biostudies-literatureSathe NAIntramural NIH HHSNCRR NIH HHSNIDDK NIH HHSNHLBI NIH HHSe13-e18https://www.ebi.ac.uk/biostudies/studies/S-EPMC9764239biostudies-literatureUnknown51(1)<h4>Objectives</h4>We sought to determine whether hyperinflammatory acute respiratory distress syndrome (ARDS) and hypoinflammatory ARDS, which have been associated with differences in plasma biomarkers and mortality risk, also display differences in bronchoalveolar lavage (BALF) biomarker profiles. We then described the relationship between hyperinflammatory ARDS and hypoinflammatory ARDS to novel subphenotypes derived using BALF biomarkers.<h4>Design</h4>Secondary analysis of a randomized control trial testing omega-3 fatty acids for the treatment of ARDS.<h4>Setting</h4>Five North American intensive care units.<h4>Patients</h4>Adults (n = 88) on invasive mechanical ventilation within 48 hours of ARDS onset.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>We classified 57 patients as hypoinflammatory and 31 patients as hyperinflammatory using a previously validated logistic regression model. Of 14 BALF biomarkers analyzed, interleukin-6 and granulocyte colony stimulating factor were higher among patients with hyperinflammatory ARDS compared with hypoinflammatory ARDS, though the differences were not robust to multiple hypothesis testing. We then performed a de novo latent class analysis of the 14 BALF biomarkers to identify two classes well separated by alveolar profiles. Class 2 (n = 63) displayed significantly higher interleukin-6, von Willebrand factor, soluble programmed cell death receptor-1, % neutrophils, and other biomarkers of inflammation compared with class 1 (n = 25). These BALF-derived classes had minimal overlap with the plasma-derived hyperinflammatory and hypoinflammatory classes, and the majority of both plasma-derived classes were in BALF-derived class 2 and characterized by high BALF biomarkers. Additionally, the BALF-derived classes were associated with clinical severity of pulmonary disease, with class 2 exhibiting lower Pao2 to Fio2 and distinct ventilatory parameters, unlike the plasma-derived classes, which were only related to nonpulmonary organ dysfunction.<h4>Conclusions</h4>Hyperinflammatory and hypoinflammatory ARDS subphenotypes did not display significant differences in alveolar biologic profiles. Identifying ARDS subgroups using BALF measurements is a unique approach that complements information obtained from plasma, with potential to inform enrichment strategies in trials of lung-targeted therapies.Critical care medicineAlveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.PMC9764239P20 RR015557F32 HL158088K23 HL144916Z01 ES102005P50 HL073996R01 HL149676K23 HL105654K12 RR023265K23 DK116967Morrell EDMikacenic CBhatraju PKWurfel MMSathe NAStapleton RDFessler MBfalseAlveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.<h4>Objectives</h4>We sought to determine whether hyperinflammatory acute respiratory distress syndrome (ARDS) and hypoinflammatory ARDS, which have been associated with differences in plasma biomarkers and mortality risk, also display differences in bronchoalveolar lavage (BALF) biomarker profiles. We then described the relationship between hyperinflammatory ARDS and hypoinflammatory ARDS to novel subphenotypes derived using BALF biomarkers.<h4>Design</h4>Secondary analysis of a randomized control trial testing omega-3 fatty acids for the treatment of ARDS.<h4>Setting</h4>Five North American intensive care units.<h4>Patients</h4>Adults (n = 88) on invasive mechanical ventilation within 48 hours of ARDS onset.<h4>Interventions</h4>None.<h4>Measurements and main results</h4>We classified 57 patients as hypoinflammatory and 31 patients as hyperinflammatory using a previously validated logistic regression model. Of 14 BALF biomarkers analyzed, interleukin-6 and granulocyte colony stimulating factor were higher among patients with hyperinflammatory ARDS compared with hypoinflammatory ARDS, though the differences were not robust to multiple hypothesis testing. We then performed a de novo latent class analysis of the 14 BALF biomarkers to identify two classes well separated by alveolar profiles. Class 2 (n = 63) displayed significantly higher interleukin-6, von Willebrand factor, soluble programmed cell death receptor-1, % neutrophils, and other biomarkers of inflammation compared with class 1 (n = 25). These BALF-derived classes had minimal overlap with the plasma-derived hyperinflammatory and hypoinflammatory classes, and the majority of both plasma-derived classes were in BALF-derived class 2 and characterized by high BALF biomarkers. Additionally, the BALF-derived classes were associated with clinical severity of pulmonary disease, with class 2 exhibiting lower Pao2 to Fio2 and distinct ventilatory parameters, unlike the plasma-derived classes, which were only related to nonpulmonary organ dysfunction.<h4>Conclusions</h4>Hyperinflammatory and hypoinflammatory ARDS subphenotypes did not display significant differences in alveolar biologic profiles. Identifying ARDS subgroups using BALF measurements is a unique approach that complements information obtained from plasma, with potential to inform enrichment strategies in trials of lung-targeted therapies.2023-01-01T00:00:00Z2023 Jan2026-05-28T01:55:44.447Z2025-04-04T03:00:20.67ZS-EPMC97642393651999510.1097/CCM.000000000000570410.1097/ccm.0000000000005704