Diagnostic indicator of acute lung injury for pediatric critically ill patients at a tertiary pediatric hospital

Abstract

Early identification of acute lung injury (ALI) in pediatric patients at risk of mortality is important for improving outcome.Assessment of soluble form of receptor for advanced glycation end products (sRAGE) as a valid biomarker for diagnosis of ALI among critically ill, pediatric patients in addition to correlating levels of sRAGE and different outcomes of those patients.A Hospital-based case-control study was conducted in pediatric intensive care units (PICUs) at Cairo University Hospital, along a period of 6 months. Total of 68 pediatric patients following inclusion criteria were classified into: patients with ALI; with both ALI and sepsis; with sepsis and control patients. They were prospectively followed and their laboratory and immunological workup (at days 1 and 9) was done to measure serum sRAGE levels and detect (sRAGE) genotypes.The age of the included children ranged from 8 to 84 months. Plasma level of sRAGE was significantly higher in plasma from patients with ALI regardless of associated sepsis. Plasma sRAGE levels were positively correlated with lung injury score. When assessing sRAGE genotypes, TA and TT genotypes were significant in most of the ALI with and without sepsis patients.Monitoring levels of sRAGE and genotypes can significantly affect the survival of ALI children.

sRAGE as severe acute bronchiolitis biomarker, prospective observational study

“…A possible explanation to our findings is that RAGE is highly expressed by type 1 alveolar epithelial cells and, whenever lung parenchyma is involved (not just the airways), there is an increased endogenous secretion of sRAGE to the plasma. This hypothesis is supported by high sRAGE levels in diseases affecting the alveoli, like ARDS 20,21,23 and lower levels in allergic airway inflammation and asthma, as well as, COPD, which mostly involve the airways like AB 25 . Although excessive pulmonary parenchymal damage leading to alveolar destruction and enlargement like emphysema in COPD patients probably decreases mRAGE availability, being sRAGE levels in consequence inversely correlated with baseline lung density in CT and its decline over time 39 …”

“…RAGE, a pattern recognition receptor most highly expressed in lung tissue, is a known biomarker of immunity and inflammation. It's role in AB, as an important pro‐inflammatory and anti‐inflammatory mediator, is of great interest and could help predict this variable disease severity 12,13,20,21 …”

“…These findings, common to other publications, are also hard to justify just assuming there is a consumption of sRAGE with inflammation, so we are probably missing some information when interpreting sRAGE in AB. To start with, it is still unclear whether sRAGE acts as an anti‐inflammatory or a pro‐inflammatory mediator 12,20 . Moreover, mRAGE can lead to opposite effects depending on it's ligands properties and the tissue affected 11 .…”

“…Moreover, mRAGE can lead to opposite effects depending on it's ligands properties and the tissue affected 11 . Some lung diseases appear to have elevated mRAGE and RAGE ligands levels (asthma, cystic fibrosis, acute lung injury [ALI], acute respiratory distress syndrome [ARDS], bronchopulmonary dysplasia [BPD] or pneumonia) while they are reduced in others (interstitial lung disease and certain lung cancers) 13,14,20‐29 . Simultaneously, sRAGE levels decrease in most of the respiratory illnesses with increased mRAGE, except for ALI/ARDS 20,23 …”

“…Again, there are probably many pieces of the puzzle we are missing, as AGE‐RAGE axis regulation is highly variable 30 . It is probably not only dependant on the cell types involved and pathophysiology of AB, but also on genetic factors 20,21,31,32 …”