Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study

Abstract

Objectives: To characterize immunocompromised-associated pediatric acute respiratory distress syndrome (I-PARDS) and contrast it to PARDS.

Design: This is a secondary analysis of the 2016-2017 PARDS incidence and epidemiology (PARDIE) study, a prospective observational, cross-sectional study of children with PARDS.

Setting: Dataset of 145 PICUs across 27 countries.

Patients: During 10 nonconsecutive weeks (from May 2016 to June 2017), data about immunocompromising conditions (ICCs, defined as malignancy, congenital/acquired immunodeficiency, posttransplantation, or diseases requiring immunosuppression) were collected.

Interventions: None.

Measurements and main results: Of 708 subjects, 105 (14.8%) had ICC. Before the development of I-PARDS, those with ICC were more likely to be hospitalized (70% vs. 35%, p < 0.001), have more at-risk for PARDS ( p = 0.046), and spent more hours at-risk (20 [interquartile range, IQR: 8-46] vs. 11 [IQR: 4-33], [ p = 0.002]). Noninvasive ventilation (NIV) use was more common in those with ICC ( p < 0.001). Of those diagnosed with PARDS on NIV ( n = 161), children with ICC were more likely to be subsequently intubated ( n = 28/40 [70%] vs n = 53/121 [44%], p = 0.004). Severe PARDS was more common (32% vs 23%, p < 0.001) in I-PARDS. Oxygenation indices were higher at diagnosis and had less improvement over the first 3 days of PARDS ( p < 0.001). Children with I-PARDS had greater nonpulmonary organ dysfunction. Adjusting for Pediatric Risk of Mortality IV and oxygenation index, children with I-PARDS had a higher severity of illness-adjusted PICU mortality (adjusted hazard ratio: 3.0 [95% CI, 1.9-4.7] p < 0.001) and were less likely to be extubated alive within 28 days (subdistribution hazard ratio: 0.47 [95% CI, 0.31-0.71] p < 0.001).

Conclusions: I-PARDS is a unique subtype of PARDS associated with hospitalization before diagnosis and increased: time at-risk for PARDS, NIV use, hypoxia, nonpulmonary organ dysfunction, and mortality. The opportunity for early detection and intervention seems to exist. Dedicated study in these patients is imperative to determine if targeted interventions will benefit these unique patients with the ultimate goal of improving outcomes.

Figure 1:

Figures 1a and b demonstrate the severity of PARDS and oxygenation failure over the first 3 days of PARDS. Figure 1A: Percentage of patients with severe PARDS over time stratified by immune status. The figure shows the difference in percentage of patients comparing those with PARDS (with no immunocompromising conditions ICC) (gray bars) to those with I-PARDS (with ICC) (black bars) at diagnosis, and the first three days of PARDS. Figure 1B: Median OSI trends over the 1^st three days of PARDS stratified by immune status. The figure shows trends in the median OSI every six hours over the first three days comparing those with PARDS (with no immunocompromising conditions ICC) (gray line) to those with I-PARDS (with ICC) (black line). Error bars represent the interquartile ranges for each time point. Using mixed effects longitudinal analysis to control for repeated measures within patients, those with I-PARDS had less improvement in OSI over time (p< 0.001) *p<0.05, **p<0.01, ***p<0.001

Figure 2:. Mortality stratified by PARDS severity.

Figure 2 illustrates mortality differences between those with PARDS (with no immunocompromising conditions ICC) (gray bars) and I-PARDS (with ICC) (black bars) stratified by initial PARDS severity and worst overall PARDS severity.