Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study

Abstract

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Keywords: Acute stroke; immunology; infection; inflammation; macrophages.

Figure 1.

Time course of biomarkers after stroke onset (days 1 to 4). Monocytic HLA-DR (mHLA-DR) levels were significantly decreased while IL-6 and LBP-levels were significantly increased in patients with stroke-associated pneumonia (SAP, panels a–c) and those receiving antibiotics (at any time point during the observation period) compared with patients not receiving antibiotics (panels d–f), respectively. Grey boxplots indicate patients with SAP or antibiotic treatment and open boxplots indicate patients without SAP or antibiotic treatment. In patients with SAP and those receiving antibiotics, alterations in biomarkers were significant already on day 1 but became even more pronounced on days 2 to 4. Dashed lines indicate the lower (mHLA-DR) and upper limit of normal (IL-6, LBP), respectively. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 (Kruskal–Wallis one-way ANOVA with Dunn’s multiple comparison test).