Abstract Rationale Despite emerging evidence of alveolar compartment contributions to pathophysiology of acute respiratory failure (ARF), bronchoalveolar lavage fluid (BALF) cellular profile is of uncertain clinical significance. In a prospective cohort of patients with ARF, we evaluated BALF cell counts to determine associations with (1) ARDS and pneumonia, (2) severity defined by length of mechanical ventilation (MV), and (3) BALF innate immune proteins. Methods We performed a nested cohort study of patients with ARF, who had available BALF cell count data from two prospective cohorts: (1) Clinical Cohort - individuals with ARF who underwent a clinical bronchoscopy for suspicion of pneumonia or clinical deterioration (n = 236) ; (2) Research Cohort - individuals with hypoxemic ARF enrolled into a research study that includes protocolized bronchoscopy (n = 65). We conducted univariate comparisons of BALF total cell count and cell subtypes (percent and absolute counts: neutrophils, lymphocytes, macrophages, and eosinophils) between groups: (1) with and without ARDS, (2) with and without pneumonia (10⁴ CFU growth on BALF culture). Next, using ordinal regression, we evaluated associations between log10 transformed BALF total cell counts and bins of ventilator free days (VFD bin 1: 0 days, bin 2: 1-19 days, bin 3: 20-28 days) adjusted for age and sex. Finally, we reported the correlation between BALF cell counts and differentials and alveolar mediators related to neutrophils (interleukin-6 (IL-6), interleukin-8 (IL-8), calprotectin). Results All participants (N = 301) were on MV, 54% had ARDS, 37% had pneumonia, and 38% had concurrent ARDS and pneumonia. Higher BALF total cell counts and neutrophils (both percent and absolute counts) were observed in participants with ARDS versus without and in participants with pneumonia versus without (Figure 1a). Amongst participants with ARDS and concurrent pneumonia, they had higher total cell counts and neutrophils (percent and absolute counts), suggesting infection may be a driver of neutrophilic alveolitis (Figure 1a). Further, amongst all participants higher total cell counts were associated with fewer ventilator free days (p = 0. 04, Figure 1b). Finally, calprotectin was strongly correlated with total cell count (r: 0. 73, p 0. 001) and neutrophil count (r: 0. 83, p 0. 001). While IL-6 and IL-8 were moderately correlated. Conclusions In ARF, BALF total cell count and neutrophils demonstrate important clinical diagnostic and prognostic associations as well as biological correlates, suggesting potential utility in clinical care. Next steps include studying whether these alveolar cells can be integrated into definitions of ARF sub-phenotypes to advance biologically informed therapeutic development. This abstract is funded by: None
Van et al. (Fri,) studied this question.