Acute Respiratory Distress Syndrome Population Research Articles

Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial

PurposeA hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes.Results66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI − 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (− 1.17 ml/kg, 95% CI − 1.87 to − 0.44).ConclusionsIV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials.Trial registrationNCT04794088, registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.

Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. Title/abstract review, full text review, and data extraction using a standardized data collection form. The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID-19 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS-CoV-2 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.

Association between ARDS Etiology and Risk of Noninvasive Ventilation Failure.

Rationale: The etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV). Objectives: To explore the association between ARDS etiology and risk of NIV failure. Methods: A multicenter prospective observational study was performed in 17 intensive care units in China from September 2017 to December 2019. Patients with ARDS who used NIV as a first-line therapy were enrolled. The etiology of ARDS was recorded at study entry. Results: A total of 306 patients were enrolled. Of the patients, 146 were classified as having pulmonary ARDS (ARDSp) and 160 were classified as having extrapulmonary ARDS (ARDSexp). From initiation to 24 hours of NIV, the respiratory rate, heart rate, arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), and arterial carbon dioxide pressure improved slower in patients with ARDSp than those with ARDSexp. Patients with ARDSp experienced more NIV failure (55% vs. 28%; P < 0.01) and higher 28-day mortality (47% vs. 14%; P < 0.01). The adjusted odds ratios of NIV failure and 28-day mortality were 5.47 (95% confidence interval [CI], 3.04-9.86) and 10.13 (95% CI, 5.01-20.46), respectively. In addition, we combined the presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 h of NIV to develop a risk score of NIV failure. With the increase of the risk score, the rate of NIV failure increased. The area under the curve of the receiver operating characteristic was 0.84 (95% CI, 0.79-0.89) and 0.81 (0.69-0.92) in the training and validation cohorts, respectively. Using 5.5 as cutoff value to predict NIV failure, the sensitivity and specificity was good. Conclusions: Among patients with ARDS who used NIV as a first-line therapy, ARDSp was associated with slower improvement, more NIV failure, and higher 28-day mortality than ARDSexp. The risk score combined presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 hours of NIV has high accuracy to predict NIV failure among ARDS population.

Outcomes of acute respiratory distress syndrome in COVID-19 patients compared to the general population: a systematic review and meta-analysis

ABSTRACT Introduction Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) often leads to mortality. Outcomes of patients with COVID-19-related ARDS compared to ARDS unrelated to COVID-19 is not well characterized. Areas covered We performed a systematic review of PubMed, Scopus, and MedRxiv 11/1/2019 to 3/1/2021, including studies comparing outcomes in COVID-19-related ARDS (COVID-19 group) and ARDS unrelated to COVID-19 (ARDS group). Outcomes investigated were duration of mechanical ventilation-free days, intensive care unit (ICU) length-of-stay (LOS), hospital LOS, and mortality. Random effects models were fit for each outcome measure. Effect sizes were reported as pooled median differences of medians (MDMs), mean differences (MDs), or odds ratios (ORs). Expert opinion Ten studies with 2,281 patients met inclusion criteria (COVID-19: 861 [37.7%], ARDS: 1420 [62.3%]). There were no significant differences between the COVID-19 and ARDS groups for median number of mechanical ventilator-free days (MDM: −7.0 [95% CI: −14.8; 0.7], p = 0.075), ICU LOS (MD: 3.1 [95% CI: −5.9; 12.1], p = 0.501), hospital LOS (MD: 2.5 [95% CI: −5.6; 10.7], p = 0.542), or all-cause mortality (OR: 1.25 [95% CI: 0.78; 1.99], p = 0.361). Compared to the general ARDS population, results did not suggest worse outcomes in COVID-19-related ARDS.

Abstract 17183: Severity of Myocardial Injury in COVID-19 Hospitalized Patients

Introduction: Myocardial injury in COVID19 is reported as high as 30% and associated with worsened prognosis (Cooper et al., Circulation). Along with elevated cardiac biomarkers, elevated inflammatory markers of cytokine storm and hemophagocytic lymphohistiocytosis (HLH) are associated with increased illness severity and mortality. Our study aimed to identify patients at highest risk for myocardial injury and subsequent cardiac decompensation. Methods: 279 consecutive patients with COVID19 from a major metropolitan academic center, discharged from 3-21-2020 to 5-17-2020, were analyzed. Primary data includes age, sex, race, and peak troponin I during hospitalization. Patients were further stratified to evaluate severe cases with acute respiratory distress syndrome (ARDS) requiring intubation (n=40), and peak levels of CRP, ferritin, and D-dimer were collected. Bivariate and multivariate measures of association between peak inflammatory marker and troponin I levels were estimated. Results: Average age of ARDS population patients was 61 +/- 15 years; 50% male and 50% female. Self-identified African Americans(AA) were 35%, Hispanic/Latinos(H/L) were 55%, and Others including two White Americans were 10%. Average peak troponin I in H/L was remarkably higher 0.51 +/-1.16 compared to AA 0.18 +/- 0.23 and Others 0.13 +/- 0.16. Per multivariate regression analysis, D-dimer had the most significant effect on the elevated troponin (p=0.027). Although weakly significant, H/L showed elevated troponin (p =0.09) compared to non-H/L. Conclusion: Elevated D-dimer is associated with increased morbidity in COVID19, and also correlates with elevated troponin concerning for increased myocardial injury. Furthermore, the H/L population may be at greater risk for developing myocardial injury and have more injury as shown by higher troponin I levels. Larger studies may better assess the relation between inflammatory markers such as CRP and ferritin and myocardial injury. Our study provides evidence of systemic inflammation contributing to significant myocardial injury in COVID19, especially in the H/L population. Identifying patients at highest risk for myocardial injury early may allow for more effective medical interventions and improved outcomes.

A Pilot Study of Patients With COVID–19-Related Respiratory Failure Utilizing Airway Pressure Release Ventilation (APRV)

ABSTRACT Background Pneumonia leading to acute respiratory distress syndrome (ARDS) is one of the devastating consequences of coronavirus disease 2019 (COVID-19). Airway pressure release ventilation (APRV) has been described as beneficial in acute lung injury and ARDS. We hypothesized that utilizing APRV would be advantageous in the COVID-19 ARDS population. Methods Prospective, observational, single-center study. Data were extracted on demographics, vasopressors, sedatives, analgesics, and oxygenation (PaO2/FiO2). A generalized linear mixed models analysis was performed to compare low tidal volume ventilation (LTV) with APRV for patients who required intubation due to ARDS from COVID-19 and who were managed with at least 48 consecutive hours of APRV in our surgical intensive care unit (SICU). Results Twelve patients met criteria; two were on APRV mode from admission to the SICU and were not included in the study. Ten patients were analyzed and were primarily male (70%), average age of 64.5 ± 12.9 years, and 70% were obese (average body mass index of 30.6 ± 8.0 kg/m2). There were no smokers in the sample, but two patients presented with underlying lung pathology. APRV was shown to significantly increase the PaO2/FiO2 ratio by 30% (5% to 61%) (p = 0.05) and was associated with up to a 12% (−26% to 5%) reduction in the level of FiO2 and reduction in the use of vasopressor support (−59% [−83% to −2%]), sedatives (−15% [−29% to 2%]), and analgesics (−16% [−38% to 12%]). Conclusions This pilot study showed that APRV was associated with decreases in FiO2, vasopressors, sedatives, and analgesic requirements with an increase in PaO2/FiO2 ratio. In the current pandemic, where providers are grappling with ways to manage COVID-19 ARDS, APRV may be the optimal ventilator mode. Prospective randomized studies are required to validate whether use of APRV in the COVID-19 population leads to improved oxygenation and a subsequent decrease of ventilator days and length of stay.

Predictors of Cisatracurium Continuous Infusion Dose in Acute Respiratory Distress Syndrome

Neuromuscular blockade (NMB) with cisatracurium may improve outcomes in the acute respiratory distress syndrome (ARDS) population; however, optimal dosing strategy remains unknown. Factors affecting pharmacokinetics and pharmacodynamics of cisatracurium may impact the dose required to achieve adequate train-of-four (TOF) response. The aims of this study were to determine cisatracurium dose requirements in a critically ill ARDS population and to identify clinical factors that affect dosing. This was a single-center, retrospective cohort study of medical intensive care patients who received cisatracurium infusion for treatment of ARDS. “Stable dose” was defined as the infusion rate producing 2 consecutive TOFs of 1/4 to 2/4. Factors examined for association with dose were temperature, pH, age, and the presence of acute kidney injury (AKI). The analysis included 39 patients. The median stable dose of cisatracurium was 2.8 (2.0, 3.1) μg/kg/min. Multivariable linear regression model for weight-normalized dose identified AKI as a factor independently associated with steady-state dose requirements (% change −31.4, 95% confidence interval [CI]: −51.9, −2.3). Our study provides information on cisatracurium doses required in patients with ARDS to reduce time required to reach goal TOF. Further studies are needed to determine effect of AKI on cisatracurium dose requirements and clinical outcomes.

DNA methylation exploration for ARDS: a multi-omics and multi-microarray interrelated analysis

BackgroundDespite advances in clinical management, there are currently no novel therapeutic targets for acute respiratory distress syndrome (ARDS). DNA methylation, as a reversible process involved in the development and progression of many diseases, would be used as potential therapeutic targets to improve the treatment strategies of ARDS. However, the meaningful DNA methylation sites associated with ARDS still remain largely unknown. We sought to determine the difference in DNA methylation between ARDS patients and healthy participants, and simultaneously, the feasible DNA methylation markers for potential therapeutic targets were also explored.MethodsMicroarray data of human blood samples for ARDS and healthy participants up to June 2019 was searched in GEO database. The difference analyses between ARDS and healthy population were performed through limma R package, and furthermore, interrelated analyses of DNA methylation and transcript were accomplished by VennDiagram R package. Perl and sva R package were used to merge microarray data and decrease heterogeneities among different studies. The biological function of screened methylation sites and their regulating genes were annotated according to UniProt database and Pubmed database. GO term and KEGG pathway enrichment analyses were conducted using DAVID 6.8 and KOBAS 3.0. The meaningful DNA methylation markers to distinguish ARDS from healthy controls were explored through ROC (receiver operating characteristic curves) analyses.ResultsFive datasets in GEO databases (one DNA methylation dataset, three mRNA datasets, and one mRNA dataset of healthy people) were enrolled in present analyses finally, and the series were GSE32707, GSE66890, GSE10474, GSE61672, and GSE67530. These databases included 99 patients with ARDS (within 48 h of onset) and 136 healthy participants. Difference analyses indicated 44,439 DNA methylation alterations and 29 difference mRNAs between ARDS and healthy controls. 40 methylation variations regulated transcription of 16 genes was explored via interrelated analysis. According to the functional annotations, 30 DNA methylation sites were related to the imbalance of inflammation or immunity, endothelial function, epithelial function and/or coagulation function. cg03341377, cg24310395, cg07830557 and cg08418670, with AUC up to 0.99, might be the meaningful characteristics with the highest performance to distinguish ARDS from healthy controls.Conclusions44,439 DNA methylation alterations and 29 difference mRNAs exist between ARDS and healthy controls. 30 DNA methylation sites may regulate transcription of 10 genes, which take part in pathogenesis of ARDS. These findings could be intervention targets, with validation experiments to be warranted to assess these further.

Patient-specific optimization of mechanical ventilation for patients with acute respiratory distress syndrome using quasi-static pulmonary P-V data.

Quasi-static, pulmonary pressure-volume (P-V) curves were combined with a respiratory system model to analyze tidal pressure cycles, simulating mechanical ventilation of patients with acute respiratory distress syndrome (ARDS). Two important quantities including 1) tidal recruited volume and 2) tidal hyperinflated volume were analytically computed by integrating the distribution of alveolar elements over the affected pop-open pressure range. We analytically predicted the tidal recruited volume of four canine subjects and compared our results with similar experimental measurements on canine models for the validation. We then applied our mathematical model to the P-V data of ARDS populations in four stages of Early ARDS, Deep Knee, Advanced ARDS and Baby Lung to quantify the tidal recruited volume and tidal hyperinflated volume as an indicator of ventilator-induced lung injury (VILI). These quantitative predictions based on patient-specific P-V data suggest that the optimum parameters of mechanical ventilation including PEEP and Tidal Pressure (Volume) are largely varying among ARDS population and are primarily influenced by the degree in the severity of ARDS.

Imaging in acute respiratory distress syndrome.

Imaging has become increasingly important across medical specialties for diagnostic, monitoring, and investigative purposes in acute respiratory distress syndrome (ARDS). This review addresses the use of imaging techniques for the diagnosis and management of ARDS as well as gaining knowledge about its pathogenesis and pathophysiology. The techniques described in this article are computed tomography, positron emission tomography, and two easily accessible imaging techniques available at the bedside-ultrasound and electrical impedance tomography (EIT). The use of computed tomography has provided new insights into ARDS pathophysiology, demonstrating that ARDS does not homogeneously affect the lung parenchyma and that lung injury severity is widely distributed in the ARDS population. Positron emission tomography is a functional imaging technique whose value resides in adding incremental insights to morphological imaging. It can quantify regional perfusion, ventilation, aeration, lung vascular permeability, edema, and inflammation. Lung ultrasound and EIT are radiation-free, noninvasive tools available at the bedside. Lung ultrasound can provide useful information on ARDS diagnosis when x-rays or CT scan are not available. EIT is a useful tool to monitor lung ventilation and to assess the regional distribution of perfusion. The future of imaging in critical care will probably develop in two main directions: easily accessible imaging techniques that can be used at the bedside and sophisticated imaging methods that will be used to aid in difficult diagnostic cases or to advance our understanding of the pathogenesis and pathophysiology of an array of critical illnesses.

Pattern recognition in ARDS: a crucial first step toward personalised treatment

The development of standardised clinical criteria for diagnosing acute respiratory distress syndrome (ARDS) has led to substantial advances in our understanding of the syndrome's epidemiology and pathogenesis. The current ARDS definition relies on clinical rather than pathological characteristics and is intentionally broad, capturing the extent of the public health impact of ARDS.1 However, even the most strict application of standard criteria results in a heterogeneous ARDS population with easily detectable differences in clinical features and outcomes.

Evaluation of the physiological properties of ventilatory ratio in a computational cardiopulmonary model and its clinical application in an acute respiratory distress syndrome population

BackgroundOwing to complexities of measuring dead space, ventilatory failure is difficult to quantify in critical care. A simple, novel index called ventilatory ratio (VR) can quantify ventilatory efficiency at the bedside. The study objectives were to evaluate physiological properties of VR and examine its clinical applicability in acute respiratory distress syndrome (ARDS) patients. MethodsA validated computational model of cardiopulmonary physiology [Nottingham Physiology Simulator (NPS)] was used to evaluate VR ex vivo in three virtual patients with varying degrees of gas exchange defects. Arterial Pco2 and mixed expired Pco2 were obtained from the simulator while either dead space or CO2 production was altered in isolation. VR and deadspace fraction was calculated using these values. A retrospective analysis of a previously presented prospective ARDS database was then used to evaluate the clinical utility of VR. Basic characteristics of VR and its association with mortality were examined. ResultsThe NPS showed that VR behaved in an intuitive manner as would be predicted by its physiological properties. When CO2 production was constant, there was strong positive correlation between dead space and VR (modified Pearson's r 0.98, P<0.01). The ARDS database had a mean VR of 1.47 (standard deviation 0.58). Non-survivors had a significantly higher VR compared with survivors [1.70 vs 1.34, mean difference 0.35, 95% confidence interval (CI) 0.16–0.56, P<0.01]. VR was an independent predictor of mortality (odds ratio 3.05, CI 1.35–6.91, P<0.01). ConclusionsVR is influenced by dead space and CO2 production. In ARDS, high VR was associated with increased mortality.

Rebuttal from Jeremy R. Beitler, Rolf D. Hubmayr and Atul Malhotra

More than a decade after low tidal volume ventilation for acute respiratory distress syndrome (ARDS) first gained widespread acceptance, it is still unknown how best to manage its effects on minute ventilation. High respiratory rate, or permissive hypercapnia? Limiting respiratory rate has been shown in preclinical models to reduce lung injury even at a constant arterial CO2 tension (; Vaporidi et al. 2008). Curley and colleagues (2013) go one step further, making the case for additional benefit from hypercapnia during low tidal volume ventilation. As we find no great fault with the balanced case put forward by our Canadian colleagues, our rebuttal focuses on challenges in designing more definitive trials. First, how might the independent effects of respiratory rate, and pH each be considered? Tris-hydroxymethyl amino-methane (THAM) buffer might be used to identify the effects of hypercapnia independent of acidaemia. To isolate the effects of respiratory rate from , inspired CO2 could be administered during high respiratory rate to induce hypercapnia to a degree comparable to a low-rate strategy. Optimizing respiratory rate must also consider airflow dynamics since high rates may lead to auto-positive end-expiratory pressure (auto-PEEP). Second, what is the minimum acceptable pH, and how should severe acidaemia be managed? A minimum pH approaching 7.15 was well tolerated haemodynamically in a heterogeneous ARDS population (Carvalho et al. 1997), while other studies specified a pH nadir between 7.05 (Brochard et al. 1998) and 7.30 (Brower et al. 2000) before encouraging intervention. THAM has shown promise as an effective buffer during fixed minute ventilation (Kallet et al. 2000), although further study is warranted before its widespread adoption as a rescue therapy. Finally, how do we ensure the protection of patients at highest risk of harm from hypercapnia? Patients with intracranial hypertension may fare poorly from hypercapnia-induced cerebral vasodilatation, as may patients with pre-existent right ventricular compromise facing hypercapnic pulmonary vasoconstriction (Curley et al. 2010). Similarly, anti-inflammatory effects of hypercapnia may be deleterious in pulmonary or extra-pulmonary sepsis compared to other ARDS precipitants. Moreover, increased sedation or paralysis, with associated risk of iatrogenic injury, may be required during hypercapnia to maintain patient–ventilator synchrony and minimize large swings in transpulmonary pressures from spontaneous breathing efforts (Malhotra & Drazen, 2013). Only with carefully designed studies will the role be defined for optimizing respiratory rate, and pH in individual patients with varying comorbidities and ARDS severity. The range of preclinical findings and heterogeneity of current clinical practice indicate a great need for further research in this area.

Positive end-expiratory pressure

In the last 2 years, several reports have dealt with recruitment/positive end-expiratory pressure (PEEP) selection. Most of them confirm previous results and few add new information. It has been definitely confirmed that opening pressures are different throughout the acute respiratory distress syndrome lung parenchyma, ranging from 5-10 up to 30-40 cmH2O. The highest opening pressures are required to open the most dependent lung regions. It has been found that in 2 s, most of the recruitable lung regions may be open when a proper pressure is applied. The best way to assess recruitment is computed tomography scanning, whereas lung mechanics are a reasonable bedside surrogate. Impedance tomography has been increasingly tested, whereas gas exchange is the less reliable indicator of recruitment. A large outcome study showed that higher PEEP might provide survival benefit in a subgroup of more severe patients as compared with lower PEEP. To set PEEP in each individual patient, the use of the expiratory limb of the pressure-volume curve has been suggested. Setting PEEP according to transpulmonary pressure has a robust physiological background, although it requires confirmatory study. Indiscriminate application of recruitment maneuver in unselected acute respiratory distress syndrome population does not provide benefits. However, in the most severe patients, recruitment maneuver has to be considered and higher PEEP applied. To individualize PEEP, the expiratory phase has to be considered, and the esophageal pressure measurement to compute the transpulmonary pressure should be progressively introduced in clinical practice.

Systemic and bronchoalveolar cytokines as predictors of in-hospital mortality in severe community-acquired pneumonia

Objectives The aim of this study was to determine whether cytokine expression (interleukin [IL]-1 β, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]- α), C-reactive protein, and endotoxins on the first day of intensive care unit (ICU) admission are associated with hospital mortality in severe community-acquired pneumonia (CAP). Design This was a prospective study with bronchoalveolar lavage (BAL) and blood sampling. Setting This study was carried out in a 44-bed medical ICU of a 1700-bed university hospital. Patients Participants included 112 mechanically ventilated patients with severe CAP. Interventions Serum and BAL fluid IL-1 β, IL-6, IL-8, IL-10, TNF- α, C-reactive protein, and endotoxins on the first day of ICU admission were obtained. Measurements and Main Results The concentrations of TNF- α in BALF and IL-6, IL-8, IL-10, and TNF- α in serum were higher in nonsurvivors than in survivor patients with CAP. Of these 112 patients with severe CAP (39%), 44 developed acute respiratory distress syndrome (ARDS); these patients seemed to have higher serum IL-6, IL-8, and IL-10 levels than did the non-ARDS group. Furthermore, in the ARDS population, we found that the endotoxin levels in the BAL fluid were higher in the survival than in the nonsurvival group and BAL fluid concentrations of IL-6, IL-8, and IL-1 β and sera levels of IL-6 and IL-10 were lower in the survival than in the nonsurvival group, and they were associated with a high negative predictive value. Conclusions Serum and BAL fluid levels of the studied cytokines on admission may provide valuable prognostic information for patients with severe CAP.

Effects of different levels of end-expiratory positive pressure on lung recruitment and protection in patients with acute respiratory distress syndrome

It is still controversial as to the implementation of higher positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). This study was conducted to compare the lower and higher PEEP in patients with ARDS ventilated with low tidal volume, to investigate the relationship between the recruited lung volume by higher PEEP and relevant independent variables and to provide a bedside estimate of the percentage of potentially recruitable lung by higher PEEP. Twenty-four patients with ARDS were studied. A lung recruiting maneuver was performed, then each patient was ventilated with PEEP of 8 cmH(2)O for 4 hours and subsequently with PEEP of 16 cmH(2)O for 4 hours. At the end of each PEEP level period, gas exchange, hemodynamic data, lung mechanics, stress index "b" of the dynamic pressure-time curve, intrinsic PEEP and recruited volume by PEEP were measured. Fourteen patients were recruiters whose alveolar recruited volumes induced by PEEP 16 cmH(2)O were (425 +/- 65) ml and 10 patients were non-recruiters. Compared with the PEEP 8 cmH(2)O period, after the application of the PEEP 16 cmH(2)O, the PaO(2)/FiO(2) ratio and static lung compliance both remained unchanged in non-recruiters, whereas they increased significantly in recruiters. Changes in PaO(2)/FiO(2) and static lung compliance after PEEP increase were independently associated with the alveolar recruitment. Analyzing the relationship between recruiting maneuver (RM)-induced change in end-expiratory lung volume and the alveolar recruitment induced by PEEP, we found a notable correlation. The results of this study indicated that the potential for alveolar recruitment might vary among the ARDS population and the higher PEEP levels should be limited to recruiters. Improving in PaO(2)/FiO(2), static lung compliance after PEEP increase and the shape of the pressure-time curve could be helpful for PEEP application.

Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS.

An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one polymorphism (C/T) at nucleotide 1580 [C/T (1580)], within codon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence or absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. When the ARDS population was divided into subgroups, idiopathic (i.e., pneumonia, etc.) or exogenic (i.e., trauma, etc.), significant differences were observed for the C/T (1580), for the idiopathic ARDS group, and the frequency of the C/C genotype was increased in this group. Based on the odds ratio, the C allele may be viewed as a susceptibility factor for ARDS. Although the expression of both C and T alleles occurs in heterozygous individuals, it is currently not known whether these alleles correspond to similar levels of SP-B protein. These data suggest that SP-B or a linked gene contributes to susceptibility to ARDS.