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pulmonary

New Pulmonary Faculty Join Children’s of Alabama

Left to right, Spencer Poore, M.D., Ryne Simpson, M.D., and Christopher Fowler, M.D. All three are assistant professors in the Division of Pediatric Pulmonary & Sleep Medicine, University of Alabama at Birmingham Department of Pediatrics.

The Division of Pulmonary and Sleep Medicine at Children’s of Alabama has added three physicians to its team.

Christopher Fowler, M.D.

Christopher Fowler, M.D., is used to the South, having completed medical school at the Medical College of Georgia, his pediatric residency in South Carolina, and his pediatric pulmonary fellowship at the University of Alabama at Birmingham. So leaving simply wasn’t on the table. “I enjoyed being here so much as a fellow that I really wanted to stay and keep working with this awesome team,” he said.

Dr. Fowler entered pediatrics because, as his wife put it, when he was on the pediatrics rotation in medical school, he was happiest and most excited to come home and tell her about his day.

The pulmonology specialty came after caring for his first cystic fibrosis (CF) patients, all of whom were hospitalized with pneumonia. “These kids had a lot going on. And they were very smart. They taught me all about their disease and how they take care of themselves when they’re at home and then how I should take care of them while they were in the hospital. I enjoyed getting to know them and learn from them so much that I decided pulmonology was the thing for me.”

His research focuses on investigating adrenal complications from steroids CF patients take. Chronic use leads to adrenal insufficiency, with symptoms mimicking a respiratory disease. Studies in adults with CF show that about 8 percent develop adrenal problems over a 10-year period, but there are no studies in children, he said. “I don’t know if it’s going to be as big a problem in children as it is in the adults. But I think it’s a good question to answer.”

When he’s not trying to answer complex research questions, Dr. Fowler can be found corralling his own children and playing the drums.

T. Spencer Poore, M.D.

Spencer Poore, M.D., is quite familiar with Children’s of Alabama, having completed his pediatric internship and residency in Birmingham. Now, after three years in Colorado for his pulmonology fellowship, he’s back as one of the pulmonology division’s newest faculty.

He chose Children’s for his first academic position because it provides the opportunity to treat a wide variety of patients, from urban to rural, with common conditions like asthma to extremely rare pulmonary conditions. “I wanted a big program that could expose me to anything and everything,” he said, “as well as springboard me into any direction I wanted to go given its world-renowned experts.”

He brought with him his research on fungal infections and lung inflammation in children with cystic fibrosis. “Fungus is an interesting organism in that in some people it causes infection and in some an allergic reaction,” he said. “And there’s probably some degree of overlap, but we don’t know the pathways. So it feels like chipping away at an iceberg.”

Whatever they find, he said, the recognition should go to the patients. “If it weren’t for the patients willing to help people they’ll never even meet, we couldn’t do this,” he said.

Outside of work, Dr. Poore enjoys cycling, both mountain biking and road biking.

Ryne Simpson, M.D.

Having grown up in Chattanooga, Tennessee, and attended medical school at the University of Tennessee in Memphis, Ryne Simpson, M.D., was not quite prepared for the weather when he completed his residency in Kansas City, Missouri, and his fellowship in Cincinnati, Ohio. So Children’s of Alabama — with its warm climate and proximity to his family — was a perfect fit. “I was tired of the cold Midwestern winters that never ended,” he said.

His focus on pediatric pulmonology comes from the “complex nature of the patients,” he said. “I enjoy that we get to do procedures like bronchoscopy, and also the continuity of working with the patients.”

Dr. Simpson’s prior research focused on identifying best practices for flexible bronchoscopy and chronic ventilation in children based on outcomes and readmission rates. He enjoys such quality improvement and systems process studies, he said, given their more immediate impact on clinical outcomes compared to basic or clinical research. “I don’t always have the mindset for multi-year longitudinal studies,” he said.

Since coming to Birmingham, he’s enjoyed trying new restaurants. Now that he has his own house, he said, he’s looking forward to getting a set of drums “and playing when I want.”

February 15, 2022 by childrensal

Inside Pediatrics, Pulmonology

Solving the Mystery of Lung Disease in Children with Sickle Cell Disease

Dr-Saadoon-Ammar-Pulmonology-Headhsot-Resized

Children’s of Alabama pulmonologist Ammar Alishlash, M.D.

If lung disease is the leading cause of death in children with sickle cell disease, then why aren’t pulmonologists more involved in their care earlier? That’s a question Children’s of Alabama pulmonologist Ammar Alishlash, M.D., wanted to answer. “I felt for us to take care of those patients, especially those with underlying lung disease, would serve them better clinically,” Dr. Alishlash said.

In the past, the leading cause of death in those with sickle cell disease was infections. But the use of prophylactic antibiotics changed that. Today, it’s acute chest syndrome (ACS), marked by shortness of breath, low oxygen levels and fever. Many patients progress to respiratory failure, and some die. Yet lung specialists are not usually involved in their care while in the hospital or after discharge. Instead, in most children’s hospitals they are managed solely by hematologists.

“The problem is, we don’t have any specific treatment targeted for acute chest syndrome,” said Dr. Alishlash. Instead, patients are managed with supportive therapy, including oxygen, fluids, antibiotics and sometimes invasive or non-invasive ventilation.

Now Dr. Alishlash is on a mission to change that dynamic. He’s launched a three-pronged research initiative: identifying risk factors for ACS to proactively recognize children with a higher risk, developing clinical pathways to prevent progression and mortality and researching novel therapies to treat the condition.

“I became interested in this condition because I feel that, as pulmonologists, we have experience with other lung diseases,” he said. “We can apply our knowledge from other lung diseases to the sickle cell population, which could open a lot of doors for diagnosis and new treatments.”

So far, Dr. Alishlash has instituted a clinical pathway to standardize the care children with ACS receive after admission. The pathway has been in place for about 18 months, and the results are encouraging, with a nearly 50 percent reduction in length of stay. In addition, all patients have survived. Previously, one out of every 100 children would die. “That’s pretty significant, especially when you’re talking about children, who are typically between 2 and 4 years of age when they are most likely to develop ACS,” he said.

Dr. Alishlash has also made progress in identifying risk factors for ACS in children with sickle cell disease. One is nocturnal hypoxemia, when oxygen levels drop at night. This seems to induce the sickling and is associated with increased risk of ACS.¹ He also found a correlation between the neighborhood where patients live and ACS, due to, he thinks, air quality, socioeconomic factors and greater stress.²

On the laboratory side, Dr. Alishlash and his team are using a sickle cell mouse model to test potential treatments as well as identify triggers. One interesting finding is that chlorine can cause sickling, leading to the release of heme from red blood cells, which is toxic to the lung endothelium and subsequent development of ACS. A medication called hemopexin, however, scavenges the free heme. When given to mice exposed to chlorine who developed ACS, hemopexin reduced the death rate from 80 percent to 20 percent.³

At the same time, Dr. Alishlash has started a twice-monthly clinic for sickle cell patients with underlying lung disease. The clinic is very busy, he said. “And patients’ outcomes are improving, which is very encouraging.”

¹ Nourani AR, Rahman AKMF, Pernell B, et al. Nocturnal hypoxemia measured by polysomnogram is associated with acute chest syndrome in pediatric sickle cell disease. J Clin Sleep Med. 2021;17(2):219–226.

² Alishlash, AS, Rutland, SB, Friedman, AJ, et al. Acute chest syndrome in pediatric sickle cell disease: Associations with racial composition and neighborhood deprivation. Pediatr Blood Cancer. 2021; 68:e28877

³ Alishlash AS, Sapkota M, Ahmad I, et al. Chlorine inhalation induces acute chest syndrome in humanized sickle cell mouse model and ameliorated by postexposure hemopexin. Redox Biol. 2021;44:102009. doi:10.1016/j.redox.2021.102009

August 27, 2021 by childrensal

Cardiology, Inside Pediatrics, Pulmonology

Saving Children with Pulmonary Hypertension – One Patient at a Time

Children’s of Alabama cardiologist Frank Bennett Pearce, M.D.

When the cardiology team at Children’s of Alabama heard the family history of a 6-year-old boy who presented with an episode of syncope, they knew immediately what was wrong. His father had undergone a double lung transplant at the University of Alabama at Birmingham to cure his pulmonary hypertension (PH). Now his son had been diagnosed with the same thing.

But that wasn’t the only problem. The boy had also developed a supraventricular tachycardia requiring radiofrequency ablation, which was successful.

“So we cured that,” said Children’s cardiologist Frank Bennett Pearce, M.D., the boy’s cardiologist. But then the patient continued having episodes of syncope, particularly during exertion. “When that happens in patients with PH, it’s because the blood can’t get through the lungs to the left side of the heart, limiting cardiac output,” said Dr. Pearce. To address that problem, Dr. Pearce and his team performed an atrial septostomy, creating a tiny hole between the atria in the atrial septum. Second problem fixed.

Discharged on oral medications, the child did well with close follow up for several years, said Dr. Pearce, although he was vulnerable to pneumonia and other infections.

Then in 2020, at age 13, he took a turn for the worse. “There are three principal metabolic pathways involved in treatment of PH,” said Dr. Pearce. Two—endothelin and phosphodiesterase—have effective oral drugs for treatment. The third, the prostaglandin pathway, is more difficult to address, he said. In the past, it required a central line for IV infusions of treprostinil, a prostaglandin pathway medication. “Most families are very reluctant to go to the central line because it creates major problems in their lifestyle and is a quantum leap in terms of the negative effects on these children,” he said.

However, treprostinil can also be administered subcutaneously through a small catheter and external pump, much like an insulin pump. Unfortunately, the day the teen was scheduled for cardiac cath and initiation of subcutaneous treprostinil, he became very cyanotic. “We didn’t think it was safe,” Dr. Pearce said. Instead, the boy was admitted to the CVICU on inhaled and oral prostacyclin inhibitors. Despite increasing the dosage, his disease progressed. Finally, the team put him on the intravenous form of treprostinil, and he improved. Eventually, they were able to transition him to the subcutaneous form of the drug via the pump, and he became the first patient at Children’s to be initiated onto subcutaneous treprostinil.

He’s now home and undergoing evaluation for a lung transplant. “He’s a typical teenage kid but able to deal with all these challenges and keep a pretty good attitude, thanks to support from his family,” said Dr. Pearce. “He just hangs in there.”

August 27, 2021 by childrensal

Inside Pediatrics, Pulmonology

Children’s of Alabama Muscular Dystrophy Care Center Offers Life-Saving Treatment for Rare, Fatal Disease

Brad Troxler, M.D., director of the Muscular Dystrophy Care Center (MDA) at Children’s of Alabama, chats with a patient. The MDA Care Center is the only MDA clinic in Alabama and one of only a few in the region.

The Muscular Dystrophy Care Center (MDA) at Children’s of Alabama sees about 280 patients a year with a wide variety of neuromuscular conditions. They require multidisciplinary care from neuromuscular specialists, neurologists, pulmonologists, genetic counselors and cardiologists, among others. They also need respiratory, physical and occupational therapies, nutritional counseling and social work support.

One of the most devastating conditions the clinic sees is spinal muscular atrophy (SMA), a rare autosomal recessive genetic disorder that is the leading cause genetic cause of death in infants. It is characterized by degeneration and loss of lower motor neurons, leading to muscle atrophy. Infants with the most serious form of the disease, Type 0, can be diagnosed prenatally and typically die before 6 months, while those with Type 1 begin showing symptoms around 6 months, require ventilation and typically die before age 2. Other types of SMA may not manifest until childhood or even adulthood and are less severe, although all of those affected experience some neuromuscular effects.

Until recently, SMA was primarily treated with supportive care. Today, however, there are two groundbreaking treatments and Children’s is the only MDA clinic in the state, and one of only few in the region, to offer both: nusinersen (Spinraza), approved for children and adults, which is administered in several doses the first year and annually after that; and onasemnogene abeparvovec-xioi (Zolgensma), a single-dose treatment approved for use in children with SMA Type 1 under age 2.

Both are gene therapies designed to address genetic mutations in the SMN1 and/or SMN2 genes, which make the protein required to control muscle movement. Both are also extremely expensive, with the first 10 years of treatment with Spinraza estimated at $4 million and a single dose of Zolgensma costing $2.1 million, making it the most expensive drug ever marketed.[1]

The cost could be worth it, though, given the benefits of the drugs. “Clinical trials showed huge improvement,” said Brad Troxler, M.D., who MDA Care Center director. Indeed, after four years, infants treated with Spinraza before they turned 6 weeks were still achieving and maintaining motor milestones such as walking and sitting without assistance, things SMA babies would not normally be able to do.[2]

Participants in the Zolgensma trials were demonstrating similar results, with all children who received the drug still alive at 2 years and none requiring ventilation.[3]

Don’t call the treatments cures, however, says Troxler. “‘Cure’ is a hard word to define,” he said. While improved, patients still don’t have normal neuromuscular function after receiving the drug, with some muscle weakness remaining and an increased risk of scoliosis and other issues related to the disease. “But if we give it early enough, they are able to walk and talk and eat so it’s pretty close to a cure,” he said.

The earlier the drugs are administered, the greater the benefit. “Time is neurons,” said Shelley Coskery, MSN, CRNP-AC, MDA Care Center coordinator. However, Alabama is one of the few states that doesn’t screen newborns for SMA, which could delay treatment until symptoms appear. “We’re working on it,” Coskery said. “We need to start treating these patients before they develop symptoms and then, hopefully, we will see fewer and fewer affected with the disease.”

Becoming one of the first centers to offer SMA treatments, she said, “puts us at the forefront of the gene replacement movement.” Indeed, the center is also beginning clinical trials for genetic therapies for children with Duchenne, one of the most common neuromuscular diseases.

The ability to provide such effective treatments to children who otherwise would have died before age 2 “is very profound,” Troxler said. “You can see the difference it makes on individual families in a really powerful way. Conversations historically been about how ‘this is a terrible disease that will likely end in your child’s death.’” Now, Troxler said, the conversation has changed to, “‘Your child has a horrible disease, but we have some therapies that are going to change what this looks like.’ It’s completely different.”

“There is a lot of excitement throughout the SMA community,” Coskery said. “We are very grateful when the parents send emails of the child standing and achieving milestones we didn’t think they would.”

[1] Thomas K. his New Treatment Could Save the Lives of Babies. But It Costs $2.1 Million. The New York Times. May 24, 2019.

[2] Biogen Announces New Data Further Establishing SPINRAZA® (nusinersen) as a Foundation of Care in Spinal Muscular Atrophy for a Broad Range of Patients. Available at: http://investors.biogen.com/news-releases/news-release-details/biogen-announces-new-data-further-establishing-spinrazar

[3] New Data Shows Long-Term Benefits of Zolgensma in SMA Patients. Available at: https://www.biospace.com/article/in-wake-of-data-manipulation-scandal-avexis-releases-long-term-efficacy-of-zolgensma-at-conference/

January 16, 2020 by childrensal

Inside Pediatrics, Pulmonology

Using Pharmacogenetics to Help Identify Patients with Cystic Fibrosis Most Likely to Respond to Targeted Therapies

Children’s of Alabama and the University of Alabama at Birmingham (UAB) are on a mission to determine how patients use Cystic Fibrosis Transmembrane Conductance Regulator modulators at the cellular level.

The discovery of the genetic mutation responsible for cystic fibrosis (CF) and the subsequent development of drugs that target this mutation, called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, together with improved supportive treatments, has revolutionized the management of the disease. Today, the median life expectancy of someone with CF has increased from age 10 in 1962 to 47, with many patients living into their 50s or 60s. With the newer drugs, many expect those with CF will be able to live a normal lifespan.

However, studies of the four currently available CFTR modulator therapies, three of which are combination drugs, find that between 20 and 25 percent of patients who should respond based on their disease’s genetic fingerprint don’t.^1,2 Given that the drugs can cost up to $300,000 a year, it is important to find biomarkers to identify which drug will be most effective for which patient.³Currently, the only option is a rectal biopsy followed by complicated testing or nasal brushing, neither of which are approved by the U.S. Food and Drug Administration, accepted by insurance or widely used.

Children’s of Alabama pulmonologist Jennifer S. Guimbellot, M.D., Ph.D., together with Steven M. Rowe M.D., who directs the Gregory Fleming James Cystic Fibrosis Research Center at the University of Alabama at Birmingham (UAB), and Edward P. Acosta, Pharm.D., who directs UAB’s Division of Clinical Pharmacology, are on a mission to change that. Their research focuses on how patients use CFTR modulators at the cellular level.

Until fairly recently, Guimbellot said, “We didn’t have the tools to measure levels in the tissue.” Now they can use a simple, minimally invasive test Guimbellot helped develop. The assay measures concentrations of CFTR modulators in plasma and nasal epithelial cells, which, like epithelial cells in the lungs, are the drug’s site of action. Obtaining the cells is simple and inexpensive, requiring only a nasal brush, and can be done repeatedly to monitor drug levels.

After obtaining cells from patients, Guimbellot said, her team found that while plasma concentrations seem to correlate with the drug response, concentrations in tissue differ from those in plasma.

The question is why.

The answer may be related to pharmacogenomics, or the genetic variation in the way individuals metabolize drugs. Thanks to the epithelial tissue assays, she said, “our lab found that there may be substantial differences in the levels of modulators and also of metabolism proteins in people with CF.” Thus, once the drug is delivered to the cell, the effect may differ between patients. For instance, one person may be a fast metabolizer and clear the drug quickly; while the other may be a slow metabolizer and the drug accumulates in the tissue.

The protein known to metabolize CFTR modulators, CYP3A4, is primarily active in the liver. But in about 20 percent of people, it may also be produced in other tissues. While Guimbellot’s team has not found CYP3A4 in the epithelial cells from CF patients they’ve examined, they have found substantial levels of mRNA from the almost identical CYP3A7 protein and its cousin, CYP3A5. “So we hypothesize the CFTR modulator drugs are substantially metabolized by those proteins since it’s so similar to CYP3A4, and that this could affect how well patients respond to the drug.” They also found wide variation in the expression levels of both, which could contribute to the amount of available modulator at the target site.

“By understanding how genetic variation may influence the expression of these proteins and how that might affect the amount of drug available to do its job in the target tissue we can then relate the findings back to whether or not a patient can be expected to respond well to it or not,” she said.

Which is the next step in their research.

The team’s work is currently funded by the Cystic Fibrosis Foundation.

[1] National Institutes of Health. Cystic Fibrosis. 2019; https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=36&key=C.

[2] Cystic Fibrosis News Today. Cystic Fibrosis Statistics. 2019; https://cysticfibrosisnewstoday.com/cystic-fibrosis-statistics/. Accessed June 19, 2019.

[3] Starner CI. How much is too much? Prime Therapeutics. May 31, 2019. Available at: https://www.primetherapeutics.com/en/news/prime-insights/2019-insights/Story_Cystic_Fibrosis_Treatments.html.

January 16, 2020 by childrensal

Pulmonology

Using Antisense Oligonucleotides to Improve CFTR Function in Cystic Fibrosis

Therapeutic development in cystic fibrosis (CF), a fatal pediatric lung disease affecting 1 in 3500 newborns annually, is rapidly advancing. “Although exciting progress has been made,” said Children’s of Alabama pediatric pulmonologist William T. Harris, M.D., an associate scientist at the Gregory Fleming James CF Research Center at the University of Alabama at Birmingham (UAB) who treats patients at Children’s of Alabama, “we are just midstream.”

Where previous advances focused on the downstream consequences of disease, such as malnutrition, chronic infection and mucopurulent secretion, recent drug developments target genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein itself. Dr. Harris’ research focuses on improving the efficacy of these agents, called CFTR modulators.

One key therapeutic clue is to identify why certain children with exactly the same CFTR genotype have widely different disease trajectories. Dr. Harris has studied the mechanisms behind this disease disparity and has discovered the mechanism through which transforming growth factor beta (TGF-β), a leading gene modifier of CF lung disease severity, inhibits CFTR functional expression. Dr. Harris now targets this mediator of disease progression as a therapeutic opportunity to optimize CFTR modulator response.

His research discovered that small, non-coding nucleotide sequences called microRNA (miRNA) regulate CFTR function. miRNA diminish gene expression by degrading the gene transcript or inhibiting protein translation. In CF, TGF-β stimulates miR-145 expression, which binds to and degrades the CFTR gene transcript. This prevents protein expression and diminishes channel function. Both TGF-β and miR-145 are markedly increased in CF lungs and airway epithelia, posing a significant barrier to effective intervention.

Introducing miR-145 antagonists to airway epithelia reverses TGF-β suppression of CFTR and potentiates CFTR modulator response. However, TGF-β signaling and miR-145 activity are involved in multiple functions throughout the body, raising concern for off-target consequences. “As CF outcomes improve, the tolerance for side effects becomes very low,” he said. “Thus, the therapeutic intervention must be highly specific with a clearly defined target that only blocks the effects on CFTR.”

Antisense oligonucleotides (ASOs) offer that option. These short nucleic acid sequences bind to specific molecules of RNA, regulating expression of the gene. The FDA has already approved a handful of ASOs to treat congenital pediatric diseases such as Duchenne muscular dystrophy and spinal muscular atrophy.

“ASOs are appealing in CF because they can be delivered directly to the lungs (via inhalation) to bypass systemic side effects,” Dr. Harris said. He is partnering with Ionis Pharmaceuticals, a leader in the development of ASOs, to test an ASO that prevents miR-145 binding to the CFTR transcript. This approach is called target site blockade (TSB).

“TSB offers a nuanced strategy to address the problem of CFTR inhibition without interrupting TGF-β/miR-145 availability for other regulatory processes,” he explained. “I expect oligotherapeutics to benefit CF patients across genotype and improve next-generation therapeutics whether that be small molecule correctors or evolving gene editing strategies.”

Get More Information
Learn more about the Cystic Fibrosis Center’s resources for physicians.

August 20, 2019 by childrensal

Pulmonology

Secondhand Smoke Exposure in Kids with Cystic Fibrosis May Impact Treatment Efficacy, Researchers Suspect

The introduction of cystic fibrosis transmembrane conductance regulator (CTFR) modulators, which target the basic genetic defect in cystic fibrosis (CF), has revolutionized the treatment of the disease over the past five years. With a new, triple CTFR modulator expected to be approved by the end of 2019, in the next year, 90% of those with CF may benefit from these new drugs. However, studies of currently available modulator therapies find that between 20% to 25% of patients who should respond based on their disease’s genetic fingerprint don’t.[1][2]

Researchers from the University of Alabama at Birmingham (UAB) think they may know why: patients’ exposure to secondhand smoke. Now they have embarked upon a study to test this hypothesis.

While it might seem counterintuitive that families with a child with CF would expose them to secondhand smoke, approximately one-third of pediatric CF patients are exposed to tobacco smoke, half of whom have been around a smoker in the past 3 months.[3] And yet, said Gabriela Oates, Ph.D., assistant professor in the UAB Division of Pediatric Pulmonary and Sleep Medicine at Children’s of Alabama and an associate scientist in the UAB Cystic Fibrosis Research Center, “many think their child isn’t exposed to the smoke if the family member is smoking outside.”

But that’s simply not true.

“We’re not just talking about secondhand smoke but also about thirdhand smoke exposure,” Oates said. Tobacco particulates remain on the hair, skin and clothes of the smoker, even if he or she smokes outside, and are also found on household surfaces. “You can find relatively high level of nicotine metabolites in the urine of kids whose parents smoke out of doors,” she said. In fact, children demonstrate exposure even if their household members do not smoke but they live in multifamily housing that shares a wall with a smoking household.

This all ties into the new CFTR modulators because in-vitro, animal and non-CF studies indicate that “even indirect exposure to tobacco smoke actually blunts the effect of the drug,” she said. So while the CFTR modulators are designed to correct the underlying genetic mutation that causes the disease, “the smoke exposure undermines that.”

Her project will define the consequences of secondhand smoke on CF respiratory decline and CFTR modulator response using both self-reported and objective measures of exposure such as urine biomarkers. Results will underscore the necessity of clinically driven smoking cessation programs for CF families and will inform recommendations for smoke exposure screening and control.

Given that most children exposed to smoke are clustered in the low-income segment of the CF population, this becomes a health equity issue, Oates said. “It’s particularly concerning because the smoke exposure may be outside of the household and there’s nothing the family can do about it,” she said. “I worry that in the era of CFTR modulators we may see an increased gap in CF outcomes between kids living in poorer environments and their advantaged counterparts. This issue needs to be watched carefully.”

Oates also fears that if her hypothesis is supported, payers may institute smoke exposure screening programs and base drug coverage on the results. This creates quite the conundrum for researchers like herself. “As scientists, we have a responsibility to determine why drugs work or don’t work,” she said, “yet we have little control over how the results of our science are used.” If her study does show that smoke exposure limits the benefits of CFTR modulators, she said, “the very first step is major education on several levels, including CF families, clinicians and insurance providers.”

Her team is being proactive in this regard, already holding interviews with current and former smokers who have a family member with CF, as well as with CF clinicians and other stakeholders. The goal is to develop materials to better inform caregivers and clinical providers about the impact of second-hand smoke and to test a smoking cessation intervention tailored to CF families. “You would be amazed that there is not a single U.S. study evaluating smoking cessation programs in the CF community,” Oates said.

[1] Hebestreit H, Sauer-Heilborn A, Fischer R, Kading M, Mainz JG. Effects of ivacaftor on severely ill patients with cystic fibrosis carrying a G551D mutation. J Cyst Fibros. 2013;12(6):599-603.

[2] Taylor-Cousar J, Niknian M, Gilmartin G, Pilewski JM, investigators VX. Effect of ivacaftor in patients with advanced cystic fibrosis and a G551D-CFTR mutation: Safety and efficacy in an expanded access program in the United States. J Cyst Fibros. 2016;15(1):116-122.

[3] Ong T, Schechter M, Yang J, et al. Socioeconomic Status, Smoke Exposure, and Health Outcomes in Young Children With Cystic Fibrosis. Pediatrics. 2017;139(2).

Breathe Easier

Learn more about the Cystic Fibrosis Center at Children’s of Alabama.

August 20, 2019 by childrensal

Pulmonology

Network for Change

Pulmonology_CFTN-LA

From his office on the south side of Birmingham, Alabama, pediatric pulmonologist Hector Gutierrez, M.D., shares his passion to help cystic fibrosis (CF) patients around the world. In addition to being director of the University of Alabama at Birmingham (UAB) Division of Pediatric Pulmonology and the Cystic Fibrosis Center at Children’s of Alabama, Gutierrez is also principal investigator of the Cystic Fibrosis Training Network for Latin America (CFTN-LA). He leads a specialized team whose goal is to establish CFTN-LA as a permanent presence in Latin America.

“Unlike the United States, most Latin American countries lack a center network to provide shared information and collaboration to help improve the care of patients. Because of this, they have been at a great disadvantage,” Gutierrez said. “A sustainable training program for CF centers can help improve quality of care, clinical outcomes and life expectancy for Latin American CF patients.”

The CFTN-LA strives to meet the same goals of the CF Foundation, which over the past 60 years has established itself as a global leader in rare disease research and advancement of new CF therapies in the U.S. The network aims to provide high-quality care for thousands of Latin American patients, to establish comprehensive, multidisciplinary CF centers and to address preventive barriers. Gutierrez said the network would open important avenues for future research and drug development.

“Several factors limit the optimal CF delivery of care in these countries,” Gutierrez said. “Whereas diagnostic testing and medications are increasingly available here in the United States, there has been a paucity of expert manpower and a lack of multidisciplinary team approach in Latin America.”

Gutierrez said the CFTN-LA would lay the foundation for a well-integrated infrastructure for CF centers and their teams, with future training efforts led in qualified Latin America centers, ensuring continued growth and sustainability of the network. Since 2014, Gutierrez has led eight benchmarking visits to Chile to help ensure access to high-quality care and establish the CFTN-LA. In turn, the Santiago, Chile-based Hospital Clínico San Borja Arriaran (HCSBA) CF team, among the partners in this endeavor, visited Birmingham for a two-week training to accelerate the project.

Because the current Latin America healthcare delivery systems do not integrate or share information, patients may change from one system to another without proper follow-up and data acquisition. In addition, some health professionals essential to the CF team work as independent contractors to both public and private systems, resulting in higher costs to insurers and families.

The CF Center at Children’s has proposed establishing a multidisciplinary CF Center in Santiago, Chile, providing care adhering to CF Foundation standards. Collaborative work has led to significant improvement in clinical outcomes and team expertise for a number of hospitals in Chile. In 2015, the HCSBA CF team was approached by five other Santiago-based hospitals that are now part of the project as affiliate hospitals. After the incorporation of the affiliate hospitals, the HCSBA CF Center renamed itself Regional CF Center Santiago.

“This project started with one center, one hospital, and other hospitals in Santiago started to get interested,” Gutierrez said. “They joined by participating in our visits in Chile, and we provided similar information and feedback, but the first center (HCSBA) that came to Birmingham became their leader and the point group for the others to learn from them.”

Efforts thus far have shown a marked improvement in nutritional outcomes, lung function and microbiology among CF patients cared for by the participating hospitals in Chile, Gutierrez said.

“We have been in discussion for two years with the government officials in Chile and other Latin American countries to work toward developing a solid CF network similar to what we have in the United States,” Gutierrez said. “We have explained the benefits, however, the structure of care deliveries, health care benefits, et cetera are different. Although we have started small, we feel we are making progress and hope to continue to do so in the years to come.”

A mentorship by high-performing, U.S.-based CF teams, namely Children’s, UAB and the Baylor College of Medicine in Houston, plans to expand and train Latin America-based CF teams in Chile, Mexico and Uruguay. The mentorship would continue the development of an effective, adaptable and scalable training program for both mentors and trainees, and adapt transformative care management to local resources, culture, customers and healthcare delivery.

Pulmonary Clinics
Learn more about some specialized pulmonary services at Children’s of Alabama.

December 28, 2018 by childrensal