Browsing Tag

pulmonology

Pulmonology

Teaching youth about the dangers of vaping

More than 5% of all middle- and high-school students say they use vaping devices. (Stock photo)

When Children’s of Alabama pediatric pulmonologists Isabel Lowell, M.D. and Brett Turner, M.D. speak to kids or their parents about vaping—which remains prevalent in middle- and high-school students despite a simultaneous decline in cigarette smoking—they continually find themselves battling the misconception that vaping is somehow safer.

Social media and advertisements for vapes, which are marketed in hundreds of teen-tempting flavors, have convinced kids that vaping isn’t the major health threat it is. But Lowell and Turner vigorously dispel such myths as part of a Youth Tobacco Prevention Program run in partnership with the Children’s of Alabama Tobacco-Free Task Force.

Brett Turner, M.D.

According to the U.S. Food and Drug Administration’s National Youth Tobacco Survey, about 5.2% of all middle- and high-school students say they use vaping devices, and 27.5% of those say they use these products every day.

“We’re uniquely positioned to take this on, since it’s an issue that affects both patients and families,” said Turner, who’s also the medical director of Children’s Respiratory Care Services and an associate professor of pulmonology at University of Alabama at Birmingham (UAB).

“This has been a very important part of how we provide education about vaping not only to kids in the community, but the Department of Pediatrics and the Division of Pulmonary Medicine,” added Lowell, who’s the medical director of Children’s Pediatric Pulmonary Care Unit and a professor of pulmonology and sleep medicine at UAB.

Lowell and Turner took over the program two years ago. Funded by a grant from the Alabama Department of Public Health, it involves several goals, including:

  • Teaching about the dangers of vaping to at least 1,000 students in grades 5 through 12 in Birmingham and the surrounding areas.
  • Providing anti-tobacco and vaping information at four or more community events.
  • Working with students at local middle schools and high schools to train them on vaping and facilitate their ability to lead peer-to-peer presentations.
  • Conducting 10 community adult presentations on the dangers of smoking and vaping.
  • Creating social media content on vaping to post on Alabama Department of Public Health social media sites.
  • Providing material and resources on vaping to school nurses and counselors, as well as answering questions.
  • Conducting assessments of vape and cigarette advertising at local gas stations and other retailers who sell vapes.
Isabel Lowell, M.D.

Independently of the grant, Lowell and the Pulmonary Asthma Team are surveying adolescents at Children’s severe asthma clinics on the use of vapes and cigarettes, as well as second-hand exposure. While anyone who vapes is exposed to many toxic chemicals that can damage and inflame airways and compromise the immune and cardiovascular systems, “in kids, there are harmful effects on the brain, affecting learning, impulse control, and mood,” Lowell said. “Vaping can also be especially dangerous for children with underlying lung disease.”

“We often see adolescent patients struggling to compete at the same level sports-wise as they had, feeling like they can’t take a deep breath,” Turner explained. “As we dig deeper into their social habits, we discover they’re vaping and that the timing of their respiratory symptoms aligned with when they developed chronic vape use.”

During their school presentations, Lowell and Turner also dispel the popular misconception that using nicotine boosts mood. In contrast, it “becomes something that drives more worry and fear and mood swings,” Turner said.

Students seem very open to the program’s message, Lowell and Turner say, and they plan to continue the program as long as funding remains. “We also provide them with resources to quit,” Lowell added. “If they’re vaping, they know there’s help out there, and people and programs they can go to that will help them without punishment.”

July 29, 2026 by
Pulmonology

Finding Early Warning Signs of CF-Related Kidney Disease

William “Tom” Harris, M.D., is a pulmonologist at Children’s of Alabama and UAB.

By Charles Buchanan

Cystic fibrosis (CF) is often defined as a disease of the lungs. But as advanced therapies help today’s young patients breathe easier and live longer—many will reach their 60s, according to the 2024 Cystic Fibrosis Foundation Registry—attention is shifting to the disease’s impact on other organs that may be vulnerable to the consequences of aging. This evolving landscape of CF clinical care has prompted Tom Harris, M.D., a pulmonologist at Children’s of Alabama and the University of Alabama at Birmingham (UAB), to investigate the kidneys.

“Interestingly, there’s more CFTR [cystic fibrosis transmembrane conductance regulator], the protein that causes cystic fibrosis, in the kidneys than the lungs,” Harris said. That means that as people with CF grow older, they face a higher incidence of chronic kidney disease than the general population, where the risk is about one in seven, according to Harris. Acute kidney injury (AKI), is more prevalent among people living with CF due to frequent antibiotic exposure and previous hospitalizations, and recurrent AKI is a major risk factor for development of chronic kidney disease. Harris also suspects loss of CFTR function takes away some of the kidney’s reserve.

Protecting the kidneys and other organs that express CFTR is crucial as lung disease stabilizes and people with CF age to help prevent health complications that can consume the patients’ hard-earned longevity. “The priorities of CF are changing,” Harris said. “We are now very much prioritizing quality of life across the years.”

Not every person with cystic fibrosis will develop kidney disease, of course. The challenge for researchers like Harris is to find biomarkers that will identify the ones at risk—and sound the alarm early enough for therapeutic intervention to preserve kidney function. “Right now, we are trying to establish which biomarkers are important and how they might indicate the progression of chronic kidney disease over time,” Harris said. Joining him in this mission are a team of scientists across the country who are part of a landmark project funded by the Cystic Fibrosis Foundation (CFF). Together they will follow a group of inpatients and outpatients for three years to study promising new diagnostic tools for CF-related kidney disease. They also are looking at kidney disease in the CF animal model that was pioneered at UAB. “We are very grateful to the CFF for having such vision to allow us to lay such a firm foundation to study kidney disease, combining both human observational study with mechanistic analyses in gene-edited animal models,” Harris said. “We are hopeful this project will allow us to pioneer the field of CF kidney disease and health.”

The researchers are focusing on urine in their quest to find novel biomarkers because of its direct connection to kidney health. Urine is “like a liquid biopsy,” Harris said. “With every urinary output, you can measure how well the kidney is working.” Physicians traditionally have tested urine or blood for elevated levels of specific proteins, electrolytes, and waste products such as creatinine to find proof of disease. But organ damage has already occurred by the time those reveal a problem, Harris said. Instead, he and his colleagues are investigating more subtle, sensitive measures that could flash the earliest warning signs of trouble. Candidates include kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), two urinary biomarkers indicating minute structural changes in the kidney that precede a deterioration in function.

“In addition to detecting which patients might have some evidence of disease, we also want to use those biomarkers to help us understand the pathways of disease,” Harris said. “Is it more fibrotic? Is it more inflammatory?” Exosomes, which are the molecular packages transmitted between cells, offer a prime example. Exosomes can be informative about the intercellular communication in health and disease, but they also often carry the mediators that affect change. For instance, neutrophil-derived exosomes may shed light on the inflammatory triggers of kidney disease.

Such detailed methods of diagnosis could hold promise for designing personalized treatments for patients. CF already is a precision medicine success story following breakthrough discoveries about the CFTR gene that causes the disease, including the distinct ways in which each CFTR mutation affects protein function. Some mutations impact how much CFTR is made; some affect how well CFTR gets to the cell surface; some impact how well CFTR transports electrolytes. Knowing each patient’s genetic mutation plays a role in the choice of CFTR-directed therapy.

Now, researchers are applying what they know about CFTR’s impact in the lungs to the kidneys, where they suspect it plays a different role. In the lungs, CFTR is needed to transport chloride ions, and a lack of it can cause airway secretions to thicken. But in the kidneys, CFTR is involved in acid-base metabolism, which may be disrupted in chronic kidney disease. “Part of the reason CF-related kidney disease has been overlooked previously is that, instead of being a disease of obstructed lumens from mucus plugging, the kidney disease is an organ of pH balance and fluid transport,” Harris said. Scientists want to pinpoint the specific cell types and regions of the kidney that are affected most by CFTR dysfunction. “CFTR expression is not the same across all cell types in either the lung or the kidney. In the lung, an ionocyte that is positioned near mucus glands is the highest CFTR-producing cell,” Harris said. “Investigators at UAB have recently discovered a similarly high CFTR-expressing cell in the kidney. Future steps will be to define how this high CFTR-expressing cell promotes renal health.” These findings could illuminate new targets for potential treatments to protect kidney function and help patients thrive as they age.

“The future’s bright,” Harris said. “CF has primarily been considered a pediatric disease. Now it’s very much an adult disease. And we as pediatricians have to think about the future . . . to transition our focus from disease to health—and to celebrate the wonderful, previously unimaginable question of how can we help our pediatric patients with CF age well into senior adulthood.”

For more information about Harris’ research, check out this episode of the Children’s of Alabama PedsCast.

July 24, 2026 by
Pulmonology

New study explains ETI’s effectiveness on Cystic Fibrosis

A new study’s findings “moved the needle” on researchers’ understanding of how ETI works. (Stock illustration)

The 2019 approval of the transmembrane conductance regulator (CFTR) modulator elexacaftor, ivacaftor, and tezacaftor (ETI) for cystic fibrosis (CF) dramatically changed the landscape of the disease. For the first time, nearly 90% of those with CF had 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 exactly how the drug worked still needed explaining.

Now, a major new study, called PROMISE, involving pediatric pulmonologist Spencer Poore, M.D., and University of Alabama at Birmingham (UAB) pulmonologist George M. Solomon, M.D., clearly demonstrates 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.

But as PROMISE showed, ETI dramatically reduces that inflammation. The PROMISE trial is a prospective, multi-center, observational study following 487 people ages 12 and older with CF. A group of 223 participants agreed to participate in the inflammation substudy, in which their blood and sputum were collected prior to starting ETI and then five times over the next 30 months.

The team measured markers of inflammation in the lungs, including neutrophil elastase (NE), a powerful enzyme linked to tissue damage; calprotectin, a marker of neutrophilic inflammation; and pro-inflammatory cytokines such as IL-1β and IL-8. In the blood, they tracked levels of the inflammatory markers high-sensitivity C-reactive protein (hsCRP); calprotectin; and HMGB-1, another inflammatory mediator. All are tied to lung destruction, bronchiectasis, exacerbations and outcomes.

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 (hsCRP and calprotectin), also significantly declined.

As the authors wrote, “These changes represent a disease-modifying benefit of this transformative therapy.”

What made the findings even more powerful was how closely inflammation tracked with clinical outcomes. So, lower neutrophil elastase levels meant better lung function, while lower hsCRP led to improved respiratory symptoms. Interestingly, an increase in airway IL-6 also correlated with improved lung function, a puzzle since IL-6 is often thought of as inflammatory. However, the authors noted, it also plays a role in regulating inflammation. This suggests its increase may reflect a shift toward a more normal immune response rather than chronic destructive inflammation.

Although ETI quelled much of the inflammation, it was still there, especially in older patients and those with more advanced lung disease.

“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, he said. “What I was taught versus what I see now is different.”

This includes fewer patient admissions; less dependence on feeding supplementation, advanced feeding support and feeding tubes; improved growth; and more stable disease.

One of the biggest questions lies with children who start therapy very early given that ETI is now approved for kids as young as 2.

If they never experience that chronic inflammatory engine, “what does their health and outcomes look like when they’re 25?” Poore asked. Does early treatment prevent the damage entirely? Or does it simply delay it? “We’ve moved the needle,” he said. “But how far?”

That uncertainty is fueling ongoing research. “This isn’t done,” he said. “This is a living, breathing assessment.”

February 17, 2026 by
Pulmonology

Bringing Asthma Care Closer to Home in Alabama’s Black Belt

Dr. Isabel L. Virella-Lowell with a patient.

Dallas, Marengo, Perry and Wilcox counties, part of the Black Belt (so named for its rich, dark soil), are four of the poorest counties in Alabama. They also have some of the highest rates of childhood asthma—nearly 12% compared to the state’s 8%—and are severely underserved when it comes to medical care. Two of the counties don’t even have a pediatrician.

Yet just 4% of the more than 5,000 patients seen at Children’s of Alabama’s Specialty Asthma Clinic hail from those areas. “We realized these kids weren’t getting to us for help,” pediatric pulmonologist Isabel L. Virella-Lowell, M.D., said. “But Medicaid data showed a high number of asthma-related claims from the area. So we knew there was a gap.”

One reason is distance, with families having to drive up to three hours to reach Birmingham. Thus, many children receive care only during asthma flare-ups at urgent care clinics or emergency rooms rather than ongoing, preventive treatment, said Children’s and University of Alabama at Birmingham (UAB) Pediatric Asthma Program Director Teresa G. Magruder, M.D. Without a primary care physician overseeing their child’s asthma, families find themselves caught in a cycle of crisis-driven care.

So instead of hoping kids will come to Birmingham, Virella-Lowell and Magruder are bringing their expertise to the Black Belt. Their mission: improve those dismal asthma statistics by engaging the community at a grass-roots level.

The initiative began when Children’s and UAB infectious disease specialist Claudette Poole, M.D., spent time in the area studying water sanitation and parasites. She kept hearing about an asthma crisis and recruited Virella-Lowell and Magruder.

The three applied for and received a Health Resources and Services Administration (HRSA) grant, which provides salary support for the core team and local community and health care partners. It also helps fund the virtual continuing medication education (CME) Project ECHO sessions, health fairs and supplies—such as spirometers and educational materials.

Magruder and Virella-Lowell stress the community-based approach of their efforts rather than having Children’s swoop in for just a few months. “We are really trying to improve the capacity of the community and their understanding of delivering asthma care in their own communities,” said Magruder. That means educating the front-line people caring for children, including school nurses, teachers, daycare workers and parents, while providing access to subspecialty care for the severe high-risk patients.

“If the community doesn’t buy in, if they are not engaged, if they’re not supportive, then there’s a limited amount of good we can do,” Lowell said.

“There’s some fatigue in these communities from programs that come and go,” Magruder added. “We know it takes time to build trust.”

The two doctors are also partnering with local physicians at Selma Pediatrics and Whitfield Regional Hospital in Demopolis. They hope to open a monthly clinic in 2026 in a space provided by Selma Pediatrics, so families don’t have to travel so far for specialty care.

They are also educating clinicians and others who see children with asthma through the aforementioned CME approach Project ECHO (which stands for Extension of Community Healthcare Outcomes), an interactive program that helps clinicians address their own cases. “It’s incredibly important that local physicians are comfortable managing asthma. And asthma care has changed a lot through the years,” said Lowell, who noted the recent release of new guidelines for diagnosing and treating the disease. The program, which is virtual, is available to any clinician throughout the state and beyond who’s interested in maintaining their expertise in pediatric asthma.

The Alabama State Asthma Coalition, a statewide group with a diverse mix of experts including environmental experts and respiratory educators, is also playing a role. The coalition helped train the first group of community health workers and hopes to continue that work.

Given that asthma affects one out of 10 children, it must be managed locally, Lowell said. “There’s no way that we will ever be able to manage all the really sick asthmatics here at Children’s. So it’s incredibly important that local pediatricians and family doctors are comfortable managing asthma.”

“Our goal is to raise the level of asthma care across the state,” Magruder said, “not just at Children’s, but everywhere kids need it.”

July 29, 2025 by
Neonatology, Pulmonology

Improving lung function for COPD and BPD patients

A study led by Children’s researchers shows that inhalation of live Lactobacilli reduces inflammatory markers in BPD and COPD.

By Jeff Hansen, UAB

In preclinical models, the inhalation of a mixture of living Lactobacilli bacteria attenuated pulmonary inflammation and improved lung function and structure for the chronic lung diseases bronchopulmonary dysplasia (BPD) and chronic obstructive pulmonary disease (COPD).

This study, published in the journal Nature Communications, determined the mechanism of this live biotherapeutic product—a powder mixture of living Lactobacilli bacteria—to reduce neutrophilic inflammation and reduce a broad swath of inflammatory markers in BPD and COPD, says Charitharth Vivek Lal, M.D., a neonatologist at Children’s of Alabama and the University of Alabama at Birmingham (UAB). Lal co-led the research with Amit Gaggar, M.D., Ph.D., a UAB pulmonologist.

Their findings “provide a paradigm for the progression of structural lung disease,” Lal said, because they identify the Lactobacilli as critical to regulating lung protease activity that is linked to the destruction caused by matrikine generation, extracellular matrix turnover and chronic neutrophilic inflammation that damages air sacs in the lungs. 

A possible protective role for Lactobacilli in the lung and the possible use of Lactobacilli to treat chronic lung disease had its foundation in 2016 when Lal and UAB colleagues discovered that the airways of infants with severe bronchopulmonary dysplasia had decreased numbers of Lactobacilli, increased numbers of proteobacteria and increased concentrations of proteobacterial endotoxin. In this latest study, the UAB researchers provided a mechanism of action for the Lactobacilli treatment to decrease downstream disease development and showed safety and effectiveness of the live biotherapeutic treatment in a mouse pup model for BPD and three mouse models of COPD. 

Bronchopulmonary dysplasia develops in some extremely premature infants after damage induced by high oxygen tension or mechanical ventilation needed to keep them alive. COPD occurs in older people, especially smokers, and kills about 130,000 Americans a year and about 3 million more worldwide.

“Inhaled live biotherapeutic products show promise in addressing common pathways of disease progression that in the future can be targeted at a variety of lung diseases,” Lal said. “Preclinical animal data is suggestive, and safety of the potential drug in humans will be tested in a forthcoming clinical trial. Human adult safety data in COPD will help de-risk the pathway to approval for use of the drug in bronchopulmonary disease infants.”

The UAB researchers hypothesized that mouse models of BPD would show heightened levels of acetylated proline-glycine-proline, or Ac-PGP, an extracellular matrix-derived peptide, as had been seen in premature infants with BPD.

This was demonstrated in BPD mouse models, and gain- or loss-of-function studies showed the impact of Ac-PGP. Intranasal instillation of Ac-PGP increased neutrophilic inflammation and lung degradation. When an inhibitor of Ac-PGP was given with the Ac-PGP, markers of neutrophilic inflammation decreased and lung structure improved.

Researchers then showed that a proprietary Lactobacilli blend of L. planatarum, L. acidophilus and L. rhamnosus performed best in synergy to reduce the inflammatory proteinase MMP-9, which helps release the Ac-PGP from extracellular matrix. Furthermore, supernatant from Lactobacilli growth medium also reduced MMP-9 at a similar magnitude as live Lactobacilli bacteria. 

A key finding was that L(+) lactic acid, which is produced in Lactobacilli growth medium supernatant, reduced MMP-9 in vitro, showing an important role for this lactic acid as an anti-inflammatory molecule. Researchers found that live Lactobacilli in the lungs provided an ongoing, sustained release of L(+) lactic acid in a controlled and well-tolerated manner.

A major technological advance reported in the study was creating the inhaled Lactobacilli powder through particle engineering—particles small enough to reach deep into the lungs while preserving viable bacteria. This live biotherapeutic product was then tested in the BPD and COPD models. In the COPD mouse models, the blend successfully reduced inflammation in the lung microenvironment whether treated concurrently or post-injury, showing anti-inflammatory effects, decrease of several pro-inflammatory markers and elevation of the anti-inflammatory marker IgA. 

An interesting finding was the favorable performance of the live biotherapeutic product. It reduced MMP-9 and other pro-inflammatory cytokines as effectively as—or in some cases better than—fluticasone furoate, a United States Food and Drug Administration-approved inhaled corticosteroid found in COPD combination therapies. 

Safety and biodistribution studies in one of the COPD mouse models showed that inhalation of the bacterial powder did not initiate adverse reactions or disease, and the Lactobacilli did not translocate to distal tissues or accumulate in the lungs.

January 8, 2025 by
Pulmonology

Addressing the increase in pediatric sleep disorders

The Children’s of Alabama Sleep Disorders Center is taking a multifaceted approach to pediatric sleep disorders. (Stock photo)

Pediatric sleep disorders affect 25-40% of children and adolescents in the U.S. However, the incidence is increasing, said Brad Troxler, M.D., who directs the Children’s of Alabama Sleep Disorders Center. The reasons for the increase are multi-factorial, Troxler said, but the problems are exacerbated by expanding screen time, which affects the quality of sleep; childhood obesity, which increases the risk of obstructive sleep apnea and other sleep disorders; and the after-effects of the pandemic, when sleep schedules were disrupted. Troxler and his team are addressing the increase through innovation, research and training.

About the center

The Children’s Sleep Disorders Center is the only multidisciplinary pediatric sleep disorders program in Alabama and one of just a handful of in the country. It features a 12-bed unit, in which the team performs about 2,000 overnight sleep studies and up to 100 daytime studies each year. Most patients are seen for insomnia, daytime sleepiness and snoring, as well as chronic conditions like sleep apnea, narcolepsy, idiopathic hypersomnia and periodic limb movement disorders.

Troxler

The pediatric sleep program differs significantly from adult programs in its approach, Troxler said. “Certainly, a pediatric sleep program is going to be much more patient and family centered and more holistic than what you might see in an adult sleep center,” he added. In addition, it requires more technicians and nurses—usually one for every two patients—to make children, especially those with autism or other developmental disabilities, feel comfortable with the electrodes and other equipment required for a sleep study.

“Pediatric patients require lengthier visits,” sleep specialist Mohini Gunnett, M.D., said. “And there’s definitely a need for more specialized protocols for the complex scenarios children can present with.” The team also manages many comorbidities associated with sleep disorders, particularly pulmonary conditions.

Innovation

“We are always trying to create and improve on innovative models of care,” said Gunnett, who’s also an assistant professor in the Division of Pulmonary and Sleep Medicine. For instance, she recently worked with pediatric otolaryngologist Philip Rosen, M.D., to implant the first pediatric patient with an upper airway stimulation device to assist with management of sleep apnea.

Gunnett

This nerve stimulator device, which is currently approved for patients with Down syndrome, works by producing gentle pulses to the nerve that controls airway muscles and tongue movement, helping keep the airway open and the tongue protruded forward so breathing is more comfortable during sleep.

“We are excited to see how this intervention can help manage sleep apnea in a population that often struggles to achieve control of their sleep apnea with conventional positive airway pressure therapy alone,” Gunnett said.

Research

Research is also becoming more of a focus in the program. Anis Nourani, M.D., an assistant professor in the Division of Pediatric Pulmonary and Sleep Medicine, is creating a database that can be used for research and quality improvement projects, and the team recently received multiple grants to study behavioral modifications for certain sleep disorders. Several other grants are pending. “The research component is growing and adding to the fun of the job,” Gunnett said. “Hopefully, it will lead to even better patient care improvement and growth in our group.”

Training

Nourani also serves as the director of the Sleep Medicine Fellowship Program, which is one of the few programs of its kind in the country, training a pediatric and an adult specialist each year. Nourani says the fellowship is crucial given a significant shortage of pediatric sleep specialists nationwide. Currently, there are only about 420 pediatric board-certified sleep medicine specialists in the U.S., or just 0.51 sleep physicians for every 100,000 children.

Nourani

To address this gap, the team at Children’s is working to incorporate more sleep education into the curriculum for medical students and residents, hoping to spark interest in the field and encourage more trainees to pursue sleep medicine fellowships. Students are also now rotating through the center. And, as more research emerges about the complex relationship between sleep and health, more practitioners are becoming interested in the field, Nourani said, including those from primary care, pulmonary medicine, neurology and anesthesiology.

The basics

Despite new technology and innovative treatments for sleep disorders, the basics for getting a good night’s sleep remain the same: “Creating a consistent bedtime routine that limits screen time and does not vary widely from day to day,” Troxler said.

August 9, 2024 by
Pulmonology

Developing treatments for patients with the most severe Cystic Fibrosis

Dr. Isabel Virella-Lowell and the pulmonology team at Children’s of Alabama are working on two clinical trials to help CF patients.

The evolution of cystic fibrosis (CF) treatment is considered one of the major success stories in medicine, with average life expectancy for patients skyrocketing from early teens in the 1970s to well over 50 years today. But Children’s of Alabama specialists continue dogged efforts to help the 5% of CF patients who don’t qualify for or respond to groundbreaking disease-modulating drugs—which Children’s faculty helped develop and test—that have transformed CF treatment over recent years.

Co-directed by Isabel Virella-Lowell, M.D., and George “Marty” Solomon, M.D., the University of Alabama at Birmingham (UAB) Cystic Fibrosis Therapeutics Development Center—a joint pediatric and adult endeavor—boasts more than 25 years of prominence in CF research. Nationally recognized as one of the top centers of its kind, it’s one of only 13 national resource centers for the more than 90 clinical trial centers that comprise the CF Clinical Trials Network.

Gene mutations in an epithelial membrane protein called CFTR trigger chloride transport defects that drive CF symptoms. Much-heralded disease-modulating drugs to target those defects—including Trikafta, a triple combination therapy approved in 2019 to treat patients with the most common CF mutation—have greatly improved both health and quality of life for the vast majority of these patients, Virella-Lowell said.

But the research team wants all CF patients—about 30,000 in the United States and 70,000 worldwide—to have those same advantages.

“About 5% of patients don’t have a life-changing medication,” Virella-Lowell explained. “The answer for them will be introducing a corrected gene or fixing the CFTR gene with gene editing techniques so the epithelia will produce its own normal chloride channels. If genetic therapies are successful, they could be extended to the entire CF population. Ultimately, the goal is to develop a genetic therapy that cures cystic fibrosis.”

Two of the team’s current clinical trials are focusing on these potential approaches. One is an mRNA-CFTR therapy, while the other is an adeno-associated virus (AAV)-based CFTR gene therapy. Both are phase 1 trials to determine safety and potential side effects. Other genetic therapy trials are in the pipeline as well.

With this research, the UAB CF Therapeutics Development Center is again setting itself apart in the region. It’s one of only four centers in the Southeast conducting the mRNA genetic therapy trial and one of only three performing the AAV gene therapy trial.

January 19, 2024 by
Pulmonology

CF Research Cooperative Expands Patients’ Options

A mother helps her son use a nebulizer. (Stock photo)

In the last few decades, scientific collaboration has played a vital role in improving quality of life and extending life expectancy for patients with cystic fibrosis (CF). Now, the members of a new cooperative hope that sharing their research and expertise will lead to more progress. The Southeast Cystic Fibrosis Research Cooperative connects specialists from about two dozen high-volume centers across the Southeast region, including Children’s of Alabama. Members have been meeting for the last year with the goal of advancing a sea change in available CF treatments.

Launched by the Cystic Fibrosis Foundation, the research cooperative blends a social component with the work of effectively treating CF, for which breakthrough therapies targeting gene defects have transformed care in just the last several years. Members of the cooperative—who, in many cases, have attended the same medical conferences over the years—have held virtual meetings in recent months but hope to gather in person as more join the group.

“Our region is big, and our patients are spread out—all the way from eastern Texas to the tip of Florida,” Children’s of Alabama pulmonologist and sleep medicine specialist Christopher “Miles” Fowler, M.D., said. “Every big center is working on different research and has different strengths to offer, so I think we’re all bringing something different to the table.”

About 600 CF patients are receiving treatment at any given time from the combined adult and pediatric program at Children’s and the University of Alabama at Birmingham (UAB). “There are more than 30,000 patients with CF in the United States, and the Southeast represents a big percentage of those patients,” Fowler said.

Accordingly, each CF center in the Southeast is tackling diverse aspects of CF, from groundbreaking gene therapy studies to clinical trials assessing new infection-fighting protocols or ways to optimize nutrition or exercise. UAB will soon be enrolling patients for gene therapy trials, but other centers in the region will be analyzing both similar and different gene therapy endpoints.

“There are going to be different options: The drugs will be different, and the risks will be different,” Fowler explained. “There’s a need to disseminate information about the trials being offered and educate providers about the risks and benefits of the drugs we’re still learning about. That’s been part of our focus.”

Ultimately, CF patients here and elsewhere should greatly benefit from the research cooperative’s efforts, Fowler said. The collaboration makes it easy for patients to learn about trial options and for centers to refer patients to other studies.

“There’s so much going on with cystic fibrosis that I think it’s impossible for any one center to do all of this,” he said. “We all have different resources and expertise that allow us to do the studies we do, so one way the regional cooperative helps is by making more types of studies available to patients in our region.”

August 25, 2023 by
Pulmonology

Interventional Pulmonology Now More Common for Kids

New technology is enabling Children’s of Alabama pulmonologists to offer more interventional procedures.

In his career as a pediatric pulmonologist at Children’s of Alabama, Ryne Simpson, M.D., has typically cared for children with conditions such as cystic fibrosis, prematurity and asthma. But as more children born with premature lungs survive and require tracheostomies and ventilators at home, “the flavor of the field has changed a bit,” Simpson said, “and interventional pulmonology is becoming more prevalent in pediatrics.” That’s why earlier this year Children’s began using new technology to offer more interventional procedures to its patients.

Interventional pulmonology is a subspecialty of pulmonary medicine dealing with minimally invasive, advanced bronchoscopic procedures, an example being removal of foreign bodies or other non-native material. Previously, that required surgery or a referral to an otolaryngologist, but both strategies have limitations. “Pulmonologists receive specific training in pediatric lung disease, which a surgeon or ENT physician may not always have,” Simpson said. With specialized equipment, “it can be a better situation for the patient.”

Historically, that equipment has been better suited for use in adults, and adult pulmonologists perform many more interventional procedures than pediatric pulmonologists. Thanks to the development of smaller tools and equipment, Children’s of Alabama can now offer certain interventional procedures to its patients.

One example is flexible bronchoscopic cryotherapy, something previously offered only in the adult setting. Children’s began using it in February 2023. It involves performing a bronchoscopy, then using a special probe to freeze a foreign body, piece of tissue or blood clot and pull it out for examination. “Previously, it could take hours because we often wouldn’t get the whole thing at once,” Simpson said. “Now we’re able to complete these procedures in significantly less time, which has been pretty amazing for the patients.”

Children’s also is working closely with the adult interventional pulmonology program at the University of Alabama at Birmingham (UAB), which has even more sophisticated equipment—such as robotic bronchoscopy—that in some cases is small enough to be used in the pediatric setting.

“It’s been a nice marriage between adult pulmonology at UAB and pediatric pulmonology at Children’s,” Simpson said. The pediatric department has been able to borrow certain equipment or, if needed, send children to UAB pulmonologists for help. “Sort of like: ‘You have the equipment, we have the knowledge, we can work together to get something done that previously we would have never been able to do,’” he said.

August 25, 2023 by
Pulmonology

New Protocol Dramatically Improves Outcomes for Children with Acute Chest Syndrome

An initiative led by Dr. Ammar Saadoon Alishlash is helping children with acute chest syndrome.

Acute chest syndrome (ACS) is a respiratory disease that starts suddenly, progresses rapidly and is the leading cause of death in children with sickle cell disease in the U.S. and other countries. However, in the last three years, since Children’s of Alabama instituted a standardized ACS protocol, there have been no ACS-related deaths among the hospital’s patients included in the protocol.

Children’s admits as many as 100 children with ACS every year, and the new protocol has improved outcomes among these patients, decreasing the average number of inpatient days from seven to four (a 42% drop) and reducing ICU admissions and mortality.

“We did not expect such significant results,” pediatric pulmonologist Ammar Saadoon Alishlash, M.D., the leader of the initiative, said. When the initiative began, it was up to each child’s physician whether to follow the protocol or standard procedure because it wasn’t clear if the protocol would actually improve outcomes. “But now we’re pushing to have all patients diagnosed with acute chest syndrome be put on the protocol,” he said.

The protocol is based on the latest evidence on the management of ACS. It includes order sets for tests and medications that are embedded in the electronic medical record, which makes it possible for the patient to receive appropriate care in the emergency room rather than waiting until they’re admitted. It also provides three order sets depending on where the child is in the hospital: in the emergency department, the hematology floor or the ICU. “Each has a specific set of orders designed for that specific population to improve outcomes wherever they are in the hospital,” Alishlash said. The standardization also reduces variation in how physicians treat the patients, which is one reason for the improved outcomes, he said. The protocol involves initiating therapy early in the emergency department before the condition progresses. The main interventions include oxygen supplementation and respiratory support.

To further improve ACS outcomes, Alishlash, who leads the pediatric pulmonary sickle cell disease program at Children’s and the University of Alabama at Birmingham, is performing clinical and laboratory research on the condition. He received a National Institutes of Health grant to study the effects of environmental exposures on its development and to test novel therapies. He has also identified risk factors for ACS, including low oxygen levels during sleep and an association between where the child lives and the condition. “To prevent death in these small children is a great achievement,” he said. “Hopefully it will dramatically improve outcomes in our sickle cell patient community.”

January 17, 2023 by