Pulmonary infections and respiratory illnesses are common in immunocompromised patients, some of whom may progress to such severity that they require admission to the PICU because of meeting criteria for pediatric acute respiratory distress syndrome (PARDS), or the state of “at-risk” of PARDS. Now, in this issue of the Pediatric Critical Care Medicine, Gertz et al (1) present data from a secondary analysis of the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology (PARDIE) study. Essentially, they would like us to consider immunocompromise-associated PARDS (I-PARDS) a unique subtype of PARDS. Hence, the questions for our community are: 1) can we recognize I-PARDS; 2) if we identify I-PARDS as different to PARDS, are there particular risks or vulnerabilities to supportive respiratory care and invasive mechanical ventilation (IMV); and 3) could knowing the diagnosis of I-PARDS alter what we do now?

In 2023, there were two studies published using the 2016/2017 PARDIE dataset. The first report examined the first 2 days of meeting criteria for being at-risk of PARDS and subsequent PARDS diagnosis, and treatments early in this time course associated with unfavorable outcome (2). The supplemental files included some details about comorbidities that were considered in the multivariable analyses, which included oncology/immunology diagnoses. In the accompanying editorial, there was a focus on the meaning of an association between platelet transfusion and PARDS progression (3). The second report studied the use of noninvasive ventilation (NIV) at PARDS diagnosis and the association with shorter exposure to IMV (4). Here, the authors found that half of the NIV-supported patients were eventually placed on IMV and, of many factors, immunosuppression was associated with NIV failure. The accompanying editorial highlighted the need to be vigilant for risk of NIV failure in the immunosuppressed, as well of the implications of the work in guiding how we should change to a 6-hour time-limited NIV-trial (5). (Cross reference with the Second Pediatric Acute Lung Injury Consensus Conference group international guidelines for the diagnosis and management of PARDS [6]). Now, with this background to the PARDIE dataset, Gertz et al (1) have concentrated on the category “at-risk of PARDS,” use of NIV, and NIV failure, in the one-in-seven PARDS cases in the PARDIE dataset with an immunocompromised state (1). So, in answer to our first question “Can we recognize I-PARDS?,” Gertz et al (1) show us that I-PARDS cases are hospitalized before the diagnosis of PARDS, they receive more support with NIV, and we are providing high-intensity medical care. We agree with the authors that more research is needed in these patients in the pre-PICU period, but do we have a strategy for identifying patients needing intervention early? We are reminded of the Study of early Continuous positive Airway pressure in acute Respiratory Failure randomized trial in children with impaired immunity, and the discussion around its failure to provide evidence to support early PICU admission for continuous positive airways pressure in children with acute respiratory failure and impaired immunity (7–9). Perhaps monitoring use of platelet transfusion in the pre-PICU period or another biomarker is one strategy that will be informative?

Our second question is whether there are risks or vulnerabilities when using supportive respiratory care and IMV in I-PARDS cases. Immunocompromised patients with respiratory failure are usually first treated in general departments and admitted to the PICU when in severe distress. The focus is often two-pronged: one, on medical treatment of potential infection and progression to multiple organ dysfunction; and two, on the appropriateness and timing of supplemental oxygen, use of NIV, and progression to IMV. The academically honest answer to the second question is that we do not know. We know a lot about the pathophysiology underlying approaches to NIV/IMV in PARDS, which has recently been discussed in the Journal, in a 2023 Pediatric Critical Care Medicine Concise Clinical Physiology Review (10). The mechanisms of volutrauma, barotrauma, and ventilator-induced injury, do not need to be repeated here. That said, it is worth noting that the PARDIE dataset is 7–8 years old, and we likely need more granular and contemporary information about I-PARDS cases undergoing NIV and IMV. Perhaps, too, we need to think about more modern approaches to evaluating the trajectory or time course in respiratory metrics during severe acute respiratory illness, as in the modified clinical progression scale (11).

The third question to address is whether we would, could, or should do anything different in I-PARDS cases in 2024? What follows is our speculation and bias. Do read on. Our bias is that appropriate nursing care is crucial in determining patient outcomes. This practice is exemplified by attention to detail. There is a strong body of evidence to support the importance of prompt mobilization and the management of sedation as needed (12). We also need to move forward with artificial intelligence (AI)-based systems in this space. For example, the PARDIE investigators have been exploring the use of a web-based platform for the automatic stratification of PARDS severity using the AI-assessment of chest radiographs (13). Finally, more attention will need to be given to real-time biomarkers that ultimately have potential to lead to interventions. Pediatric Critical Care Medicine has had a focus on PARDS, plasma biomarkers, and changing lung injury severity (14–16), but how is this to be translated into bedside care?

In summary, the report by Gertz et al (1) from the 2016/2017 PARDIE study generates lots of questions and connects much recent work in Pediatric Critical Care Medicine. We recommend reading all of the material, and this is an area of much needed research.

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