Evaluation of risk factors for invasive pulmonary aspergillosis and detection of diagnostic values of galactomannan and PCR methods in bronchoalveolar lavage samples from non-neutropenic intensive care unit patients

Abstract

Non-neutropenic intensive care unit (ICU) patients are at particular risk for invasive pulmonary aspergillosis. In these cases, radiological and microbiological methods (direct microscopy, culture), which can be used for diagnosis, have quite low sensitivity and specificity. The aims of this study were to evaluate the risk factors for invasive pulmonary aspergillosis (IPA) in non-neutropenic ICU patients and to determine the diagnostic values of galactomannan (GM) antigen and Aspergillus nucleic acid detection methods. A total of 44 patients (13 female, 31 male; age range: 36-96 years) who had been followed at pulmonary ICU with invasive mechanical ventilation and undergone bronchoscopy between January to December 2013, were included in the study. Consecutive bronchoalveolar lavage (BAL) and serum samples were obtained from all of the patients. BAL samples were tested for the presence of Aspergillus DNA by polymerase chain reaction (PCR) and both serum and BAL samples were tested for GM antigen by EIA method (Piatelia Aspergillus, BioRad, France). EORTC/MSG criteria were used for the case definition of IPA. Patients were classified as high-probable IPA, possible IPA and non-IPA. ROC (receiver operating characteristics) analysis was used to determine the diagnostic values of BAL Aspergillus PCR and BAL GM in the diagnosis of IPA. Five patients were defined as high-probable IPA and six were defined as possible IPA; thus the incidence rate of IPA was estimated as 11.4% (5/44) among non-neutropenic intensive care unit patients. In high-probable IPA patients, BAL GM levels were significantly higher than non-IPA patients (p< 0.05). The prolonged duration in ICU, presence of septic shock and the use of high cumulative doses (> 460 mg) of steroid were found to be risk factors for IPA development. The cut-off value for GM in BAL samples was determined as 0.7, with a sensitivity rate of 100% (95% confidence interval: 47.9-100) and a specificity rate of 87.9% (95% confidence interval: 71.7-96.5), so optimal GM level in BAL was considered as ≥ 0.7 for the diagnosis of IPA. The specificity rates of serum GM and BAL Aspergillus PCR methods were high (97.1 % and 93.9%, respectively), however their sensitivity rates were found quite low (33.3% and 40%, respectively), in the diagnosis of IPA. In conclusion, development of IPA should be assessed in non-neutropenic patients when the stay in ICU extends and high dose cumulative steroids are used. GM antigen detection in BAL can be used effectively for diagnosis of IPA in these patients compared to other diagnostic methods.