrosinated alpha-tubulin as well as microtubule-associated protein-2. PMA-differentiated THP-1 cells had increased levels of alpha-tubulin, beta-tubulin, microtubule-associated protein-5, microtubule-associated protein-2, and tau after endotoxin stimulation. These results indicate that endotoxin can alter mononuclear phagocyte microtubules by causing an increase in certain microtubule component proteins.
Blotting, Western↗
Detection of IL-5 and IL-1 receptor antagonist in bronchoalveolar lavage fluid in acute eosinophilic pneumonia.
BACKGROUND: Acute eosinophilic pneumonia is an idiopathic cause of respiratory failure, characterized by very high numbers of alveolar eosinophils without significant blood eosinophilia. OBJECTIVE: The purpose of this study was to determine which cytokines are associated with acute eosinophilic pneumonia. METHODS: Soluble IL-1 type II receptor and the cytokines IL-1 beta, IL-1ra, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha were measured in serum and in bronchoalveolar lavage fluid from two patients with acute eosinophilic pneumonia during both acute and convalescent phases. RESULTS: Compared with patients with adult respiratory distress syndrome, the patients with acute eosinophilic pneumonia had high bronchoalveolar lavage fluid levels of IL-5, IL-1ra, and soluble type II IL-1 receptor but not IL-1 beta, tumor necrosis factor-alpha, IL-3, or granulocyte-macrophage colony-stimulating factor. Bronchoalveolar lavage fluid levels of IL-5 and IL-1ra fell after resolution of symptoms. In the serum of patients with acute eosinophilic pneumonia, IL-5 was not detectable, and IL-1ra was initially high but fell after corticosteroid treatment. CONCLUSION: Acute eosinophilic pneumonia is characterized by locally high levels of IL-5, IL-1ra, and soluble type II IL-1 receptor in the alveolar space.
Acute Disease↗
Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature.
Idiopathic acute eosinophilic pneumonia (AEP) is an acute febrile illness that may be mistaken for an infectious pneumonia. Patients are often young and otherwise healthy. Clues to considering this disorder in a differential diagnosis include the acuity and severity of the clinical presentation and an initial chest X-ray with diffuse infiltrates, often interstitial, and the presence of Kerley B lines and/or evidence of pleural fluid. The diagnosis can be made through examination of bronchoalveolar lavage fluid in most cases, with careful exclusion of other similar eosinophilic lung disease. Although it can lead to life-threatening respiratory failure, AEP is easily treatable with corticosteroids. This disease has not been reported to recur in any patients to this point.
Acute Disease↗
Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion. A role for microtubules in the regulation of IL-1 beta production.
IL-1 beta is a proinflammatory cytokine secreted chiefly by monocytes and macrophages. Currently, much of its mechanism of processing and secretion is poorly understood, but there is increasing evidence that the microtubule system may be involved. For example, it is known that taxol and colchicine, two drugs that affect microtubule structure and function, increase LPS-induced IL-1 beta release. However, it is not known whether these drugs affect the synthesis of the 31-kDa precursor (pro-IL-1 beta) or the processing and release of mature IL-1 beta. To test this, an assay was used that allowed for the temporal separation of IL-1 beta synthesis and release. The addition of taxol or colchicine to the secretory phase of the assay resulted in no significant change in IL-1 beta release. However, when these drugs were added to the stimulus for IL-1 beta production, there was a significant increase in both IL-1 beta release and total IL-1 beta production, as measured by ELISA. These findings indicate that taxol and colchicine increase LPS-induced IL-1 beta release by an increase in the production of the precursor molecule. Thus, it is unlikely that microtubules are involved in the IL-1 beta secretory machinery in any significant manner, but they do play a role in the regulation of pro-IL-1 beta production.
Animals↗
Immunosuppressive properties of surfactant and plasma on alveolar macrophages.
Alveolar macrophages have been shown to be major producers of the potent proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha, and of the antiinflammatory cytokine interleukin-1 receptor antagonist. During the adult respiratory distress syndrome the normally surfactant-coated alveolus becomes flooded with plasma proteins, altering the milieu of alveolar cells such as alveolar macrophages. To understand alveolar macrophage function during the adult respiratory distress syndrome, the individual and combined effects of surfactant and plasma on alveolar macrophage cytokine production was examined. A synthetic surfactant (Exosurf) and a bovine-derived surfactant (Survanta) both inhibited production of interleukin-1 beta, pro-interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist in a dose-dependent manner. This inhibition was noted when both endotoxin and heat-killed Staphylococcus aureus were used as stimuli. Autologous plasma also inhibited interleukin-1 beta and tumor necrosis factor-alpha release in a dose-dependent manner, but, unlike surfactant, plasma did not inhibit interleukin-1 receptor antagonist release. Similarly, the combination of plasma and surfactant inhibited interleukin-1 beta and tumor necrosis factor-alpha release but not interleukin-1 receptor antagonist release. In support of these data, interleukin-1 receptor antagonist was detectable in five of six bronchoalveolar lavage fluid samples from patients with adult respiratory distress syndrome at a mean concentration of 465 pg/ml; on the other hand, interleukin-1 beta was not detectable in any of these samples. These results indicate that the relative production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist can be altered depending on the local concentration of both surfactant and plasma.
Biological Products↗
Eosinophilic lung diseases.
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Acute Disease↗
Taxol enhances but does not induce interleukin-1 beta and tumor necrosis factor-alpha production.
Taxol is a potent, microtubule-stabilizing, antineoplastic drug that induces interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) release by thioglycolate-elicited mouse peritoneal macrophages. Because taxol use and subsequent cytokine release in human subjects could be associated with toxicity, the present study was performed to determine how taxol affects cytokine production from fresh human mononuclear cells. Cells were incubated overnight with varying doses of bacterial endotoxin, either with or without taxol, 10 mumol/L. Taxol alone did not induce IL-1-beta or TNF-alpha release by mononuclear cells. However, at all doses of endotoxin from 1 pg/ml to 1 microgram/ml, the addition of taxol resulted in a 50% to 100% increase in IL-1-beta release (p < 0.001) and a 25% to 50% increase in TNF-alpha release (p < 0.01). In contrast, taxol caused a reduction in intracellular pro-IL-1-beta levels. Kinetic studies demonstrated that taxol enhanced IL-1-beta release by mononuclear cells at all time points tested from 4.5 hours to 18 hours after stimulation. Taxol alone did not stimulate IL-1-beta or TNF-alpha mRNA transcription. A similar enhancement of IL-1-beta release was noted in endotoxin-stimulated alveolar macrophages. In summary, these results show that under endotoxin-free conditions, the microtubule-stabilizing agent taxol does not induce IL-1-beta or TNF-alpha production by human mononuclear cells or alveolar macrophages but does enhance production of both of these cytokines in conjunction with a second stimulus.
Blotting, Northern↗
Macrophage and monocyte IL-1 beta regulation differs at multiple sites. Messenger RNA expression, translation, and post-translational processing.
Maturation of blood monocytes into macrophages is accompanied by a number of functional changes including decreased IL-1 beta release in response to LPS. This limitation has previously been ascribed to transcriptional regulation. However, in seeming conflict with the observed depression in IL-1 beta mRNA levels, recent work demonstrates increased intracellular IL-1 beta in macrophages. Therefore, the present study sought to explain these differences by comparing IL-1 beta production from autologous alveolar macrophage and blood monocyte pairs at multiple regulatory sites, including endotoxin responsiveness, mRNA expression, protein translation, and post-translational processing. Macrophages did not differ from monocytes in endotoxin sensitivity, but when analyzed by both ELISA and Western blot, were confirmed to have limitations in IL-1 beta release. Gene expression studies demonstrated that at 4 h, macrophage IL-1 beta steady state mRNA levels were 3-fold lower than the monocyte's. However, total IL-1 beta protein production, as measured by [35S]methionine labeling with immunoprecipitation, demonstrated three- to sixfold higher amounts in macrophages at comparable time points. The enhanced protein production in the face of relatively low mRNA levels suggests that macrophages translate IL-1 beta mRNA more efficiently. Furthermore, characterization of IL-1 beta release into supernatants revealed that whereas monocyte release occurred early, represented 5 to 20% of the intracellular amounts, and contained largely processed IL-1 beta, macrophage release was delayed, represented 1 to 5% of the intracellular amounts, and contained primarily unprocessed IL-1 beta. Taken together, these data demonstrate that the limitations in alveolar macrophage IL-1 beta release occur due to slower export and conversion of 35- to 17-kDa protein and are not due to differences in sensitivity to endotoxin or to transcriptional control mechanisms.
Blotting, Northern↗
Sandwich ELISA formats designed to detect 17 kDa IL-1 beta significantly underestimate 35 kDa IL-1 beta.
The IL-1 beta precursor (proIL-1 beta) represents a significant component of total IL-1 beta production in certain cell types such as keratinocytes, fibroblasts and alveolar macrophages. It has been presumed that immunodetection systems for the mature 17 kDa IL-1 beta can be used interchangeably for the 35 kDa intracellular proIL-1 beta. However, during attempts to purify alveolar macrophage proIL-1 beta, we found that conventional enzyme-linked immunoassays (ELISAs) (using antibodies directed against the 17 kDa mature IL-1 beta) underestimated the amounts of 35 kDa proIL-1 beta by at least ten-fold compared to detection by Western blot techniques. This difference was due to the fact that ELISAs, with an antigen capture format (i.e., that use more than one epitope), can more readily see these distinct epitopes on mature or partially processed IL-1 beta than on the proIL-1 beta molecule. This problem does not occur with the Western blot technique, either because only one antibody is needed and hence there is no stearic blockade of a second epitope or because it denatures 35 kDa proIL-1 beta during the immobilization step, presumably better exposing epitopes as expressed on mature 17 kDa IL-1 beta. The problem with the ELISA can be partially corrected by proteolytic removal of the aminoterminus of 35 kDa proIL-1 beta with neutrophil elastase. More accurate determinations of proIL-1 beta by ELISA can be made by using 35 kDa proIL-1 beta as the reference standard (when the 35 kDa proIL-1 beta is free of molecular weight IL-1 beta). These data suggest that there are conformational differences between the carboxyterminus of 35 kDa proIL-1 beta and mature 17 kDa IL-1 beta which may affect immunodetection when using antibodies directed against mature 17 kDa IL-1 beta.
Blotting, Western↗
What is eosinophilic pneumonia?
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Acute Disease↗
Human whole blood interleukin-1-beta production: kinetics, cell source, and comparison with TNF-alpha.
Because removal of monocytes from their natural milieu may alter their subsequent immune response patterns, we have compared the production of interleukin-1 beta (IL-1-beta) and tumor necrosis factor alpha (TNF-alpha) by cultured human whole blood to that by purified monocytes. IL-1-beta was released in a dose-dependent fashion by whole blood after stimulation with lipopolysaccharide. Immunofluorescence studies indicated that monocytes were the main producers of IL-1-beta in whole blood cultures. On a per monocyte basis, after stimulation with 10 micrograms/ml lipopolysaccharide, much more IL-1-beta was released by cultured whole blood (56.2 +/- 8.3 ng/10(6) monocytes) than by purified mononuclear cells maintained in tissue culture medium (7.1 +/- 2.6 ng/10(6) monocytes). However, maintaining purified mononuclear cells in autologous plasma restored IL-1-beta release to levels observed in whole blood cultures. IL-1-beta release by whole blood peaked at 9 to 12 hours, in contrast to release of TNF-alpha, which peaked at 6 hours. In parallel with protein production, IL-1-beta messenger RNA levels peaked later and were more sustained than TNF-alpha messenger RNA levels. These experiments suggest that plasma augments the stimulatory effect of endotoxin and that IL-1-beta and TNF-alpha have differing kinetics in whole blood.
Blood Cells↗