Background: Pneumonia is the leading cause of infectious deaths and the most common infection identified in ICU patients. Assessment of bronchoalveolar lavage fluid (BALF) cellularity can aid in pneumonia diagnosis. Low percentages (<50%) of BALF neutrophils have a high negative predictive value for bacterial pneumonia in a general medical ICU population, but unclear operating characteristics in patients with immunocompromise and neutropenia remain unknown. Methods: We analyzed a large cohort of BALF specimens obtained for routine care for suspected pneumonia in mechanically ventilated patients and enrolled in the single-center Successful Clinical Response In Pneumonia Therapy (SCRIPT) study. BALF neutrophils were reported as a percentage of leukocytes by the clinical laboratory. The etiology of each episode of suspected pneumonia was adjudicated by a committee of critical care physicians using a predefined protocol. Immunocompromise was defined using predetermined criteria by the study research team. Neutropenia was defined here as a peripheral ANC <1500 cells/ul. Data are expressed as median [Quartile (Q) 1, Q3] and compared using the Mann-Whitney U test. Results: 688 mechanically ventilated patients with suspected pneumonia were included. 409 (59.4%) were male; median age was 62 [51,71]. 461 patients (67.0%) were immunocompetent, 149 (21.7%) were immunocompromised without neutropenia and 78 (11.3%) were neutropenic at some point during their admission. A total of 1746 BALs were performed. Fifty-seven BALs were obtained on a day where the patient's ANC<1500. Amongst pneumonia episodes classified as bacterial, no difference was found amongst BALF percent neutrophils taken patients who were immunocompetent and those who were immunocompromised but not neutropenic on day of sampling: 84.0% [69.0, 93.0] vs 87.0% [68.3, 93.0], p = 0.878 (Figure 1B). However, BALF percent neutrophils were significantly lower in patients neutropenic on day of sampling, with median BALF percent neutrophils of only 65.0% [22.3, 70.5] (p=0.016 compared with immunocompromised group, p=0.0096 compared with immunocompetent group). Conclusion: Among patients with bacterial pneumonia, BALF neutrophil percentage was not significantly decreased by a spectrum of immunocompromise. However, the subset of patients who were acutely neutropenic at the time of BAL sampling had significantly lower BALF % neutrophils. A traditional approach using BALF<50% to suggest against bacterial pneumonia may be inaccurate in this particular population.
Competing Interest StatementThe authors have declared no competing interest.
Funding StatementSCRIPT is supported by NIH/NIAID U19AI135964. CAG is supported by NIH/NHLBI K23HL169815. RGW is supported by NIH grants U19AI135964, U01TR003528, P01HL154998, R01HL149883, R01LM013337. The funding sources did not have a role in the design, execution, or prior review of the study or in the data presented in this manuscript. Opinions expressed in this work do not necessarily reflect those of the funding sources.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This study was approved by the Northwestern University Institutional Review Board with study ID STU00204868.
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Data AvailabilityA significant portion of this data has been already made available through PhysioNet at https://physionet.org/content/script-carpediem-dataset/1.1.0/, a future update will include new patients and updated data since the publication of the original dataset.
https://physionet.org/content/script-carpediem-dataset/1.1.0/
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