Development Of Adult Respiratory Distress Syndrome Research Articles

Hypoalbuminemia: incidence and its impact on acute respiratory distress syndrome and 28-day outcome in trauma patients.

This prospective observational study explored the effect of early onset hypoalbuminemia (EOH) on the development of adult respiratory distress syndrome (ARDS) in orthopedic trauma victims. Serum albumin levels were measured for the initial 7days of injury for adult trauma patients (18-65years). Patients were recruited into group A (any serum albumin value < 3.5mg/dl) and group B (all serum albumin ≥ 3.5mg/dl), based on serum albumin values. Patients were followed for the development of ARDS and outcome until 28days. The primary outcome of the study was to explore the effects of EOH on ARDS. EOH (any serum albumin value < 3.5g/dl within 7days of injury) was present in 205/386 (53.1%) patients. The majority of 174/205 (84.9%) patients had EOH by the fourth day after the injury, with the mean time for development of EOH being 2.15 ± 1.87days. ARDS manifested in 87/205 (42.4%) and 15/181 (8.3%) patients in group A and group B, respectively (p < 0.001). EOH had 8.2 times greater odds of ARDS (OD 8.2 95% CL 4.7-14.0, p = 0.000). The mean time for the onset of ARDS was 5.63 ± 2.62days. No statistically significant causal relationship occurred between the onset of EOH and the development of ARDS (Pearson's correlation coefficient = 0.14, p = 0.16). At serum albumin cutoff concentrations of 3.4 gm/dl on D1 (AUC 0.68, 95% CI: 0.61-0.74, p = 0.000), ARDS may be anticipated in 62.8% of patients. The commencement of ARDS was independently correlated with EOH (p = 0.000), Respiratory rate on admission (p = 0.000), inotrope use (p = 0.000), and soft tissue injury (p = 0.000) (R2 = 0.466). The odds of 28-day all-cause death were 7.7 times higher in EOH (OD 7.7 95% CL 3.5-16.7, p = 0.00) and 9 times higher in ARDS (OD 9 95% CL 4.9-16.16, p = 0.00). EOH is a frequent occurrence and has a strong influence development of ARDS and 28-day mortality in trauma patients.

Does lack of thoracic trauma attenuate the severity of pulmonary failure? An 8-year analysis of critically injured patients.

PurposePatients with thoracic trauma are presumed to be at higher risk for pulmonary dysfunction, but adult respiratory distress syndrome (ARDS) may develop in any patient, regardless of associated chest injury. This study evaluated the impact of thoracic trauma and pulmonary failure on outcomes in trauma patients admitted to the intensive-care unit (ICU).MethodsAll trauma patients admitted to the ICU over an 8-year period were identified. Patients that died within 48 h of arrival were excluded. Patients were stratified by baseline characteristics, injury severity, development of ARDS, and infectious complications. Multiple logistic regression was used to determine variables significantly associated with the development of ARDS.Results10,362 patients were identified. After exclusions, 4898 (50%) patients had chest injury and 4975 (50%) did not. 200 (2%) patients developed ARDS (3.6% of patients with chest injury and 0.5% of patients without chest injury). Patients with ARDS were more likely to have chest injury than those without ARDS (87% vs 49%, p < 0.001). However, of the patients without chest injury, the development of ARDS still led to a significant increase in mortality compared to those patients without ARDS (58% vs 5%, p < 0.001). Multiple logistic regression found ventilator-associated pneumonia (VAP) to be the only independent predictor for the development of ARDS in ICU patients without chest injury.ConclusionsARDS development was more common in patients with thoracic trauma. Nevertheless, the development of ARDS in patients without chest injury was associated with a tenfold higher risk of death. The presence of VAP was found to be the only potentially preventable and treatable risk factor for the development of ARDS in ICU patients without chest injury.

Adult respiratory distress syndrome risk factors for injured patients undergoing damage-control laparotomy: AAST multicenter post hoc analysis.

Severely injured patients undergoing damage-control laparotomy (DCL) have multiple risk factors for adult respiratory distress syndrome (ARDS), making it challenging to differentiate the contributions of individual causative factors. We aimed to determine the relative contributions of ARDS risk factors. Analysis of the prospectively collected American Association for the Surgery of Trauma Multi-institutional Open Abdomen Database was performed. Inclusion criteria were any patient, 18 years or older, undergoing DCL at 1 of 14 participating Level I trauma centers. Univariable and multivariable Cox regression analyses were performed to determine the association of variables with the development of ARDS during hospitalization. A total of 563 patients (78% men; mean [SD] age, 40 [18] years) were identified, of whom 77 developed ARDS (14%). Overall mortality was 23%, with a 39% mortality rate for ARDS patients. Univariable analysis demonstrated that Injury Severity Score (ISS, 1.03; 95% confidence interval [CI], 1.02-1.05), intraoperative (IO) estimated blood loss (hazard ratio [HR], 1.09; 95% CI, 1.04-1.13), IO plasma transfusion (HR, 1.17; 95% CI, 1.10-1.25), 24-hour colloid volume (HR, 1.07; 95% CI, 1.04-1.10), and 24-hour crystalloid volume (HR, 1.01; 95% CI, 1.00-1.01) were associated with the development of ARDS. Cox multivariable analysis demonstrated that ISS, IO plasma transfusions, and total fluid balance through 23 hours all increased the risk of ARDS development. Severity of injury, plasma transfusions, and greater fluid administration by 24 hours were independently associated with ARDS development. Judicious use of plasma and other fluids may reduce rates of ARDS in this critically injured population. Prognostic study, level III; therapeutic study, level IV.

Azathioprine associated acute respiratory distress syndrome: case report and literature review

A 58-year-old Caucasian man treated with azathioprine to prevent rejection of an orthotopic liver transplant, presented to the Carl Hayden VA Medical Center with rapid respiratory decline and appeared septic. He required urgent intubation, mechanical ventilator support and empiric antibiotics. His clinical picture and imaging studies were consistent with acute respiratory distress syndrome; however, extensive infectious work up failed to reveal an offending organism. Review of his current medications implicated azathioprine and upon discontinuation of this agent, the patient made a rapid recovery. He was subsequently extubated, transferred out of the ICU and soon discharged home in good health. Prescribed for organ transplant rejection and a wide array of autoimmune diseases, azathioprine has been rarely correlated with pneumonitis and rapid respiratory failure. No reported cases were found in which azathioprine was used to treat liver transplant rejection and associated with development of the adult respiratory distress syndrome (ARDS). However, there have been ARDS cases in which azathioprine was used for other purposes. We review all the available cases of azathioprine associated ARDS. The patients in these reports had similar clinical symptoms on presentation as our patient: hypoxia, febrile episodes and rapid development of ARDS with no infectious etiology. Most notable is the rapid resolution of ARDS after discontinuation of azathioprine. Although azathioprine toxicity related respiratory failure is rare, this correlation should still be considered in the differential for immunosuppressed patients presenting with rapid pulmonary decline. Further studies are needed and warranted to better correlate this connection, but it is imperative to recognize that the relationship exists.

Blood alcohol content, injury severity, and adult respiratory distress syndrome.

Elevated blood alcohol content (BAC) is a risk factor for injury. Associations of BAC with adult respiratory distress syndrome (ARDS) have not been conclusively established.We evaluated the association of a BAC greater than 0 mg/dL with the intermediate outcomes, Injury Severity Score (ISS) and Glasgow Coma Scale (GCS) score, and their association with ARDS development. This is an observational retrospective cohort study of 26,305 primary trauma admissions to a statewide referral trauma center from July 11, 2003, to October 31, 2011. Logistic regression was performed to assess the relationship between admission BAC, ISS, GCS score, and ARDS development within 5 days of admission. The case rate for ARDS was 5.5% (1,447). BAC greater than 0 mg/dL was associated with ARDS development in adjusted analysis (odds ratio, 1.50; 95% confidence interval [CI], 1.33-1.71; p < 0.001). High ISS (≥16) had a stronger association with ARDS development (odds ratio, 17.99; 95% CI, 15.51-20.86), as did low GCS score (≤8) (odds ratio, 8.77; 95% CI, 7.64-10.07; p < 0.001). Patients with low GCS score and high ISS had the most frequent ARDS (33.6%) and the highest case-fatality rate without ARDS (24.7%). Elevated BAC is associated with ARDS development. In the analysis of alcohol exposure, ISS and GCS score occur after alcohol ingestion, making them intermediate outcomes. ISS and GCS score were strong predictors of ARDS and may be useful to identify at-risk patients. Elevated BAC may increase the frequency of the ARDS through influence on injury severity or independent molecular mechanisms, which can be discriminated only in experimental models. Epidemiologic study, level III.

An innovative approach to predict the development of adult respiratory distress syndrome in patients with blunt trauma

Pulmonary contusion (PC) is a common injury associated with blunt chest trauma. Complications such as pneumonia and adult respiratory distress syndrome (ARDS) occur in up to 50% of patients with PC. The ability to predict which PC patients are at increased risk of developing complications would be of tremendous clinical utility. In this study, we test the hypothesis that a novel method that objectively measures percent PC can be used to identify patients at risk to develop ARDS after injury. Patients with unilateral or bilateral PC with an admission chest computed tomographic angiogram were identified from the trauma registry. Demographic, infectious, and outcome data were collected. Percent PC was determined on admission chest computed tomography using our novel semiautomated, attenuation-defined computer-based algorithm, in which the lung was segmented with minimal manual editing. Factors contributing to the development of ARDS were identified by both univariate and multivariable logistic regression analyses. ARDS was defined as PaO2/FiO2 ratio of less than 200 with diffuse bilateral infiltrates on chest radiograph with no evidence of congestive heart failure. Quantifying percent PC from our objective computer-based approach proved successful. We found that a contusion size of 24% of total lung volume or greater was most significant at predicting ARDS, which occurred in 78% of these patients. Such patients also had a significantly higher incidence of pneumonia when compared with those with contusions less than 24%. The specificity of contusion size of 24% or greater was 94%, although sensitivity was 37%; positive predictive value was 78%, and negative predictive value was 72%. We developed and describe a software-based methodology to accurately measure the size of lung contusion in patients of blunt trauma. In our analyses, contusions of 24% or greater most significantly predict the development of ARDS. Such an objective approach can identify patients with PC who are at increased risk for developing respiratory complications before they happen. Further research is needed to use this novel methodology as a means to prevent posttraumatic lung injury in patients with blunt trauma. Prognostic/epidemiologic study, level III; diagnostic study, level IV.

Pathophysiological Aspects of the Development of Respiratory Distress Syndrome in Pregnant Women with Preeclampsia

Objective: to estimate the incidence of adult respiratory distress syndrome (ARDS) and to define the main biochemical parameters characterizing the severity of preeclampsia in pregnant women. Subjects and methods. The study was conducted in 117 pregnant women aged 18 to 42 years with varying preeclampsia at 36—38 weeks of gestation. Results. According to the severity of preeclampsia in pregnant women, there was an increase in the rate of free radical oxidation that caused direct damage to the vascular endothelium, by inhibiting the total antioxidant activity of plasma, which largely depended on the state of the nitroxidergic system. There was an inverse correlation between nitrite levels and hemodynamic parameters and a functional relationship between systemic hemodynamic disorders and nitrite levels in pregnant women with preeclampsia. There was a reduction in the count of platelets and a significant increase in platelet aggregation in stages III and IV ARDS. Conclusion. Varying interstitial lung edemas develop in relation to the severity of preeclampsia. The maximum impairment of lipid peroxidation processes and lower nitrate levels were noted in severe preeclampsia. There was a progressive platelet count fall in Stages III and IV ARDS. In the authors&#8217; opinion, the magnitude of involvement of platelets in aggregates and free radical damage to the pulmonary vascular endothelium play a significant role in the development of ARDS in pregnant women with preeclampsia. However, impairments in the thrombocytic link are likely to be regarded as a direct cause of lung dysfunction. Key words: preeclampsia, respiratory distress syndrome, nitrites, lipid peroxidation.

Complement activation and the prognostic value of C3a in patients at risk of adult respiratory distress syndrome

In vivo and in vitro studies have shown that complement activation plays an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). In a prospective study of polytrauma patients at risk of ARDS (n = 38) complement parameters were determined over a period of 14 days in serial plasma samples (obtained every 6 h during the first 48 h). Polytrauma induced a rapid and remarkable complement activation. Low levels of the complement proteins C3, C4, C1 inhibitor (C1 INH) factor I and factor H during the first 48 h indicated complement consumption in all patients. Elevated C3a levels in the first few hours after injury were associated with the later development of ARDS. A more sensitive indicator than C3a alone was the calculated C3a:C3 ratio discriminating ARDS and non-ARDS patients. A second rise of C3a levels and C3a:C3 ratio from day 4 on paralleled the course of extravascular lung water. To assess the mode of complement activation, the activation-specific protein complexes C1rC1s-C1 INH and C3b(Bb)P were measured in some of the patients. We demonstrate that in the first 48 h complement activation occurred via the alternative pathway only and was later followed by an additional activation via the classical pathway. Our observations suggest that monitoring of C3a and C3 in plasma can identify polytrauma patients at high risk for ARDS at an early stage of the disease.

Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study

BackgroundIt has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients.MethodOne hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis.ResultsThere is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care.ConclusionThe ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.

Iron signalling regulated directly and through oxygen: implications for sepsis and the acute respiratory distress syndrome

Reactive oxygen species produced at toxic levels are damaging species. When produced at sub-toxic levels, however, they are involved as second messengers in numerous signal transduction pathways. In addition to these findings, we can add the concept that iron (often viewed as the "villain" in free radical biology) can also be considered as a signalling species. Iron is intimately involved in the regulation of its own storage, compartmentalization and turnover. During adult respiratory distress syndrome (ARDS) and sepsis, such regulation may be aberrant or altered in some predisposed way. Such changes may have profound implications for tissue damage, and for the modulation of the inflammatory response in these patients. The search for a genetic predisposition in patients that leads to the development of ARDS associated with abnormalities in iron turnover and signalling would seem to be an important and logical progression for studies into the disease. These may lead eventually to the design of effective treatment regimens that involve the control of iron.

ARDS in patients with thermal injury.

To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population. Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions. Regional, tertiary referral, adult burn unit in a university teaching hospital. Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995. None. Of 469 consecutive admissions, 126 (26.9%) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 +/- 5.2 and 8.2 +/- 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2% developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2%) in those with ARDS compared to those without (p = 0.27). According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.

The role of intrapulmonary nitric oxide generation in the development of adult respiratory distress syndrome.

This study was conducted to investigate the role of nitric oxide (NO) in the development of adult respiratory distress syndrome (ARDS). An experimental model of endotoxemia-induced ARDS was prepared in guinea pigs and the following parameters were measured: pulmonary vascular permeability, the nitrate and nitrite concentrations in blood and bronchoalveolar lavage fluid (BALF), and the activities of constitutive and inducible NO synthase in lung tissue following the administration of lipopolysaccharide (LPS). Following the intravenous administration of 0.5 mg/kg LPS, the pulmonary vascular permeability increased, as did the concentrations of nitrate and nitrite in the BALF and blood. The activities of both constitutive and inducible NO synthase (NOS) increased significantly in the lung tissue 4 h after the intravenous administration of LPS, the constitutive form showing significantly higher activity than the inducible form. Furthermore, the increase of vascular permeability in the lungs after LPS injection was blocked by the subcutaneous administration of N(G)-monomethyl-l-arginine. These observations indicate that the intrapulmonary generation of NO may play an important role in the development of ARDS.

Effect of Granulocyte/Colony-Stimulating Factor on the Onset of the Adult Respiratory Distress Syndrome

To evaluate the effect of granulocyte/colony-stimulating factor (G-CSF) on the onset of the adult respiratory distress syndrome (ARDS), we investigated whether the incidence of ARDS due to pulmonary infection differed between the G-CSF group which received chemotherapy with G-CSF and historical controls without G-CSF. We evaluated 132 patients with hematological malignancy in complete remission without any main organ dysfunction who had been treated between April 1983 and December 1997. We compared the incidence of ARDS due to pulmonary infection between those who received G-CSF and those who did not. There was no remarkable difference in the number of patients, gender, age, or distribution of primary diseases between the two groups. The intensity of chemotherapy was not considered to significantly differ between the two groups, though the chemotherapy regimens administered differed slightly. In the G-CSF group, the duration of neutropenia was significantly shorter and the frequency of documented infection was significantly decreased. We could not find any relationship between ARDS due to pulmonary infection and any anticancer agent or antibiotics. There was no relationship between the kind of G-CSF and the incidence of ARDS due to pulmonary infection (per chemotherapy session; p > 0.10, per case; p > 0.30, χ² test). The incidence of ARDS due to pulmonary infection per chemotherapy session was 4.21%, and showed a higher tendency in the G-CSF group (p < 0.100, χ² test). The incidence of ARDS due to pulmonary infection per case was 25.4% and was significantly higher in the G-CSF group (p < 0.025, χ² test). The incidence of ARDS due to pulmonary infection was higher in the G-CSF group than in the controls, suggesting that G-CSF promotes the development of ARDS due to pulmonary infection.

Adult respiratory distress syndrome - an update.

In adults, acute lung injury or adult respiratory distress syndrome (ARDS) may complicate a wide range of serious medical and surgical conditions, only some of which involve direct pulmonary insult. The characteristic histological feature of ARDS is an intense inflammatory process in the lungs, which may progress to fibrosis. The earliest physiological characteristic is an increase in the protein permeability across the endothelial and epithelial barriers of the lungs. This clinical syndrome is characterized by arterial hypoxaemia and bilateral radiographic infiltrates, which represent protein-rich oedema fluid. In addition there is a neutrophilic and macrophage infiltrate. Pulmonary endothelium is actively involved in the development of ARDS. It alters cell-cell adhesion as the initial step in leucocyte migration which, in turn, changes the permeability that allows protein-rich fluid to move into the interstitium. The quantity of this interstitial oedema may be sufficient to cause bulk flow through the epithelial barrier. There is probably independent epithelial injury. Finally, the endothelium can release and metabolize vasoactive and inflammatory substances, such as endothelins, nitric oxide and cytokines, etc. No single substance is responsible for acute lung injury, but rather a complex interplay exists between diverse pro- and anti-inflammatory mediators.

Prevalence of acute respiratory distress syndrome after cardiac surgery

J Thorac Cardiovasc Surg 1999;117:620-1

Maternal Mortality Associated With Adult Respiratory Distress Syndrome

Background Pregnancy-related adult respiratory distress syndrome (ARDS) can lead to maternal mortality and morbidity. Methods Records of all pregnant patients diagnosed with ARDS over a 14-year period were reviewed and the cases were stratified into survivors and nonsurvivors. Results Forty-one cases were identified and 31 survived (maternal mortality rate of 24.4%). Adult respiratory distress syndrome was diagnosed in the antepartum period in 23 (56.1%) of the patients and the majority of these cases occurred in the third trimester (73.9%). There was no statistically significant difference in demographic characteristics, preexisting diseases, or probable precipitating cause for the development of ARDS between the two groups. The cause of death among the nonsurvivors included multisystem organ failure, sepsis, cardiac arrest, and disseminated intravascular coagulopathy. Conclusion Pregnancy-related ARDS continues to be associated with a high maternal mortality rate (25%). Unfortunately, the etiology for ARDS during pregnancy is not predictive of maternal outcome.

Adult respiratory distress syndrome after microvascular free tissue reconstruction in head and neck malignancy

Adult respiratory distress syndrome (ARDS) is an important cause of morbidity and mortality after major operations. We undertook a 10 year retrospective analysis of patients undergoing major surgery in combination with microvascular free tissue transfer for head and neck malignancy at a Regional Maxillofacial Unit to try and identify predisposing factors. In the 10 year period to 31 April 1995, roughly 418 patients underwent major head and neck reconstructions, of which 399 (95.5%) were admitted to the intensive care unit (ICU) postoperatively. Thirty patients (7.2%) spent more than 72 h in the ICU, eight developed ARDS (1.9%) of whom four died. The factors that seemed to contribute to the development of ARDS were massive blood transfusion and early postoperative complications that required a further operation under general anaesthesia.

Maternal mortality associated with adult respiratory distress syndrome.

Pregnancy-related adult respiratory distress syndrome (ARDS) can lead to maternal mortality and morbidity. Records of all pregnant patients diagnosed with ARDS over a 14-year period were reviewed and the cases were stratified into survivors and nonsurvivors. Forty-one cases were identified and 31 survived (maternal mortality rate of 24.4%). Adult respiratory distress syndrome was diagnosed in the antepartum period in 23 (56.1%) of the patients and the majority of these cases occurred in the third trimester (73.9%). There was no statistically significant difference in demographic characteristics, preexisting diseases, or probable precipitating cause for the development of ARDS between the two groups. The cause of death among the nonsurvivors included multisystem organ failure, sepsis, cardiac arrest, and disseminated intravascular coagulopathy. Pregnancy-related ARDS continues to be associated with a high maternal mortality rate (25%). Unfortunately, the etiology for ARDS during pregnancy is not predictive of maternal outcome.

Secretory phospholipase A2 cleavage of intravasated bone marrow primes human neutrophils.

Recent clinical reports suggest that early femoral intramedullary rod (IMR) fixation in patients with multiple injuries increases the risk of adult respiratory distress syndrome (ARDS). We have shown that lipid-mediated neutrophil (PMN) priming and elevated circulating levels of secretory phospholipase A2 (sPLA2) within the first 24 hours after injury correlate with the development of ARDS. We thus hypothesized that circulating lipid products, generated by sPLA2 cleavage of intravasated bone marrow, prime PMNs for enhanced superoxide anion (O2-) production. Isolated PMNs from healthy volunteers were incubated for 5 minutes with buffer or sPLA2-lysed bone marrow (100 U/mL) collected from trauma patients. After formyl-methionyleucylphenylalanine (fMLP) activation, O2- production was quantified by the superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were also drawn from five injured patients before and 24 hours after femoral IMR fixation. PMNs were isolated and assessed for in vivo priming. PMNs incubated with sPLA2-lysed bone marrow were primed for more than 3.5 times greater fMLP-induced O2- production. Furthermore, in patients with femoral fractures, PMN O2- release in response to fMLP after IMR fixation was more than 2.5 times higher than before fixation. Collectively, the findings suggest that bone marrow released from acute fracture sites may become a lipid substrate for the elevated sPLA2 levels found in injured patients. The resultant priming of PMNs may thus render the injured patient at risk for ARDS. Although clearly hypothetical at present, we submit that these observations warrant further investigation because of their clinical implications.

Prostaglandin E1 attenuates cytotoxic mechanisms of primed neutrophils.

In a recent clinical trial, liposomal prostaglandin E1 (PGE1) improved oxygenation, increased compliance, and decreased ventilator dependency in patients with adult respiratory distress syndrome (ARDS), thus renewing interest in PGE1 as a potential modulator of inflammation. The neutrophil (PMN) is believed to play a key role in the development of ARDS. Consequently, we investigated the effects of PGE1 on three components of the neutrophil inflammatory response: reactive oxygen species (ROS) generation, protease release, and surface expression of adhesion molecules. Human neutrophils were incubated with PGE1 and then primed with platelet-activating factor (PAF) and activation with N-formyl-methionyl-leucylphenylalanine (fMLP). PGE1 at a dose range of (10[-8] to 10[-5] M) attenuated primed/activated (PAF/fMLP) PMN superoxide anion generation and elastase release. In contrast, PGE1 doses > or =10[-5] M were required to attenuate PAF-stimulated neutrophil upregulation of CD11b/CD18 adhesion molecules. PGE1 also diminished the duration of the PAF-induced cytosolic calcium (Ca2+) flux. Our results suggest that plasma levels of PGE1 attained in patients with ARDS may attenuate ROS and protease neutrophil cytotoxicity but may not effectively block PMN-endothelial cell (EC) adhesion. This attenuation may occur through abrogation of the Ca2+ influx.