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1.
J Clin Invest ; 90(6): 2209-19, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1281827

RESUMO

A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs.


Assuntos
Proteínas de Fase Aguda , Proteínas de Transporte/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos Alveolares/fisiologia , Glicoproteínas de Membrana , Síndrome do Desconforto Respiratório/fisiopatologia , Fator de Necrose Tumoral alfa/biossíntese , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Cálcio/metabolismo , Proteínas de Transporte/genética , Expressão Gênica , Humanos , Concentração de Íons de Hidrogênio , Interleucina-8/genética , Receptores de Lipopolissacarídeos , Permeabilidade , RNA Mensageiro/genética , Coelhos
2.
J Clin Invest ; 88(6): 1976-81, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1752956

RESUMO

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant pellet was analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, and minimum surface tension (STmin). PL was decreased in both AR and A (3.48 +/- 0.61 and 2.47 +/- 0.40 mumol/ml, respectively) compared to N (7.99 +/- 0.60 mumol/ml). Phosphatidylcholine was decreased in A (62.64 +/- 2.20% PL) compared to N (76.27 +/- 2.05% PL). Phosphatidylglycerol was 11.58 +/- 1.21% PL in N and was decreased to 6.48 +/- 1.43% PL in A. SP-A was 123.64 +/- 20.66 micrograms/ml in N and was decreased to 49.28 +/- 21.68 micrograms/ml in AR and to 29.88 +/- 8.49 micrograms/ml in A. SP-B was 1.28 +/- 0.33 micrograms/ml in N and was decreased to 0.57 +/- 0.24 micrograms/ml in A. STmin was increased in AR (15.1 +/- 2.53 dyn/cm) and A (29.04 +/- 2.05 dyn/cm) compared to N (7.44 +/- 1.61 dyn/cm). These data demonstrate that the chemical composition and functional activity of surfactant is altered in ARDS. Several of these alterations also occur in AR, suggesting that these abnormalities occur early in the disease process.


Assuntos
Surfactantes Pulmonares/análise , Síndrome do Desconforto Respiratório/metabolismo , Doença Aguda , Adulto , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/análise , Risco , Tensão Superficial
3.
J Clin Invest ; 84(2): 695-705, 1989 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2788176

RESUMO

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.


Assuntos
Coagulação Sanguínea , Fibrina/metabolismo , Fibrinólise , Alvéolos Pulmonares/metabolismo , Síndrome do Desconforto Respiratório/sangue , Adulto , Antitrombina III/análise , Líquido da Lavagem Broncoalveolar/análise , Fator X/metabolismo , Glicoproteínas/análise , Humanos , Pessoa de Meia-Idade , Ativadores de Plasminogênio/análise , Inativadores de Plasminogênio , Síndrome do Desconforto Respiratório/etiologia
4.
Arch Intern Med ; 144(7): 1447-53, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6375617

RESUMO

Subcutaneous emphysema and pneumomediastinum occur frequently in critically ill patients in association with blunt or penetrating trauma, soft-tissue infections, or any condition that creates a gradient between intra-alveolar and perivascular interstitial pressures. A continuum of fascial planes connects cervical soft tissues with the medlastinum and retroperitoneum, permitting aberrant air arising in any one of these areas to spread elsewhere. Diagnosis is made in the appropriate clinical setting by careful physical examination and inspection of the chest roentgenogram. While the presence of air in subcutaneous or mediastinal tissue is not dangerous in itself, prompt recognition of the underlying cause is essential. Certain trauma-related causes may require surgical intervention, but the routine use of chest tubes tracheostomy, or mediastinal drains is not recommended.


Assuntos
Enfisema , Enfisema Mediastínico , Enfisema Subcutâneo , Enfisema/diagnóstico , Enfisema/etiologia , Enfisema/fisiopatologia , Enfisema/terapia , Humanos , Enfisema Mediastínico/diagnóstico , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/fisiopatologia , Enfisema Mediastínico/terapia , Enfisema Subcutâneo/diagnóstico , Enfisema Subcutâneo/etiologia , Enfisema Subcutâneo/fisiopatologia , Enfisema Subcutâneo/terapia
5.
Intensive Care Med ; 20(5): 328-34, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-7930026

RESUMO

OBJECTIVE: To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS. DESIGN: Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients. PATIENTS: 63 septic patients with ARDS at the time of study entry. INTERVENTION: A single intravenous injection of HA-1A (100 mg) or placebo. RESULTS: A quantitative radiographic score, the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p = 0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p = 0.03) but not at 14 and 28 days. CONCLUSION: A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Endotoxinas/imunologia , Imunoglobulina M/uso terapêutico , Síndrome do Desconforto Respiratório/terapia , Sepse/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Feminino , Humanos , Incidência , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/mortalidade , Fatores de Risco , Sepse/complicações , Sepse/diagnóstico por imagem , Sepse/mortalidade , Fatores de Tempo
6.
J Appl Physiol (1985) ; 64(2): 697-704, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3286599

RESUMO

Neutrophils have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. Data from in vitro systems and experimental animals have suggested that neutrophil-derived oxidants, particularly H2O2, may be primarily responsible for endothelial damage, vasoconstriction, and lung edema. With the use of endotoxin infusion as an in vivo model of sepsis we tested the hypothesis that pretreatment with catalase, a peroxide scavenger, would ameliorate the resultant changes in pulmonary vasoconstriction and lung fluid balance. Paired experiments were performed in 16 goats with chronic lung lymph fistulas. One group of animals (n = 7) received endotoxin first alone and then again, several days later, after pretreatment with Ficoll-linked catalase. As a control, identical experiments were performed in a separate group (n = 6) with Ficoll-linked albumin substituted for Ficoll-catalase. A third group (n = 3) was given endotoxin alone and then again during a continuous infusion of catalase. Plasma and lymph levels of catalase were comparable to or exceeded those previously shown to be completely protective in isolated perfused lung preparations and in vitro systems. Endotoxin caused neutropenia, pulmonary arterial hypertension, decreased cardiac output, and increases in lymph flow to approximately three times base line, with a return of all variables toward control values by 6 h. Catalase pretreatment produced no significant differences in any of these variables. These experiments do not support a role for H2O2 as a mediator of acute lung injury due to endotoxemia.


Assuntos
Catalase/farmacologia , Endotoxinas/sangue , Escherichia coli , Pulmão/irrigação sanguínea , Linfa/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Catalase/sangue , Cabras , Pulmão/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Tromboxano B2/sangue
7.
Clin Chest Med ; 6(3): 413-26, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3000686

RESUMO

The use of clinical, physiologic, and laboratory parameters in the prediction or early detection of ARDS has been reviewed. From both a clinical and research standpoint, the ability to identify patients at risk is extremely important. The selection of patients according to predisposing clinical events has been the most successful thus far. The use of physiologic variables and gauges of injury severity have been of limited value, particularly for assessing ARDS risk in the individual patient. Only a handful of the proposed mediators or markers of acute lung injury have been studied prospectively in patients at risk. Of these, factor VIII antigen, lactoferrin, and phospholipase A2 appear the most promising as laboratory tests for selecting patients at risk. In the future it may be possible by using sophisticated statistical analysis techniques to combine important clinical, physiologic, and laboratory information into a numerical ARDS risk index, essentially assigning a probability of ARDS in individual patients.


Assuntos
Síndrome do Desconforto Respiratório/etiologia , Plaquetas/fisiologia , Ativação do Complemento , Endotélio/fisiologia , Fibronectinas/fisiologia , Coração/fisiopatologia , Humanos , Leucopenia/etiologia , Pulmão/fisiopatologia , Neutrófilos/fisiologia , Peptidil Dipeptidase A/sangue , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Risco
9.
Am Rev Respir Dis ; 144(2): 254-62, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1650151

RESUMO

Pulmonary infections are a frequent cause of morbidity and mortality in patients with the adult respiratory distress syndrome (ARDS), but the reason is uncertain. Because neutrophils are important for lung defense and are found in increased numbers in the bronchoalveolar lavage fluid of patients with ARDS, we compared the functional activities of neutrophils obtained from lavage fluid and pulmonary artery blood of 28 patients shortly after the onset of ARDS. The lavage fluids contained 81.3 +/- 9.9% neutrophils, of which more than 95% were viable by vital dye exclusion, and the total protein concentrations were increased (98.8 +/- 98.5 mg/dl). The production of superoxide anion and hydrogen peroxide by the neutrophils in lavage fluid was significantly impaired compared with simultaneously tested pulmonary artery and normal neutrophils, and the microbicidal activity of the lavage neutrophils for Staphylococcus aureus was significantly impaired. The migration of alveolar neutrophils in response to a variety of stimuli was markedly reduced as compared with both pulmonary artery and normal neutrophils. The alterations in superoxide anion production and chemotaxis could be reproduced by exposure of normal neutrophils to oxidants (glucose:glucose oxidase), but not to other mediators that have been found in ARDS lavage fluids. Although the pulmonary artery neutrophils from the same patients had impaired production of superoxide anion and hydrogen peroxide, their microbicidal activity and chemotactic responses were normal. These findings indicate that the function of alveolar neutrophils is impaired in the lungs of patients with ARDS. This could contribute to the high incidence of pulmonary infections in these patients.


Assuntos
Pulmão/imunologia , Neutrófilos/fisiologia , Síndrome do Desconforto Respiratório/imunologia , Infecções Respiratórias/etiologia , Atividade Bactericida do Sangue/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Quimiotaxia/imunologia , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/imunologia , Staphylococcus aureus/imunologia , Superóxidos/metabolismo
10.
Am Rev Respir Dis ; 132(2): 254-60, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-4026050

RESUMO

Bronchoalveolar lavage is used to evaluate parenchymal inflammation in patients with diffuse lung disease. Normal values for lavage cell counts and proteins are derived primarily from young subjects who are free from lung disease; however, older patients who undergo bronchoalveolar lavage often have used cigarettes for long periods of time and have developed variable degrees of chronic bronchitis and/or chronic air-flow obstruction. Therefore, we evaluated the effects of cigarette use, chronic bronchitis, and chronic air-flow obstruction on lavage cell populations by performing bronchoalveolar lavage in 48 male patients who were undergoing diagnostic fiberoptic bronchoscopy. Sixteen patients (33%) had elevated percentages of neutrophils (greater than or equal to 10%) in lavage fluid. Fourteen of these (87.5%) had chronic cough and/or phlegm production, but only 9 (64.3%) met criteria for definite chronic bronchitis. Patients with moderate or severe air-flow obstruction, defined spirometrically, had significantly greater percentages of lavage neutrophils and lower percentages of macrophages than did patients with mild or no air-flow obstruction. The first lavage aliquot contained the greatest proportion of neutrophils and the smallest proportion of macrophages. The percentage of neutrophils declined and the percentage of macrophages increased in sequential aliquots. The data indicate that patients with chronic cough and/or phlegm production and chronic air-flow obstruction may have increased proportions of neutrophils in bronchoalveolar lavage fluid in the absence of diffuse parenchymal lung disease or infections. These variables must be taken into account when interpreting lavage cellular analyses.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Bronquite/patologia , Pneumopatias Obstrutivas/patologia , Pulmão/patologia , Brônquios , Bronquite/imunologia , Doença Crônica , Epitélio/patologia , Volume Expiratório Forçado , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Pulmão/imunologia , Pneumopatias Obstrutivas/imunologia , Linfócitos/patologia , Macrófagos/patologia , Masculino , Neutrófilos/patologia , Alvéolos Pulmonares , Fumar , Irrigação Terapêutica , Capacidade Vital
11.
JAMA ; 255(18): 2463-5, 1986 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-3701964

RESUMO

In this report, we challenge the commonly held assumption that the adult respiratory distress syndrome (ARDS) is a homogeneous process associated with generalized and relatively uniform damage to the alveolar capillary membrane. We studied 13 patients with ARDS, comparing the pulmonary parenchymal changes seen by standard bedside chest roentgenograms with those seen by computed tomography of the chest. Three patients demonstrated generalized lung involvement by both radiologic techniques. In another eight patients, despite the appearance of generalized involvement on the standard chest x-ray film, the computed tomographic scans showed patchy infiltrates interspersed with areas of normal-appearing lung. Two patients showed patchy involvement by both techniques. The fact that ARDS spares some regions of lung parenchyma is useful knowledge in understanding the gas-exchange abnormalities of ARDS, the variable responsiveness to positive end-expiratory pressure, and the occurrence of oxygen toxicity. The problem of regional inhomogeneity should also be kept in mind when interpreting lung biopsy specimens or bronchoalveolar lavage fluid in patients with ARDS.


Assuntos
Pulmão/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Humanos , Pulmão/patologia , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/patologia
12.
Am Rev Respir Dis ; 133(2): 313-6, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3511807

RESUMO

Neutrophils are believed to play an essential role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This concept is largely based on the observation that neutrophil depletion protects against altered pulmonary vascular permeability in several models of acute lung injury produced in laboratory animals. Four patients who developed ARDS during periods of profound neutropenia are presented. These patients met commonly accepted clinical and roentgenographic criteria for the syndrome, and each had the characteristic findings of diffuse alveolar damage by lung histologic examination. The failure of this degree of neutropenia to protect against ARDS in humans raises questions about whether neutrophils or neutrophil products are essential in the pathogenesis of the syndrome.


Assuntos
Agranulocitose/complicações , Neutropenia/complicações , Síndrome do Desconforto Respiratório/complicações , Adolescente , Adulto , Biópsia , Transplante de Medula Óssea , Feminino , Humanos , Pulmão/patologia , Masculino , Neutrófilos/patologia , Síndrome do Desconforto Respiratório/patologia
13.
Am J Respir Crit Care Med ; 151(2 Pt 1): 293-301, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7842182

RESUMO

To further understanding of the epidemiology of acute respiratory distress syndrome (ARDS), we prospectively identified 695 patients admitted to our intensive care units from 1983 through 1985 meeting criteria for seven clinical risks, and followed them for development of ARDS and eventual outcome. ARDS occurred in 179 of the 695 patients (26%). The highest incidence of ARDS occurred in patients with sepsis syndrome (75 of 176; 43%) and those with multiple emergency transfusions (> or = 15 units in 24 h) (46 of 115; 40%). Of patients with multiple trauma, 69 of 271 (25%) developed ARDS. If any two clinical risks for trauma were present, the incidence of ARDS was 23 of 57, or 40%. During the study period, we identified 48 patients with ARDS who did not have one of the defined clinical risks, yielding a sensitivity of 79% (179 of 227). Secondary factors associated with increased risk for ARDS in clinical risk subgroups include an elevated Acute Physiologic and Chronic Health Evaluation II (APACHE II) score in patients with sepsis and increased APACHE II and Injury Severity Scores (ISS) in trauma victims. Mortality was threefold higher when ARDS was present (62%) than among patients with clinical risks who did not develop ARDS (19%; p < 0.05). The difference in mortality if ARDS developed was particularly striking in patients with trauma (56% versus 13%), but less in those with sepsis (69% versus 49%). The mortality data should be interpreted with caution, since the fatality rate in ARDS patients appears to have decreased in our institution from the time that these data were collected.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Síndrome do Desconforto Respiratório/epidemiologia , APACHE , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Fatores de Risco , Sensibilidade e Especificidade , Síndrome de Resposta Inflamatória Sistêmica/complicações , Índices de Gravidade do Trauma , Ferimentos e Lesões/complicações
14.
Am Rev Respir Dis ; 148(3): 556-61, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8368623

RESUMO

Although shown to be safe in many other lung disorders, the safety of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in critically ill patients with adult respiratory distress syndrome (ARDS) remains unproven. We conducted a prospective study to evaluate the safety of BAL in patients with ARDS. There were 438 patients with ARDS at our institution during the study period. Of these, 110 underwent FOB and BAL for either research or clinical purposes. Data were collected at baseline, at 5-min intervals during the procedure, and 1 h after the procedure. We did not detect any statistically or clinically significant changes in PaO2/FlO2, mean arterial pressure, heart rate, peak inspiratory pressure, or static thoracic compliance after the procedure. A small decrease in SaO2 occurred after BAL. Although this change was statistically significant, the magnitude was not of clinical importance. Five patients (4.5%) had transient arterial oxygen desaturation to < 90% during FOB and one patient (0.9%) experienced desaturation to < 80%. There were no prolonged episodes of severe hypoxemia. No serious bleeding occurred. One pneumothorax developed during the procedure. No deaths occurred that were related to the procedure. We conclude that FOB and BAL can be performed safely and are reasonably well-tolerated in patients with ARDS.


Assuntos
Líquido da Lavagem Broncoalveolar , Síndrome do Desconforto Respiratório/diagnóstico , Irrigação Terapêutica/efeitos adversos , Adolescente , Adulto , Idoso , Broncoscópios , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Broncoscopia/estatística & dados numéricos , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva , Estudos Prospectivos , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Segurança , Irrigação Terapêutica/estatística & dados numéricos , Fatores de Tempo
15.
J Lab Clin Med ; 113(5): 586-97, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2715681

RESUMO

Using an enzyme-linked immunosorbent assay, we measured the concentration of fibronectin containing an extra type III domain (ED1) in the circulation of humans. Plasma levels of ED1 + fibronectin averaged 2.8 +/- 1.0 micrograms/ml in healthy individuals and did not differ substantially according to age or sex. In comparison with those from normal subjects, plasma samples obtained from patients with collagen vascular disorders contained increased average levels of ED1 + fibronectin. Among this group, levels of ED1 + fibronectin were significantly greater in samples taken from individuals with clinical evidence of vasculitis. Although levels of total (ED1 + plus ED1 -) fibronectin were also elevated in plasma samples from patients with vasculitis, only the concentration of the ED1 + variant correlated with severity of disease in two patients examined serially. Elevations in plasma content of ED1 + fibronectin, but not total fibronectin, were also noted in patients with acute vascular tissue injury associated with major trauma or sepsis syndrome. Western blot examination revealed the presence of intact dimeric ED1 + fibronectin in the circulation of all patients studied, although fragments bearing the ED1 were also detected. Human plasma normally contains small quantities of soluble ED1 + ("cellular") fibronectin, and these levels are increased in disorders involving vascular injury.


Assuntos
Fibronectinas/sangue , Doenças Vasculares/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Doenças do Colágeno/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/sangue , Vasculite/sangue , Ferimentos e Lesões/sangue
16.
Am J Respir Crit Care Med ; 150(1): 113-22, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8025736

RESUMO

To characterize the evolution of inflammation in the adult respiratory distress syndrome (ARDS) and test the hypothesis that sustained alveolar inflammation is associated with a poor outcome in patients with ARDS, we performed fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in 125 patients and compared BAL cells and protein concentrations in survivors and nonsurvivors. ARDS followed sepsis syndrome in 35 patients, major trauma in 41, and other causes in 49. When possible, BAL was performed on Days 3, 7, and 14 after the onset of ARDS. Sixty-five patients (52%) had more than one BAL. We first performed analyses on each BAL day using information from all 212 BAL in the 125 patients (cross-sectional analysis). All patients had increased leukocytes and total protein in the first BAL (Day 3 after onset of ARDS). In patients with ARDS following sepsis, the percentage of BAL polymorphonuclear leukocytes (PMN) was higher on Day 7 (p = 0.11) and particularly Day 14 (p = 0.02) in patients who died; there was a consistent trend of a higher PMN concentration on all days in patients who died then in those who lived. In patients with ARDS following trauma and other risks, however, BAL PMN measures did not distinguish survivors from patients who died. Analysis of serial data from the patients with more than one BAL showed that alveolar macrophages (AM) increased in survivors of ARDS, both in absolute numbers and as a percentage of total cells; this pattern was most pronounced in the sepsis patients. The cross-sectional data analysis suggests that sustained alveolar inflammation occurs frequently in patients with ARDS following sepsis and is associated with a high mortality.


Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Síndrome do Desconforto Respiratório/patologia , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/química , Feminino , Humanos , Infecções/complicações , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas/análise , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/mortalidade , Taxa de Sobrevida , Ferimentos e Lesões/complicações
17.
Am J Respir Crit Care Med ; 150(1): 90-4, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8025779

RESUMO

We performed a prospective cohort analysis to determine the rate and extent of improvement in pulmonary function abnormalities and self-perceived health for 1 yr after surviving an episode of the acute respiratory distress syndrome (ARDS). We also examined the effect of ARDS severity and etiology, age, and sex on functional recovery. Patients were recruited from the intensive care units of one hospital and followed at regular time intervals from extubation to 1 yr. Fifty-two of 82 eligible adult survivors (63%) consented to participate; 37 of 82 (45%) had at least two examinations, and 20 (24%) had complete follow-up. Risk factors for ARDS included sepsis (n = 12), trauma (n = 15), and other (n = 10). Pulmonary function and self-perceived health scores improved considerably in the first 3 mo after extubation, with only slight additional improvement at 6 mo. No further changes were evident at 1 yr. Patients with more severe ARDS had significantly lower pulmonary function tests than did other survivors throughout follow-up. These observations should be useful for clinical follow-up of ARDS survivors and provide specific information concerning the expected rate of functional recovery in these patients.


Assuntos
Síndrome do Desconforto Respiratório/fisiopatologia , Mecânica Respiratória , Adulto , Idoso , Atitude Frente a Saúde , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Síndrome do Desconforto Respiratório/etiologia , Fatores de Risco , Inquéritos e Questionários , Capacidade Pulmonar Total , Capacidade Vital
18.
Am J Physiol ; 261(4 Pt 1): L240-8, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1928357

RESUMO

We studied the changes of coagulation and fibrinolysis in bronchoalveolar lavage (BAL) and plasma obtained serially at intervals after the onset of adult respiratory distress syndrome (ARDS). BAL procoagulant activity was increased at 3 days and tended to decrease thereafter. Tissue factor associated with factor VII was the major BAL procoagulant. Fibrinopeptide A was increased, indicating increased thrombin-mediated conversion of fibrinogen to fibrin. Fibrinolytic activity was usually undetectable in BAL at 3 days post-ARDS and remained depressed for up to 14 days despite unchanged concentrations of urokinase and variably detectable tissue plasminogen activator. Depressed fibrinolytic activity was associated with increased antiplasmin activity and plasminogen activator inhibitor 1 (PAI-1) while PAI-2 concentrations approximated those of control samples and did not change during evolving ARDS. Evidence of systemic coagulopathy and increased systemic fibrin degradation were commonly found in serial ARDS plasma samples, consistent with accelerated vascular and/or extravascular fibrin deposition in these patients. The data indicate that intra-alveolar as well as systemic derangements of fibrin turnover are common features of evolving ARDS. Concurrent local abnormalities of both coagulation and fibrinolytic pathways favor persistence of alveolar fibrin for up to 14 days after clinical recognition of ARDS.


Assuntos
Fibrina/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Adulto , Idoso , Coagulação Sanguínea , Líquido da Lavagem Broncoalveolar/metabolismo , Líquido da Lavagem Broncoalveolar/patologia , Fibrinogênio/análise , Fibrinólise , Humanos , Pessoa de Meia-Idade , Proteínas/metabolismo , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/patologia , Trombina/análise
19.
Am J Respir Crit Care Med ; 152(2): 550-6, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7633706

RESUMO

Pulmonary infection is thought to be a common complication of ARDS. We undertook this prospective study to determine the incidence of pulmonary infection in patients with ARDS, and to evaluate the impact of nosocomial pneumonia on severity of ARDS and on survival. Two hundred one bronchoscopies were performed in 105 patients with ARDS with retrieval of distal airway secretions by bronchoalveolar lavage (BAL) and protected specimen brush (PSB). Whenever possible, bronchoscopy was performed at predetermined times: Day 3, Day 7, Day 14, and Day 21 after the onset of ARDS. The majority of patients were receiving antibiotics at the time of study. Changes in bacterial flora over time were determined by quantitative cultures of BAL and PSB. Bacterial growth was common, but usually at small concentrations. Only 16 patients met quantitative culture criteria for pneumonia (PSB > or = 10(3) cfu/ml or BAL > or = 10(4) cfu/ml). Correlation was poor between clinical evidence of pneumonia and pneumonia by quantitative culture criteria: clinical criteria had a very low sensitivity (24%) for predicting positive quantitative culture results, and a low specificity (77%) for predicting negative quantitative culture results. There was no correlation between total colony counts on BAL or PSB and severity of ARDS as judged by Pao2/FIo2 ratios, days receiving ventilation, or compliance. Furthermore, there was no correlation between bacterial growth and survival. We conclude that pneumonia defined by quantitative bacteriology is uncommon in ARDS. The potentially confounding role of broad-spectrum antibiotics should be studied further.


Assuntos
Pneumonia Bacteriana/etiologia , Síndrome do Desconforto Respiratório/complicações , Adulto , Antibacterianos/uso terapêutico , Bactérias/crescimento & desenvolvimento , Técnicas Bacteriológicas/instrumentação , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Contagem de Colônia Microbiana , Infecção Hospitalar/etiologia , Infecção Hospitalar/microbiologia , Feminino , Previsões , Humanos , Incidência , Masculino , Oxigênio/sangue , Pneumonia Bacteriana/microbiologia , Respiração com Pressão Positiva , Estudos Prospectivos , Síndrome do Desconforto Respiratório/microbiologia , Sensibilidade e Especificidade , Taxa de Sobrevida
20.
J Lab Clin Med ; 104(4): 583-90, 1984 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6481218

RESUMO

Depletion of plasma fibronectin has been observed in certain clinical conditions predisposing to the adult respiratory distress syndrome and has been associated with cardiopulmonary dysfunction in experimental lung injury. We evaluated prospectively the relationship between plasma fibronectin concentration and the development of the adult respiratory distress syndrome in patients known to be at high risk. Although plasma fibronectin levels in participants at study entry were lower in this population (mean 258 +/- 132 micrograms/ml) than in normal volunteers (461 +/- 127 micrograms/ml, p less than 0.0025), there was no difference between patients who subsequently developed the adult distress syndrome (mean 255 +/- 149 micrograms/ml) and those with similar illness or injury who did not develop the syndrome (260 +/- 126 micrograms/ml). Fibronectin concentration was not further depressed even after development of adult respiratory distress syndrome and did not correlate with degree of pulmonary dysfunction. These data suggest that fibronectin depletion is not an important determinant of respiratory failure in humans. Patients with sepsis syndrome had significantly lower plasma fibronectin levels than those without sepsis (187 +/- 119 micrograms/ml vs. 273 +/- 131 micrograms/ml, p less than 0.05), suggesting a possible role for fibronectin in the pathogenesis of sepsis.


Assuntos
Fibronectinas/sangue , Síndrome do Desconforto Respiratório/sangue , Adulto , Humanos , Síndrome do Desconforto Respiratório/mortalidade , Risco , Fatores de Tempo
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