Acute Respiratory Distress Syndrome in Patients with Lymphopenia: Results from the National Inpatient Sample (2017–2021)

<b>Background:</b> Lymphopenia has been associated with in-hospital, early, and late mortality. We aimed to elucidate differences in baseline characteristics in patients with lymphopenia with and without acute respiratory distress syndrome (ARDS) and determine predictors of in-hospital mortality in this patient population. <b>Methods:</b> Patients ≥ 18 years of age with lymphopenia were identified in the National Inpatient Sample (2017-2021) and stratified according to ARDS diagnosis. Predictors of in-hospital mortality were determined using multivariate analyses with a logistic regression model. <b>Results:</b> From 183,185 patients with lymphopenia, 10,420 (5.7%) had ARDS, of which 92.8% had coronavirus disease 2019. The patients with ARDS suffered from more in-hospital mortality (47% versus 6.7%, <i>p</i> < 0.001). ARDS increased the odds of in-hospital mortality by eight-fold (odds ratio [OR]: 7.91 [7.06-8.86], <i>p</i> < 0.001). Age ≥ 65 years (OR: 4.88 [3.98-5.99]), moderate/severe liver disease (OR: 2.53 [1.87-3.42]), and metastatic cancer (OR: 2.18 [1.68-2.82]) were among the strongest positive predictors of in-hospital mortality (all <i>p</i> < 0.001). <b>Conclusions:</b> Patients with lymphopenia who have ARDS have higher in-hospital mortality, likely due to the condition's clinical course. Lymphopenia may be a marker of immune dysregulation and systemic involvement in ARDS.