Lung Fluid Biomarkers for Acute Respiratory Distress Syndrome

A Systematic Review and Meta-analysis

Yishan Wang; Huijuan Wang; Chunfang Zhang; Chao Zhang; Huqin Yang; Ruiyue Gao; Zhaohui Tong


Crit Care. 2019;23(43) 

In This Article


Acute respiratory distress syndrome (ARDS) is a clinical syndrome comprising a rapid onset of respiratory failure in patients with risk factors, such as refractory arterial hypoxemia with low reaction to supplemental oxygen and the presence of bilateral infiltrates on radiographic imaging.[1] To date, the diagnosis of ARDS and acute lung injury (ALI) is mostly based on clinical characterization. Frequently-used criteria are the American European Consensus Conference (AECC) criteria[2] and the Berlin definition.[3]

As the accuracy of a diagnosis of ARDS based only on the clinical syndrome has been questioned, countless studies have focused on the identification of biomarkers for ARDS. Terpstra et al. conducted a meta-analysis in 2014 focused on plasma biomarkers for ARDS in humans and provided a ranking system for distinguishing the disease from at-risk patients and determining the prognosis.[4] They reviewed multiple plasma biomarkers for ARDS, ranked by pooled odds ratio (OR). However, they only summarized biomarkers for ARDS in plasma; biomarkers in other fluids, such as bronchoalveolar lavage fluid (BALF), were not evaluated.

BALF and other lung fluids, such as pulmonary edema fluid (PEF), epithelial lining fluid (ELF), and lung aspirational fluid (LAF), are definitive in respiratory disease diagnosis. Since BALF provides a sample closest to the site of the disease process, it reflects the local lung environment directly. In 2017, García-Laorden et al. reported that biomarkers representing epithelial apoptosis, such as Fas and FasL, as well as biomarkers reflecting extracellular matrix injury, such as procollagen peptide III (PCP III) and procollagen peptide I (PCP I), were elevated in ARDS BALF samples.[5] The aim of the present study was to compare biomarker levels in lung fluid samples among patients with ARDS and the at-risk controls, as well as those of non-survivors versus survivors of ARDS.