Elevated Plasma and Alveolar Levels of Soluble Receptor for Advanced Glycation Endproducts Are Associated with Severity of Lung Dysfunction in ARDS Patients

Elevated Plasma and Alveolar Levels of Soluble Receptor for Advanced Glycation Endproducts Are Associated with Severity of Lung Dysfunction in ARDS Patients

TOMMASO MAURI,^1,2 SERGE MASSON,³ ANDREA PRADELLA,^1,2 GIACOMO BELLANI,^1,2 ANDREA COPPADORO,^1,2 MICHELA BOMBINO,² SONIA VALENTINO,⁴ NICOLO' PATRONITI,^1,2 ALBERTO MANTOVANI,^4,5 ANTONIO PESENTI^1,2 and ROBERTO LATINI³

¹Department of Experimental Medicine, University of Milan-Bicocca, Monza, Italy
²Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy
³Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
⁴Research Laboratory in Immunology and Inflammation, Istituto Clinico Humanitas (ICH), Rozzano (MI), Italy
⁵Institute of General Pathology, University of Milan, Milan, Italy

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are severe forms of bilateral lung inflammation with poor clinical outcomes. However, the pathophysiology of ALI/ARDS remains largely obscure. Soluble receptor for advanced glycation endproducts (sRAGE) plays a key regulatory role during the acute phase of inflammation, and baseline plasma levels of sRAGE were recently found to be associated with severity of ALI/ARDS. We analyzed, in ALI/ARDS patients, plasma and alveolar levels of sRAGE over time and the association with severity of lung injury. We enrolled 21 ALI/ARDS patients admitted to our intensive care unit (ICU) and assayed plasma sRAGE on the first 2 days after diagnosis, every three days for the first month and then once a week, until ICU discharge or death. We also measured sRAGE levels in bronchoalveolar lavage fluids, obtained when clinically indicated. At each sampling time, we recorded physiological and clinical data of the patients. Plasma sRAGE levels peaked at day 1 and decreased over time. When all samples were considered, plasma and alveolar sRAGE levels were significantly higher in patients with worse oxygenation and higher need for ventilatory support (i.e., patients with more severe lung dysfunction). Moreover, the presence of lung infection yielded higher alveolar sRAGE levels. In conclusion, we show that the plasma and alveolar levels of sRAGE in ALI/ARDS patients are correlated to lung injury severity and to lung infection. Our findings may, in time, lead to the development of more effective therapies against ALI/ARDS.

keywords —— soluble receptor for advanced glycation endproducts; pentraxin 3; acute lung injury/acute respiratory distress syndrome; marker; severity

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Tohoku J. Exp. Med., 2010, 222, 105-112

Correspondence: Antonio Pesenti, M.D., Department of Experimental Medicine, University of Milan-Bicocca, Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Via Pergolesi 33, 20052 Monza, Italy.

e-mail: antonio.pesenti@unimib.it