About one in five U.S. children who develop pediatric Acute Respiratory Distress Syndrome (ARDS) dies each year. There are no known medications that benefit most patients with this condition. Clinicians provide primarily supportive care, such as ventilator management, sedation, nutrition, and fluid management.

One therapy in use is effective for some patients but not others. Now, a research team seeks to improve the ability of clinicians to identify which children could benefit from this therapy as well as which children are at greater risk of dying from ARDS.

“Our eventual goal is to find therapies that improve mortality for kids with this severe condition,” said Anoopindar Bhalla, MD, associate professor of clinical pediatrics at the Keck School of Medicine of the University of Southern California.

Dr. Bhalla is the primary investigator of a National Institutes of Health grant for a prospective observational study of mechanically ventilated pediatric patients with moderate to severe ARDS. The study will involve nine clinical centers, including the Children’s Hospital Los Angeles (CHLA), focusing on infants to young adults aged 21. Patients are enrolled in the study within 72 hours of the start of mechanical ventilation.

As part of Bhalla’s NIH-supported study, routine data from patient monitors will enable researchers to observe the effects of “elevated dead space,” which refers to the lowered amount of fresh breathing gas reaching the alveoli during each breath. Some ARDS patients have elevated dead space, while others do not.

Clinicians can calculate dead space from routine ventilator data points, revealing the alveolar dead space fraction (AVDSf). This study could validate previous single-center studies by Bhalla, showing that a higher AVDSf correlates with higher mortality risk. If so, the AVDSf could be a better indicator of lung dysfunction than oxygenation measurements for some patients.

The research group will explore the feasibility of using AVDSf to guide treatment options for different patient subgroups. A higher dead space marker may predict whether patients respond positively to nitric oxide therapy. Clinical trials have shown that nitric oxide therapy is effective for some patients but not others, and it can even harm patients. Findings from this study could help identify ARDS patients most likely to benefit from nitric oxide treatments.

“It could be simple for the bedside practitioner to calculate if a patient has very high dead space and then try nitric oxide, or this patient has very low dead space, so they’re unlikely to respond to nitric oxide,” said Robinder Khemani, MD, pediatric intensive Care Physician and Clinical Researcher at the CHLA, and a member of the study team.

The Bhalla group will examine patient blood samples to understand the underlying mechanisms of ARDS. By analyzing biomarkers in each patient, researchers will gain deeper insights into the biology driving ARDS, which is needed to guide new therapies.

Bhalla is a past recipient of the three-year KL2 Mentored Career Development award, supported by the Southern California Clinical and Translational Science Institute (SC CTSI). She credits the program with providing invaluable training and experience that allowed her to develop the NIH grant proposal. The program offers protected research time for clinicians, enabling scholars to conduct multidisciplinary projects. With this support, clinician-scientists can focus on designing, conducting, and analyzing studies in a team-based setting.

“Dr. Bhalla is an inspirational example of a successful scholar in the KL2-MCD program; she exhibits the key characteristics of a translational scientist. She committed herself to developing team science skill in addition to analytic skills,” said Elizabeth Burner, MD, PhD, who is the SC CTSI MCD-KL2 director. “Her work highlights the value that early-stage clinician scientists can gain from time dedicated to developing all these key skills.”

Bhalla expresses the value of the program, even though the road to being accepted into the program wasn’t easy.

“The KL2 program provides opportunities for a faculty member during a key part of our development,” Bhalla added. “It’s a competitive program—I applied four times before I finally got it—that offers focused time to understand how to advance your career.”

Bhalla gained critical data from her KL2 program research that allowed her to pursue this major grant.

“Some of the preliminary data we used to obtain the grant is from data we had gained during the KL2 program research,” Bhalla said.

One of the advantages of the KL2 program for Bhalla was the chance to develop relationships with mentors such as Wendy Mack, director of the SC CTSI Biostatistics, Epidemiology, and Research Design (BERD) core.

“I had an opportunity to meet people, including Wendy, one of the key personnel on this grant,” she said. “It has been a natural progression since my KL2 program experience to work with her on other research projects as well.”

Mack values the relationships she and her team members forge with researchers.

“Our BERD biostatisticians have the opportunity to develop early collaborative relationships with clinician investigators and provide key mentoring and insights into study designs, data collection, and analytic approaches,” said Wendy Mack, PhD, director of the BERD core at SC CTSI. “We are always excited to work with such promising early investigators as Dr. Bhalla and contribute to their research and translational research careers. Dr. Bhalla is a prime example of this, as we have provided biostatistical mentoring to her in K23-, R03- and now her R01-funded research.”