The ABO histo-blood group, endothelial activation, and acute respiratory distress syndrome risk in critical illness
Bibliographic record
Abstract
and microthrombosis (1, 2).Clinically, it is recognized as diffuse noncardiogenic pulmonary edema and severe hypoxemia leading to acute respiratory failure in the setting of a precipitating illness (3).It is estimated that ARDS affects at least 190,000 people in the United States annually, and mortality ranges from 30% to 50% (4).Currently, ARDS therapies are largely supportive, including lung-protective mechanical ventilation, fluid restrictive management, and prone positioning (5-7).Despite many clinical trials, however, no pharmacological therapy aimed at its pathogenesis has been consistently shown to either prevent ARDS or reduce mortality (8-11).One potential explanation for this failure of translation from promising preclinical therapeutics to human disease is pathogenic heterogeneity of ARDS, in which genetic factors may play a role (12-16). BACKGROUND.The ABO histo-blood group is defined by carbohydrate modifications and is associated with risk for multiple diseases, including acute respiratory distress syndrome (ARDS).We hypothesized that genetically determined blood subtype A1 is associated with increased risk of ARDS and markers of microvascular dysfunction and coagulation. METHODS.We conducted analyses in 3 cohorts of critically ill trauma and sepsis patients (n = 3710) genotyped on genomewide platforms to determine the association of the A1 blood type genotype with ARDS risk.We subsequently determined whether associations were present in FUT2-defined nonsecretors who lack ABO antigens on epithelium, but not endothelium.In a patient subgroup, we determined the associations of blood type with plasma levels of endothelial glycoproteins and disseminated intravascular coagulation (DIC).Lastly, we tested whether blood type A was associated with less donor lung injury recovery during human ex vivo lung perfusion (EVLP). RESULTS.The A1 genotype was associated with a higher risk of moderate to severe ARDS relative to type O in all 3 populations.In sepsis, this relationship was strongest in nonpulmonary infections.The association persisted in nonsecretors, suggesting a vascular mechanism.The A1 genotype was also associated with higher DIC risk as well as concentrations of thrombomodulin and von Willebrand factor, which in turn were associated with ARDS risk.Blood type A was also associated with less lung injury recovery during EVLP. CONCLUSION.We identified a replicable association between ABO blood type A1 and risk of ARDS among the critically ill, possibly mediated through microvascular dysfunction and coagulation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".