Idiopathic respiratory distress syndrome and the phospholipids in the amniotic fluid

A simple potentiometric method is described for the automated assay of lipase in duodenal juice. The procedure utilizes a pH meter connected to a classical blood pH assembly made of a reference and a capillary electrode. A potentiometric recorder connected to the pH meter is adjusted for a full scale deflection corresponding to 0.5 pH unit.Samples containing 0.4 to 2 enzyme units in 2 ml are analyzed at a rate of 30 assays per hour. Each sample is incubated for 4 min with a tributyrin emulsion prepared in a mixed buffer at pH 8. The buffer composition ensures a linear response of pH versus H* liberated by lipolysis.     

Pathogenesis of the adult respiratory distress syndrome. Evidence of oxidant activity in bronchoalveolar lavage fluid.

Evidence is presented indicating that oxidants are generated in lungs of patients with the adult respiratory distress syndrome (ARDS). The evidence was derived from observations that alpha-1-PI, recovered in bronchoalveolar lavage (BAL) fluid, had been inactivated by oxidation, presumably oxidation of the methionyl residue in the reaction site of the molecule. This was indicated by findings that activity of the alpha-1-PI could be restored by exposure to the reducing agent, dithiothreitol in the presence of methionyl sulfoxide peptide reductase. The amount of activity restored was proportional to the amount of inactive alpha-1-PI present at 52,000 D. Oxidation of the 52,000-D alpha-1-PI was also revealed by the finding that the inactive molecule was subject to proteolytic cleavage to 47,000 D when exposed to porcine pancreatic elastase, a characteristic of alpha-1-PI with oxidized methionyl residues in the reactive site. Inactivation of the alpha-1-PI in vivo also resulted from complexing to an active enzyme, shown previously to be neutrophil elastase, and from proteolytic cleavage in vivo, that produced a fragment of 47,000 mol wt. In contrast to that in BAL fluids, the alpha-1-PI in plasma of patients with respiratory distress syndrome was found to be greater than 90% active in 14 of 22 cases and 50-90% active in 8 cases. This suggested that for the most part, alpha-1-PI was inactivated after leaving the vessels and entering the lung. The circulating alpha-1-PI in patients with the respiratory distress syndrome was found to be equally susceptible to oxidative inactivation as alpha-1-PI from normal individuals. It seems improbable therefore that patients develop ARDS because of labile alpha-1-PI inhibitor.     

急性呼吸窘迫综合征患者血清和支气管肺泡灌洗液中白介素-1β的变化

目的 :探讨白细胞介素 1β(IL 1β)在急性呼吸窘迫综合征 (ARDS)发病中的作用。方法 :用酶联免疫吸附试验检测了 13例 ARDS患者和 9例健康者支气管肺泡灌洗液 (BAL F)和血清中 IL 1β含量。结果 :ARDS患者 BAL F及血清中 IL 1β含量〔分别为 (14 4 .6 7± 80 .79) ng/ L 和 (4 5 .71± 7.0 9) ng/ L〕明显高于对照组〔分别为 (2 0 .39± 1.87) ng/ L 和 (35 .0 6± 5 .4 6 ) ng/ L,P=0 .0 0 0和 P=0 .0 0 1〕,且 ARDS患者 BAL F中IL 1β含量也明显高于血清 (P=0 .0 0 0 )。结论 :IL 1β参与了 ARDS的发病过程 ,早期测定 ARDS患者肺内细胞因子可能比血液或血浆中更有价值。     

Lethal adult respiratory distress syndrome after meningococcal septicemia biochemical markers in bronchoalveolar lavage

A lethal case of Adult Respiratory Distress Syndrome (ARDS) consequent to meningococcal septicemia is clinically and physiologically described. Very high levels of eosinophil cationic protein and lactoferrin in bronchoalveolar lavage were observed in spite of peripheral eosinopenia and neutropenia. These findings provide support for the hypothesis that activated granulocytes are involved in the pathogenesis of septic-induced ARDS.     

Chronic eosinophilic pneumonia: a cause of adult respiratory distress syndrome

It is important that physicians not overlook the diagnosis of chronic eosinophilic pneumonia (CEP), since this disorder is readily reversible with corticosteroid therapy. Six patients with CEP were seen at our institution between 1979 and 1983. We present their clinical features, chest films, and pathologic findings, and review the literature on CEP. While most of our patients had the classic chest x-ray pattern of peripheral opacities in a nonsegmental distribution, two had atypical features with diffuse abnormalities on x-ray films. In fact, the two patients who had adult respiratory distress syndrome (ARDS), presented diagnostic difficulty and required admission to the intensive care unit. In contradistinction to the four patients with classic CEP, the two with ARDS had a delayed response to corticosteroids. Therefore, we conclude that chronic eosinophilic pneumonia is an important entity to recognize as a potentially fatal cause of the adult respiratory distress syndrome.     

Autoantibodies to lipids in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome

OBJECTIVE: To investigate the presence of autoantibodies to lipids in the bronchoalveolar lavage (BAL) fluid from adult patients with acute respiratory distress syndrome (ARDS). DESIGN: Analysis of immunoglobulin G (IgG) in BAL fluid by electrophoresis followed by immunoblotting and characterization of immunoglobulins as antilipid autoantibodies. SETTING: Intensive care unit of a university hospital and two research university laboratories. SUBJECTS: Twenty-seven mechanically ventilated patients in total, including nine patients with ARDS and two control groups. INTERVENTIONS: Patients were ventilated with a mechanical ventilation mode. Six aliquots of 20-mL sterile normal saline at 37 degrees C were infused through the working channel of the bronchoscope. MEASUREMENTS: Total protein, detection of IgG by electrophoresis followed by immunoblotting, and characterization of IgG by enzyme-linked immunosorbent assay using different lipids as target antigens. MAIN RESULTS: Antiphospholipid autoantibodies are present in BAL fluid of ARDS patients. Among the phospholipids tested, phosphatidic acid and phosphatidylserine gave the most significant activity. The IgG fraction, purified from BAL fluids by affinity chromatography, gave the same pattern of binding as that of the BAL fluid. CONCLUSION: The presence of antiphospholipid autoantibodies in BAL fluid suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS.     

Intravenous immunoglobulin in adult varicella pneumonia complicated by acute respiratory distress syndrome

Pneumonia is a rare but serious complication of varicella in adults. We report a case of a previously healthy 32-year-old man with varicella pneumonia that was complicated by acute respiratory distress syndrome. He was treated successfully with acyclovir and intravenous immunoglobulin in addition to mechanical ventilation. We conclude that intravenous immunoglobulin, in combination with acyclovir, is a safe and probably effective therapy for adult varicella pneumonia that is complicated by acute respiratory distress syndrome.     

The adult respiratory distress syndrome

The adult respiratory distress syndrome (ARDS) is an extreme form of noncardiogenic pulmonary edema associated with alveolar-capillary damage. Clinical features include acute respiratory distress, dyspnea and tachypnea, severe hypoxemia refractory to oxygen therapy, and diffuse bilateral pulmonary infiltrates. Any number of serious disorders can cause ARDS, but the processes leading to the alveolar permeability defect are not understood. Therefore, therapy remains nonspecific and supportive. Treatment includes positive end-expiratory pressure, careful fluid management, steroid therapy, and adequate nutrition. Unfortunately, even with the most sophisticated intensive care, the mortality of ARDS is still greater than 50%.     

Pathology of the adult respiratory distress syndrome

Despite the wide range of insults that can lead to the development of ARDS, a common sequence of pathologic changes can be identified in the lung. These changes can be divided into three phases: the acute, or exudative, phase (up to 6 days), in which hyaline membranes are a characteristic feature; the subacute, or proliferative, phase (4 to 10 days), in which metaplasia of the alveolar lining cells and early evidence of fibrosis are seen; and the chronic phase (8 days and on), when organizing fibrosis is a major finding. Structural changes of chronic pulmonary hypertension are also found in the patients with ARDS of longer duration. The mechanism by which these pulmonary changes occur is unknown. Studies of experimental models of ARDS may offer the best opportunity to elucidate the mechanisms. For example, a single infusion of E. coli endotoxin into sheep mimics the pathophysiologic changes of ARDS, offering a model for study of the initial insult on the lung. In addition, animals exposed to high concentrations of oxygen also show morphologic changes similar to those seen in patients with ARDS. Whether the hyperoxia is responsible for such changes, or whether it potentiates the injury induced by some other insult, is not certain.     

Generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome.

OBJECTIVE: To determine the generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: ICU in a university hospital. PATIENTS: Severely traumatized patients at risk for the ARDS (n = 25). INTERVENTION: EDTA plasma samples and bronchoalveolar lavage fluid were obtained. MEASUREMENTS and MAIN RESULTS: Complement proteins C3, C4, C5, and the inhibitors C1-inhibitor, Factor H, and Factor I were quantitated in EDTA-plasma samples obtained every 6 hrs during the first 48 hrs after ICU admission and every morning from days 4 to 14 after injury. In bronchoalveolar lavage fluid, the complement activation production of C3a-desArg was quantitated and the volume of epithelial lining fluid was calculated. All patients showed a decrease of the complement proteins C3, C4, C5 and of the inhibitors C1-inhibitor, Factor H, and Factor I during the first 24 hrs, indicating complement consumption. Patients developing ARDS (n = 11) showed significantly higher C3 concentrations and a higher C3a/C3 ratio in the first few hours after multitrauma. Follow-up bronchoalveolar lavages demonstrated highly increased amounts of C3a in epithelial lining fluid during the first 24 hrs, mainly in ARDS patients and, to a lesser degree, in non-ARDS patients. To determine the origin of C3a in bronchoalveolar lavages, the ratio of C3a in epithelial lining fluid and plasma was calculated. CONCLUSION: The C3a of epithelial lining fluid to plasma ratio was extremely high in patients developing ARDS, but even the non-ARDS group had a ratio greater than 1, indicating that a substantial local complement activation occurs in the lung.     

Immunoreactive trypsin in the adult respiratory distress syndrome

With the purpose of studying the role of proteinases in the development of ARDS, plasma levels of immunoreactive trypsin (IRT) and amylase were measured in 43 intensive care patients at risk of developing ARDS (22 polytrauma, seven abdominal surgery, four burns, two DIC and eight pancreatitis). Twenty four of these 43 patients developed ARDS and 31 presented abnormal IRT values (above 70 g/L). Twenty-one of these 31 patients had ARDS; a significant correlation thus appeared between ARDS and abnormal IRT values. In nine patients, IRT values were higher than 800 g/L and remained high for 3 to 4 days. A statistically significant correlation also appeared between abnormal IRT and septic phenomena: 20 patients with high IRT values presented septic problems. When IRT values were high, amylase values were often also abnormal: 12 of 23 patients with high IRT had abnormal amylase levels (the eight patients with documented pancreatitis were excluded); no other clinical signs or symptoms of pancreatitis were present in these patients. IRT could be one of the mediators of ARDS in septic patients. It is not clear that the pancreas is the origin of IRT in all cases.     

Keratinocyte growth factor and hepatocyte growth factor in bronchoalveolar lavage fluid in acute respiratory distress syndrome patients

OBJECTIVES: To determine bronchoalveolar lavage (BAL) fluid concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), two potent growth factors for alveolar type II epithelial cells, in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: An adult trauma/surgical intensive care unit in an urban teaching hospital. PATIENTS: A total of 32 ventilated patients with pulmonary infiltrates prospectively identified with ARDS (n = 17) or without ARDS (n = 15), including eight patients with hydrostatic edema (HE), and ten nonventilated patients serving as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL was performed 2.88 days +/- 2.4, 3.5 days +/- 2.4, and 2.3 days +/- 2.2 after the lung insult in ARDS, HE, and other non-ARDS patients respectively (p = .32). KGF was detected in BAL fluid in 13 of the 17 ARDS patients (median, 31.6 pg/mL), in one patient with HE, and in none of other non-ARDS patients. In ARDS patients, detection of KGF in BAL was associated in BAL fluid with the detection of type III procollagen peptide (PIIIP), a biological marker of fibroproliferation. In ARDS patients, detection of KGF in BAL was associated with death (p = .02). HGF was detected in 15 ARDS patients (median, 855 pg/mL), in seven patients with HE (median, 294 pg/mL; p = .05 for the comparison with ARDS group), in six of other non-ARDS patients (median, 849 pg/mL; p = .32 with ARDS group). HGF concentrations were higher in nonsurvivors than in survivors (p = .01). None of the ten BAL of controls contained either KGF or HGF. CONCLUSION: KGF was detected almost exclusively in BAL fluid from ARDS patients and correlated with a poor prognosis in this group. In contrast, HGF was detected in the BAL fluid from a majority of patients with or without ARDS. Elevated HGF concentrations were associated with a poor prognosis in the overall group.     

Miliary tuberculosis and adult respiratory distress syndrome

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role.     

Tumor necrosis factor in serum and in bronchoalveolar lavage of patients at risk for the adult respiratory distress syndrome

Tumor necrosis factor-alpha (TNF) production was analyzed in 30 mechanically ventilated patients at high risk for the adult respiratory distress syndrome (ARDS) as defined by the presence of septic syndrome or following multiple trauma. Ten patients mechanically ventilated with acute cerebral hemorrhage were studied as a control group. Serum samples were drawn on entry into the study every 30 minutes for 90 minutes (0hr), 24 hours (24hr), and 48 hours (48hr) after enrollment. Bronchoalveolar lavage (BAL) was performed on the first and third day serum and BAL fluid were essayed for TNF content. No detectable amount of TNF was observed in 10 nonseptic controls. Production of TNF did not vary over the study period and was observed not only in patients with septic syndrome but also in patients without sepsis. Tumor necrosis factor did not correlate with mortality, severity of illness, and clinical parameters. Patients developing ARDS showed a significantly higher concentration of TNF in BAL than in serum (96 ± 25v 28 ± 27 pg/mL at 0hr; 91 ± 29 v 22 ± 25 pg/mL at 48hr; P < .05). These data support the concept of local pulmonary production of this cytokine in ARDS.     

Genetics and the pathogenesis of adult respiratory distress syndrome

Most human diseases are substantially affected by genetic factors. It now seems clear that the pathogenesis of most diseases lies in complex interactions among the genotype, the environment, and the nature of the process that leads to cell, tissue, organ, or systemic injury. The information derived from the knowledge of the recent completion of the human genome, when combined with the sophisticated tools of molecular biology, will provide the framework for more rapid identification of the genes responsible for susceptibility to disease. Genetic approaches to complex disorders offer great potential to improve our understanding of their pathophysiology, but they also offer significant challenges. There is evidence that cellular and humoral immune responses are subject to polymorphic genetic control, which could explain the well-known diversity of clinical manifestations and outcomes in critically ill patients with the same disease. Therefore, genetic differences between people may affect the likelihood of the development of diseases. Markers of susceptibility will indicate differences in individuals or populations that affect the body's response. The underlying principle of susceptibility markers is the interindividual differences that confer sensitivity or resistance to environmentally induced diseases. This article reviews some of those susceptibility factors for critical illness and acute lung injury.