Pulmonary Capillary Permeability Research Articles

Changes in plasma fibronectin in children after elective repair of congenital heart defects

Plasma fibronectin is an attachment protein important for maintaining capillary integrity and host defense mechanisms. Depletion of plasma fibronectin has been shown to occur in adults after septic shock, major trauma, and burns. Limited laboratory and clinical studies suggest a correlation between decreased plasma fibronectin levels and increased pulmonary capillary permeability and tissue perfusion. Mild and transient plasma fibronectin depletion has been observed in adults after cardiovascular operations. We measured plasma fibronectin by immunoturbidometric assay in 20 children (age 6 months to 12 years) undergoing repair of congenital heart defects. Plasma fibronectin levels immediately after operations and daily thereafter were compared with the preoperative values. Plasma fibronectin declined on postoperative days 1, 2, 3, 4, and 5 (p < 0.05). A nadir was reached on day 3 with a tendency toward recovery thereafter. Patients with a therapeutic intervention score of more than 35 had greater magnitude of plasma fibronectin decline than those with a score of less than 35 at 24 hours after the operation (p < 0.005). We conclude that (1) significant and prolonged plasma fibronectin depletion occurs after cardiovascular operations in children; and (2) postoperative plasma fibronectin depletion is associated with increasingly complex surgical intervention. Reduced plasma fibronectin synthesis and more extensive operations for congenital heart defects are likely reasons for children being more susceptible than adults to plasma fibronectin depletion after cardiovascular operations.

Changes in lung function and pulmonary capillary permeability after cardiopulmonary bypass.

To assess the possibility that changes in lung function following cardiopulmonary bypass are associated with increased pulmonary capillary permeability. A prospective, descriptive study. Adult cardiothoracic ICU in a post-graduate teaching hospital. Ten sequential patients undergoing cardiac surgery requiring cardiopulmonary bypass. Arterial blood gas tensions, helium dilution end-expiratory lung volume, and carbon monoxide transfer were measured by a rebreathing technique preoperatively and 2 hrs postoperatively. Lung extravascular protein accumulation index was measured by a double-isotope technique 2 hrs postoperatively and in a group of normal controls. Mean +/- SEM alveolar-arterial PO2 gradient increased from 77 +/- 14 torr (10.3 +/- 1.8 kPa) to 138 +/- 24 torr (18.5 +/- 3.2 kPa) (p less than .01). Functional residual capacity decreased by 20.2 +/- 5.6% (p less than .01). Carbon monoxide transfer decreased by 26.7 +/- 5.3% (p less than .01) for the lung as a whole and by 17.9 +/- 3.2% (p less than .01) per liter of accessible gas volume. Protein accumulation index ranged from 0.03 to 3.2 x 10(-3) (median 0.6) postoperatively (median for normal subjects 0.4; p less than .05), although only one patient had a value indicative of clinically important endothelial injury. Cardiac surgery involving cardiopulmonary bypass results in a deterioration in lung function characterized by a loss of lung volume, a reduction in carbon monoxide transfer, and an increase in the alveolar-arterial PO2 gradient. These changes do not appear to be mediated by an increase in pulmonary endothelial permeability.

Simultaneous liver and lung injury following gut ischemia is mediated by xanthine oxidase.

We have previously shown that gut ischemia/reperfusion (I/R) causes simultaneous liver and lung dysfunction and that neutrophils play a critical role in this process. The purpose of this study was to ascertain whether xanthine oxidase (XO) was likewise operational. Normal and XO-inactivated rats (given a tungsten-enriched, molybdenum-depleted diet for 3 weeks) underwent 45 minutes of occlusion of the superior mesenteric artery, and control rats were subjected to a sham laparotomy. After zero and six hours of reperfusion, blood was sampled and livers and lungs harvested. Iodine-125-labeled albumin leak was used as a marker for pulmonary and liver capillary permeability barrier function, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) levels as an index of hepatic mitochondrial redox state. Gut ischemia/six hours of reperfusion (I/R) increased the 125I albumin lung/blood ratio and the 125I albumin liver/blood ratio; AcAc/3-OHB levels decreased significantly. Xanthine oxidase activation eliminated the observed lung and liver capillary leak as well as the hepatic metabolic derangement induced by gut I/R. In conclusion, the simultaneous lung and liver dysfunction produced by gut I/R is mediated by XO.

Compounds that increase cAMP prevent ischemia-reperfusion pulmonary capillary injury.

This study evaluated the physiological effects of compounds that increase adenosine 3',5'-cyclic monophosphate (cAMP) on changes in pulmonary capillary permeability and vascular resistance induced by ischemia-reperfusion (I-R) in isolated blood-perfused rabbit lungs. cAMP was elevated by 1) beta-adrenergic stimulation with isoproterenol (ISO, 10(-5) M), 2) post-beta-receptor stimulation of adenylate cyclase with forskolin (FSK, 10(-5) M), 3) and dibutyryl cAMP (DBcAMP, 1 mM), a cAMP analogue. Vascular permeability was assessed by determining the capillary filtration coefficient (Kf,c), and capillary pressure was measured using the double occlusion technique. The total, arterial, and venous vascular resistances were calculated from measured pulmonary arterial, venous, and capillary pressures and blood flow. Reperfusion after 2 h of ischemia significantly (P less than 0.05) increased Kf,c (from 0.115 +/- 0.028 to 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1). These I-R-induced changes in capillary permeability were prevented when ISO, FSK, or DBcAMP was added to the perfusate at reperfusion (0.110 +/- 0.022 and 0.103 +/- 0.021, 0.123 +/- 0.029 and 0.164 +/- 0.024, and 0.153 +/- 0.030 and 0.170 +/- 0.027 ml.min-1.cmH2O-1.100 g-1, respectively). I-R significantly increased total, arterial, and venous vascular resistances. These increases in vascular resistance were also blocked by ISO, FSK, and DBcAMP. These data suggest that beta-adrenergic stimulation, post-beta-receptor activation of adenylate cyclase, and DBcAMP prevent the changes in pulmonary vascular permeability and vascular resistances caused by I-R in isolated rabbit lungs through a mechanism involving an increase in intracellular levels of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Ipsilateral Reexpansion Pulmonary Edema Developed Following Decortication

Surgery and anesthesia-related ipsilateral reexpansion pulmonary edema has been seldom reported. The pathogenic mechanism of this rare complication is not clearly understood. A 23 year-old male had a decortication for left lung empyema under one-lung anesthesia. It took 6 hours to finish the scheduled operation. The patient came back to surgery again because of postoperative bleeding and he developed an ipsilateral pulmonary edema during the reexpansion of the collapsed lung. Fortunately, he was well tolerated with the developed edema which was resolved gradually without any specific management. The most likely mechanism is the increased pulmonary capillary permeability due to capillary injury resulting from hypoxia, oxygen free radicals, stretching, or surgieal manipulation. Secondly, the rise of the pulmonary capillary transmural pressure gradient and decreased lymphatic pump activity might also be involved as well.

Pulmonary oedema in isolated lung lobe after inhalation injury

Pulmonary oedema was produced in isolated lung lobes with steam and provided direct continuous measurements of transudation as it occurred. Transvascular flux (Q f) and weight gain (G w) of the lobe increased immediately and the transudation reached its peak within half an hour after inhalation injury. Studies of protein content, colloid osmotic pressure of bronchial exudate and water content of lung, reconfirmed the increase in pulmonary capillary permeability. Marked haemoconcentration was revealed. Plasma leaked 113g (25 per cent), plasma protein leaked 1.96g (9.7 per cent) during the experiment. Based on the measured arterial pressure (P a), vein pressure (P v), arterial occlusion (P ao), venous occlusion (P vo), double occlusion (P do) and blood flow through the lobe (Q t), the total vascular (R t), arterial (R a), middle compartment (R mid) and venous (R v) resistances were calculated. All the resistances were increased and the Q t showed a decrease after inhalation injury.

Pulmonary capillary leak syndrome complicating generalized pustular psoriasis: possible role of cytokines

Two cases are reported of generalized pustular psoriasis complicated by profound alterations in pulmonary capillary permeability. Several features suggest the involvement of cytokines in the pathogenesis of this condition.

Participation of collagenase and elastase in LPS-induced airway hyperresponsiveness in guinea pigs.

Bacterial lipopolysaccharide (LPS) cause airway hyperreactivity in guinea pigs pretreated with metopirone. LPS inhalation resulted in an increase in airway muscarinic reactivity measured by intravenous acetylcholine injection 1-4 h after the inhalation of LPS. The increase of pulmonary capillary permeability was observed 1-24 h after the inhalation of LPS, whereas the increase of leukocytes in bronchoalveolar lavage fluid (BALF) was observed 2 and 24 h after the inhalation of LPS. Increased cells are mainly neutrophil, eosinophil, and macrophage. From the histopathological study, acute mucosal injury and loss of epithelial cilia were observed 1-24 h after the inhalation of LPS. In order to investigate the phlogistic substance in LPS-induced hyperreactivity, the roles of collagenase and elastase were investigated. The activities of both enzymes were elevated 2 h after the inhalation of LPS. The inhalation of collagenase and elastase caused bronchial hyperreactivity and increased pulmonary permeability. The combined administration of prednisolone (10 mg/kg/day) and cyclophosphamide (10 mg/kg/day) for five days decreased LPS-induced hyperreactivity, pulmonary capillary increase, collagenase and elastase activities, and the number of nucleated cells in BALF 2 h after the inhalation of LPS. These results indicate the participation of collagenase and elastase in the onset of LPS-induced airway hyperreactivity in guinea pigs.

Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs

To determine the mechanism governing pulmonary edema induced by an organophosphorus compound, S-(2-diisopropylaminoethyl)- O-ethylmethyl phosphonothiolate (VX), lung lymph flow and lymph-to-plasma protein concentration ratio were measured in six anesthetized, open-chest, mechanically ventilated beagle dogs before and after intravenous injection of 6 μg/kg of VX. Systemic and pulmonary hemodynamic data (heart rate, aortic blood flow, and left atrial, systemic arterial, pulmonary arterial, and pulmonary capillary pressures) were continuously recorded. Arterial blood gases and pH were measured every 30 min. Histological examinations and lung water content measurements were also carried out. Following VX injection, lung lymph flow increased (from 109 ± 38 to 179 ± 66 μl/min, p < 0.05) while lymph-to-plasma protein concentration ratio remained unchanged (from 0.64 ± 0.14 to 0.62 ± 0.12, N.S.). Neither systemic nor pulmonary hemodynamics were changed. Lung water content expressed as blood-free wet-to-dry weight ratio increased from 4.31 ± 0.23 to 5.35 ± 0.26 ( p < 0.05). Histological examinations revealed in many cases diffuse congestion of lungs and interstitial edema. These results suggest that VX injection induces an increase in pulmonary capillary permeability which may lead to a high-permeability edema.

The Role of Platelet-Activating Factor in the Pulmonary Response to Inhaled Bacterial Endotoxin

Quantitative morphometric analyses were carried out on animals subjected to aerosols of bacterial endotoxin (LPS) to further define the role of platelet-activating factor (PAF) in the development of pulmonary injury. Hamsters were exposed to either saline aerosol or dilute aerosols of LPS (4 micrograms/m3) for standard lengths of time. Within each aerosol exposure group, animals were further subdivided into groups receiving either the PAF receptor binding antagonist, RP 48740, or saline injections. LPS inhalation resulted in decreased fixed lung volume, increased sequestration of polymorphonuclear leukocytes and platelets in pulmonary capillaries, increased type I epithelial and endothelial cellular volumes, increased cellular interstitium, and increased endothelial pinocytotic vesicles. Treatment with RP 48740 either attenuated or abolished the ability of inhaled LPS to induce these structural alterations. The PAF antagonist also inhibited LPS-induced increases in pulmonary capillary permeability. It is concluded that PAF is one of the major injury-promoting mediators released upon inhalation exposure to environmentally realistic concentrations of bacterial endotoxin. A major but not exclusive target of this mediator is the pulmonary vascular endothelium.

Pathogenesis of pulmonary edema during interleukin-2 therapy: correlation of chest radiographic and clinical findings in 54 patients.

The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability.

Ibuprofen Prevents Deterioration in Static Transpulmonary Compliance and Transalveolar Protein Flux in Septic Porcine Acute Lung Injury

The effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis-induced porcine acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized, cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume). Three groups were studied: septic animals (Ps, n = 10) received Pseudomonas aeruginosa for 1 hr IV, controls (C, n = 9) received 0.9% NaCl, and ibuprofen-treated septic animals (Ps + Ibu, n = 7) received ibuprofen 12.5 mg/kg at 0 and 120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2, cardiac index (CI), static lung compliance (CL), EVLW (thermal cardiogreen), and peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage (BAL) was performed for protein and % neutrophil (%PMN) content. Ps produced significant (p less than 0.05) decreases in CL, PaO2, SAP, CI, and peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMN's vs. controls. Ibu prevented the early increase in PAP and attenuated the late increase in PAP and EVLW. Ibu also maintained PaO2, CL, BAL protein, and %PMN's in BAL at control levels, but exhibited no significant effect on peripheral leukopenia. These data strongly suggest that ibuprofen administered before and at 120 min after onset of Pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis.

Ibuprofen Prevents Deterioration in Static Transpulmonary Compliance and Transalveolar Protein Flux in Septic Porcine Acute Lung Injury

The effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis-induced porcine acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized, cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume). Three groups were studied: septic animals (Ps,n= 10) receivedPseudomonas aeruginosafor 1 hr IV, controls (C,n= 9) received 0.9% NaCl, and ibuprofen-treated septic animals (Ps + Ibu,n= 7) received ibuprofen 12.5 mg/kg at 0 and 120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2, cardiac index (CI), static lung compliance (Cl), EVLW (thermal cardiogreen), and peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage (BAL) was performed for protein and % neutrophil (%PMN) content.Results:Ps produced significant (p< 0.05) decreases in CL, PaO2, SAP, CI, and peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMN's vs. controls. Ibu prevented the early increase in PAP and attenuated the late increase in PAP and EVLW. Ibu also maintained PaO2,CL, BAL protein, and %PMN's in BAL at control levels, but exhibited no significant effect on peripheral leukopenia. These data strongly suggest that ibuprofen administered before and at 120 min after onset of Pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis.

Role of xanthine oxidase and neutrophils in ischemia-reperfusion injury in rabbit lung

This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R.

Pulmonary Edema in Severe Falciparum Malaria: Hemodynamic Study and Clinicophysiologic Correlation

This study was performed to extend the knowledge of the pathogenesis of PE in severe falciparum malaria. Sequential hemodynamic studies were conducted in 13 patients with severe falciparum malaria. Seven patients developed PE, while the other six patients had NPE. Two patients died, one in each group. Hemodynamic changes were found in both groups, including an initial reduction in SVR and PVR, along with an increased CI and variable values (normal and increased) of PCWP. All abnormalities persisted for at least two days; changes in PVR lasted especially longer (throughout five days). The initial hemodynamic changes cannot predict the development of PE; however, heavy parasitemia of more than 60 percent and severe hypoalbuminemia were found to be more common in PE than NPE. Of three patients with PE who had normal PCWP, one died, with postmortem findings of increased pulmonary capillary permeability. The increased PCWP which was found in the other four cases of PE was proven to be volume overload without evidence of CHF. It was concluded that the pathophysiologic changes in severe falciparum malaria were systemic and pulmonary vasodilation. The abnormal pulmonary vascular change was found to be the cause of PE. Volume overload and hypoalbuminemia could aggravate further pulmonary capillary leakage in these cases.

The effects of neutrophils and phospholipase A 2 on transvascular albumin flux in isolated rabbit lungs

In this study, addition of phospholipase A 2 (PLA 2) to salt-perfused isolated rabbit lungs containing rabbit polymorphonuclear leukocytes leads to an increase in pulmonary capillary permeability. We add 1.5 × 10 8 polymorphonuclear leukocytes to the perfusate. Next, indomethacin is added to the perfusate and 40 units of PLA 2 are infused into the pulmonary arterial inflow of the lungs. At the end of the study, a lung sample is removed for measurement of transvascular albumin flux using I 125-albumin as a measure of the permeability-surface area product. Control studies demonstrate no increase in transvascular albumin flux. Addition of a dual cyclooxygenase and lipoxygenase inhibitor, BW755C, to the perfusate prevents the increase in transvascular albumin flux. We conclude that PLA 2 interacts with polymorphonuclear leukocytes to increase protein permeability. Since PLA 2 can release endogenous arachidonic acid and platelet-activating factor from cells, this suggests that release of such products may contribute to an increase in pulmonary capillary permeability from polymorphonuclear leukocytes. The ability of BW755C to prevent the increase suggests the possibility that lipoxygenase products contribute.

THE PRODUCTION OF TUMOR NECROSIS FACTOR ALPHA AND THE DEVELOPMENT OF A PULMONARY CAPILLARY INJURY FOLLOWING HEPATIC ISCHEMIA/REPERFUSION

The large mass of fixed macrophages resident in the liver make it a potentially rich source of cytokines. We have previously demonstrated that an isolated and severe ischemia/reperfusion injury to the liver results in cytokine release, specifically tumor necrosis factor alpha, and that TNF is then involved in the development of pulmonary pathology. This study was designed to determine the kinetics of TNF release following varying periods of hepatic ischemia and to further investigate the acute lung injury that follows. Suprahepatic blood samples were obtained at serial time points following a 45-, 60-, 75-, or 90-min ischemic insult to a segment of the rat liver with subsequent reperfusion. Using a bioassay based on the WEHI 164 cell line, plasma TNF levels were measured in all experimental animals; sham-operated control animals had undetectable levels. Changes in pulmonary capillary permeability were then measured using a standard 125I-labeled albumin washout technique following a 90-min ischemic insult with subsequent reperfusion. A significant increase in the mean permeability index was observed 9 to 12 hr following hepatic reperfusion (.601 +/- 102 as compared with .114 +/- .085 in sham-operated controls, P less than 0.005). Animals treated with anti-TNF antiserum prior to the induction of hepatic ischemia had a significantly reduced pulmonary capillary leak compared to animals pretreated with rabbit serum without TNF-blocking properties (.184 +/- .029 versus .694 +/- 052 for the control serum, P less than 0.005). TNF release follows both moderate and severe ischemic injury to the liver and the results reported here implicate TNF as an important mediator of increased pulmonary capillary permeability. These experiments confirm previous histologic studies that demonstrated pulmonary edema and intra-alveolar hemorrhage following hepatic ischemia/reperfusion, with subsequent blockade of the histologic injury by pretreatment with anti-TNF antiserum.

Pulmonary capillary dynamics and fluid distribution after burn and inhalation injury

A non-linear macroscopic mathematical model is described for the simulation of the different mechanisms that regulate the pulmonary capillary dynamics in patients with thermal injury. The techniques used in the construction of the model are those of ‘system's dynamics’. This model has been incorporated into a patient simulator, which makes it possible to analyse the fluid and protein exchanges in a burn patient. The regulating mechanisms involved are: the pulmonary circulation, the fluid and protein transfer between the plasma and the interstitial space at the pulmonary capillary level, and the pulmonary lymphatic system. As a result of the sensitivity analyses of the model we propose that, for the simulation of the effects of an inhalation injury at the pulmonary capillary level, the parameters to be altered will be the pulmonary capillary permeability coefficient for proteins and the pulmonary capillary surface damaged by the injury. To verify the validity and utility of the model, the clinical progress of a series of burn patients with lung injuries has been compared with the results obtained using simulation.

Increase in pulmonary capillary permeability in dogs exposed to 100% O 2

Increase in pulmonary capillary permeability in dogs exposed to 100% O 2

The radiographic differentiation of pulmonary oedema.

A radiographic scoring system has been reported to have a high diagnostic accuracy in the differentiation of pulmonary oedema of renal, cardiac and capillary origin. In the present study, a similar scoring system was used in 51 patients with radiographic appearances of pulmonary oedema due to renal failure (n = 16), cardiac failure (n = 13) and to adult respiratory distress syndrome (ARDS) (n = 22). Evidence of increased pulmonary capillary permeability to transferrin was sought in all patients using a double-isotope method to derive a protein accumulation index (PAI). Using the clinical diagnosis of each type of pulmonary oedema as the "gold standard", sensitivity, specificity and accuracy for the chest radiographic scoring system in pulmonary oedema of cardiac origin were 46, 84 and 75%, respectively. For renal patients these values were 63, 86 and 78% and for ARDS, 89, 33 and 77%. For the PAI in ARDS, sensitivity was 85%, specificity 67% and accuracy 86%. The radiographic scoring system failed to distinguish between pulmonary oedema of renal and cardiac origin and cannot be considered of diagnostic value, but it was more successful in assessment of ARDS. Radiographic appearances suggestive of capillary injury and increased capillary permeability to transferrin occurred in all groups and such findings are not specific to ARDS as currently defined.