The TNF-α (-238 G/A) polymorphism could protect against development of severe sepsis.

Primary responses in sepsis-mediated inflammation are regulated by pro-inflammatory cytokines. Variations in the cytokine genes might modify their transcription or expression, plasma cytokines levels and response to sepsis. Activation protein-1 (AP-1) and NF-κB regulate cytokines gene expression in sepsis. A total of 90 severely septic and 91 non-infected patients were prospectively studied. IL-1α (-889 C/T), IL-1ß (+3954 C/T), IL-6 (-174 G/C), TNF-α (-238 G/A), TNF-α (-308G/A), IL-8 (-251A/T) and IL-10 (-1082 G/A) SNPs, plasma IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, TNF-α and monocyte chemoattractant protein 1 (MCP-1) levels, and AP-1 and NF-κB gene expression by neutrophils were assessed. A allele carriers of TNF-α (-238 G/A) SNP were less frequent among septic patients. IL-6, IL-8, IL-10, TNF-α and MCP-1 levels were higher, and AP-1 and NF-κB gene expressions lower in septic patients. Sepsis was independently associated with higher fibrinogen, neutrophils counts and IL-8 levels, lower prothrombin, absence of the variant A allele of the TNF-α (-238 G/A) SNP, and haemodynamic failure. Death was independently associated with a higher APACHE II score, higher IL-8 levels, and the diagnosis of sepsis. TNF-a (-238 G/A) SNP could protect against sepsis development. Higher IL-8 levels are predictive of sepsis and mortality.

Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development.

INTRODUCTION: Nitric oxide (NO) influences susceptibility to infection and hemodynamic failure (HF) in sepsis. NOS3 and NOS2 SNPs might modify plasma nitrite/nitrate (NOx) levels, sepsis development, hemodynamics and survival. METHODS: 90 severely septic and 91 non-infected ICU patients were prospectively studied. NOS3 (E298D), NOS3 (-786 T/C), NOS3 (27 bp-VNTR), and NOS2A (exon 22) SNPs and plasma NOx levels were assessed. RESULTS: 21 patients (11.6%) died, 7 with sepsis. TT homozygotes and T allele carriers of NOS3 (E298D) and AG carriers of the NOS2A (exon 22) SNPs were more frequent among septic compared to non-infected ICU patients (p < 0.05). Plasma NOx was higher in septic, especially in septic with hemodynamic failure (HF) or fatal outcome (p < 0.006). Plasma NOx was higher in carriers of the T allele of the NOS3 (E298D) SNP (p = 0.006). Sepsis independently associated with HF, increased NOx, peripheral neutrophils, and fibrinogen levels, decreased prothrombin and the presence of the NOS3 (E298D) and NOS2A (exon 22) SNPs. A low APACHE II score was the only variable associated with sepsis survival. NOx was independently associated with sepsis, HF, decreased neutrophils and higher APACHE. CONCLUSIONS: NOS3 (E298D) and NOS2A (exon 22) SNPs, individually and in combination, and plasma NOx, associated with sepsis development. NOx associated with HF and fatal outcome.

Role of plasma matrix-metalloproteases (MMPs) and their polymorphisms (SNPs) in sepsis development and outcome in ICU patients.

Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs), modulated by different single nucleotide polymorphisms (SNPs), are critical in sepsis development. Ninety ICU severely septic and 91 ICU uninfected patients were prospectively studied. MMP-1 (-1607 1G/2G), MMP-3 (-1612 5A/6A), MMP-8 (-799 C/T), MMP-9 (-1562 C/T), and MMP-13 (-77A/G) SNPs were genotyped. Plasma MMPs (-1, -2, -3, -8, -9, -10, -13) and TIMPs (-1,-2,-4) were measured. AA homozygotes and A allele carriers of MMP-13 (-77 A/G) and 1G2G carriers of the MMP-1 (-1607 1G/2G) SNPs frequencies were different between septic and uninfected patients (p < 0.05), as well as plasma MMP-3, -8, -9 -10 and TIMP-2 levels (p < 0.04). No differences in MMPs levels among MMP-13 or MMP-1 SNPs genotypes carriers were observed. The area under the ROC curve for MMP-8 in the diagnosis of sepsis was 0.87 (95% CI 0.82-0.92), and that of CRP was 0.98 (0.94-0.998), whereas the area of MMP-9 in the detection of non-septic state was 0.73 (0.65-0.80), p < 0.0001 for all curves. Sepsis associated with increased MMP-8 and decreased MMP-9 levels in multivariate analysis (p < 0.0002). We report for the first time an association between MMP-13 and MMP-1 SNPs and sepsis. An independent association of MMP-8 and MMP-9 levels with sepsis was also observed.

Inflammation and matrix remodeling during repair of ventilator-induced lung injury.

High-pressure ventilation triggers different inflammatory and matrix remodeling responses within the lung. Although some of them may cause injury, the involvement of these mediators in repair is largely unknown. To identify mechanisms of repair after ventilator-induced lung injury (VILI), mice were randomly assigned to baseline conditions (no ventilation), injury [90 min of high-pressure ventilation without positive end-expiratory pressure (PEEP)], repair (injury followed by 4 h of low-pressure ventilation with PEEP), and ventilated controls (low-pressure ventilation with PEEP for 90 and 330 min). Histological injury and lung permeability increased during injury, but were partially reverted in the repair group. This was accompanied by a proinflammatory response, together with increases in TNF-α and IFN-γ, which returned to baseline during repair, and a decrease in IL-10. However, macrophage inflammatory protein-2 (MIP-2) and matrix metalloproteinases (MMP)-2 and -9 increased after injury and persisted in being elevated during repair. Mortality in the repair phase was 50%. Survivors showed increased cell proliferation, lower levels of collagen, and higher levels of MIP-2 and MMP-2. Pan-MMP or specific MMP-2 inhibition (but not MIP-2, TNF-α, or IL-4 inhibition) delayed epithelial repair in an in vitro wound model using murine or human alveolar cells cultured in the presence of bronchoalveolar lavage fluid from mice during the repair phase or from patients with acute respiratory distress syndrome, respectively. Similarly, MMP inhibition with doxycycline impaired lung repair after VILI in vivo. In conclusion, VILI can be reverted by normalizing ventilation pressures. An adequate inflammatory response and extracellular matrix remodeling are essential for recovery. MMP-2 could play a key role in epithelial repair after VILI and acute respiratory distress syndrome.

Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury.

Mechanical ventilation is a life-saving therapy that can also damage the lungs. Ventilator-induced lung injury (VILI) promotes inflammation and up-regulates matrix metalloproteinases (MMPs). Among these enzymes, MMP-8 is involved in the onset of inflammation by processing different immune mediators. To clarify the role of MMP-8 in a model of VILI and their relevance as a therapeutic target, we ventilated wild-type and MMP-8-deficient mice with low or high pressures for 2 hours. There were no significant differences after low-pressure ventilation between wild-type and knockout animals. However, lack of MMP-8 results in better gas exchange, decreased lung edema and permeability, and diminished histological injury after high-pressure ventilation. Mmp8(-/-) mice had a different immune response to injurious ventilation, with decreased neutrophilic infiltration, lower levels of IFN-γ and chemokines (LPS-induced CXC chemokine, macrophage inflammatory protein-2), and significant increases in anti-inflammatory cytokines (IL-4, IL-10) in lung tissue and bronchoalveolar lavage fluid. There were no differences in MMP-2, MMP-9, or tissue inhibitor of metalloproteinase-1 between wild-type and knockout mice. These results were confirmed by showing a similar protective effect in wild-type mice treated with a selective MMP-8 inhibitor. We conclude that MMP-8 promotes acute inflammation after ventilation with high pressures, and its short-term inhibition could be a therapeutic goal to limit VILI.

Diagnosing brain death by CT perfusion and multislice CT angiography.

INTRODUCTION: Although the diagnosis of brain death (BD) is usually based on clinical criteria, in sedated patients, ancillary techniques are needed. This study was designed to assess the accuracy of cerebral multislice computed tomographic angiography (CTA) and CT perfusion (CTP) in diagnosing BD. METHODS: Prospective observational study in 27 BD patients. RESULTS: All patients were diagnosed as BD based on clinical and electroencephalogram findings. After BD diagnosis, CTP was performed followed by 64-detector multislice CTA from the aortic arch to the vertex. Images were reconstructed from 0.5 mm sections. In 24 patients, a lack of cerebral blood flow (CBF) was detected by CTP, and CTA revealed luminal narrowing of the internal carotid artery in the neck and absence of anterior and posterior intracranial circulation (sensitivity 89%). CTA detected CBF exclusively in extracranial portions of the internal carotid and vertebral arteries. Two patients with anoxic brain injury and decompressive craniectomy showed CBF in the CTA such that the CTP results were considered false negatives, given BD had been confirmed by clinical and EEG findings, along with evoked potentials. In one clinically BD patient, in whom an alpha rhythm was detected in the electroencephalogram, CBF was only observed in the intracranial internal carotid with no posterior circulation noted. This patient was therefore considered exclusively brain stem dead. CONCLUSIONS: The radiological protocol used shows a high sensitivity and excellent specificity for detecting the cerebral circulatory arrest that accompanies BD. As a rapid, non-invasive, and widely available technique it is a promising alternative to conventional 4-vessel angiography.

Predicting the probability of survival in intensive care unit patients from a small number of variables and training examples.

OBJECTIVE: Survival probability predictions in critically ill patients are mainly used to measure the efficacy of intensive care unit (ICU) treatment. The available models are functions induced from data on thousands of patients. Eventually, some of the variables used for these purposes are not part of the clinical routine, and may not be registered in some patients. In this paper, we propose a new method to build scoring functions able to make reliable predictions, though functions whose induction only requires records from a small set of patients described by a few variables. METHODS: We present a learning method based on the use of support vector machines (SVM), and a detailed study of its prediction performance, in different contexts, of groups of variables defined according to the source of information: monitoring devices, laboratory findings, and demographic and diagnostic features. RESULTS: We employed a data set collected in general ICUs at 10 units of hospitals in Spain, 6 of which include coronary patients, while the other 4 do not treat coronary diseases. The total number of patients considered in our study was 2501, 19.83% of whom did not survive. Using these data, we report a comparison between the SVM method proposed here with other approaches based on logistic regression (LR), including a second-level recalibration of release III of the acute physiology and chronic health evaluation (APACHE, a scoring system commonly used in ICUs) induced from the available data. The SVM method significantly outperforms them all from a statistical point of view. Comparison with the commercial version of APACHE III shows that the SVM scores are slightly better when working with data sets of more than 500 patients. CONCLUSIONS: From a practical point of view, the implications of the research reported here may be helpful to address the construction of cheap and reliable prediction systems in accordance with the peculiarities of ICUs and kinds of patients.

Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study.

INTRODUCTION: Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain. METHODS: We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death. RESULTS: A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, DeltaSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days. CONCLUSIONS: We found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.

Effects of melatonin in an experimental model of ventilator-induced lung injury.

Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has well-documented immunomodulatory effects. We studied the effects of this hormone on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Swiss mice (n = 48). Animals were randomized into three experimental groups: control (not ventilated); low-pressure ventilation [peak inspiratory pressure 15 cmH(2)O, positive end-expiratory pressure (PEEP) 2 cmH(2)O], and high-pressure ventilation (peak inspiratory pressure 25 cmH(2)O, PEEP 0 cmH(2)O). Each group was divided into two subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before the onset of ventilation) and the remaining eight with vehicle. After 2 h of ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio, and histological analysis. Levels of malondialdehyde, glutathione peroxidase, interleukins IL-1beta, IL-6, TNF-alpha, and IL-10, and matrix metalloproteinases 2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti-inflammatory cytokines, and matrix turnover, respectively. Ventilation with high pressures induced severe lung damage and release of TNF-alpha, IL-6, and matrix metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased histological lung injury but significantly increased oxidative stress quantified by malondialdehyde levels. There were no differences in TNF-alpha, IL-1beta, IL-6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels were significantly higher in treated animals. These results suggest that melatonin decreases VILI by increasing the anti-inflammatory response despite an unexpected increase in oxidative stress.

Mechanical ventilation causes monocyte deactivation in intact and endotoxin-treated mice.

BACKGROUND: Monocyte deactivation, defined as the decrease of surface expression of class II molecules of the main histocompatibility complex (MHC) on circulating monocytes, can occur after severe injuries, like trauma, sepsis, or major surgery. We hypothesized that mechanical ventilation could also be a cause. METHODS: Prospective experimental study. Intact and endotoxin-treated (20 mg/kg of intraperitoneal lipopolysaccharide, 4 hours before the experiment) Swiss mice were tracheotomized and ventilated with one of four possible ventilatory settings: control (no ventilation), low pressure (peak pressure 20 cm H2O, positive end-expiratory pressure [PEEP] 4 cm H2O), high pressure (peak pressure 30 cm H2O, PEEP 0 cm H2O), or high pressure plus an intraperitoneal dose of interferon (IFN)-gamma (40,000 units). After 1 hour, an arterial blood sample was obtained, and the right lung removed to measure gas exchange and the lung wet-to-dry weight ratio. Expression of class II MHC molecules was assessed in peripheral monocytes using flow cytometry. RESULTS: High-pressure ventilation was related to a decrease in oxygenation and to an increase in lung wet-to-dry weight ratio. The expression of class II MHC molecules in blood monocytes decreased in the high-pressure group, but not in IFN-gamma-treated mice. The results were similar in both intact and endotoxin-treated mice. CONCLUSIONS: Mechanical ventilation with high pressure and zero PEEP can cause monocyte deactivation. This phenomenon can be avoided by treatment with IFN-gamma.

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury.

Matrix metalloproteinase-9 (MMP-9) is released by neutrophils at the sites of acute inflammation. This enzyme modulates matrix turnover and inflammatory response, and its activity has been found to be increased after ventilator-induced lung injury. To clarify the role of MMP-9, mice lacking this enzyme and their wild-type counterparts were ventilated for 2 h with high- or low-peak inspiratory pressures (25 and 15 cmH2O, respectively). Lung injury was evaluated by gas exchange, respiratory mechanics, wet-to-dry weight ratio, and histological analysis. The activity of MMP-9 and levels of IL-1beta, IL-4, and macrophage inflammatory protein (MIP-2) were measured in lung tissue and bronchoalveolar lavage fluid (BALF). Cell count and myeloperoxidase activity were measured in BALF. There were no differences between wild-type and Mmp9-/- animals after low-pressure ventilation. After high-pressure ventilation, wild-type mice exhibited an increase in MMP-9 in tissue and BALF. Mice lacking MMP-9 developed more severe lung injury than wild-type mice, in terms of impaired oxygenation and lung mechanics, and higher damage in the histological study. These effects correlated with an increase in both cell count and myeloperoxidase activity in the BALF, suggesting an increased neutrophilic influx in response to ventilation. An increase in IL-1beta and IL-4 in the BALF only in knockout mice could be responsible for the differences. There were no differences between genotypes in MMP-2, MMP-8, or tissue inhibitors of metalloproteinases. These results show that MMP-9 protects against ventilator-induced lung injury by decreasing alveolar neutrophilic infiltration, probably by modulation of the cytokine response in the air spaces.

Comparative study of four sigmoid models of pressure-volume curve in acute lung injury.

BACKGROUND: The pressure-volume curve of the respiratory system is a tool to monitor and set mechanical ventilation in acute lung injury. Mathematical models of the static pressure-volume curve of the respiratory system have been proposed to overcome the inter- and intra-observer variability derived from eye-fitting. However, different models have not been compared. METHODS: The goodness-of-fit and the values of derived parameters (upper asymptote, maximum compliance and points of maximum curvature) in four sigmoid models were compared, using pressure-volume data from 30 mechanically ventilated patients during the early phase of acute lung injury. RESULTS: All models showed an excellent goodness-of-fit (R2 always above 0.92). There were significant differences between the models in the parameters derived from the inspiratory limb, but not in those derived from the expiratory limb of the curve. The within-case standard deviations of the pressures at the points of maximum curvature ranged from 2.33 to 6.08 cmH2O. CONCLUSION: There are substantial variabilities in relevant parameters obtained from the four different models of the static pressure-volume curve of the respiratory system.

Therapeutic implications of immunoparalysis in critically ill patients.

In opposite to the classic view of the systemic inflammatory response, there is increasing evidence that, during critical illness, there is a systemic antiinflammatory state intended to avoid the spread of the local proinflammatory response. The resulting immunosuppression increases the risk of nosocomial infections, and has been related to an increase in morbidity and mortality in critically ill patients. Monocytes play a key role in orchestrating the inflammatory response, and a functional impairment of this population is the responsible for these phenomena. The decreased surface expression of class II molecules of the Main Histocompatibility Complex is both a marker of this state and a pathogenetic mechanism, as it decreases the antigen presentation capabilities of the mononuclear phagocytes. There are some therapeutic strategies to overcome this situation. Cytokines like IFNgamma or GM-CSF have been tested in animal models and patients, but there are no conclusive data. Other drugs like Flt3, AS101 or antibodies against IL-10 have been tested only in experimental models. The development of a new framework on the inflammatory response, the need for a consensus in immune monitoring and the development of experimental and clinical trials are required to improve the outcome of severe patients with systemic injuries.

Inspiratory vs. expiratory pressure-volume curves to set end-expiratory pressure in acute lung injury.

OBJECTIVE: To study the effects of two levels of positive end-expiratory pressure (PEEP), 2 cm H(2)O above the lower inflection point of the inspiratory limb and equal to the point of maximum curvature on the expiratory limb of the pressure-volume curve, in gas exchange, respiratory mechanics, and lung aeration. DESIGN AND SETTING: Prospective clinical study in the intensive care unit and computed tomography ward of a university hospital. PATIENTS: Eight patients with early acute lung injury. INTERVENTIONS: Both limbs of the static pressure-volume curve were traced and inflection points calculated using a sigmoid model. During ventilation with a tidal volume of 6 ml/kg we sequentially applied a PEEP 2 cm H(2)O above the inspiratory lower inflection point (15.5+/-3.1 cm H(2)O) and a PEEP equal to the expiratory point of maximum curvature (23.5+/-4.1 cmH(2)O). MEASUREMENTS AND RESULTS: Arterial blood gases, respiratory system compliance and resistance and changes in lung aeration (measured on three computed tomography slices during end-expiratory and end-inspiratory pauses) were measured at each PEEP level. PEEP according to the expiratory point of maximum curvature was related to an improvement in oxygenation, increase in normally aerated, decrease in nonaerated lung volumes, and greater alveolar stability. There was also an increase in PaCO(2), airway pressures, and hyperaerated lung volume. CONCLUSIONS: High PEEP levels according to the point of maximum curvature of the deflation limb of the pressure-volume curve have both benefits and drawbacks.

Tomographic study of the inflection points of the pressure-volume curve in acute lung injury.

The inflection points of the pressure-volume curve have been used for setting mechanical ventilation in patients with acute lung injury. However, the lung status at these points has never been specifically addressed. In 12 patients with early lung injury we traced both limbs of the pressure-volume curve by means of a stepwise change in airway pressure, and a computed tomography (CT) scan slice was obtained for every pressure level. Although aeration (increase in normally aerated lung) and recruitment (decrease in nonaerated lung) were parallel and continuous along the pressure axis during inflation, loss of aeration and derecruitment were only significant at pressures below the point of maximum curvature on the deflation limb of the pressure-volume curve. This point was related to a higher amount of normally aerated tissue and a lower amount of nonaerated tissue when compared with the lower inflection point on both limbs of the curve. Aeration at the inflection points was similar in lung injury from pulmonary or extrapulmonary origin. There were no significant changes in hyperinflated lung tissue. These results support the use of the deflation limb of the pressure-volume curve for positive end-expiratory pressure setting in patients with acute lung injury.

Application of continuous positive airway pressure to trace static pressure-volume curves of the respiratory system.

OBJECTIVE: To evaluate a new technique for pressure-volume curve tracing. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Six anesthetized rats. INTERVENTIONS: Two pressure-volume curves were obtained by means of the super-syringe method (gold standard) and the continuous positive airway pressure (CPAP) method. For the CPAP method, the ventilator was switched to CPAP and the pressure level was raised from 0 to 50 cm H2O in 5 cm H2O steps and then decreased, while we measured lung volume using respiratory inductive plethysmography. Thereafter, lung injury was induced using very high-volume ventilation. Following injury, two further pressure-volume curves were traced. Pressure-volume pairs were fitted to a mathematical model. MEASUREMENTS AND MAIN RESULTS: Pressure-volume curves were equivalent for each method, with intraclass correlation coefficients being higher than.75 for each pressure level measured. Bias and precision for volume values were 0.46 +/- 0.875 mL in basal measurements and 0.31 +/- 0.67 mL in postinjury conditions. Lower and upper inflection points on the inspiratory limb and maximum curvature point on the deflation limb obtained using both methods and measured by regression analysis also were correlated, with intraclass correlation coefficients (95% confidence interval) being.97 (.58,.99),.85 (.55,.95), and.94 (.81,.98) (p <.001 for each one). When inflection points were estimated by observers, the correlation coefficient between methods was.90 (.67,.98) for lower inflection points (p <.001). However, estimations for upper inflection points and maximum curvature point were significantly different. CONCLUSIONS: The CPAP method for tracing pressure-volume curves is equivalent to the super-syringe method. It is easily applicable at the bedside, avoids disconnection from the ventilator, and can be used to obtain both the inspiratory and the deflation limbs of the pressure-volume curve. Use of regression techniques improves determination of inflection points.

Differences in the deflation limb of the pressure-volume curves in acute respiratory distress syndrome from pulmonary and extrapulmonary origin.

OBJECTIVE: To assess the differences in the deflation pressure-volume (PV) curves between acute respiratory distress syndrome from pulmonary (ARDSp) and extrapulmonary (ARDSe) origin. DESIGN: . Prospective study. SETTING: Twenty-bed intensive care unit in an university hospital. PATIENTS: Ten patients within the first 24 h from meeting ARDS criteria, classified as ARDSp or ARDSe in a clinical basis. INTERVENTIONS: A deflation PV curve was recorded by means of decreasing steps of continuous positive airway pressure (CPAP) from 35 to 0 cmH(2)O. RESULTS: The simultaneous recording of pressure at the airway opening (Pao), esophageal pressure (Pes) and volumes (V) allows us to trace the Pao-V, Pes-V and transpulmonary pressure (Ptp)-V curves. These data were fitted to a sigmoid model and ARDSp and ARDSe groups were compared. ARDSp has lower lung compliance and higher chest wall compliance than ARDSe (35.9+/-11.3 vs. 77.2+/-50.6 and 199.6+/-44.4 vs. 125.5+/-16.5 ml/cmH(2)O, respectively, P<0.05). The Pao-V curve in ARDSp is shifted down and right with respect to ARDSe. The Ptp-V curve shows a similar displacement. The Pes-V curve in the ARDSp group is, however, shifted to the left. When relative values (percentage to the maximum volume achieved at 35 cmH(2)O) are considered, these differences persist, but, in the Ptp-V curves, are only significant in the low-pressure range. CONCLUSIONS: Differences between ARDSp and ARDSe PV curves are present all along the pressure axis and are related to differences not only in the Pes-V curve, but also in the Ptp-V curve.