From the Journals

Higher sRAGE found in nonfocal ARDS

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sRAGE hints at mortality cause

“Mechanical stress is concentrated at the border zones between well-[aerated] and poorly aerated lung units, which is thought to predispose to mechanical lung injury in these regions during tidal ventilation. … The results of the current study support this possibility that mechanical lung injury persists in regions of stress concentration during low tidal volume ventilation, contributing to higher mortality in nonfocal ARDS.

“The current study also provides additional evidence that a plasma biomarker, such as sRAGE, could improve our ability to endotype patients with [acute respiratory distress syndrome], forecast prognosis, and identify subgroups for targeting of specific therapies early in the course of [acute respiratory distress syndrome].”

Michael A. Matthay , MD, is a professor of medicine and anesthesia at the University of California, San Francisco, and is with the Cardiovascular Research Institute. Jeremy R. Beitler, MD, is with the department of medicine at the University of California, San Diego. Dr. Matthay consults for Cerus Therapeutics, GlaxoSmithKline, Boerhinger-Ingleheim, Bayer, Biogen, Quark Pharmaceuticals, and Incardia. Dr. Beitler has received research support from Amgen and GlaxoSmithKline.


 

FROM CHEST

A biomarker may show whether acute respiratory distress syndrome (ARDS) is focal or nonfocal, a study showed.

This is an important distinction because some research suggests nonfocal ARDS, characterized by diffuse lung aeration loss, may have a worse prognosis and the two subtypes may respond differently to interventions such as positive end-expiratory pressure and recruitment maneuvers.

At present, the only way to identify focal versus nonfocal ARDS is a computed tomography scan, but that is often impractical because of the risks of moving the patient.

The current research, published in the November issue of CHEST (2016;150:998-1007), revealed that patients with nonfocal ARDS have higher plasma levels of the soluble form of the receptor for advanced glycation end product (sRAGE). At a cutoff of 1,188 pg/ml, the blood test differentiated between focal and nonfocal ARDS with a 94% sensitivity and an 84% specificity.

“Elevated baseline plasma sRAGE is a strong marker of nonfocal CT-based lung-imaging pattern in patients with early ARDS,” reported Jean-Michel Constantin of University Hospital of Clermont-Ferrand (France) and colleagues in the Azurea network.

The researchers recruited 119 consecutive ARDS patients from 10 intensive care units in France. They measured plasma levels of sRAGE, plasminogen activator inhibitor–1 (PAI-1), soluble intercellular adhesion molecule–1, and surfactant protein–D within 24 hours of ARDS onset. Each patient underwent a lung CT scan within 48 hours to assess focal versus nonfocal lung morphology.

Twenty-seven percent of patients had focal ARDS, while 73% were categorized as nonfocal. Mean plasma levels of sRAGE were much higher in nonfocal patients (3,074 pg/ml vs. 877 pg/ml, P less than .001). A cutoff value of 1,188 ng/ml distinguished focal and nonfocal ARDS with a sensitivity of 93% (95% confidence interval, 85%-97%) and a specificity of 84% (95% CI, 66%-95%). The test’s positive predictive value was 94% (95% CI, 87%-98%), and its negative predictive value was 81% (95% CI, 64%-93%).

The research is still in its early stage, but has a couple possible applications, according to Daniel R. Ouellette, MD, of Henry Ford Hospital, Detroit. “We might conceive of using this as a marker for nonfocal ARDS, and potentially use it to identify patients with worse outcomes. The other thing is, it may be a clue to help us learn about the underlying physiology of the disease,” he said in an interview.

If physicians can confidently categorize a patient, it could inform treatment. “We know that patients who have diffuse disease may be more likely to be treated successfully with advanced ventilator techniques. These techniques would be more useful and likely to lead to recovery in patients that don’t have focal disease,” said Dr. Ouellette.

However, he added that more research is needed. “These results are exciting, but they are very preliminary,” Dr Ouellette said.

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