Calprotectin in the risk stratification of patients with acute dyspnoea in the emergency department

Introduction

Acute dyspnoea is one of the most common presenting symptoms in the emergency department (ED) and is challenging for the emergency physician. The subjective experience of dyspnoea and the variety of underlying causes, particularly in elderly patients with multiple comorbidities, often makes the diagnostic assessment difficult. Investigations beyond history and clinical examination, such as laboratory and radiological examinations, are frequently required. This means that risk stratification must be performed simultaneously with diagnostic assessment. A common aid to improve risk stratification in the emergency department is biomarkers^1,2.

Calprotectin, a heterodimer of S100A8 and S100A9, is primarily found in the cytosol of neutrophils. It is released upon neutrophil activation and acts as a mediator in the immune response³. Calprotectin has been hypothesised to be an early marker of inflammation and studies have shown that circulating calprotectin increases as early as 1.5 h, peaks at 5 h and remains elevated at 24 h after exposure to endotoxin or bacteria^4,5. C-reactive protein (CRP) is an acute-phase protein and the most commonly used biomarker in Swedish EDs to detect inflammation and infection. It is synthesised by the liver in response to inflammatory stimuli and circulating levels start rising after about six hours and peaks around 48 h⁶.

Calprotectin is routinely analysed in faeces in the evaluation of inflammatory bowel disease and circulating calprotectin is associated with disease activity in chronic inflammatory rheumatic diseases^7,8. More recently, studies have shown an association between increased levels of circulating calprotectin and adverse outcomes in acute cardiovascular and infectious diseases^{9, 10, 11–12}. However, the prognostic value of calprotectin in acute dyspnoea is so far unknown. The aim of this study is to investigate the association between circulating calprotectin and mortality as well as illness severity in patients presenting to the ED with acute dyspnoea.

Methods

Study population

The study was performed by analysing a sub cohort of the Acute DYspnoea Study (ADYS)¹³. ADYS was a prospective observational cohort study conducted at the ED of Skåne University Hospital in Malmö, Sweden. Inclusion criteria were age 18 years or older and acute dyspnoea as the presenting symptom. Patients transferred directly from the resuscitation room to the intensive care unit (ICU) and patients...