Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study

Tommaso Mauri, Andrea Coppadoro, Michela Bombino, Giacomo Bellani, Vanessa Zambelli, Carla Fornari, Lorenzo Berra, Edward A Bittner, Ulrich Schmidt, Marina Sironi, Barbara Bottazzi, Paolo Brambilla, Alberto Mantovani, Antonio Pesenti

IntroductionTimely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute phase mediator produced by various cell types in the lungs. Animal studies showed that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbes¿ clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The present study aimed to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia.MethodsWe recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy and Massachusetts General Hospital, Boston, MA) undergoing broncho-alveolar lavage (BAL) as per clinical decision. We collected BAL and plasma samples, together with relevant clinical and microbiological data. We assayed: in BAL, PTX3 and soluble triggering receptor expressed on myeloid cells (sTREM-1); in plasma, PTX3, sTREM-1, C-reactive protein (CRP) and Procalcitonin (PCT). Two blinded independent physicians reviewed patients¿ data to confirm pneumonia. Finally, we determined BAL PTX3 threshold for pneumonia and we compared it to other biomarkers.ResultsMicrobiologically confirmed pneumonia of bacterial (n¿=¿12), viral (n¿=¿4) or fungal (n¿=¿8) etiology was diagnosed in 24 patients (29%). BAL PTX3 predicted pneumonia with AUCROC¿=¿0.815 (95% CI¿=¿0.710 to 0.921, P <0.0001), while all other biomarkers were not effective. In particular, BAL PTX3¿¿¿1 ng/mL predicted pneumonia at univariate analysis (ß¿=¿2.784 with SE¿=¿0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index values of BAL PTX3¿¿¿1 ng/mL for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 cases that fulfilled clinical criteria for the diagnosis of pneumonia at BAL sampling, PTX3 diagnostic accuracy was confirmed at univariate and ROC curve analysis.ConclusionsIn this hypothesis generating convenience sample, BAL PTX3¿¿¿1 ng/mL was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.