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What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage.

ABSTRACT: Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and

SUBMITTER: Rios F

PROVIDER: S-EPMC5632979 | biostudies-literature | 2017 Jul-Sep

REPOSITORIES: biostudies-literature

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What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage.

Rios Fernando F Iscar Teresa T Cardinal-Fernández Pablo P

Revista Brasileira de terapia intensiva 20170701 3

Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive ...[more]

PMID: 28977098

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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: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.

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What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage.

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What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage.

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