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Original Research: CRITICAL CARE MEDICINE |

Mortality Rates for Patients With Acute Lung Injury/ARDS Have Decreased Over Time* FREE TO VIEW

Massimo Zambon, MD; Jean-Louis Vincent, MD, PhD, FCCP
Author and Funding Information

*From the Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Belgium.

Correspondence to: Jean-Louis Vincent, MD, PhD, FCCP, Department of Intensive Care, Erasme Hospital, Route de Lennik, 808, 1070 Brussels, Belgium; e-mail: jlvincen@ulb.ac.be



Chest. 2008;133(5):1120-1127. doi:10.1378/chest.07-2134
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Background: Over the last decade, several studies have suggested that survival rates for patients with acute lung injury (ALI) or ARDS may have improved. We performed a systematic analysis of the ALI/ARDS literature to document possible trends in mortality between 1994 and 2006.

Methods: We used the Medline database to select studies with the key words “acute lung injury,” “ARDS,” “acute respiratory failure,” and “mechanical ventilation.” All studies that reported mortality rates for patients with ALI/ARDS defined according to the criteria of the American European Consensus Conference were selected. We excluded studies with < 30 patients and studies limited to specific subgroups of ARDS patients such as sepsis, trauma, burns, or transfusion-related ARDS.

Results: Seventy-two studies were included in the analysis. There was a wide variation in mortality rates among the studies (15 to 72%). The overall pooled mortality rate for all studies was 43% (95% confidence interval, 40 to 46%). Metaregression analysis suggested a significant decrease in overall mortality rates of approximately 1.1%/yr over the period analyzed (1994 to 2006). The mortality reduction was also observed for hospital but not for ICU or 28-day mortality rates.

Conclusions: In this literature review, the data are consistent with a reduction in mortality rates in general populations of patients with ALI/ARDS over the last 10 years.

Figures in this Article

Since the first description of ARDS in 1967 by Ashbaugh and coworkers,1many studies have been performed in an attempt to develop new therapies and new ventilatory strategies that could improve outcomes for patients with acute lung injury (ALI)/ARDS. ALI and ARDS remain a major problem in the ICU; in a recent publication, the incidence of ALI in the United States was reported to be 78.9/100,000 persons per year, with a mortality rate of approximately 40%.2However, reported mortality rates vary widely. An analysis by Krafft et al3published in 1996 concluded that the mortality rate of ARDS patients had remained constant from 1967 to 1994. In more recent years, however, some authors45 have suggested that survival rates may have improved, mainly as a result of the implementation of new protective ventilatory strategies. Nevertheless, although some studies68 do show decreased mortality rates compared to historical control groups, some studies910 still report mortality rates > 50%.

Importantly, ARDS is a syndrome and not an illness, and therefore difficult to define. Nevertheless, criteria were developed to define ALI/ARDS at the American European Consensus Conference in 199411 and have been widely adopted, facilitating comparison of studies. We were interested to see whether recent improvements in management may have resulted in improved outcomes and performed a systematic analysis of the literature about ALI/ARDS to document possible trends in mortality rates.

We used the Medline database and selected studies with the key words “acute lung injury,” “ARDS,” “acute respiratory failure,” or “mechanical ventilation,” limiting the research to adult patients and to studies published in the English language. We also limited the search to studies that used the criteria defined by the American European Consensus Conference,11 so we did not include publications that appeared before 1994. The reference lists from identified articles were also reviewed to locate any articles that had been missed in the original search. We included all studies up to August 2006.

From the identified studies, we selected those that included an assessment of mortality of a group of patients with ALI/ARDS. We arbitrarily decided to exclude studies that included < 30 patients. We also excluded studies that were limited to specific subgroups of ARDS patients, such as sepsis, trauma, burns or transfusion-related ARDS, because there may be different mortality rates among these subgroups.1215 If the same group of patients was used in different publications, we analyzed only the first in chronological order.

To take into account the inevitable time delays in publication, we took as the year of the study the last year of patient enrolment, whenever this was reported. We noted separately the ICU, hospital, and 28- to 30-day mortality rates. In controlled trials, we considered the mortality rate of the control group, so we excluded groups of patients whose mortality rate may have been altered because of treatment. In studies with historical cohorts, we considered the mortality rate of the most recent cohort. We attempted to compare the severity of the patient populations based on available severity scores. We also tried to analyze the differences in patient selection (inclusion/exclusion criteria) among studies, to determine how they may influence mortality rates, and analyzed separately studies without any exclusion criteria (primarily noninterventional/epidemiologic) and studies with exclusion criteria (primarily interventional) such as preexisting pulmonary disease, lung contusion, head injury, malignancy disease, hepatic disease, or other comorbidities.

Statistical Analysis

Separate metaanalyses16were performed for different mortality outcomes: overall mortality, ICU mortality, hospital mortality, 28- to 30-day mortality, and mortality for the studies with and without exclusion criteria. These were performed using random-effects models on a logit of the outcome. The presence of between-studies heterogeneity was assessed using the standard χ2 test (noted Q). Results were transformed to the proportion scale to ease interpretation.17 Additional metaregression analyses were performed to explore the effect of time. A mixed model, again using the logit of the outcome, was utilized for this purpose.18

Sensitivity analysis was performed to examine whether there was systematic variation in the results. Funnel plots were drawn, and their asymmetry19 was examined to assess whether publication bias was likely to be a problem, and the method of trim and fill, which assesses how many studies are likely to be missing and the potential impact of their exclusion on the analysis, was applied to both outcomes. Analyses were conducted using statistical software (Comprehensive Meta-Analysis Version 2; Biostat; Englewood NJ; and SPSS 14.0 for Windows; SPSS; Chicago, IL).

We identified 535 articles, of which 354 reported mortality rates for patients with ALI or ARDS. A total of 173 studies were excluded because the number of patients was < 30, and 92 studies were excluded because they treated a specific etiologic subgroup of ARDS patients, 11 studies because the same population was analyzed in another study, and 6 studies because the study period was not defined. Hence, 72 studies, including 11,426 patients, were included in the analysis (Table 1 ). Analysis of disease severity was not possible because of the wide variation in severity scores used in the studies.

Mortality rates varied considerably among the studies, from 15 to 72% (Table 1); the overall pooled mortality rate for all studies was 43% (95% confidence interval, 39.9 to 46.1%), and the differences in pooled mortality rates over time are shown in Figure 1 . There was heterogeneity between study results in the logit rate (Q = 682.0; p < 0.001, between-study variance, 0.24). Data from the other mortality analyses are provided in Table 2 .

When including time as a covariate in the metaregression model, there was an approximately constant linear reduction in overall mortality over the years covered by the literature (p = 0.02). The regression equation was logit(death) = 94.4689 − 0.0474 × time; when the regression line was transformed on the proportion scale, this translated into a 1.1% reduction in mortality per 1-year period over the analyzed time span. When analyzed separately, there was also a reduction in hospital mortality (slope coefficient, − 0.0621; p = 0.04), but there were no significant changes in the other mortality outcomes (Table 3 ).

Funnel plots were constructed for all the studies included in the analysis, examining overall mortality and hospital mortality, in order to assess the degree of publication bias. For the overall mortality, the funnel plot was symmetrical, indicating that publication bias is unlikely to have had a major influence in the analysis of mortality rates (plots not shown).

In a single-center study, Milberg et al86 reported no overall change in mortality rates for patients with ARDS from 1983 to 1987, a slight decline in 1988 and 1989, and a decrease to a low of 36% in 1993. In another study from the same center, Stapleton et al7 observed that mortality rates decreased in the 1980s until the mid-1990s, plateauing thereafter; there were no changes in the distribution of causes of death during the time period studied. Similar results were reported from a French center.6 However, an analysis by Krafft et al3 concluded that mortality rates had remained constant until 1994. Single-center studies8,45 with historical cohorts have suggested a decrease in mortality rates.

Our literature review suggests that there has indeed been a reduction in mortality rates for patients with ALI/ARDS over the last decade. The reasons for this observation cannot be determined from the current study. There was a similar reduction in mortality rates in studies with or without exclusion criteria, indicating that the differences seen over time were not related simply to the large number of inclusion criteria and highly selective populations included in interventional studies. The decrease in mortality was more pronounced for hospital mortality than for ICU mortality; this finding is probably more meaningful, and makes it less likely that the changes could have been due to changes in ICU discharge criteria over time.

The decrease in mortality may have been a result of improvement in the specific management of patients with ALI/ARDS as well as in the general management of ICU patients. Respiratory failure is an uncommon cause of death in ALI/ARDS patients, and a large proportion of patients with ALI/ARDS die of sepsis-related multiorgan failure.23,55,60 In a monocenter study, Suchyta et al87reported that compared to an historical cohort, a more recent cohort of patients with ARDS, which had a lower mortality rate, also had fewer nonpulmonary organ failures. Hence, the improved survival rates do not necessarily suggest that the respiratory management of these patients has improved. Many other nonpulmonary factors can be implicated, such as improved hygiene, better glucose control, more judicious use of blood transfusions, improved imaging to identify sources of sepsis, and methods to control sepsis. Interestingly, Ciesla et al88 recently showed a decreased progression from ALI to ARDS and multiple organ failure in a large cohort of trauma patients.

We did not separate patients meeting the ALI criteria from those having ARDS. Although the severity of hypoxemia has some prognostic value in a few studies,89a review90 reported that the Pao2/fraction of inspired oxygen ratio at the onset of disease was not an independent predictor of mortality, and the initial degree of gas exchange is a poor predictor of outcome unless severe (eg, Pao2/fraction of inspired oxygen < 50).,13Indeed, the difference in outcome between ALI and ARDS is relatively limited in the studies14,36,55,6566 that report results for both groups of patients.

Our study has a number of limitations, including the heterogeneity in patient populations, in inclusion and exclusion criteria, and outcome measures. Nevertheless, to increase comparability, we limited our search to studies that used the criteria for ALI/ARDS published by the American-European Consensus Conference.11 Even though these have been criticized,40,91 they are widely used and provide some homogeneity by which to compare studies. The present definitions of ALI/ARDS are considered by some authors91as arbitrary, and others92have called for new definitions to be developed that include prognostic measures and reduce patient heterogeneity. Moreover, in a comparison of autopsy findings with clinical definitions, including the American-European Consensus Conference definition, ARDS appeared to be underrecognized by clinicians, and the specificity of the definitions highly variable.93 A second potential limitation was that the absolute mortality rate may be affected by the type of study, with randomized clinical trials often having strict exclusion and inclusion criteria resulting in the selecting of populations of patients that may not always reflect the outcome of general ICU patients. However, to avoid this kind of “selection” bias, we separately analyzed studies with and without exclusion criteria, and noted a similar trend for both groups. Moreover, even if absolute mortality rates may be affected by this form of selection bias, trends over time may remain valid. A third limitation was that survival was assessed at different time periods (eg, at ICU discharge, hospital discharge, or at fixed time periods of 28 days or 30 days). The hospital stay following discharge from the ICU contributes 3 to 15% of the mortality in the few studies,35,59 that have reported both; this could be related to factors occurring after the ICU stay, which may be independent of the ARDS diagnosis and management. Unfortunately, it was impossible to compare disease severity in the patients because of the high variability in the severity scores used in the studies, which included acute physiology and chronic health evaluation II or III, simplified acute physiology score II, and the lung injury score, among others.

This literature review supports a reduction in mortality rates in the last 10 years in general populations of patients with ALI/ARDS. The same trend was observed in interventional and in epidemiologic studies.

Abbreviation: ALI = acute lung injury

The authors received no external funding for this study and have no conflicts of interest to declare.

Table Graphic Jump Location
Table 1. The Selected Studies
Table Graphic Jump Location
Table 1A. Continued
Figure Jump LinkFigure 1. Variation in overall pooled mortality rates over time in the 72 ALI/ARDS studies.Grahic Jump Location
Table Graphic Jump Location
Table 2. Overall and Selected Mortality Rates in Metaregression Analysis
* 

p < 0.001 for the heterogeneity test.

Table Graphic Jump Location
Table 3. Slope Values for Overall and Specific Mortality Outcomes
* 

Metaregression analysis using the logit outcome.

Ashbaugh, DG, Bigelow, DB, Petty, TL, et al (1967) Acute respiratory distress in adults.Lancet2,319-323. [PubMed]
 
Rubenfeld, GD, Caldwell, E, Peabody, E, et al Incidence and outcomes of acute lung injury.N Engl J Med2005;353,1685-1693. [PubMed] [CrossRef]
 
Krafft, P, Fridrich, P, Pernerstorfer, T, et al The acute respiratory distress syndrome: definitions, severity and clinical outcome: an analysis of 101 clinical investigations.Intensive Care Med1996;22,519-529. [PubMed]
 
Bernard, GR Acute respiratory distress syndrome: a historical perspective.Am J Respir Crit Care Med2005;172,798-806. [PubMed]
 
Rubenfeld, GD, Herridge, MS Epidemiology and outcomes of acute lung injury.Chest2007;131,554-562. [PubMed]
 
Jardin, F, Fellahi, JL, Beauchet, A, et al Improved prognosis of acute respiratory distress syndrome 15 years on.Intensive Care Med1999;25,936-941. [PubMed]
 
Stapleton, RD, Wang, BM, Hudson, LD, et al Causes and timing of death in patients with ARDS.Chest2005;128,525-532. [PubMed]
 
Kallet, RH, Jasmer, RM, Pittet, JF, et al Clinical implementation of the ARDS network protocol is associated with reduced hospital mortality compared with historical controls.Crit Care Med2005;33,925-929. [PubMed]
 
Mancebo, J, Fernandez, R, Blanch, L, et al A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome.Am J Respir Crit Care Med2006;173,1233-1239. [PubMed]
 
Singer, P, Theilla, M, Fisher, H, et al Benefit of an enteral diet enriched with eicosapentaenoic acid and γ-linolenic acid in ventilated patients with acute lung injury.Crit Care Med2006;34,1033-1038. [PubMed]
 
Bernard, GR, Artigas, A, Brigham, KL, et al The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med1994;149,818-824. [PubMed]
 
Petty, TL, Ashbaugh, DG The adult respiratory distress syndrome: clinical features, factors influencing prognosis and principles of management.Chest1971;60,233-239. [PubMed]
 
Montgomery, BA, Stager, MA, Carrico, J, et al Causes of mortality in patients with the adult respiratory distress syndrome.Am Rev Respir Dis1985;132,485-491. [PubMed]
 
Zilberberg, MD, Epstein, SK Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and hospital outcome.Am J Respir Crit Care Med1998;157,1159-1164. [PubMed]
 
Shander, A, Popovsky, MA Understanding the consequences of transfusion-related acute lung injury.Chest2005;128,598S-604S. [PubMed]
 
Stroup, DF, Berlin, JA, Morton, SC, et al Meta-analysis of observational studies in epidemiology: a proposal for reporting: Meta-analysis of Observational Studies in Epidemiology (MOOSE) group.JAMA2000;283,2008-2012. [PubMed]
 
Sutton, AJ, Jones, DR, Abrams, KR, et al. Methods for meta-analysis in medical research. 2000; John Wiley and Sons. London, UK:.
 
Thompson, SG, Sharp, SJ Explaining heterogeneity in meta-analysis: a comparison of methods.Stat Med1999;18,2693-2708. [PubMed]
 
Sterne, JA, Egger, M, Smith, GD Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis.BMJ2001;323,101-105. [PubMed]
 
Doyle, LA, Szaflarski, N, Modin, GW, et al Identification of patients with acute lung injury: predictors of mortality.Am J Respir Crit Care Med1995;152,1818-1824. [PubMed]
 
Nolan, S, Burgess, K, Hopper, L, et al Acute respiratory distress syndrome in a community hospital ICU.Intensive Care Med1997;23,530-538. [PubMed]
 
De Backer, D, Creteur, J, Zhang, H, et al Lactate production by the lungs in acute lung injury.Am J Respir Crit Care Med1997;156,1099-1104. [PubMed]
 
Ferring, M, Vincent, JL Is outcome from ARDS related to the severity of respiratory failure?Eur Respir J1997;10,1297-1300. [PubMed]
 
Lewandowski, K, Rossaint, R, Pappert, D, et al High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.Intensive Care Med1997;23,819-835. [PubMed]
 
Monchi, M, Bellenfant, F, Cariou, A, et al Early predictive factors of survival in the acute respiratory distress syndrome.Am J Respir Crit Care Med1998;158,1076-1081. [PubMed]
 
Chastre, J, Trouillet, JL, Vuagnat, A, et al Nosocomial pneumonia in patients with acute respiratory distress syndrome.Am J Respir Crit Care Med1998;157,1165-1172. [PubMed]
 
Valta, P, Uusaro, A, Nunes, S, et al Acute respiratory distress syndrome: frequency, clinical course, and costs of care.Crit Care Med1999;27,2367-2374. [PubMed]
 
Manktelow, C, Bigatello, LM, Hess, D, et al Physiologic determinants of the response to inhaled nitric oxide in patients with acute respiratory distress syndrome.Anesthesiology1997;87,297-307. [PubMed]
 
Dellinger, RP, Zimmerman, JL, Taylor, RW, et al Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial.Crit Care Med1998;26,15-23. [PubMed]
 
Gallart, L, Lu, Q, Puybasset, L, et al Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome: the NO Almitrine Study Group.Am J Respir Crit Care Med1998;158,1770-1777. [PubMed]
 
Brochard, L, Roudot-Thoraval, F, Roupie, E, et al Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome: the Multicenter Trail Group on Tidal Volume reduction in ARDS.Am J Respir Crit Care Med1998;158,1831-1838. [PubMed]
 
Roupie, E, Lepage, E, Wysocki, M, et al Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients.Intensive Care Med1999;25,920-929. [PubMed]
 
Lundin, S, Mang, H, Smithies, M, et al Inhalation of nitric oxide in acute lung injury: results of a European multicentre study: the European Study Group of Inhaled Nitric Oxide.Intensive Care Med1999;25,911-919. [PubMed]
 
Vieillard-Baron, A, Girou, E, Valente, E, et al Predictors of mortality in acute respiratory distress syndrome: focus on the role of right heart catheterization.Am J Respir Crit Care Med2000;161,1597-1601. [PubMed]
 
Esteban, A, Alia, I, Gordo, F, et al Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS: for the Spanish Lung Failure Collaborative Group.Chest2000;117,1690-1696. [PubMed]
 
Luhr, OR, Antonsen, K, Karlsson, M, et al Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland: the ARF Study Group.Am J Respir Crit Care Med1999;159,1849-1861. [PubMed]
 
Ullrich, R, Lorber, C, Roder, G, et al Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS.Anesthesiology1999;91,1577-1586. [PubMed]
 
Abraham, E, Baughman, R, Fletcher, E, et al Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome (ARDS): a controlled, randomized, double-blind, multicenter clinical trial.Crit Care Med1999;27,1478-1485. [PubMed]
 
Abel, SJ, Finney, SJ, Brett, SJ, et al Reduced mortality in association with the acute respiratory distress syndrome (ARDS).Thorax1998;53,292-294. [PubMed]
 
Villar, J, Perez-Mendez, L, Kacmarek, RM Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome.Intensive Care Med1999;25,930-935. [PubMed]
 
Gadek, JE, DeMichele, SJ, Karlstad, MD, et al Effect of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome: Enteral Nutrition in ARDS Study Group.Crit Care Med1999;27,1409-1420. [PubMed]
 
The ARDS Network.. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med2000;342,1301-1308. [PubMed]
 
Ferguson, ND, Frutos-Vivar, F, Esteban, A, et al Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome.Crit Care Med2005;33,21-30. [PubMed]
 
Markowicz, P, Wolff, M, Djedaini, K, et al Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome: incidence, prognosis, and risk factors; ARDS Study Group.Am J Respir Crit Care Med2000;161,1942-1948. [PubMed]
 
Rocco, TR, Jr, Reinert, SE, Cioffi, W, et al A 9-year, single-institution, retrospective review of death rate and prognostic factors in adult respiratory distress syndrome.Ann Surg2001;233,414-422. [PubMed]
 
Ware, LB, Conner, ER, Matthay, MA von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury.Crit Care Med2001;29,2325-2331. [PubMed]
 
Esteban, A, Anzueto, A, Frutos, F, et al Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study.JAMA2002;287,345-355. [PubMed]
 
Matthay, MA, Ware, LB Plasma protein C levels in patients with acute lung injury: prognostic significance.Crit Care Med2004;32,S229-S232. [PubMed]
 
Brun-Buisson, C, Minelli, C, Bertolini, G, et al Epidemiology and outcome of acute lung injury in European intensive care units: results from the ALIVE study.Intensive Care Med2004;30,51-61. [PubMed]
 
Gattinoni, L, Tognoni, G, Pesenti, A, et al Effect of prone positioning on the survival of patients with acute respiratory failure.N Engl J Med2001;345,568-573. [PubMed]
 
Papazian, L, Paladini, MH, Bregeon, F, et al Is a short trial of prone positioning sufficient to predict the improvement in oxygenation in patients with acute respiratory distress syndrome?Intensive Care Med2001;27,1044-1049. [PubMed]
 
Vincent, JL, Brase, R, Dhainaut, JF, et al A multicenter, double blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.Intensive Care Med2001;27,1578-1583. [PubMed]
 
The ARDS Network.. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.JAMA2000;283,1995-2002. [PubMed]
 
Albertine, KH, Soulier, MF, Wang, Z, et al Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome.Am J Pathol2002;161,1783-1796. [PubMed]
 
Bersten, AD, Edibam, C, Hunt, T, et al Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States.Am J Respir Crit Care Med2002;165,443-448. [PubMed]
 
Taylor, RW, Zimmerman, JL, Dellinger, RP, et al Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial.JAMA2004;291,1603-1609. [PubMed]
 
Derdak, S, Mehta, S, Stewart, TE, et al High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial.Am J Respir Crit Care Med2002;166,801-808. [PubMed]
 
Nuckton, TJ, Alonso, JA, Kallet, RH, et al Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.N Engl J Med2002;346,1281-1286. [PubMed]
 
Fialkow, L, Vieira, SR, Fernandes, AK, et al Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil: an epidemiological study using the American-European Consensus Criteria.Intensive Care Med2002;28,1644-1648. [PubMed]
 
Estenssoro, E, Dubin, A, Laffaire, E, et al Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome.Crit Care Med2002;30,2450-2456. [PubMed]
 
Spragg, RG, Lewis, JF, Walmrath, HD, et al Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.N Engl J Med2004;351,884-892. [PubMed]
 
Kacmarek, RM, Wiedemann, HP, Lavin, PT, et al Partial liquid ventilation in adult patients with acute respiratory distress syndrome.Am J Respir Crit Care Med2006;173,882-889. [PubMed]
 
Villar, J, Kacmarek, RM, Perez-Mendez, L, et al A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.Crit Care Med2006;34,1311-1318. [PubMed]
 
O'Brien, JM, Jr, Phillips, GS, Ali, NA, et al Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury.Crit Care Med2006;34,738-744. [PubMed]
 
Ishizaka, A, Matsuda, T, Albertine, KH, et al Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome.Am J Physiol Lung Cell Mol Physiol2004;286,L1088-L1094. [PubMed]
 
David, M, Weiler, N, Heinrichs, W, et al High-frequency oscillatory ventilation in adult acute respiratory distress syndrome.Intensive Care Med2003;29,1656-1665. [PubMed]
 
Weinert, CR, Gross, CR, Marinelli, WA Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals.Am J Respir Crit Care Med2003;167,1304-1309. [PubMed]
 
Manzano, F, Yuste, E, Colmenero, M, et al Incidence of acute respiratory distress syndrome and its relation to age.J Crit Care2005;20,274-280. [PubMed]
 
Richard, C, Warszawski, J, Anguel, N, et al Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial.JAMA2003;290,2713-2720. [PubMed]
 
Venet, C, Guyomarc'h, S, Pingat, J, et al Prognostic factors in acute respiratory distress syndrome: a retrospective multivariate analysis including prone positioning in management strategy.Intensive Care Med2003;29,1435-1441. [PubMed]
 
Frenckner, B, Palmer, P, Linden, V Extracorporeal respiratory support and minimally invasive ventilation in severe ARDS.Minerva Anestesiol2002;68,381-386. [PubMed]
 
Lu, Y, Song, Z, Zhou, X, et al A 12-month clinical survey of incidence and outcome of acute respiratory distress syndrome in Shanghai intensive care units.Intensive Care Med2004;30,2197-2203. [PubMed]
 
Brower, RG, Lanken, PN, Macintyre, N, et al Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.N Engl J Med2004;351,327-336. [PubMed]
 
Ferguson, ND, Kacmarek, RM, Chiche, JD, et al Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial.Intensive Care Med2004;30,1111-1116. [PubMed]
 
Gong, MN, Thompson, BT, Williams, P, et al Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion.Crit Care Med2005;33,1191-1198. [PubMed]
 
Sakr, Y, Vincent, JL, Reinhart, K, et al High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury.Chest2005;128,3098-3108. [PubMed]
 
Schmidt, R, Luboeinski, T, Markart, P, et al Alveolar antioxidant status in patients with acute respiratory distress syndrome.Eur Respir J2004;24,994-999. [PubMed]
 
Gando, S, Kameue, T, Matsuda, N, et al Systemic inflammation and disseminated intravascular coagulation in early stage of ALI and ARDS: role of neutrophil and endothelial activation.Inflammation2004;28,237-244. [PubMed]
 
Zeiher, BG, Artigas, A, Vincent, JL, et al Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.Crit Care Med2004;32,1695-1702. [PubMed]
 
Salari, P, Mojtahedzadeh, M, Najafi, A, et al Comparison of the effect of aminophylline and low PEEP vs high PEEP on EGF concentration in critically ill patients with ALI/ARDS.J Clin Pharm Ther2005;30,139-144. [PubMed]
 
Ware, LB, Kaner, RJ, Crystal, RG, et al VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema.Eur Respir J2005;26,101-105. [PubMed]
 
Vieira, SR, Nieszkowska, A, Lu, Q, et al Low spatial resolution computed tomography underestimates lung overinflation resulting from positive pressure ventilation.Crit Care Med2005;33,741-749. [PubMed]
 
Wheeler, AP, Bernard, GR, Thompson, BT, et al Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.N Engl J Med2006;354,2213-2224. [PubMed]
 
Gattinoni, L, Caironi, P, Cressoni, M, et al Lung recruitment in patients with the acute respiratory distress syndrome.N Engl J Med2006;354,1775-1786. [PubMed]
 
Wiedemann, HP, Wheeler, AP, Bernard, GR, et al Comparison of two fluid-management strategies in acute lung injury.N Engl J Med2006;354,2564-2575. [PubMed]
 
Milberg, JA, Davis, DR, Steinberg, KP, et al Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983–1993.JAMA1995;273,306-309. [PubMed]
 
Suchyta, MR, Orme, JF, Jr, Morris, AH The changing face of organ failure in ARDS.Chest2003;124,1871-1879. [PubMed]
 
Ciesla, DJ, Moore, EE, Johnson, JL, et al Decreased progression of postinjury lung dysfunction to the acute respiratory distress syndrome and multiple organ failure.Surgery2006;140,640-647. [PubMed]
 
Suchyta, MR, Clemmer, TP, Elliot, CG, et al The adult respiratory distress syndrome: a report of survival and modifying factors.Chest1992;101,1074-1079. [PubMed]
 
Ware, LB Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design.Crit Care Med2005;33,S217-S222. [PubMed]
 
Wood, KA, Huang, D, Angus, DC Improving clinical trial design in acute lung injury.Crit Care Med2003;31,S305-S311. [PubMed]
 
Rice, P, Bernard, GR Acute lung injury and the acute respiratory distress syndrome: challenges in clinical trial design.Clin Chest Med2006;27,733-754. [PubMed]
 
Ferguson, ND, Frutos-Vivar, F, Esteban, A, et al Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions.Crit Care Med2005;33,2228-2234. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Variation in overall pooled mortality rates over time in the 72 ALI/ARDS studies.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. The Selected Studies
Table Graphic Jump Location
Table 1A. Continued
Table Graphic Jump Location
Table 2. Overall and Selected Mortality Rates in Metaregression Analysis
* 

p < 0.001 for the heterogeneity test.

Table Graphic Jump Location
Table 3. Slope Values for Overall and Specific Mortality Outcomes
* 

Metaregression analysis using the logit outcome.

References

Ashbaugh, DG, Bigelow, DB, Petty, TL, et al (1967) Acute respiratory distress in adults.Lancet2,319-323. [PubMed]
 
Rubenfeld, GD, Caldwell, E, Peabody, E, et al Incidence and outcomes of acute lung injury.N Engl J Med2005;353,1685-1693. [PubMed] [CrossRef]
 
Krafft, P, Fridrich, P, Pernerstorfer, T, et al The acute respiratory distress syndrome: definitions, severity and clinical outcome: an analysis of 101 clinical investigations.Intensive Care Med1996;22,519-529. [PubMed]
 
Bernard, GR Acute respiratory distress syndrome: a historical perspective.Am J Respir Crit Care Med2005;172,798-806. [PubMed]
 
Rubenfeld, GD, Herridge, MS Epidemiology and outcomes of acute lung injury.Chest2007;131,554-562. [PubMed]
 
Jardin, F, Fellahi, JL, Beauchet, A, et al Improved prognosis of acute respiratory distress syndrome 15 years on.Intensive Care Med1999;25,936-941. [PubMed]
 
Stapleton, RD, Wang, BM, Hudson, LD, et al Causes and timing of death in patients with ARDS.Chest2005;128,525-532. [PubMed]
 
Kallet, RH, Jasmer, RM, Pittet, JF, et al Clinical implementation of the ARDS network protocol is associated with reduced hospital mortality compared with historical controls.Crit Care Med2005;33,925-929. [PubMed]
 
Mancebo, J, Fernandez, R, Blanch, L, et al A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome.Am J Respir Crit Care Med2006;173,1233-1239. [PubMed]
 
Singer, P, Theilla, M, Fisher, H, et al Benefit of an enteral diet enriched with eicosapentaenoic acid and γ-linolenic acid in ventilated patients with acute lung injury.Crit Care Med2006;34,1033-1038. [PubMed]
 
Bernard, GR, Artigas, A, Brigham, KL, et al The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med1994;149,818-824. [PubMed]
 
Petty, TL, Ashbaugh, DG The adult respiratory distress syndrome: clinical features, factors influencing prognosis and principles of management.Chest1971;60,233-239. [PubMed]
 
Montgomery, BA, Stager, MA, Carrico, J, et al Causes of mortality in patients with the adult respiratory distress syndrome.Am Rev Respir Dis1985;132,485-491. [PubMed]
 
Zilberberg, MD, Epstein, SK Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and hospital outcome.Am J Respir Crit Care Med1998;157,1159-1164. [PubMed]
 
Shander, A, Popovsky, MA Understanding the consequences of transfusion-related acute lung injury.Chest2005;128,598S-604S. [PubMed]
 
Stroup, DF, Berlin, JA, Morton, SC, et al Meta-analysis of observational studies in epidemiology: a proposal for reporting: Meta-analysis of Observational Studies in Epidemiology (MOOSE) group.JAMA2000;283,2008-2012. [PubMed]
 
Sutton, AJ, Jones, DR, Abrams, KR, et al. Methods for meta-analysis in medical research. 2000; John Wiley and Sons. London, UK:.
 
Thompson, SG, Sharp, SJ Explaining heterogeneity in meta-analysis: a comparison of methods.Stat Med1999;18,2693-2708. [PubMed]
 
Sterne, JA, Egger, M, Smith, GD Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis.BMJ2001;323,101-105. [PubMed]
 
Doyle, LA, Szaflarski, N, Modin, GW, et al Identification of patients with acute lung injury: predictors of mortality.Am J Respir Crit Care Med1995;152,1818-1824. [PubMed]
 
Nolan, S, Burgess, K, Hopper, L, et al Acute respiratory distress syndrome in a community hospital ICU.Intensive Care Med1997;23,530-538. [PubMed]
 
De Backer, D, Creteur, J, Zhang, H, et al Lactate production by the lungs in acute lung injury.Am J Respir Crit Care Med1997;156,1099-1104. [PubMed]
 
Ferring, M, Vincent, JL Is outcome from ARDS related to the severity of respiratory failure?Eur Respir J1997;10,1297-1300. [PubMed]
 
Lewandowski, K, Rossaint, R, Pappert, D, et al High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.Intensive Care Med1997;23,819-835. [PubMed]
 
Monchi, M, Bellenfant, F, Cariou, A, et al Early predictive factors of survival in the acute respiratory distress syndrome.Am J Respir Crit Care Med1998;158,1076-1081. [PubMed]
 
Chastre, J, Trouillet, JL, Vuagnat, A, et al Nosocomial pneumonia in patients with acute respiratory distress syndrome.Am J Respir Crit Care Med1998;157,1165-1172. [PubMed]
 
Valta, P, Uusaro, A, Nunes, S, et al Acute respiratory distress syndrome: frequency, clinical course, and costs of care.Crit Care Med1999;27,2367-2374. [PubMed]
 
Manktelow, C, Bigatello, LM, Hess, D, et al Physiologic determinants of the response to inhaled nitric oxide in patients with acute respiratory distress syndrome.Anesthesiology1997;87,297-307. [PubMed]
 
Dellinger, RP, Zimmerman, JL, Taylor, RW, et al Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial.Crit Care Med1998;26,15-23. [PubMed]
 
Gallart, L, Lu, Q, Puybasset, L, et al Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome: the NO Almitrine Study Group.Am J Respir Crit Care Med1998;158,1770-1777. [PubMed]
 
Brochard, L, Roudot-Thoraval, F, Roupie, E, et al Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome: the Multicenter Trail Group on Tidal Volume reduction in ARDS.Am J Respir Crit Care Med1998;158,1831-1838. [PubMed]
 
Roupie, E, Lepage, E, Wysocki, M, et al Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients.Intensive Care Med1999;25,920-929. [PubMed]
 
Lundin, S, Mang, H, Smithies, M, et al Inhalation of nitric oxide in acute lung injury: results of a European multicentre study: the European Study Group of Inhaled Nitric Oxide.Intensive Care Med1999;25,911-919. [PubMed]
 
Vieillard-Baron, A, Girou, E, Valente, E, et al Predictors of mortality in acute respiratory distress syndrome: focus on the role of right heart catheterization.Am J Respir Crit Care Med2000;161,1597-1601. [PubMed]
 
Esteban, A, Alia, I, Gordo, F, et al Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS: for the Spanish Lung Failure Collaborative Group.Chest2000;117,1690-1696. [PubMed]
 
Luhr, OR, Antonsen, K, Karlsson, M, et al Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland: the ARF Study Group.Am J Respir Crit Care Med1999;159,1849-1861. [PubMed]
 
Ullrich, R, Lorber, C, Roder, G, et al Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS.Anesthesiology1999;91,1577-1586. [PubMed]
 
Abraham, E, Baughman, R, Fletcher, E, et al Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome (ARDS): a controlled, randomized, double-blind, multicenter clinical trial.Crit Care Med1999;27,1478-1485. [PubMed]
 
Abel, SJ, Finney, SJ, Brett, SJ, et al Reduced mortality in association with the acute respiratory distress syndrome (ARDS).Thorax1998;53,292-294. [PubMed]
 
Villar, J, Perez-Mendez, L, Kacmarek, RM Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome.Intensive Care Med1999;25,930-935. [PubMed]
 
Gadek, JE, DeMichele, SJ, Karlstad, MD, et al Effect of enteral feeding with eicosapentaenoic acid, γ-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome: Enteral Nutrition in ARDS Study Group.Crit Care Med1999;27,1409-1420. [PubMed]
 
The ARDS Network.. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med2000;342,1301-1308. [PubMed]
 
Ferguson, ND, Frutos-Vivar, F, Esteban, A, et al Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome.Crit Care Med2005;33,21-30. [PubMed]
 
Markowicz, P, Wolff, M, Djedaini, K, et al Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome: incidence, prognosis, and risk factors; ARDS Study Group.Am J Respir Crit Care Med2000;161,1942-1948. [PubMed]
 
Rocco, TR, Jr, Reinert, SE, Cioffi, W, et al A 9-year, single-institution, retrospective review of death rate and prognostic factors in adult respiratory distress syndrome.Ann Surg2001;233,414-422. [PubMed]
 
Ware, LB, Conner, ER, Matthay, MA von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury.Crit Care Med2001;29,2325-2331. [PubMed]
 
Esteban, A, Anzueto, A, Frutos, F, et al Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study.JAMA2002;287,345-355. [PubMed]
 
Matthay, MA, Ware, LB Plasma protein C levels in patients with acute lung injury: prognostic significance.Crit Care Med2004;32,S229-S232. [PubMed]
 
Brun-Buisson, C, Minelli, C, Bertolini, G, et al Epidemiology and outcome of acute lung injury in European intensive care units: results from the ALIVE study.Intensive Care Med2004;30,51-61. [PubMed]
 
Gattinoni, L, Tognoni, G, Pesenti, A, et al Effect of prone positioning on the survival of patients with acute respiratory failure.N Engl J Med2001;345,568-573. [PubMed]
 
Papazian, L, Paladini, MH, Bregeon, F, et al Is a short trial of prone positioning sufficient to predict the improvement in oxygenation in patients with acute respiratory distress syndrome?Intensive Care Med2001;27,1044-1049. [PubMed]
 
Vincent, JL, Brase, R, Dhainaut, JF, et al A multicenter, double blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.Intensive Care Med2001;27,1578-1583. [PubMed]
 
The ARDS Network.. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.JAMA2000;283,1995-2002. [PubMed]
 
Albertine, KH, Soulier, MF, Wang, Z, et al Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome.Am J Pathol2002;161,1783-1796. [PubMed]
 
Bersten, AD, Edibam, C, Hunt, T, et al Incidence and mortality of acute lung injury and the acute respiratory distress syndrome in three Australian States.Am J Respir Crit Care Med2002;165,443-448. [PubMed]
 
Taylor, RW, Zimmerman, JL, Dellinger, RP, et al Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial.JAMA2004;291,1603-1609. [PubMed]
 
Derdak, S, Mehta, S, Stewart, TE, et al High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial.Am J Respir Crit Care Med2002;166,801-808. [PubMed]
 
Nuckton, TJ, Alonso, JA, Kallet, RH, et al Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.N Engl J Med2002;346,1281-1286. [PubMed]
 
Fialkow, L, Vieira, SR, Fernandes, AK, et al Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil: an epidemiological study using the American-European Consensus Criteria.Intensive Care Med2002;28,1644-1648. [PubMed]
 
Estenssoro, E, Dubin, A, Laffaire, E, et al Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome.Crit Care Med2002;30,2450-2456. [PubMed]
 
Spragg, RG, Lewis, JF, Walmrath, HD, et al Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.N Engl J Med2004;351,884-892. [PubMed]
 
Kacmarek, RM, Wiedemann, HP, Lavin, PT, et al Partial liquid ventilation in adult patients with acute respiratory distress syndrome.Am J Respir Crit Care Med2006;173,882-889. [PubMed]
 
Villar, J, Kacmarek, RM, Perez-Mendez, L, et al A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.Crit Care Med2006;34,1311-1318. [PubMed]
 
O'Brien, JM, Jr, Phillips, GS, Ali, NA, et al Body mass index is independently associated with hospital mortality in mechanically ventilated adults with acute lung injury.Crit Care Med2006;34,738-744. [PubMed]
 
Ishizaka, A, Matsuda, T, Albertine, KH, et al Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome.Am J Physiol Lung Cell Mol Physiol2004;286,L1088-L1094. [PubMed]
 
David, M, Weiler, N, Heinrichs, W, et al High-frequency oscillatory ventilation in adult acute respiratory distress syndrome.Intensive Care Med2003;29,1656-1665. [PubMed]
 
Weinert, CR, Gross, CR, Marinelli, WA Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals.Am J Respir Crit Care Med2003;167,1304-1309. [PubMed]
 
Manzano, F, Yuste, E, Colmenero, M, et al Incidence of acute respiratory distress syndrome and its relation to age.J Crit Care2005;20,274-280. [PubMed]
 
Richard, C, Warszawski, J, Anguel, N, et al Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial.JAMA2003;290,2713-2720. [PubMed]
 
Venet, C, Guyomarc'h, S, Pingat, J, et al Prognostic factors in acute respiratory distress syndrome: a retrospective multivariate analysis including prone positioning in management strategy.Intensive Care Med2003;29,1435-1441. [PubMed]
 
Frenckner, B, Palmer, P, Linden, V Extracorporeal respiratory support and minimally invasive ventilation in severe ARDS.Minerva Anestesiol2002;68,381-386. [PubMed]
 
Lu, Y, Song, Z, Zhou, X, et al A 12-month clinical survey of incidence and outcome of acute respiratory distress syndrome in Shanghai intensive care units.Intensive Care Med2004;30,2197-2203. [PubMed]
 
Brower, RG, Lanken, PN, Macintyre, N, et al Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.N Engl J Med2004;351,327-336. [PubMed]
 
Ferguson, ND, Kacmarek, RM, Chiche, JD, et al Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial.Intensive Care Med2004;30,1111-1116. [PubMed]
 
Gong, MN, Thompson, BT, Williams, P, et al Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion.Crit Care Med2005;33,1191-1198. [PubMed]
 
Sakr, Y, Vincent, JL, Reinhart, K, et al High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury.Chest2005;128,3098-3108. [PubMed]
 
Schmidt, R, Luboeinski, T, Markart, P, et al Alveolar antioxidant status in patients with acute respiratory distress syndrome.Eur Respir J2004;24,994-999. [PubMed]
 
Gando, S, Kameue, T, Matsuda, N, et al Systemic inflammation and disseminated intravascular coagulation in early stage of ALI and ARDS: role of neutrophil and endothelial activation.Inflammation2004;28,237-244. [PubMed]
 
Zeiher, BG, Artigas, A, Vincent, JL, et al Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.Crit Care Med2004;32,1695-1702. [PubMed]
 
Salari, P, Mojtahedzadeh, M, Najafi, A, et al Comparison of the effect of aminophylline and low PEEP vs high PEEP on EGF concentration in critically ill patients with ALI/ARDS.J Clin Pharm Ther2005;30,139-144. [PubMed]
 
Ware, LB, Kaner, RJ, Crystal, RG, et al VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema.Eur Respir J2005;26,101-105. [PubMed]
 
Vieira, SR, Nieszkowska, A, Lu, Q, et al Low spatial resolution computed tomography underestimates lung overinflation resulting from positive pressure ventilation.Crit Care Med2005;33,741-749. [PubMed]
 
Wheeler, AP, Bernard, GR, Thompson, BT, et al Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.N Engl J Med2006;354,2213-2224. [PubMed]
 
Gattinoni, L, Caironi, P, Cressoni, M, et al Lung recruitment in patients with the acute respiratory distress syndrome.N Engl J Med2006;354,1775-1786. [PubMed]
 
Wiedemann, HP, Wheeler, AP, Bernard, GR, et al Comparison of two fluid-management strategies in acute lung injury.N Engl J Med2006;354,2564-2575. [PubMed]
 
Milberg, JA, Davis, DR, Steinberg, KP, et al Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983–1993.JAMA1995;273,306-309. [PubMed]
 
Suchyta, MR, Orme, JF, Jr, Morris, AH The changing face of organ failure in ARDS.Chest2003;124,1871-1879. [PubMed]
 
Ciesla, DJ, Moore, EE, Johnson, JL, et al Decreased progression of postinjury lung dysfunction to the acute respiratory distress syndrome and multiple organ failure.Surgery2006;140,640-647. [PubMed]
 
Suchyta, MR, Clemmer, TP, Elliot, CG, et al The adult respiratory distress syndrome: a report of survival and modifying factors.Chest1992;101,1074-1079. [PubMed]
 
Ware, LB Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design.Crit Care Med2005;33,S217-S222. [PubMed]
 
Wood, KA, Huang, D, Angus, DC Improving clinical trial design in acute lung injury.Crit Care Med2003;31,S305-S311. [PubMed]
 
Rice, P, Bernard, GR Acute lung injury and the acute respiratory distress syndrome: challenges in clinical trial design.Clin Chest Med2006;27,733-754. [PubMed]
 
Ferguson, ND, Frutos-Vivar, F, Esteban, A, et al Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions.Crit Care Med2005;33,2228-2234. [PubMed]
 
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