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2.
Expert Rev Respir Med ; : 1-10, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32168460

RESUMO

Introduction: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury common in critically ill patients and characterized by significant morbidity and mortality. It frequently manifests long-lasting effects beyond hospitalization, from cognitive impairment to physical weakness.Areas covered: Several complications of ARDS have been identified in patients after hospital discharge. The authors conducted literature searches to identify observational studies, randomized clinical trials, systematic reviews, and guidelines. A summary of is presented here to outline the sequelae of ARDS and their risk factors with a focus on the limited but growing research into possible therapies. Long term sequelae of ARDS commonly identified in the literature include long-term cognitive impairment, psychological morbidities, neuromuscular weakness, pulmonary dysfunction, and ongoing healthcare utilization with reduced quality of life.Expert opinion: Given the public health significance of long-term complications following ARDS, the development of new therapies for prevention and treatment is of vital importance. Furthering knowledge of the pathophysiology of these impairments will provide a framework to develop new therapeutic targets to fuel future clinical trials in this area of critical care medicine.

3.
Intensive Care Med ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32206845

RESUMO

PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes.

4.
PLoS One ; 15(2): e0228727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012200

RESUMO

Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31968182

RESUMO

RATIONALE: Gender gaps exist in academic leadership positions in critical care. Peer-reviewed publications are crucial to career advancement, yet little is known regarding gender differences in authorship of critical care research. OBJECTIVES: To evaluate gender differences in authorship of critical care literature. METHODS: We used a validated database of author gender to analyze authorship of critical care articles indexed in PubMed between 2008-2018 in 40 frequently-cited journals. High-impact journals were defined as those in the top 5% of all journals. We used mixed-effects logistic regression to evaluate the association of senior author gender with first and middle author gender, and first author gender with journal impact factor. RESULTS: Among 18,483 studies, 30.8% had female first authors and 19.5% had female senior authors. Female authorship rose slightly over the last decade (average annual increase of 0.44% (p<0.01) and 0.51% (p<0.01) for female first and senior authors, respectively). When the senior author was female, the odds of female co-authorship rose substantially (first author aOR1.93, 95%CI:1.71-2.17; middle author aOR1.48, 95%CI:1.29-1.69). Female first authors had higher odds of publishing in lower-impact journals than men (aOR1.30, 95%CI:1.16-1.45). CONCLUSIONS: Women comprise less than one-third of first authors and one-quarter of senior authors of critical care research, with minimal increase over the past decade. When the senior author was female, the odds of female co-authorship rose substantially. However, female first authors tend to publish in lower-impact journals. These findings may help explain the underrepresentation of women in critical care academic leadership positions and identify targets for improvement.

7.
J Crit Care ; 56: 94-99, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31896448

RESUMO

PURPOSE: Delirium is prevalent but with unclear pathogenesis. Neuronal injury repair pathways may be protective. We hypothesized that higher concentrations of neuronal repair biomarkers would be associated with decreased delirium in critically ill patients. MATERIALS AND METHODS: We performed a nested study of hospital survivors within a prospective cohort that enrolled patients within 72 h of respiratory failure or shock. We measured plasma concentrations of ubiquitin carboxyl-terminal-esterase-L1 (UCHL1) and brain-derived neurotrophic factor (BDNF) from blood collected at enrollment. Delirium was assessed twice daily using the CAM-ICU. Multivariable regression was used to examine the associations between biomarkers and delirium prevalence/duration, adjusting for covariates and interactions with age and IL-6 plasma concentration. RESULTS: We included 427 patients with a median age of 59 years (IQR 48-69) and APACHE II score of 25 (IQR 19-30). Higher plasma concentration of UCHL1 on admission was independently associated with lower prevalence of delirium (p = .04) but not associated with duration of delirium (p = .06). BDNF plasma concentration was not associated with prevalence (p = .26) or duration of delirium (p = .36). CONCLUSIONS: During critical illness, higher UCHL1 plasma concentration is associated with lower prevalence of delirium; BDNF plasma concentration is not associated with delirium. Clinical trial number: NCT00392795; https://clinicaltrials.gov/ct2/show/NCT00392795.

8.
Eur Respir J ; 55(1)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31619475

RESUMO

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study.We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF).In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1-1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2-2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2-2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2-2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1-6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort.Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.

10.
Am J Respir Crit Care Med ; 201(1): 47-56, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31487195

RESUMO

Rationale: Acute respiratory distress syndrome (ARDS) lacks known causal biomarkers. Plasma concentrations of sRAGE (soluble receptor for advanced glycation end products) strongly associate with ARDS risk. However, whether plasma sRAGE contributes causally to ARDS remains unknown.Objectives: Evaluate plasma sRAGE as a causal intermediate in ARDS by Mendelian randomization (MR), a statistical method to infer causality using observational data.Methods: We measured early plasma sRAGE in two critically ill populations with sepsis. The cohorts were whole-genome genotyped and phenotyped for ARDS. To select validated genetic instruments for MR, we regressed plasma sRAGE on genome-wide genotypes in both cohorts. The causal effect of plasma sRAGE on ARDS was inferred using the top variants with significant associations in both populations (P < 0.01, R2 > 0.02). We applied the inverse variance-weighted method to obtain consistent estimates of the causal effect of plasma sRAGE on ARDS risk.Measurements and Main Results: There were 393 European and 266 African ancestry patients in the first cohort and 843 European ancestry patients in the second cohort. Plasma sRAGE was strongly associated with ARDS risk in both populations (odds ratio, 1.86; 95% confidence interval [1.54-2.25]; 2.56 [2.14-3.06] per log increase). Using genetic instruments common to both populations, plasma sRAGE had a consistent causal effect on ARDS risk with a ß estimate of 0.50 (95% confidence interval [0.09-0.91] per log increase).Conclusions: Plasma sRAGE is genetically regulated during sepsis, and MR analysis indicates that increased plasma sRAGE leads to increased ARDS risk, suggesting plasma sRAGE acts as a causal intermediate in sepsis-related ARDS.

11.
Crit Care Clin ; 36(1): 155-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733677

RESUMO

Critical illness syndromes, including sepsis and the acute respiratory distress syndrome (ARDS), are identified using consensus definitions that are based on broad, clinically available criteria and include patients with heterogeneous biology. This heterogeneity is a barrier to developing and testing effective therapies for these syndromes. Biomarkers identify clinically distinct molecular phenotypes of ARDS and sepsis. These molecular phenotypes are associated with differences in mortality and predict response to several treatments in retrospective analyses of clinical trials. Biomarkers can be used for prognostic and predictive enrichment of clinical trials in critical illness to incorporate precision medicine in critical care.

12.
Crit Care Med ; 48(1): 22-30, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31599812

RESUMO

OBJECTIVES: New-onset atrial fibrillation during critical illness is an independent risk factor for mortality. The ability to identify patients at high risk for new-onset atrial fibrillation is limited. We hypothesized that genetic susceptibility contributes to risk of new-onset atrial fibrillation in the ICU. DESIGN: Retrospective sub-study of a prospective observational cohort study. SETTING: Medical and general surgical ICUs in a tertiary academic medical center. PATIENTS: One-thousand three-hundred sixty-nine critically ill patients admitted to the ICU for at least 2 days with no known history of atrial fibrillation who had DNA available for genotyping. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We genotyped 21 single-nucleotide polymorphisms associated with atrial fibrillation in ambulatory studies using a Sequenom platform (San Diego, CA). We collected demographics, medical history, and development of new-onset atrial fibrillation during the first four days of ICU admission. New-onset atrial fibrillation occurred in 98 patients (7.2%) and was associated with age, male sex, coronary artery disease, and vasopressor use. Single-nucleotide polymorphisms associated with new-onset atrial fibrillation were rs3853445 (near PITX2, p = 0.0002), rs6838973 (near PITX2, p = 0.01), and rs12415501 (in NEURL, p = 0.03) on univariate testing. When controlling for clinical factors, rs3853445 (odds ratio, 0.47; 95% CI, 0.30-0.73; p = 0.001) and rs12415501 (odds ratio, 1.72; 95% CI, 1.27-2.59; p = 0.01) remained significantly associated with new-onset atrial fibrillation. The addition of genetic variables to clinical factors improved new-onset atrial fibrillation discrimination in a multivariable logistic regression model (C-statistic 0.82 vs 0.78; p = 0.0009). CONCLUSIONS: We identified several single-nucleotide polymorphisms associated with new-onset atrial fibrillation in a large cohort of critically ill ICU patients, suggesting there is genetic susceptibility underlying this common clinical condition. This finding may provide new targets for future mechanistic studies and additional insight into the application of genomic information to identify patients at elevated risk for a common and important condition in the ICU.

13.
PLoS One ; 14(12): e0226412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856187

RESUMO

BACKGROUND: Delirium's pathophysiology is poorly understood. We sought to determine if plasma biomarkers of inflammation, coagulation, endothelial activation, and blood brain barrier (BBB) injury were associated with emergency department (ED) delirium duration. METHODS: We enrolled hospitalized patients who were 65 years or older from the ED. Plasma biomarkers of inflammation (interleukin-6 [IL-6], IL-8, soluble tumor necrosis factor receptor I [sTNFRI]), coagulation (Protein C), endothelial activation (plasminogen activating inhibitor-1 [PAI-1]), and BBB injury (S100B) at were measured using blood obtained at enrollment. The dependent variable was ED delirium duration which was determined by the Brief Confusion Assessment Method assessed in the ED and hospitalization. Proportional odds logistic regression analyses were performed adjusted for relevant confounders and allowing for interaction by baseline dementia status. RESULTS: A total of 156 patients were enrolled. IL-6 (POR = 1.59, 95%CI: 1.09-2.32) and PAI-1 (POR = 2.96, 95%CI: 1.48 to 6.85) were independently associated with more prominent ED delirium duration in subjects without dementia only. No significant associations between IL-8, Protein C, sTNRFI, and S100B and ED delirium duration were observed. CONCLUSIONS: Plasma Biomarkers of systemic inflammation and endothelial activation are associated with ED delirium duration in older ED patients without dementia.


Assuntos
Coagulação Sanguínea , Lesões Encefálicas/complicações , Delírio/sangue , Delírio/diagnóstico , Hospitalização , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Barreira Hematoencefálica/lesões , Estudos de Coortes , Delírio/complicações , Delírio/fisiopatologia , Feminino , Humanos , Inflamação/complicações , Masculino , Prognóstico , Fatores de Tempo
14.
JCI Insight ; 4(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573976

RESUMO

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical and environmental risk factors exist, not all patients with risk factors develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported that circulating cell-free hemoglobin (CFH) is elevated during sepsis, and higher levels predict worse outcomes. Excess CFH is rapidly scavenged by haptoglobin (Hp). A common HP genetic variant, HP2, is unique to humans and is common in many populations worldwide. HP2 haptoglobin has reduced ability to inhibit CFH-mediated inflammation and oxidative stress compared with the alternative HP1. We hypothesized that HP2 increases ARDS susceptibility during sepsis when plasma CFH levels are elevated. In a murine model of sepsis with elevated CFH, transgenic mice homozygous for Hp2 had increased lung inflammation, pulmonary vascular permeability, lung apoptosis, and mortality compared with wild-type mice. We then tested the clinical relevance of our findings in 496 septic critically ill adults, finding that HP2 increased ARDS susceptibility after controlling for clinical risk factors and plasma CFH. These observations identify HP2 as a potentially novel genetic ARDS risk factor during sepsis and may have important implications in the study and treatment of ARDS.

15.
J Heart Lung Transplant ; 38(12): 1246-1256, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31474492

RESUMO

BACKGROUND: Obesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown. METHODS: We performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD. RESULTS: A total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02-3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD. CONCLUSIONS: Subcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation.

16.
Am J Physiol Renal Physiol ; 317(4): F922-F929, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364379

RESUMO

Acute kidney injury is a common complication of severe sepsis and contributes to high mortality. The molecular mechanisms of acute kidney injury during sepsis are not fully understood. Because hemoproteins, including myoglobin and hemoglobin, are known to mediate kidney injury during rhabdomyolysis, we hypothesized that cell-free hemoglobin (CFH) would exacerbate acute kidney injury during sepsis. Sepsis was induced in mice by intraperitoneal injection of cecal slurry (CS). To mimic elevated levels of CFH observed during human sepsis, mice also received a retroorbital injection of CFH or dextrose control. Four groups of mice were analyzed: sham treated (sham), CFH alone, CS alone, and CS + CFH. The addition of CFH to CS reduced 48-h survival compared with CS alone (67% vs. 97%, P = 0.001) and increased the severity of illness. After 24 and 48 h, CS + CFH mice had a reduced glomerular filtration rate from baseline, whereas sham, CFH, and CS mice maintained baseline glomerular filtration rate. Biomarkers of acute kidney injury, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), were markedly elevated in CS+CFH compared with CS (8-fold for NGAL and 2.4-fold for KIM-1, P < 0.002 for each) after 48 h. Histological examination showed a trend toward increased tubular injury in CS + CFH-exposed kidneys compared with CS-exposed kidneys. However, there were similar levels of renal oxidative injury and apoptosis in the CS + CFH group compared with the CS group. Kidney levels of multiple proinflammatory cytokines were similar between CS and CS + CFH groups. Human renal tubule cells (HK-2) exposed to CFH demonstrated increased cytotoxicity. Together, these results show that CFH exacerbates acute kidney injury in a mouse model of experimental sepsis, potentially through increased renal tubular injury.

17.
JCI Insight ; 4(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167972

RESUMO

Respiratory diseases are among the leading causes of death and disability worldwide. However, the pathogenesis of both acute and chronic lung diseases remains incompletely understood. As a result, therapeutic options for important clinical problems, including acute respiratory distress syndrome and chronic obstructive pulmonary disease, are limited. Research efforts have been held back in part by the difficulty of modeling lung injury in animals. Donor human lungs that have been rejected for transplantation offer a valuable alternative for understanding these diseases. In 2007, our group developed a simple preparation of an ex vivo-perfused single human lung. In this Review, we discuss the availability of donor human lungs for research, describe the ex vivo-perfused lung preparation, and highlight how this preparation can be used to study the mechanisms of lung injury, to isolate primary cells, and to test novel therapeutics.

18.
Semin Respir Crit Care Med ; 40(1): 31-39, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31060086

RESUMO

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by noncardiogenic pulmonary edema. Despite five decades of basic and clinical research, there is still no effective pharmacotherapy for this condition and the treatment remains primarily supportive. It is critical to study the molecular and physiologic mechanisms that cause ARDS to improve our understanding of this syndrome and reduce mortality. The goal of this review is to describe our current understanding of the pathogenesis and pathophysiology of ARDS. First, we will describe how pulmonary edema fluid accumulates in ARDS due to lung inflammation and increased alveolar endothelial and epithelial permeabilities. Next, we will review how pulmonary edema fluid is normally cleared in the uninjured lung, and describe how these pathways are disrupted in ARDS. Finally, we will explain how clinical trials and preclinical studies of novel therapeutic agents have further refined our understanding of this condition, highlighting, in particular, the study of mesenchymal stromal cells in the treatment of ARDS.

19.
Am J Transplant ; 19(8): 2366-2373, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31017370

RESUMO

Acute kidney injury (AKI) is common after lung transplantation, but molecular markers remain poorly studied. The endothelial activation markers soluble thrombomodulin (sTM), protein C, and plasminogen activator inhibitor-1 (PAI-1) are implicated in kidney microcirculatory injury in animal models of AKI. We tested the association of 6-hour postreperfusion plasma levels of these markers with posttransplant AKI severity in patients enrolled in the Lung Transplant Outcomes Group prospective cohort study at the University of Pennsylvania during two eras: 2004-06 (n = 61) and 2013-15 (n = 67). We defined AKI stage through postoperative day 5 using Kidney Disease Improving Global Outcomes creatinine criteria. We used multivariable ordinal logistic regression to determine the association of each biomarker with AKI, adjusted for primary graft dysfunction and extracorporeal life support. AKI occurred in 57 (45%) patients across both eras: 28 (22%) stage 1, 29 (23%) stage 2-3. Higher sTM and lower protein C plasma levels were associated with AKI stage in each era and remained so in multivariable models utilizing both eras (sTM: OR 1.76 [95% CI 1.19-2.60] per standard deviation, P = .005; protein C: OR 0.54 [1.19-2.60], P = .003). We conclude that 6-hour postreperfusion plasma sTM and protein C levels are associated with early postlung transplant AKI severity.

20.
Biomarkers ; 24(4): 352-359, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30744430

RESUMO

Purpose: Bronchoalveolar fluid (BALF) and plasma biomarkers are often endpoints in early phase randomized trials (RCTs) in acute respiratory distress syndrome (ARDS). With ARDS mortality decreasing, we analyzed baseline biomarkers in samples from contemporary ARDS patients participating in a prior RCT and compared these to historical controls. Materials and methods: Ninety ARDS adult patients enrolled in the parent trial. BALF and blood were collected at baseline, day 4 ± 1, and day 8 ± 1. Interleukins-8/-6/-1ß/-1 receptor antagonist/-10; granulocyte colony stimulating factor; monocyte chemotactic protein-1; tumour necrosis factor-α; surfactant protein-D; von Willebrand factor; leukotriene B4; receptor for advanced glycosylation end products; soluble Fas ligand; and neutrophil counts were measured. Results: Compared to historical measurements, our values were generally substantially lower, despite our participants being similar to historical controls. For example, our BALF IL-8 and plasma IL-6 were notably lower than in a 1999 RCT of low tidal volume ventilation and a 2007 biomarker study, respectively. Conclusions: Baseline biomarker levels in current ARDS patients are substantially lower than 6-20 years before collection of these samples. These findings, whether from ICU care changes resulting in less inflammation or from variation in assay techniques over time, have important implications for design of future RCTs with biomarkers as endpoints.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Adulto , Idoso , Antígenos de Neoplasias/sangue , Biomarcadores/sangue , Biomarcadores/química , Quimiocina CCL2/sangue , Proteína Ligante Fas/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Contagem de Leucócitos , Leucotrieno B4/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/sangue , Neutrófilos/imunologia , Neutrófilos/patologia , Proteína D Associada a Surfactante Pulmonar/sangue , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Volume de Ventilação Pulmonar/fisiologia , Fator de Necrose Tumoral alfa/sangue , Fator de von Willebrand/metabolismo
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