Steven Bruzek (Saint Petersburg, FL / US), Vera Ignjatovic (Saint Petersburg, FL / US; Baltimore, MD / US), Neil Goldenberg (Saint Petersburg, FL / US; Baltimore, MD / US), John Morrison (Saint Petersburg, FL / US; Baltimore, MD / US)
Background: Children with tracheostomy represent a complex population that increasingly requires frequent hospitalization after receiving inpatient care for tracheostomy-associated respiratory infections (TARI). While certain conditions may contribute to the risk of readmission, it is currently unknown if specific factors such as inflammatory markers could define pathophysiologic mechanisms associated with recurrent hospitalization for TARI.
Aims: To characterize cytokine signaling and inflammatory signatures across multiple specimen types in children hospitalized for TARI.
Methods: We performed a prospective proof of concept study in children <17 years of age hospitalized for TARI. Blood, tracheal aspirate, and urine samples were collected within 48 hours of hospital admission and 24 hours before discharge. Platelet-poor plasma, tracheal aspirate, and urine were processed according to Olink® recommendations. The Olink Target 48 Cytokine Panel targeting 45 protein biomarkers of key pathways related to cytokine signaling and inflammatory processes was used. Olink normalized protein expression (NPX) values were uploaded into the Mass Dynamics platform for data interpretation. Principal component analysis (PCA) was employed separately for each sample type.
Results: Forty samples from eight subjects were analyzed, consisting of 11 plasma, 24 tracheal aspirate, and five urine samples. PCA findings are shown in Fig 1A. Compared to plasma, tracheal aspirate specimens had a significantly higher abundance of IL-33, EGF, IL-1β, IL-6, CXCL8, IL-7, and OSM and a significantly lower abundance of LTA, CXCL12, FLT3LG, CCL11, IL-27, TSLP, CCL13, CCL19, and IL-17C (Fig. 1B). Compared to urine, tracheal aspirate specimens had a significantly higher abundance for 21 targets, with IL-1β, CSF3, CSCL8, and OSM comprising those with the largest difference (Fig. 1C). Compared to urine, plasma had a significantly higher abundance for 29 targets, with CCL19, MMP1, MMP12, CXCL11, and CSF3 comprising the largest difference, and a significantly lower abundance of EGF and OLR1 (Fig. 1D). Abundance of TNF, IFN-γ, IL-10, CCL8, and IL-17C in tracheal aspirate was decreased (Fig. 1E), and of TGFA, IL-7, CCL4, FLT3LG, and CCL11 in plasma was increased (Fig. 1F) for discharge vs. admission samples, although these differences were not statistically significant.
Conclusions: Proinflammatory cytokines were detected in plasma, tracheal aspirate, and urine specimens of children hospitalized with TARI, with the highest abundance observed in tracheal aspirate and plasma. Tracheal aspirate specimens showed a potentially meaningful decrease and plasma specimens showed an increase in inflammatory signatures from admission to discharge. Future research will utilize marker levels in risk prediction models for hospital readmission in pediatric TARI patients.