Dataset Information

Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

ABSTRACT: The aim of this retrospective and international study is to identify those clinical variables associated with diffuse alveolar damage (DAD), and to explore the impact of DAD on hospital mortality risk. Inclusion criteria were: adult patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy (OLB) during their intensive care unit (ICU) management. The main end-points were: DAD and hospital mortality. In the training (n = 193) and validation cohorts (n = 65), the respiratory rate (odd ratio (OR) 0.956; confidence interval (CI) 95% 0.918; 0.995) and coronary ischemia (OR 5.974; CI95% 1.668; 21.399) on the day of ARDS had an average area under the receiver operating characteristic curve (AUROC) of 0.660 (CI95% 0.585; 0.736) and 0.562 (0.417; 0.706), respectively. PEEP (OR 1.131; CI95% 1.051; 1.218) and coronary ischemia (OR 6.820; CI95% 1.856; 25.061) on the day of OLB had an average AUROC of 0.696 (CI95% 0.621; 0.769) and 0.534 (CI95% 0.391; 0.678), respectively, to predict DAD. DAD (OR 2.296; CI95% 1.228; 4.294), diabetes mellitus requiring insulin (OR 0.081; CI95% 0.009; 0.710) and the respiratory rate (OR 1.045; CI95% 1.001; 1.091) on the day of ARDS had an average AUROC of 0.659 (CI95% 0.583; 0.737) and 0.513 (CI95% 0.361; 0.664) to predict hospital mortality and DAD (OR 2.081; CI95% 1.053; 4.114), diabetes mellitus requiring insulin (OR 0.093; CI95% 0.009; 0.956), PaCO2 (OR 1.051; CI95% 1.019; 1.084), and platelets count (OR 0.999; CI95% 0.999; 0.999) the day of OLB had an average AUROC of 0.778 (CI95% 0.710; 0.843) and 0.634 (CI95%0.481; 0.787) to predict hospital mortalty in the training and validation cohorts, respectively. In conclusion, DAD could not to be predicted clinically and was significantly associated with hospital mortality.

SUBMITTER: Cardinal-Fernandez P

PROVIDER: S-EPMC6616523 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

Cardinal-Fernandez Pablo P Ortiz Guillermo G Chang Chih-Hao CH Kao Kuo-Chin KC Bertreau Emmanuelle E Philipponnet Carole C Casero-Alonso Víctor Manuel VM Souweine Bertrand B Charbonney Emmanuel E Guérin Claude C

Journal of clinical medicine 20190611 6

The aim of this retrospective and international study is to identify those clinical variables associated with diffuse alveolar damage (DAD), and to explore the impact of DAD on hospital mortality risk. Inclusion criteria were: adult patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy (OLB) during their intensive care unit (ICU) management. The main end-points were: DAD and hospital mortality. In the training (<i>n</i> = 193) and validation cohorts (<i>n</i> = 65) ...[more]

PMID: 31212621

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Project description:OBJECTIVES:Physiologic dead space is associated with mortality in acute respiratory distress syndrome, but its measurement is cumbersome. Alveolar dead space fraction relies on the difference between arterial and end-tidal carbon dioxide (alveolar dead space fraction = (PaCO2 - PetCO2) / PaCO2). We aimed to assess the relationship between alveolar dead space fraction and mortality in a cohort of children meeting criteria for acute respiratory distress syndrome (both the Berlin 2012 and the American-European Consensus Conference 1994 acute lung injury) and pediatric acute respiratory distress syndrome (as defined by the Pediatric Acute Lung Injury Consensus Conference in 2015). DESIGN:Secondary analysis of a prospective, observational cohort. SETTING:Tertiary care, university affiliated PICU. PATIENTS:Invasively ventilated children with pediatric acute respiratory distress syndrome. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Of the 283 children with pediatric acute respiratory distress syndrome, 266 had available PetCO2. Alveolar dead space fraction was lower in survivors (median 0.13; interquartile range, 0.06-0.23) than nonsurvivors (0.31; 0.19-0.42; p < 0.001) at pediatric acute respiratory distress syndrome onset, but not 24 hours after (survivors 0.12 [0.06-0.18], nonsurvivors 0.14 [0.06-0.25], p = 0.430). Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminated mortality with an area under receiver operating characteristic curve of 0.76 (95% CI, 0.66-0.85; p < 0.001), better than either initial oxygenation index or PaO2/FIO2. In multivariate analysis, alveolar dead space fraction at pediatric acute respiratory distress syndrome onset was independently associated with mortality, after adjustment for severity of illness, immunocompromised status, and organ failures. CONCLUSIONS:Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminates mortality and is independently associated with nonsurvival. Alveolar dead space fraction represents a single, useful, readily obtained clinical biomarker reflective of pulmonary and nonpulmonary variables associated with mortality.

Project description:ObjectivesPediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.DesignLeveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.SettingThe derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.PatientsThere were 624 and 640 subjects in the derivation and validation cohorts, respectively.InterventionsNone.Measurements and main resultsThe model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.ConclusionsWe describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid (BALF) and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AMs isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AMs and PBMs. Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AM isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AM and PBM.

Project description:Rationale: Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes.Objectives: To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS.Methods: We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset (N = 68 total samples). We identified biological pathways that were enriched at each time point in subjects alive and extubated within 28 days after ARDS onset (alive/extubatedDay28) versus those dead or persistently supported on mechanical ventilation at Day 28 (dead/intubatedDay28).Measurements and Main Results: "M1-like" (classically activated) and proinflammatory gene sets such as IL-6/JAK/STAT5 (Janus kinase/signal transducer and activator of transcription 5) signaling were significantly enriched in AMs isolated on Day 1 in alive/extubatedDay28 versus dead/intubatedDay28 subjects. In contrast, by Day 8, many of these same proinflammatory gene sets were enriched in AMs collected from dead/intubatedDay28 compared with alive/extubatedDay28 subjects. Serially sampled alive/extubatedDay28 subjects were characterized by an AM temporal expression pattern of Day 1 enrichment of innate immune programs followed by prompt downregulation on Days 4 and 8. Dead/intubatedDay28 subjects exhibited an opposite pattern, characterized by progressive upregulation of proinflammatory programs over the course of ARDS. The relationship between AM expression profiles and 28-day clinical status was distinct in subjects with direct (pulmonary) versus indirect (extrapulmonary) ARDS.Conclusions: Clinical outcomes in ARDS are associated with highly distinct AM transcriptional programs.

Dataset Information

Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

Publications

Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

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