Inside Pediatrics Spring/Summer 2026

DIVISION ROUNDS (cont.)

PULMONOLOGY

Patients with CF who now have access to this disease-modifying drug 90 %

New Study Explains ETI’s Effectiveness on Cystic Fibrosis A new study involving Children’s of Alabama pediatric pulmonologist Spencer Poore, M.D., and University of Alabama at Birmingham (UAB) pulmonologist George M. Solomon, M.D., answers a key question about a transformative drug for cystic fibrosis (CF)—how does it really work? The drug, a fixed-dose combination of elexacaftor, tezacaftor, and ivacaftor (ETI), is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator. When it was approved in 2019, it gave nearly 90% of patients with CF access to a disease-modifying drug. In the pivotal clinical trial, ETI significantly improved lung function and reduced pulmonary exacerbations while improving patient quality of life. But it wasn’t clear what made the drug work. Now, the PROMISE study provides part of the answer, clearly demonstrating that some of ETI’s effects are due to its ability to tamp down inflammation. Inflammation is the background noise of CF: always present, always active, contributing to lung damage, infections, fatigue, weight loss, and poor outcomes. Even when symptoms improve, some degree of inflammation continues unchecked.

487

223

Total participants in the PROMISE study

Participants specifically tracked for inflammation markers

But as PROMISE showed, ETI dramatically reduces that inflammation. The PROMISE trial is a prospective, multicenter, observational study following 487 people ages 12 and older with CF. A group of 223 participants agreed to participate in the inflammation sub-study, in which their blood and sputum were collected prior to starting ETI and then five times over the next 30 months. Within one month of starting ETI, airway inflammation markers fell sharply and remained low throughout the 30 months. At the same time, markers of system inflammation also significantly declined. As the authors wrote, “These changes represent a disease modifying benefit of this transformative therapy.” More work remains to be done. “We have not seen complete resolution,” Poore said. But, he noted, the set point has shifted. And this represents a shift in the disease itself. “What I was taught versus what I see now,” he added, “is different.”

NEONATOLOGY

A Closer Look at Chorioamnionitis

Chorioamnionitis occurs in 1–5% of births in the U.S.

1-5 %

Much of Jain’s research has delved into chorio’s potential health implications for babies once they’re born—and the effects can be devastating. One

The vast majority of preterm births—especially “micro-preemies” born at 22 or 23 weeks’ gestation—stem from a single cause: chorioamnionitis, an inflammation of the placenta and membranes surrounding the fetus. But Children’s of Alabama neonatologist Viral Jain, M.D., is on a mission to determine why the condition occurs, the ways it affects babies’ health, and how to stop it. Occurring in an estimated 1% to 5% of births in the United

of his studies shows that the incidence of cerebral palsy is far higher in infants born when chorio progresses to such a severe extent it becomes funisitis, or inflammation of the umbilical cord. To help predict the cerebral palsy risk of these infants while they’re still in the neonatal intensive care unit (NICU)—when early intervention can more easily be planned—Jain’s research has also used MRI to look for specific markers in the brain suggesting a high risk of the disabling condition. Another of Jain’s studies suggests that infants born early due to chorio have chronic lung damage. Ultimately, Jain says, his research—which has been funded by the American Heart Association and National Institutes of Health—seeks to learn how chorio propagates so doctors can impede its damage. “The goal is to find out what treatment we can give so when it’s just mild, we can stop the progression and it won’t become full-blown chorio and we end up delivering the baby preterm,” he said. “If we can do that, we can prevent a lot of organ damage to the lungs or brain.”

States, chorioamnionitis—often shortened to chorio— can be hard to spot. It’s typically diagnosed using clinical signs of inflammation, such as fever or elevated heart rates in either the mother or the baby. But chorio often eludes clinical diagnosis, silently causing damage to the placenta and triggering preterm birth, Jain says. Some of the extensive research conducted on chorio has focused on its causes, which may include infection, environmental chemicals, smoking, and bleeding. But scientists still have a poor understanding of why it happens, Jain notes, as well as how to catch it early enough to stop premature delivery.

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