Observational studyJCI insight2019
Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis.
Observational study in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- The Acute Respiratory Distress Syndrome (ARDS): epidemiology, etiology, molecular mechanisms, diagnosis and therapeutic strategies.Molecular biomedicine · 2026Review
- Diet-induced obesity alleviates epithelial damage in hyperoxic acute lung injury (HALI) in mice.Respiratory research · 2026Article
- Advanced Age in Mice Exacerbates Sepsis-Induced Inflammation, Vascular Permeability, and Multi-Organ Dysfunction.Shock (Augusta, Ga.) · 2026Article
- Clinical Benefits and Risks of Haptoglobin Therapy in Hemolytic Disorders of Diverse Etiologies: A Systematic Review.Cureus · 2025Review
- MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury.JCI insight · 2025Article
- Hemolysis, hemolytic markers, and mortality in sepsis: a scoping review.Intensive care medicine experimental · 2025Review
- Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.Microcirculation (New York, N.Y. : 1994) · 2025Article
- LIN28A-dependent lncRNA NEAT1 aggravates sepsis-induced acute respiratory distress syndrome through destabilizing ACE2 mRNA by RNA methylation.Journal of translational medicine · 2025Article
- Iron, Oxidative Stress, and Haptoglobin Gene Polymorphism in Sickle Cell Disease Patients With Inflammation in Cameroon: An Analytical Cross-Sectional Study.Biochemistry research international · 2025Article
- Matrix metalloproteinase-7 is dispensable in a mouse model of sepsis-induced acute lung injury.PloS one · 2025Article
- Regulatory mechanisms of haptoglobin on particulate matter-induced epithelial-to-mesenchymal transition in bronchial epithelial cells.Journal of thoracic disease · 2024Article
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Novel insights into the potential applications of stem cells in pulmonary hypertension therapy.Respiratory research · 2024Review
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- Observational
- Association between acetaminophen administration and outcomes in critically ill patients with gout and hypertension.Frontiers in pharmacology · 2024Article
- Homozygote drepanocytosis: Ferric status and inflammation in world and Africa: Review article and meta analysis.Health science reports · 2023Review
- Liraglutide pretreatment attenuates sepsis-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Transpulmonary generation of cell-free hemoglobin contributes to vascular dysfunction in pulmonary arterial hypertension via dysregulated clearance mechanisms.Pulmonary circulation · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
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.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.