Comparison of the Equivalence of Aspergillus Antigen and PCR Results Between Non-Directed Bronchial Lavage and Bronchoalveolar Lavage-A Prospective Exploratory Pilot Study in Critically Ill Patients.

Background: Obtaining non-directed samples from the upper bronchial tree is easier to perform and poses fewer risks for critically ill patients than deep bronchoalveolar lavage (BAL). Since invasive pulmonary aspergillosis is associated with a high mortality in critically ill patients, timely diagnosis and rapid initiation of treatment are of utmost importance.

Objectives: The objective of this study was to compare Galactomannan (GM) testing by Enzyme Immunoassay (EIA), GM Lateral Flow Assay (LFA) and the detection of Aspergillus DNA by Polymerase Chain Reaction (PCR) between directed BAL and non-directed bronchial lavage (BL) in critically ill patients.

Methods: In this prospective, exploratory pilot study, we analysed 120 samples from 40 patients admitted to 12 mixed intensive care units. Inclusion criteria required either risk factors for IPA or positive Aspergillus assessments and met the criteria published by the European Society of Clinical Microbiology and Infectious Diseases guidelines for IPA diagnosis. Both respiratory secretions and blood were collected. In each patient, LFA and PCR were performed on BAL, BL and blood serum, respectively. The EIA test was applied to the BL and BAL of each patient, and the serum of 24 patients. The study was registered on clinicaltrials.gov (NCT04848831).

Results: In a total of 80 respiratory samples, Aspergillus GM EIA yielded optical density indices (ODI) ranging from 0.04 to ≥ 3.5. We observed a high correlation between BAL and BL samples for Aspergillus GM EIA (Pearson's r = 0.78 [95% CI 0.62, 0.88]; intraclass correlation coefficient 0.78). At an ODI cutoff of 0.8 for BAL and 1.2 for BL, the sensitivity of Aspergillus GM EIA was 0.94, while the specificity was 0.67. Increasing the BAL cutoff to 1.0 ODI improved the specificity to 0.86. Aspergillus PCR examination showed good agreement between the two compartments, with a Cohen's kappa coefficient of 0.75 (95% CI 0.48, 1.00). The correlation of Aspergillus GM LFA between BAL and BL was weak.

Conclusions: Our findings demonstrate that the detection of Aspergillus GM using EIA or Aspergillus PCR in BL is comparable to that in BAL. Thus, BL samples can be reliably used for diagnosing invasive pulmonary aspergillosis.