Flow of Change: Unmasking Variability in Respiratory Support for Pediatric Critical Asthma

Authors: Andrew G. Miller, Alexandre T. Rotta

Pediatric critical asthma, generally defined as an episode of acute severe asthma that requires critical care (1), is a common reason for admission to the pediatric intensive care unit (PICU) (2). In addition to standard asthma therapies (e.g., oxygen, corticosteroids, bronchodilators), children with critical asthma are often treated with noninvasive respiratory support (NRS) (3). NRS includes use of a high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and noninvasive ventilation (NIV) (4). Each modality allows precise control of fraction of inspired oxygen, delivery of heated and humidified inspired gas, and administration of inhaled bronchodilators (5). NRS is applied electively or as a rescue treatment in patients with severe respiratory distress or respiratory failure. Parsimonious deployment of NRS is desirable to accomplish optimal treatment of these high-risk patients, because overuse can result in longer length of stay (LOS) and improper use of finite PICU resources. The challenge of determining the optimal role of each NRS modality in pediatric critical asthma treatment is compounded by the paucity of high-quality data to guide decision making (3).

In this issue of AnnalsATS, Rogerson and colleagues (pp. 612–619) used the Virtual Pediatric Systems, LLC (VPS) database to characterize the variation in NRS use in pediatric critical asthma relative to center volume (6). The VPS is a robust, multicenter, multinational, quality-controlled database of curated demographic, treatment, and patient trajectory variables from participating centers. VPS has low granularity for important clinical variables, such as standardized measures of asthma severity, vital signs, ancillary tests, and intensity of respiratory support (e.g., gas flow, fraction of inspired oxygen, airway pressures). Although it captures the use of continuous albuterol and duration of NRS therapy, it does not consistently include important variables such as hospital LOS and medical decision making. Despite these limitations, studies using the VPS database can provide valuable insight into the epidemiology of NRS use, including changes in use patterns over time and practice variability among institutions, and can establish associations between treatments and outcomes.

Rogerson and colleagues (6) studied 77,115 patients between 2 and 17 years of age who received treatment for critical asthma between 2012 and 2021 in 1 of the 163 participating centers that contributed data to VPS for the entire study period. Most patients (56.9%) were treated without NRS. For those treated with NRS, HFNC was used in 28.8% of cases, NIV in 15.7%, invasive mechanical ventilation in 5.3%, and CPAP in 4.7%. There was significant variability in NRS use among institutions, with HFNC use ranging from 0 to 96%, NIV from 3.5% to 71%, invasive ventilation from 0% to 29%, and CPAP from 0.3% to 4.3%. There were marked increases in HFNC (11–53%) and NIV (3.7–21%) use over time, a modest increase (1.6–5.4%) in CPAP use, a non–statistically significant decrease (6.1–4.0%) in invasive mechanical ventilation use, and a marked decrease (81% vs. 35%) in conventional oxygen therapy or ambient air use.

Centers in the highest-volume quintile for critical asthma volume used less HFNC and more NIV and had lower rates of invasive mechanical ventilation. PICU LOS was also shortest in the highest-volume centers, although the absolute difference was small at 0.4 days (9.6 h). In a total of 4% of patients (2.8% for HFNC, 3.8% for CPAP, and 4.5% for NIV), NRS failed and intubation was required. Intubation was associated with earlier admission year (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06–1.11), decreasing age (OR, 1.5; 95% CI, 1.03–1.06), non-Black race (OR, 1.21; 95% CI, 1.04–1.42), and higher Pediatric Risk of Mortality-3 score (OR, 1.37; 95% CI, 1.35–1.40). In multivariable logistic regression, admission year was directly associated with the use of NRS and inversely associated with the use of invasive mechanical ventilation. Institutional volume was directly associated with the use of CPAP and NIV and inversely associated with the use of HFNC and invasive mechanical ventilation.

This study by Rogerson and colleagues (6) underscored the wide variability in the use of NRS in critical asthma between high- and low-volume centers, which is consistent with use patterns for other pediatric asthma therapies (7). There are several potential explanations for the observed differences in practice among lack of high-quality data to inform the use of specific NRS modalities, variable comfort level with different NRS modalities, equipment availability, institutional protocols and preferences, disparate criteria for PICU admission, provider bias, and resulting workload, just to name a few. The individual contribution of these potential factors is further obfuscated by a lack of detailed clinical data (e.g., vital signs, gas exchange, asthma severity scores) and the relative rarity of the need for intubation because of NRS failure.

We must be careful not to attribute a causal relationship between center volume and important patient-oriented outcomes, such as lower rates of invasive mechanical ventilation and shorter PICU LOS noted by Rogerson and colleagues (6). The striking disparity in critical asthma exposure between a low-volume center (average of 2.2 critical asthma admissions per year) and a high-volume center (average of 135.7 critical asthma admissions per year) could suggest that centers that more commonly treat children with critical asthma are simply better at it. However, a myriad of other factors may influence the association between center volume and outcomes. For instance, it is possible that high-volume centers use a lower threshold for asthma admission to the PICU (a self-fulfilling prophecy that drives case volume) with lower disease severity and faster recovery. It is also possible that high-volume centers have more efficient bed flow procedures where children on a recovery trajectory are readily transferred out of the PICU to an intermediate care unit or discharged directly to home (8), thus shortening PICU LOS. This study by Rogerson and colleagues (6) leveraged the VPS database to its limit while appropriately remaining within curbs dictated by its observational methodology. Additional attempts at speculation would be counterproductive, because large database studies cannot establish causation (only correlation). Instead, we would be best served by considering how their findings can inform next steps and future research.

Ultimately, Rogerson and colleagues (6) provide us with an interesting and useful characterization of NRS use patterns for critical asthma over the past decade. Their findings confirm what many of us have observed at our own that the use of NRS, particularly HFNC, has significantly increased over time, not just for asthma but also in other respiratory conditions (9), without clear observable benefit supported by high-quality clinical trials. Because of the methodological constraints inherent to observational database studies, their findings do not get us closer to understanding the precise role of each NRS modality in the treatment of critical asthma. However, the large practice variability noted by Rogerson and colleagues (6) indicates that the field would benefit from the development of clinical practice guidelines anchored by well-curated evidence, which are currently under development (PROSPERO record CRD42023409281; accessed January 27, 2024). The existing practice variability also suggests that there might be equipoise for the conduct of a pragmatic, prospective, randomized trial of NRS in pediatric critical asthma. It is clear from their data that such a trial would require meticulous stratification based on disease severity, with comparisons between HFNC and conventional oxygen therapy in a lower disease severity cohort and between HFNC and NIV in a sicker cohort. Moreover, the relative rarity of NRS failure necessitating intubation in the current era would make this an unsuitable primary endpoint for such a trial, so selecting alternative relevant, meaningful, and consequential endpoints will be of great importance. We look forward to subsequent work that builds on the findings of Rogerson and colleagues (6) to decrease practice variability (8, 10, 11) and provide clarity on the optimal respiratory support modalities across the broad spectrum of pediatric critical asthma.