research on cystic fibrosis

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Cystic Fibrosis Research

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Cystic fibrosis is a life-shortening genetic disease that affects many organs of the body, especially the lungs. No cure for cystic fibrosis exists yet, but decades of NHLBI leadership in and support for research have led to more and better treatment options.

Effective treatments now allow many people with cystic fibrosis to live well into adulthood. Close to 40,000 children and adults are living with cystic fibrosis in the United States. 

The condition is caused by mutations, or changes, in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR helps control how chloride – a component of salt – and other ions are secreted by cells. The chloride attracts water and thins out the mucus the cells produce.

Current research supported by the NHLBI focuses on understanding how changes in the CFTR protein lead to the development of cystic fibrosis. The Institute carries out and supports studies that could lead to gene therapies and other treatments that may help the lives of people who have the condition.

NHLBI research that really made a difference

• Medicines that address underlying causes: NHLBI’s lung program supported decades of research to understand the structure and function of a lung protein that is genetically changed by cystic fibrosis. This foundational work led to the industry discovery of ivacaftor , the first drug to treat the underlying cause of cystic fibrosis, which the U.S. Food and Drug Administration (FDA) approved in 2012.
• Effective combination therapies: NHLBI-supported clinical trials led to the approval of a triple combination of CFTR modulator medicines that improves lung function in about 90% of people who have cystic fibrosis. However, further studies have shown that people of color are less likely than white people to have mutations that are eligible for treatment with current CFTR modulators. Researchers supported in part by the NHLBI are investigating these disparities. The Institute is also funding projects to develop treatments that will work for people who have less common CFTR mutations.
• Remote monitoring of lung health: As COVID-19 made in-person healthcare visits more challenging, an NHLBI-funded study developed an at-home diagnostic tool for measuring how well the lungs work. The FDA-cleared system uses a handheld breathing device and a mobile app called Breathe Easy. Patients blow into the device and communicate directly with their healthcare provider, who can monitor how well their lungs are working and adjust medicines as needed. Between April 2020 and May 2021, the Cystic Fibrosis Foundation distributed nearly 20,000 of the devices to people with cystic fibrosis in the United States. A study showed results were reliable 81% of the time for a sample of 48 patients who used the portable device with the app.

Find  funding opportunities  and  program contacts for cystic fibrosis research. 

Current research funded by the NHLBI

Our Division of Lung Diseases and its Airway Biology and Disease Branch oversee much of the research on cystic fibrosis that we fund.

• Biomarkers of declining lung function: The NHLBI Catalyze Program is supporting the development of a biomarker-based platform that predicts lung function decline in patients with cystic fibrosis and a web-based application to inform physicians when a patient may require therapeutic interventions.
• More options for disease modulators: Investigators are studying CFTR protein folding and the use of modulators for patients with rare variant mutations not typically eligible for cystic fibrosis modulator therapy.
• Monitoring methods with fewer side effects: Researchers are combining noninvasive, radiation-free imaging and proteomic biomarkers to diagnose and monitor lung disease progression in kids with cystic fibrosis.

Current research on cystic fibrosis treatments

• New treatment strategies: Although treatments improve lung function for many living with cystic fibrosis, some people have CFTR mutations that do not respond to available CFTR modulators. Even those whose disease responds to CFTR modulators still have trouble clearing bacteria out of their lungs. We are supporting a project, Novel Strategies to Clear Bacteria from the CF Lung , that aims to develop an inhaled medicine to shift the lung’s immune balance to help clear bacteria from lungs of people with cystic fibrosis.
• New treatment mechanisms: NHLBI-funded studies are testing whether a medicine to correct acid problems in the blood can also help reduce acid levels in the airways , which can then prevent or slow the development of cystic fibrosis.
• Better medicines to fight mucus: Researchers are developing new medicines to help clear and target the thick mucus found in cystic fibrosis lungs and improve how well the lungs work. This can also help prevent inflammation and infection.
• Antibiotic alternatives: Investigators are studying the thiocyanate (SCN−) analog selenocyanate (SeCN−) as an alternative therapeutic for the treatment of cystic fibrosis lung pathogens that are difficult to treat with current antibiotics.

Watch videos of a 2022 workshop that brought together experts from the NHLBI and other parts of NIH, as well as the Cystic Fibrosis Foundation, to identify future research needs for treating cystic fibrosis.

Current research on gene editing and cystic fibrosis

The NHLBI is supporting research on new genetic therapies to treat cystic fibrosis. For example, researchers are studying state-of-the-art gene delivery tools and technologies that may be better at delivering a corrected gene to lung cells. Researchers are also working on better methods to improve genetic therapies in the laboratory before moving to clinical trials.

Through the NIH Common Fund Somatic Cell Genome Editing (SCGE) Program , the NHLBI supports studies that explore new genetic therapy approaches to repair the cystic fibrosis gene, among others.

• Gene editing for lung disease: Studies using CRISPR gene editing tools will correct genes in the cells that line the airways. Using these tools could lead to new treatments for genetic and acquired lung disease.
• Gene editing for cystic fibrosis: A research program is developing combinatorial nonviral and viral CRISPR delivery for lung diseases. These studies focus on efficiently targeting gene editing tools to diseased lung cells in people who have cystic fibrosis.

To identify research barriers and challenges to using gene editing as a means to cure cystic fibrosis, the NHLBI participated in a joint workshop with the Cystic Fibrosis Foundation in 2018. The Institute also participated in a 2020 virtual workshop to discuss challenges and opportunities that could be addressed in a potential second phase of the SCGE program.

The NHLBI funds other studies of gene editing for cystic fibrosis as well.

• Molecular targets to treat cystic fibrosis: The NHLBI supports research for new molecular therapies , including gene editing. Molecular therapies have helped restore the CFTR protein function for some but not all people with cystic fibrosis. New research uses airway cells and animal models to look for more ways to prevent and treat this condition.
• How nanoparticles may improve treatment effectiveness: To improve the delivery of gene editing tools and other therapeutics, researchers are developing more effective virus-inspired nanoparticles to penetrate mucus barriers in diseases with thick mucus like cystic fibrosis. 

Find more NHLBI-funded studies on gene editing and cystic fibrosis at NIH RePORTER.

Read more about NHLBI-supported research on gene editing, which involves making changes to a specific DNA sequence to correct the mutation in the cystic fibrosis gene: Genome editing for cystic fibrosis: A Q&A with Peter Glazer, Ph.D., M.D.

Current research on understanding the causes of cystic fibrosis

• New treatment and prevention: NHLBI-supported scientists are carrying out Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease designed to build a solid foundation of knowledge about mucus, how it forms, and how it works to protect the body from infections. The resulting knowledge could lead to new ways to treat and prevent lung problems that result from the thick, sticky mucus caused by CFTR mutations.
• Origins of disease: Scientists are using a cystic fibrosis animal model to study the origins of cystic fibrosis airway disease . Researchers hope this will help speed up the development of new treatments for early lung disease.
• High-resolution imaging to better understand lung disease mechanisms: Another NHLBI-funded study uses an imaging method called optical coherence tomography (OCT) to take high-resolution images of the lungs and the nose. OCT can help researchers better understand how mucus is cleared and how cystic fibrosis affects this process.

Find more NHLBI-funded studies on the causes of cystic fibrosis at NIH RePORTER.

Learn more about how cystic fibrosis changes the airways’ cellular makeup: Molecular analysis identifies differences between healthy lung and lungs of people who have cystic fibrosis .

Cystic fibrosis research labs at the NHLBI

The Division of Intramural Research , which includes investigators from the Pulmonary Branch , is actively engaged in the study of cystic fibrosis.

Related cystic fibrosis programs

• The  Trans-Omics for Precision Medicine (TOPMed) program includes  participants who have cystic fibrosis, which may help researchers understand how genes affect people and how individuals respond to treatment.
• The NHLBI-funded LungMAP research centers are creating molecular maps of the lungs to better understand rare lung diseases in children, including cystic fibrosis.

Explore more NHLBI research on cystic fibrosis

The sections above provide you with the highlights of NHLBI-supported research on cystic fibrosis. You can explore the full list of NHLBI-funded studies on the NIH RePORTER .

To find more studies:

• Type your search words into the  Quick Search  box and press enter. 
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• Select the  Agencies  arrow, then the  NIH  arrow, then check  NHLBI .

If you want to sort the projects by budget size — from the biggest to the smallest — click on the  FY Total Cost by IC  column heading.

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News releases.

News Release

Wednesday, March 13, 2019

Scientists find new approach that shows promise for treating cystic fibrosis

NIH-funded discovery uses common antifungal drug to improve lungs’ ability to fight infection.

Researchers say a widely-used antifungal drug may hold promise for treating people with cystic fibrosis, a life-threatening genetic disorder that causes serious damage to the lungs. In studies using human cells and animals models, the researchers found that the medication, called amphotericin, helps lung cells function in a way that could make it easier for patients to fight chronic bacterial lung infections that are a hallmark of the disease. The findings from the study, which was supported in part by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, will appear in the journal Nature . 

If human studies validate the findings, the use of the drug could be good news to the more than 30,000 people in the United States and 70,000 worldwide who live with cystic fibrosis, a disease with no cure and few treatment options. It holds special promise for a subset of patients, about 10 percent of the people with cystic fibrosis, who do not respond to any treatment.

“The really exciting news is that amphotericin is a medicine that’s already approved and available on the market,” said Martin D. Burke, M.D., Ph.D., leader of the study and a professor of chemistry at the University of Illinois in Champaign.  “We think it’s a good candidate.”

Cystic fibrosis is caused by a defect in a gene called CFTR (cystic fibrosis transmembrane conductance regulator). This gene normally makes a protein that controls or channels the movement in and out of cells of such materials as salt, bicarbonate, and water—all of which are important to normal lung function. In people with cystic fibrosis, however, the defective gene makes a protein that is itself defective, causing the accumulation of acidic and sticky mucus that not only clogs the lungs and makes it hard to breathe, but also makes the lungs vulnerable to bacterial infection.

While some treatments are currently available, they are limited because different people have different types of mutated proteins, and because 10 percent of people with cystic fibrosis make no protein at all. But amphotericin, Burke said, has the potential to work regardless of the kind of mutation, and even when the protein is missing.    “Instead of trying to correct the protein or do gene therapy – the latter of which is not yet effective in the lung – we use a small molecule surrogate that can perform the channel function of the missing or defective protein,” Burke said. The researchers call this surrogate — the amphotericin — a “molecular prosthetic,” because it restores function much like a prosthetic device does when it replaces a limb.

In their studies, the researchers used lung tissue from patients with cystic fibrosis, as well as pig models of cystic fibrosis, and found that amphotericin spurred a host of changes associated with improved lung function — restoration of pH levels, improved viscosity, and increased antibacterial activity, among others.  The researchers noted that amphotericin can be delivered directly to the lungs to avoid common side effects. They cautioned that more experimental studies are needed before the drug is safe to treat cystic fibrosis in people. But experts are hopeful. “The cystic fibrosis community is truly in need of new therapies to reduce the burden of this disease. We are interested to see how this potential treatment performs in clinical trials in the future,” said James Kiley, Ph.D., director of the Division of Lung Diseases at the NHLBI. This work was supported in part by the National Heart, Lung, and Blood Institute (NHLBI grant HL091842) and the National Institute of General Medical Sciences (NIGMS grant 5R35GM118185). Both are part of the National Institutes of Health. The study was also supported by additional institutions outside of NIH. For a more complete funding disclosure, please see the full research article. About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit  www.nhlbi.nih.gov .

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

NIH…Turning Discovery Into Health ®

Burke, M. et al.  Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia .  https://www.nature.com/articles/s41586-019-1018-5

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Clinical Trials

Cystic fibrosis.

Displaying 14 studies

The purpose of this study is to determine the lowest radiation dose that allows interpretation of chest CT scan.

Our group developed a novel chest CT technology with reduced radiation exposure and procedure duration. This is a new dose optimization and efficiency technology and a tin filter, which greatly reduce the radiation dose compared to a standard chest CT. The procedure is fast and can be performed without sedation.  We therefore aim to validate this promising technology as an alternative clinical monitoring tool against current standard-of-care with CXR. 

The purpose of this study is to provide evidence of the safety and effectiveness of inhaled mannitol for adult patients with cystic fibrosis.

This trial will consist of three arms: Part A, Part B, and Part C. Part A has two groups. The first group will enroll adult subjects with cystic fibrosis (CF) into a single ascending dose (SAD) treatment group. The second group will enroll adult subjects with CF, including those on background treatment with ORKAMBI® and those not on a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, into a multiple ascending dose (MAD) treatment group. Part B will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months into a Phase II treatment group ...

The purpose of this study is to describe the prevalence of Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity (ear toxicity) in Cystic Fibrosis population.

The goal of the Cystic Fibrosis (CF) Patient Registry, the ongoing data collection effort sponsored by the Cystic Fibrosis Foundation, is to collect data on individuals with Cystic Fibrosis (CF) or individuals with Cystic Fibrosis (CF) related disorders (e.g., CFTR-related metabolic syndrome (CRMS), CFTR-related disorders).

The purpose of this study is to collect data on individuals with cystic fibrosis (CF) to better understand the illness and ultimately improve the care and survival of those with CF.

The purpose of the Cystic Fibrosis Patient Registry is to gather and maintain data on all patients with the disease so that current and accurate data can be provided to researchers and clinicians regarding practice patterns, age and gender distributions, clinical outcomes, mortality and morbidity rates, and so that epidemiologic research can be performed.

This study will explore the effects of delivering a common nebulized drug taken by Cystic fibrosis (CF) patients during exercise.

The study aims to determine if a popular dextrose candy alternative yields a similar glycemic curve compared to the standard oral Dextrose solution used in the Oral Glucose Tolerance Test. Additionally the study aims to determine if substituting the traditional oral dextrose solution used in the Oral Glucose Tolerance Test for a candy alternative yields a higher level of patient satisfaction among children ages 10-21 in the Mayo Clinic Cystic Fibrosis Center. 

The purpose of this study is to evaluate the effect of brensocatib at 10 mg and 25 mg compared with placebo on the rate of pulmonary exacerbations (PEs) over the 52-week treatment period.The study protocol allows for children ages 12-18 years to be enrolled; however, Mayo Clinic will not be enrolling any subjects <18 years old.

The purpose of this study is to investigate Pseudomonas Aeruginosa and Staphylococcus Aureus bacterial load, patient characteristics and exploratory biomarkers in adult patients with Cystic Fibrosis or Non-Cystic Fibrosis Bronchiectasis.

The purpose of this study is to obtain breath acoustic recordings and measures of lung mechanics in patients with COPD, asthma, and cystic fibrosis breathing at rest and during light submaximal exercise. The plan is to examine these respiratory acoustics and mechanics in relation to determinants of disease and/or disease states (classic respiratory pathophysiology) and quality of life measures in these patient populations to determine if any relationship or patterns exist when comparing across respiratory diseases and within a condition based on disease severity.       

The purpose of this study is to evaluate the effectiveness of inhaled molgramostim, administered open-label, to adult cystic fibrosis subjects with chronic pulmonary nontuberculous mycobacterial (NTM) infection, with or without ongoing antimycobacterial guideline based combination therapy.

The purpose of this study is to evaluate the effietiveness of remdesivir (RDV) in reducing the rate of of all-cause medically attended visits (MAVs; medical visits attended in person by the participant and a health care professional) or death in non-hospitalized participants with early stage coronavirus disease 2019 (COVID-19) and to evaluate the safety of RDV administered in an outpatient setting.

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The Cystic-Fibrosis Breakthrough That Changed Everything

The disease once guaranteed an early death—but a new treatment has given many patients a chance to live decades longer than expected. What do they do now?

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T hey call it the Purge.

You have experienced, in a modest way, something like it in the waning days of a bad cold, when your lungs finally expel their accumulated gunk. The rattle in your chest quiets. Your sinuses clear. You smell again: the animal sweetness of your children’s hair, the metallic breeze stirring a late-summer night. Your body, which oozed and groaned under the yoke of illness, is now a perfectly humming machine. Living is easy—everything is easy. How wonderful it is to breathe, simply breathe.

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Imagine, though, that you had never been able to simply breathe. Imagine that mucus—thick, copious, dark—had been accumulating since the moment you were born, thwarting air and trapping microbes to fester inside your lungs. That you spent an hour each day physically pounding the mucus out of your airways, but even then, your lung function would spiral only downward, in what amounted to a long, slow asphyxiation. This was what it once meant to be born with cystic fibrosis.

Then, in the fall of 2019, a new triple combination of drugs began making its way into the hands of people with the genetic disease. Trikafta corrects the misshapen protein that causes cystic fibrosis; this molecular tweak thins mucus in the lungs so it can be coughed up easily. In a matter of hours, patients who took it began to cough—and cough and cough and cough in what they later started calling the Purge. They hacked up at work, at home, in their car, in bed at night. It’s not that they were sick; if anything, it was the opposite: They were becoming well. In the days that followed, their lungs were cleansed of a tarlike mucus, and the small tasks of daily life that had been so difficult became unthinkingly easy. They ran up the stairs. They ran after their kids. They ran 10Ks. They ran marathons .

Cystic fibrosis once all but guaranteed an early death. When the disease was first identified, in the 1930s, most babies born with CF died in infancy. The next decades were a grind of incremental medical progress: A child born with CF in the ’50s could expect to live until age 5. In the ’70s, age 10. In the early 2000s, age 35. With Trikafta came a quantum leap. Today, those who begin taking the drug in early adolescence, a recent study projected, can expect to survive to age 82.5—an essentially normal life span.

CF was one of the first diseases to be traced to a specific gene, and Trikafta is one of the first drugs designed for a specific, inherited mutation. It is not a cure, and it doesn’t work for all patients. But a substantial majority of the 40,000 Americans with CF have now lived through a miracle—a thrilling but disorienting miracle. Where they once prepared for death, they now have to prepare for life. “It’s like the opposite of a terminal diagnosis,” Jenny Livingston told me.

Jenny spent her 20s in and out of the hospital for CF-related lung infections. During her frequent weeks-long stays, she made some of her best friends in the CF ward, only to watch them succumb, one by one, to the disease that she knew would eventually kill her too. More than anything, she hoped to live long enough to see her daughter graduate from high school.

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Today, Jenny is 36. Four years into taking Trikafta, she’s the healthiest she’s been in her adult life. Her daughter is 14, a lanky high-school freshman. They’re both obsessed with Harry Styles, and after Jenny started on Trikafta, they flew together to see him live —twice. They learned to hunt deer with Jenny’s partner, Randy. They often go up into the aspen- and fir-topped mountains that overlook their little town in central Utah. Jenny’s last hospitalization—four years ago, just before she started Trikafta—is now more distant in time than her daughter’s future graduation.

Having lived one life defined by cystic fibrosis, Jenny wonders: What is she going to do with her second life?

Jenny was born in 1987, the youngest of her parents’ five children together and the third to have cystic fibrosis. Given the family history, the doctors knew to test her as an infant, wrapping her forearm in plastic until a sheen of sweat appeared on her skin: the classic “sweat test” for cystic fibrosis. The faulty protein in CF cannot control the balance of salt and water in the body, which results in mucus that is unusually thick and sweat that is unusually salty. In medieval Europe, centuries before anyone understood why, a proverb foretold the fate of children with salt on their skin: “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.”

The 1980s, suffice it to say, were not the Middle Ages. By the time Jenny was born, her two older sisters with cystic fibrosis—Shannan, 8, and Teresa, 7—were on a strict schedule of mucus-clearing chest therapy and medications that had kept them alive past toddlerhood. Shannan wasn’t diagnosed until she was 13 months old. “I knew when she was born that there was something wrong,” their mother, Lisa, told me. As a newborn, Shannan projectile vomited and blew out her diapers constantly. When she got older, she was often so insatiably hungry that she would cry when a spoon scraped the bottom of a near-empty food jar. She scarfed down five pancakes at a time. In the baby photos in Lisa’s scrapbook, she is all skinny legs and big, swollen belly—a classic sign of malnutrition.

Shannan was starving, it turned out. Food was passing through her body undigested because her pancreas had been damaged as a result of thick mucus blocking the ducts that release digestive enzymes. Cystic fibrosis was originally named, in fact, for the fibrous cysts that a 1930s pathologist saw in the pancreases of babies who had died. An early epiphany helped doctors overcome the malfunctioning pancreas, though: The missing enzymes could be replaced with pills. By the time of Shannan’s diagnosis, CF was known as a disease of the lungs, in which sticky mucus made fertile ground for bacteria, and the cycle of infection and scarring, infection and scarring would eventually cause the lungs to fail.

Lisa relayed the news of Shannan’s diagnosis over the phone to her husband, Tom, who was at work. As she repeated the doctor’s words, their awful meaning sank in. Their daughter would not live long. They would watch her die. In that moment, the two of them broke down on the phone, the physical distance between them collapsed by grief.

Shannan died when she was 14. “I remember the sound of her oxygen machine more than her voice,” Jenny told me. The rumble and puff of the machine had run in the background of their home, punctuated by chronic coughs from all three girls with CF. But neither Teresa nor Jenny was ever as sick as Shannan was in childhood—due perhaps to chance or to being diagnosed and starting treatments earlier in life. Even when they were newborns, their mother coaxed applesauce sprinkled with enzymes into their mouth, so they could absorb nutrients from their milk.

Not long after Shannan died, Lisa and Tom divorced—their marriage had been strained even before the loss of their daughter—and they both eventually remarried. Despite the upheavals in her family, Jenny remembers her childhood as quite normal. Yes, she had to take the enzymes with every meal, and she had to clear her lungs of mucus every day—first by having her parents pound on her chest and back and later by using an oscillating vest that shook her body. As inhaled CF drugs were developed, they were added to her daily regimen. She went to the hospital for annual preventive “tune-ups,” but she was never sick enough to need emergency hospitalizations, and CF did not seem to hold her back.

Lisa thinks of Jenny as her sassy daughter. Her youngest was always stubborn, always a go-getter. Through the Make-A-Wish Foundation, she was able to get a horse, which she entered in local shows and rode through the foothills just outside town. In the summer, the salt from the dried sweat on her arms became crystals that glimmered in the sun, a subtle reminder of the disease still inside her. The invincibility of youth, however, made her think she had perhaps escaped her oldest sister’s fate.

At 19, Jenny married a local boy she had fallen in love with, and at 21, she was shocked to find herself pregnant: “A very, very happy surprise.” She had always longed to be a mother. As a young girl, she once drew a picture proclaiming that she would grow up to have six children. The drawing “broke my heart,” says her stepmother, Candy. Even if Jenny lived long enough, cystic fibrosis often causes fertility issues—in many women, thickened cervical mucus is thought to prevent pregnancy, and in almost all men, sperm ducts never develop because of blockages that occur in utero. And at the time, doctors often recommended against pregnancy for health reasons.

But Jenny pushed the worries out of her mind. She was simply happy. She set up a crib and painted the nursery. In retrospect, the fevers and shortness of breath she began to feel were not just the normal discomforts of pregnancy, but she didn’t clock it then. She had an uneventful labor, and gave birth to a healthy baby girl. They named her Morgan.

The trouble started in the following months. Six weeks after giving birth, Jenny went back to work. Between nursing and soothing and diapering a newborn, she could no longer keep up her treatment routine. She sometimes also skipped medications when she couldn’t afford them with the pay from her job as a bank teller and her husband’s as a welder.

Then she caught a bug. It was 2009, the year of swine flu, so it could have been that or a more mundane cold, but either way, it triggered something deep in her lungs. She started feeling short of breath. By the time she got to a CF specialist at a hospital two hours away, in Salt Lake City, she could not walk from the car to the front door. She was too weak to stand for her lung-function test. She collapsed into her hospital bed, and for the next several days, she was unable to use the toilet or shower on her own. Convinced that she would die 100 miles from her three-month-old daughter, she had a terrible revelation: “This is why they said ‘Don’t have kids.’ ”

This was Jenny’s first CF pulmonary exacerbation, when lung function plummets from an acute infection. Doctors inserted her first PICC line, a catheter that runs from the upper arm to the heart, delivers antibiotics, and stays in place longer than an IV. She recovered, but just months later, she was back in the hospital with another exacerbation. Then another and another, and on this went for the next several years. Jenny counted for me the PICC-line scars still visible as white dots on each arm—at least 10 on the left, 16 on the right. When the veins in her arms started to reject PICC lines, doctors placed a port under her right collarbone for easy access to her central vein.

Each infection scarred her lungs; each exacerbation eroded her lung function. The disease that had been a minor plot point in her life became one of its major storylines, and the people in the hospital became recurring characters. At the University of Utah’s CF center, she met Warren, one of her best friends, whom she came to know so well, she could identify his cough through the hospital walls. He was “so dang funny,” Jenny said, unafraid of joking about the death that would befall them both. Where she was a rule follower, he was a troublemaker. Once, he commandeered a hospital floor scrubber, waving at patients in their rooms as he drove past. Another time, he managed to procure a bootleg copy of The Avengers . Stuck in the hospital over the film’s opening weekend, he and the other CF patients organized a movie night. James brought his Xbox to play the bootleg DVD. Heather (“the biggest Swiftie”) and Angie (“gorgeous, tall blonde”) joined too. They found a waiting room with a TV, and the nurses passed around microwave popcorn.

Jenny and her friends made sure to sit several feet apart. People with cystic fibrosis have had to practice social distancing since long before COVID, because they are considered a danger to one another. Their lungs harbor destructive and often antibiotic-resistant bacteria that can become impossible to uproot once established. Certain names are spoken with an air of doom: Burkholderia cepacia , Pseudomonas aeruginosa . When doctors in the 1990s realized that people with CF were infecting and killing one another by simply gathering, they stopped allowing patients to go within several feet of one another unmasked. Camps for children with cystic fibrosis, which Jenny still remembers fondly , were all shut down. In the hospital, she once again found a community in the disease that was taking over her life. But many of those friendships ended too soon: Of the five people at the Avengers movie night, Jenny is the only one alive today. Warren, James, Heather, and Angie have all died.

As Jenny struggled with her health, the new reality of chronic illness took a toll on her marriage. She and her husband eventually divorced. After a particularly harrowing hospitalization in 2012, her doctors encouraged her to stop working and go on disability. Something in her life had to give, they told her, or it would be her body. Her disease and her daughter became her whole world.

Even as a young child, Morgan could sense when her mom was heading toward another exacerbation. If she noticed that Jenny was more tired than usual or coughing more than usual, she began to dread their coming separation. When she was 3 years old, she asked, “Do all mommies live in the hospital sometimes?” When she was 6, after Warren’s death, she asked, “Can you die from CF?” She understood that their existence together was fragile.

Jenny answered truthfully: Yes. But she assured her daughter that she was taking care of herself as best she could. Still, she made plans for what was probably inevitable. If she died, her daughter would live with her aunt and uncle. If she died, she wanted a funeral just like Warren’s, with music, candy, and an open mic for everyone to share their favorite memories.

A cure for cystic fibrosis had supposedly been imminent since 1989, when Jenny turned 2. That year, scientists identified the recessive gene behind cystic fibrosis, which encodes a protein called CFTR that controls the flow of salt and water. The discovery seemed so explosive that a Reuters reporter rushed to publish the scoop more than two weeks before the scientific papers were due to come out; two press conferences followed.

In the decades after, however, researchers came to understand the wide gulf between identifying a genetic problem and knowing how to solve it. Early attempts in the ’90s at using gene therapy to fix mutations failed again and again, both for CF and for other genetic conditions that once seemed tantalizingly close to a cure.

Then, CF researchers changed tack: Instead of correcting the gene, why not correct the mutated protein itself with small fixer molecules? This had never been done before—with any disease—but the nonprofit Cystic Fibrosis Foundation deemed the strategy promising enough to strike an unusual venture-philanthropy agreement with a company that would attempt it, which was eventually bought by Vertex Pharmaceuticals. The foundation funded the research in return for a share of the revenue.

The move paid off. In 2012, Vertex released a drug called Kalydeco that worked stunningly well—improving lung function and erasing many symptoms in the small group of CF patients who could take it. That was the catch: The FDA approved Kalydeco only for the roughly 4 percent of people with CF who carried a rare and specific mutation. Still, it provided a jolt of optimism. Kalydeco was the first drug ever tailored to a person’s inherited genetic mutation, and the breakthrough portended a new age of “personalized medicine.” It also inspired other patient-advocacy groups to copy the venture-philanthropy model. In 2014, the Cystic Fibrosis Foundation sold the rights to royalties from Kalydeco and future Vertex CF drugs for $3.3 billion, which it could invest in new research.

After Kalydeco, the next CF mutation to target was obvious. About 1,700 unique mutations have been found in people with CF, but some 90 percent of patients—including Jenny—carry at least one copy of a mutation, known as F508del, that leaves their protein channels too seriously distorted for Kalydeco alone to correct. Fixing this shape would be a much bigger task. In 2013, Jenny joined the clinical trial for a two-drug combination from Vertex, made up of Kalydeco plus a second fixer molecule. It failed to especially improve her symptoms, though it did work enough to stabilize her falling lung function. “It seemed to push pause,” she said. She stopped getting sicker, but she was still sick. The research went on.

A few years later, word began spreading of a forthcoming three-drug combination from Vertex. In clinical trials, neither patients nor doctors are told who is on the placebo and who is on the experimental drug. But in this trial, everyone could tell. The triple combo made patients’ lung function jump by a shocking 10 percentage points. Overnight, they woke up smelling for the first time the distinctive scent of their home. They could even taste their sweat becoming less salty. This was Trikafta.

In the fall of 2019, Trikafta was approved by the FDA just 10 days before a large annual gathering of CF experts in Nashville. Doctors who attended told me the atmosphere was electric. Jenny happened to be there to speak on an unrelated panel, and she remembers seeing the geneticist Francis Collins walk onstage with a guitar. Collins is best known as the longtime director of the National Institutes of Health, where he oversaw the sequencing of the human genome in the ’90s (he has since retired from the NIH). But he had made his name in 1989 as one of the scientists who discovered the gene for cystic fibrosis.

In those long years when progress was halting, Collins, who is also an amateur musician, wrote a song to inspire a gathering of CF researchers. He sang “ Dare to Dream ” again that day in Nashville, his baritone raspier with age. When he got to the verse that he had rewritten for this occasion—“That triple treatment has taken 30 years”—cheers broke out in the convention center. In the crowd were people who had waited their whole career, even their whole life, for this moment. We dare to dream, dare to dream. As they swayed to the music, perhaps no one quite understood the magnitude and velocity of the change to come.

Jenny received her first box of Trikafta on November 17, 2019, at the end of yet another two-week hospital stay. She had gotten sick again in Nashville. Actually, she had been fighting off a cold before she left, and despite assiduously staying in her hotel room to keep up her treatment routine, she felt an infection settling into her lungs. At the conference, she heard a lot about Trikafta, but she didn’t expect to get it so quickly. CF centers were being inundated with calls from patients asking for the new drug.

In the hospital in Utah, she recorded a video that she sent to her sister with CF, Teresa, who now lived in Ohio. She is sitting on her hospital bed. “My Trikafta is here,” she says, her voice shaking and her eyes tearing up. The miracle drug she had been promised her whole life was now in her hands.

Teresa was also able to start the drug not long after. For her, Trikafta’s impact was immediate and unmistakable. The Purge started on the drive back from the doctor’s visit where she took the first dose. The mucus coming up was so thin that she was confused; it was nothing like the sticky gunk she’d had to work so hard to cough up. A month later, she went back for a sweat test, and her salt level was normal. Based on the results, you would not know she had cystic fibrosis.

“I think of it like, ‘Oh, back when I used to have CF,’ ” Teresa said on a recent call with Jenny and me. “I don’t feel like I have CF. I feel completely normal.” She has been able to stop using her vest and inhaled medications, freeing up that time for her adopted children and the farm where she lives with her family. Before Trikafta, every small exertion was a negotiation with her lungs. Should she go upstairs? How many breaths would that take? Now she’s running around milking the goats, trimming their hooves, throwing 30 bales of hay into the barn.

On that same call, the sisters got to talking about an upcoming trip to see their grandmother, and Teresa asked Jenny a question that would have been inconceivable before Trikafta: Could they stay in the same hotel room? To avoid infecting each other with the bacteria in their lungs, the two had not shared a room since Teresa left Utah 15 years earlier. At family gatherings, they kept their distance. They didn’t even touch the same serving utensils, sending their partners to get their food. Now, Jenny told her sister, “I would totally stay in the same hotel room.”

When Jenny started Trikafta, it took her longer than it took Teresa to notice much change. She didn’t have the dramatic capital- P Purge because, she thinks, the hospitalization had already temporarily cleared her lungs. But two months after she started the drug, when a snowstorm blanketed their town, her family drove out to their favorite sledding hill. Jenny had never liked sledding; she would stand in the cold while everyone else ran around having fun, their easy breaths turning into white puffs in the air. This time, her nephew called out and she jogged over.

It wasn’t until she got to him that she realized she had jogged up —all the way to the top of the hill. “I don’t run, and I don’t climb hills. And I just ran up a hill and felt super fine,” she says in a video she took right after. “I’m going to see if I can do it again. Ready?”

“Yes,” her daughter, Morgan, answers next to her. They take off. “Mom!” Morgan shouts a few seconds later, as the distance between them grows larger. “You’re beating me, Mom!” At the top of the hill, Jenny looks back to see Morgan still catching up.

Jenny went down the hill and ran back up again, simply to prove that she could. “At one point, I just plopped up here on my bum and cried,” she told me during my visit in October, pointing to the spot on the hill where it had all hit her. In front of us, big gray mountains jutted into the blue sky. The sledding hill, she admitted, did not look that impressive. But for all of Morgan’s life, Jenny had been on the sidelines. She’d watch as Morgan swam in the lake or rode her bike, her low-grade fever making her too tired to join. That day on the hill, they finally ran together.

From there, Jenny began noticing changes in her body, big and small. The tips of her fingers, which had always been slightly swollen and round—a sign of low oxygen—thinned out as her lungs improved. She didn’t need as many enzyme pills to digest her meals. Her chronic cough disappeared. She hadn’t realized how much she had always suppressed her laughter to avoid triggering her cough. Now she can laugh—big belly laughs that match the warmth of her personality. “Oh my gosh, my laugh drives her crazy,” she told me in the car, laughing, after picking up Morgan from school. “That’s because you laugh at stuff that’s not funny,” her daughter shot back. Jenny laughed again.

Trikafta had effects that even doctors did not anticipate. In the months after the drugs became widely available, some patients unexpectedly got pregnant; the drug that thins lung mucus, it turns out, also thins cervical mucus. Then, patients started trying to get pregnant. The drug made many people with CF feel so healthy that they no longer worried about the physical toll of pregnancy and parenthood or the agony of leaving behind young children. Doctors began speaking of a Trikafta baby boom.

Doors opened to other once-impossible futures. A 22-year-old told me he decided to train as an aircraft mechanic, a job that would have been far too physically demanding when he was being hospitalized multiple times a year. One woman started dating. “I don’t want to fall in love with somebody, knowing that I’m not going to be around very long,” she had thought. Now she and her boyfriend have been together for four years. A father who was being evaluated for a lung transplant before Trikafta felt healthy enough to spend the summer of 2020 tearing down and rebuilding his family’s deck, and now expects his CF lungs to see him through graduations and grandkids.

Trikafta is a lifelong medication, and it is not meant to undo organ damage that has already occurred. But the earlier treatment begins, the healthier one stays. A handful of pregnant women have now used Trikafta to treat their unborn children with cystic fibrosis. Last fall, I corresponded with one such expecting mother, who does not have CF but whose son was diagnosed by genetic testing. She started Trikafta at 26 weeks. When her son was born in October, his lungs and pancreas were perfectly healthy.

Officially, Trikafta is approved in the U.S. for patients as young as 2. Unofficially, some parents give their newborns Trikafta, either indirectly through breast milk or directly by grinding up the pills into tiny doses. So long as they stay on the medication, these children may never experience any of the physical ravages of the disease. Recently, Make-A-Wish announced that children with CF would no longer automatically be eligible for the program, because “life-changing advances” had radically improved the outlook for them.

CF centers these days are unusually quiet. Fewer patients need once-routine weeks-long hospitalizations. Instead of thinking about lung function, more and more are worrying about the maladies that come with middle and old age—colon cancer, high cholesterol, heart disease. Obesity has been a confounding new issue . Before Trikafta, patients were usually underweight, and they were told to cram as many calories in as possible, by whatever means possible. Every additional pound was a small victory. One patient described microwaving pints of Ben & Jerry’s to drink mixed with heavy cream; when even that failed to make her gain weight, she got a feeding tube. Now people on Trikafta worry about getting too many calories.

In February, Vertex announced the results of a clinical trial for a next-generation triple-combination therapy, which may be even more effective than Trikafta. All of these changes have made for an existential moment for doctors, too: The disease they were trained to treat is no longer the disease most of their patients have.

Doctors told me they could think of only one other comparable breakthrough in recent memory: the arrival of powerful HIV drugs in the 1990s. Like Trikafta, those drugs were not a cure, but they transformed AIDS from a terminal illness into a manageable chronic one. Young men got up from their deathbed, newly strong and hale. AIDS hospices emptied—and then went bankrupt.

This was a remarkable turn of events. But it elicited a complicated mix of emotions, not all of them joyful. Some patients who were no longer dying grew depressed, anxious, and even suicidal at the thought of living. This phenomenon became known as “Lazarus syndrome.”

Death is an end, after all. Life comes with problems: Patients who spent lavishly during what were supposed to be their last days now had no money to live on. Those who stayed with a lover in sickness found that they could not actually stand them in health. They fretted about insurance and paperwork and chores, everyday annoyances that would no longer be obliterated by imminent death. In 1996, the writer Andrew Sullivan, who is HIV-positive, described life after the advent of the HIV drugs in his essay “ When Plagues End ”:

When you have spent several years girding yourself for the possibility of death, it is not so easy to gird yourself instead for the possibility of life. What you expect to greet with the euphoria of victory comes instead like the slow withdrawal of an excuse. And you resist it. The intensity with which you had learned to approach each day turns into a banality, a banality that refuses to understand or even appreciate the experience you have just gone through.

For some HIV patients, their reversal of fortune seemed unreal. “He doesn’t trust what’s happening to him,” one doctor said about a patient who had made a dramatic recovery, yet found himself in psychological distress.

Doubts like these crept into the minds of many people on Trikafta, too. What if the new drug stopped working? Or had horrible side effects? Or stopped being covered by insurance? Trikafta’s sticker price is more than $300,000 a year. Insurance typically covers most of that cost—minus what can be significant co-pays and deductibles—and Vertex offers co-pay assistance. But patients’ lives ultimately depend on decisions made by nameless bureaucrats in rooms far away: Insurance plans can suddenly change what they cover, and in 2022, Vertex announced that it would substantially reduce its financial assistance.

A 43-year-old woman I interviewed asked not to be named, because she feared that speaking about her improved health would cause her to lose disability benefits, which would also get her kicked off the government insurance that pays for Trikafta. Her health has not improved as dramatically as others’ has, and she still has frequent infections and occasional bleeding in her lungs. If she returns to work but her health declines, it could take a long time to get back on disability—time she would have to go without Trikafta. She would also need a job with health insurance good enough to cover the expensive drug—but could she even get one as a 40-something with no recent employment history?

For other patients, new health granted new independence, which could be scary too. As a child, Patrick Allen Brown was sick enough to miss long stretches of school. His parents didn’t expect him to do chores, let alone support himself with a job one day. So much of his life was spent in the hospital that movies became his way of understanding the outside world. In his teens and 20s, he drank heavily.

After Trikafta restored Brown’s physical health, he was no longer a chronically ill adult who lived with his parents. He was a pretty healthy adult who still lived with his parents. He was 32, and hadn’t finished college. Now he had to budget, commit to a career. He decided to get sober. When one of his parents needed back surgery recently, their roles flipped: He became the caretaker. Brown has now graduated from culinary school and found work as a chef, but he feels as if he is still catching up to his peers.

The great blossoming of possibilities on Trikafta also dredged up regret about decisions too late to undo. Kara Hansen, 41, has a daughter who was adopted, and she had always wanted another child. But in 2016, she had to be repeatedly hospitalized: in April, then again in May, July, and August. She gave up on having a second child—how could she, if she couldn’t even guarantee living for the daughter she already had? Then, in 2018, she joined the original trial for Trikafta, becoming one of the first people in the world to experience its miraculous effects. If she had known her health would improve so dramatically and hold steady six years on, she would have tried to get pregnant, but she feels like it’s too late now. To plan for such a miracle would have been foolish, but to live in its unexpected aftermath can still be painful.

After a year on Trikafta, Jenny told Teresa something that she acknowledged sounded “insane” but that her sister understood immediately: “To no longer be actively dying kind of sucks,” she said. The certainty of dying young, she realized, had been a security blanket. She’d never worried about retirement, menopause, or the loneliness of outliving a parent or a partner.

Cystic fibrosis had defined her adult life. Now what? For so long, she’d just been trying to see her daughter graduate from high school. Now she faced seeing Morgan go off and live her own life. What then? Jenny had become active in patient advocacy, and soon after the start of the pandemic, she volunteered to moderate an online patient forum on mental health for her CF center in Utah. It went so well that her longtime social worker at the center felt compelled to give some career advice: Try social work.

From the October 2022 issue: Sarah Zhang on why so many kids need glasses now

Jenny enrolled in an online master’s program in 2022, and this past fall she chose a practicum with a hospice agency. Having watched the death of so many friends and contemplated her own, she felt prepared to shepherd people through the sadness and awkwardness and even humor that accompany the end of life. She understood, too, the small dignities that mean the world when your body is no longer up to the task of living. One hospice patient, she noticed, often had trouble understanding conversations because his hearing aids were never charged correctly. She got the situation fixed, and on a recent visit, he wanted to listen to music, playing for her the favorite songs of his youth. On another man’s shelf, she recognized a birding book, and she made plans for a window feeder to bring birds to him.

Jenny doesn’t share the details of her life with patients, but in their experiences with death, she has seen her own refracted. One hospice patient, a devout elderly woman, was estranged from her adult son, who no longer believed. Jenny herself grew up religious—Mormon, in her case—but she is not anymore. Her family is still Mormon, as is virtually everyone in the town she has lived in since childhood, which has 3,500 people, several Mormon churches, and a Mormon temple. She is liberal, whereas most of her relatives voted for Donald Trump.

Still, Jenny has made a point of staying close to her large, tight-knit family. Knowing she would die young had long ago clarified that she wanted to leave with no regrets, no grudges, and no words left unsaid to the people she loved. In the foothills outside town one day, she pointed in the direction of her house, her brother’s house, her mom’s house, her dad and stepmom’s house, all minutes away from one another.

Although Trikafta looks to be a very safe drug for most people, it does have side effects. It can cause cataracts as well as liver injury. More perplexing, Trikafta may affect the brain.

For Jenny, starting Trikafta coincided with a wave of intense insomnia, brain fog, and anxiety. For months, she could sleep only two or three hours a night. She’d lose her phone and find it in the freezer. Her lungs were so much healthier, but her brain was going haywire. Soon, she realized that other CF patients had begun sharing stories online of depression, anger, or suicidal thoughts that emerged at the same time they started taking Trikafta.

Doctors sometimes chalked up these symptoms to the existential unease of no longer dying, or the fear and isolation everyone felt in the early days of the pandemic. But Jenny’s doctor took the side effects she reported seriously enough to suggest that she halve her Trikafta dose, and soon after, they subsided. (Some of her CF symptoms did return, but they were muted enough that she could pare down her regimen of treatments.)

The link between Trikafta and these symptoms in the brain is still not fully proven or understood. “We’ve done an in-depth analysis of the preclinical data, clinical data, and real-world-evidence data, and we don’t find any causal relationship,” Fred Van Goor, a vice president and the head of CF research at Vertex, told me in January. And an analysis co-authored by the company’s scientists last year found similar rates of depression and suicidality in CF patients with or without Trikafta. But in November, a group of scientists published a review arguing that the possible neuropsychiatric effects of Trikafta deserved a “serious research effort.” The protein behind CF is found in cells throughout the body, including the brain. Trikafta could be acting on the brain directly, the authors hypothesized, or it could be acting indirectly via changes to inflammation throughout the body or specifically in the gut. The drug may affect different subsets of patients differently, says Anna Georgiopoulos, a psychiatrist at Massachusetts General Hospital who co-authored the review. She believes that neuropsychiatric side effects afflict only a “small minority” of people on Trikafta, but says that studies are needed to know exactly how many.

In the meantime, some patients have quit Trikafta altogether, their neuropsychiatric symptoms too debilitating even on a lower dose. “Physically I was feeling the best I’ve ever felt,” says Aimee Lecointre of her time on the drug, but mentally, “I felt on the verge of a panic attack almost every day.” The contradiction confused her: How could she be so anxious and depressed when her health was getting so much better? When she finally decided to try stopping Trikafta, the nervous energy that had filled her body all day long dissipated. But her CF symptoms came back. During our phone conversation, she paused every few minutes to cough.

She and Jenny have known each other for years, going back to their mutual hospitalizations. The three of us were supposed to meet over apple-cider floats when I was in Utah, but Lecointre had health issues come up at the last minute, the kind of disruption that happens all the time for people with a chronic illness. For a while, her Instagram feed filled with people on Trikafta whose lives were transforming while hers stayed the same; she had to delete social media from her phone. She still feels sad, sometimes, that Trikafta didn’t work out for her. But she was able to go back to one of Vertex’s two-drug combos, and although it is less effective than Trikafta, she feels so much better. There is more to cope with, but the coping is easier.

For another group of CF patients, Trikafta simply does not work. About 10 percent lack the F508del mutation that the triple combination was specifically designed to fix. Over time, though, scientists have found that some less common mutations are similar enough to F508del that those who carry them still benefit from Trikafta. And in late 2020, word got out that the FDA would soon approve the drug for additional mutations.

Gina Ruiz remembers waiting and waiting for the list of new mutations that fall. She had spent the past year watching her peers on Trikafta be handed what she thought of as a “reverse Uno card”—reverse weight loss, reverse lung decline, reverse CF—while her own health continued to worsen. She was sitting in a car when she saw the list, and she scrolled through the 177 new mutations hoping to find hers. She was crushed when she did not. Ruiz and most people in the 10 percent have mutations that leave their CFTR protein too garbled or incomplete to correct with any combination of fixer molecules. Treating these mutations will require a different strategy altogether.

The Cystic Fibrosis Foundation continues to fund research into a cure for all, and scientists, including those at Vertex, are once again exploring genetic therapies, applying the lessons of past failures. But a genetic-therapy breakthrough specific to CF is still years, if not decades, away. After Vertex created that first drug for the 4 percent, the path toward Trikafta was clear. After Trikafta, terra incognita.

Ruiz is wary of getting her hopes up again. At age 29, she can no longer work. She lives with her parents. Her lung function has fallen to 30 percent. And in December, her weight reached a new low of 89 pounds. “I went to Target last night and I was beyond exhausted,” she told me the following month. Her knees hurt too, another complication of CF. As she’s watched her peers on Trikafta get married and chase after toddlers, her own world has shrunk. Halfway through the store, she got so tired that she had to rest in a chair in the home-goods section before she could go on.

Other patients with rare mutations told me the CF communities they once relied on for support have become quiet, as the 90 percent have gotten on with their lives. “It’s extremely isolating,” says Steph Hansen, who was steeling herself for another hospitalization when we spoke in January. She describes it as a one-two punch: Her health is no better, yet she has lost the community that once buoyed her. She’s connected with a handful of other patients who can’t take Trikafta, but CF is already a rare disease, and they are the rarest of the rare.

The F508del mutation is most common in people of European ancestry, so people with mutations ineligible for Trikafta in the U.S. are disproportionately Black or Latino. Globally, the proportion of people ineligible is higher in Latin America, Asia, and Africa, where diagnosis and treatment for CF also lag . In most developing countries, even eligible patients cannot get Trikafta—because Vertex currently does not sell its expensive drug outside a few dozen countries, concentrated in Europe and the English-speaking world. (Vertex says it has a pilot program that “provides Trikafta at no cost to people with CF in certain lower income countries.”) Its patents also block other companies from making a cheaper generic version. In early 2023, activists asked four countries to revoke or suspend patents for Trikafta in a coordinated campaign. One of the countries was India, where The New York Times wrote about a father named Seshagiri Buddana. His son would have been able to take Trikafta if he lived in the U.S., but he died in December 2022 one day before he would have turned 9.

All of this weighs on Jenny. What makes her different from those who have died, other than the luck of being born at the right time, in the right place, with the right mutations?

Two days after my visit to Utah, Jenny’s father, Tom, had a heart attack while chopping firewood. He felt short of breath, and a trip to the hospital revealed that his major arteries were 90 percent blocked.

When Jenny texted me the news, she said she had been replaying our recent conversations about life and death. She was glad to feel, upon learning her father might die, that nothing between the two of them was left unsaid or unresolved. I thought of what Tom had told me in his living room. Before we had gone over to his house that day, Jenny had warned me that her dad was a jokester, not a man prone to earnest reflection. But when the conversation shifted to the impact of Trikafta, he turned to me, completely serious. “I was going to bury my kids. And I’m not. They get to bury me, which is the way it’s supposed to be.”

We all fell silent for a moment, as we felt the weight he had been carrying all those years. After burying his eldest daughter at 14, Tom could no longer watch movies in which children die. In Jenny’s years of sickness, he had often driven her two hours to the hospital in Salt Lake City, but he rarely set foot inside. Hospitals are places where people go to be born or to die, he’d say, and all my children have already been born.

After his heart attack, Tom needed an emergency quintuple-bypass surgery. He did well, and came home to recover. He spent the time rethinking his priorities. Just before falling ill, he had skipped a family outing to an amusement park to work. Now he regretted it. He’s become more open about his emotions; still a jokester, he’s taken to saying that his heart has been opened in more ways than one since the surgery.

It’s interesting, Jenny says. Her father has lived a longer and very different life from her own, but she recognizes what he is going through. People die from this, he started saying. I could have died from this. He got close enough to see death’s shadow, only to be pulled back to a life whose familiarity suddenly felt unfamiliar. What would he do with his unexpected life? “Hey,” Jenny told her dad. “I get it.”

This article appears in the April 2024 print edition with the headline “After the Miracle.”

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CFRI seeks to fund projects that are original, probing, and/or pioneer a new approach to a therapy or cure for cystic fibrosis, through two research programs: the New Horizons Research Campaign and Elizabeth Nash Memorial Fellowship . Those involved in varied disciplines of research are encouraged to submit proposals during funding cycles, to advance the current understanding of cystic fibrosis.

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Masks Strongly Recommended but Not Required in Maryland, Starting Immediately

Due to the downward trend in respiratory viruses in Maryland, masking is no longer required but remains strongly recommended in Johns Hopkins Medicine clinical locations in Maryland. Read more .

• Vaccines  
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Pulmonary & Critical Care Medicine

Cystic fibrosis research program, on this page:, clinical research, patient resources/useful links, cystic fibrosis physicians.

The Johns Hopkins CF program is actively engaged in many different research studies covering everything from the genetics underlying cystic fibrosis, the diagnosis of CF, symptom management in CF, adherence to CF treatments, improving lung transplant outcomes in CF, and numerous clinical trials of CF therapies. We have been involved in most major trials of new therapeutic agents for CF over the past two decades. Some ongoing studies are highlighted below. Because there are new clinical trials in CF starting frequently, you can find the latest trials at the CF Foundations website  https://www.cff.org/Trials/finder .

If you are interested in learning more about CF research at Johns Hopkins you can contact Mary Rykiel at 410-614-1409 or  [email protected] .

Johns Hopkins Lung Transplant Research Project List

View complete list of lung transplant studies.

Assessment of Pain in Cystic Fibrosis

We have conducted a series of cohort studies aimed at determining the prevalence of pain in adults and adolescents with CF and determining the impact of pain on clinical outcomes in CF. Future aims include optimizing the assessment of pain in CF and designing interventions to alleviate pain for individuals with CF.

Team : Sarah Allgood, Noah Lechtzin

Funding : NIH

Cohort Studies of Lung Transplant Outcomes in Cystic Fibrosis

This series of studies utilizes data from the United Network for Organ Sharing (UNOS) and the Cystic Fibrosis Foundation Patient Registry to determine how various risk factors such as renal function and lung allocation score impact clinical outcome after lung transplantation.

Team : Christian Merlo, Errol Bush, Pali Shah

Comparative Effectiveness Study to Determine the Effectiveness of Guideline Directed Care

This study aims to use the CF Foundation Patient Registry to determine which aspects of guideline recommended care are most important for improving clinical outcomes in CF.

Team : Rebecca Dezube, Kristin Riekert, Noah Lechtzin

Development of Novel Therapies for Cystic Fibrosis

The adult CF group has been involved with many phase 1, phase 2, and phase 3 clinical trials of new treatments for CF. Recent and ongoing studies are below:

• PI: Noah Lechtzin
• Funding: Vertex Pharmaceuticals
• Funding: Astra Zeneca
• PI: Natalie West
• Funding: Galapagos
• PI: Christian Merlo
• Funding: FDA and CFF
• Funding: Corbus

Development of Standardized Measures of Barriers to Treatment Adherence: Psychometric Validation

This study aims to validate the Barriers to Adherence Screener (BAS) and the Adherence Barriers Questionnaire- Cystic Fibrosis (ABQ-CF) to help identify challenges that people with CF face in getting treatments done.

Team:  Kristin Riekert, Noah Lechtzin

Funding : Funding CF Foundation

Optimizing diagnosis and therapy for non-tuberculous mycobacterium (PREDICT and PATIENCE)

The aim of these studies is to standardize non-tuberculous mycobacterium diagnostic approaches and then to standardize treatment regimens for individuals who require therapy.

Team:  Keira Cohen, Noah Lechtzin

Funding:  CF Foundation

Optimizing Treatment of CF Exacerbations

• STOP 2: Treatment of pulmonary exacerbations in people with CF.

This study aims to determine the optimal duration of antibiotic therapy for treating CF pulmonary exacerbations.

• Funding: CF Foundation
• Biomarkers of CF Exacerbations

This is a prospective cohort study aimed at measuring novel biomarkers in blood and exhaled breath condensate with the goal of identifying markers that will identify patients who will have better responses to treatment than others.

Persistent Methicillin Resistent Staphylococcus Aureus (MRSA) Eradication Protocol

This clinical trial aims to determine if a multifaceted antimicrobial approach can eradicate MRSA from respiratory cultures from people with CF.

Team:  Mark Jennings, Rebecca Dezube, Michael Boyle

Funding : CF Foundation

Sex Differences in Treatment and Outcomes of CF Exacerbations

This is a series of observational studies aimed to determine if there a sex differences in presentation, treatment and outcomes in CF Pulmonary Exacerbations.

Team:  Kristina Montemayor, Natalie West, Noah Lechtzin

Funding:  Pending

The Success with Therapies Research Consortium (STRC)

The Johns Hopkins Adherence Research Center serves as the Data Management Core for the STRC and the Hopkins Pediatric and Adult Centers are participating centers. The mission of the STRC is to facilitate the clinical study of interventions to improve adherence and CF disease self-management in order to optimize health outcomes and quality of life. There are several ongoing studies.

Team : Kristin Riekert, Noah Lechtzin

TEACH: Testing the effect of adding oral azithromycin to inhaled tobramycin in people with CF

The aim of this study is to determine if oral azithromycin interferes with the antimicrobial effectiveness of inhaled tobramycin.

Team : Peter Mogayzel, Noah Lechtzin

Validation and Clinical Application of a Wearable Sweat Sensor

The project aims to test and validate a wearable sensor that provides real time testing of sweat chloride. Sweat chloride is a marker of CFTR function and has been shown to decrease in response to CFTR modulator drugs. This study will follow serial sweat measurements after initiation of CFTR modulator drugs in order to gain insight into the time course of sweat chloride changes and how these vary around dosing of medications.

Team : Mark Jennings, Garry Cutting, DH Choi

• Currently enrolling studies can be found at https://www.cff.org/Trials/finder & https://clinicaltrials.gov
• Interventions to improve adherence in CF
• Assessments of Pain in CF
• Optimizing CF Exacerbation Treatment
• Observational Study of Non-tuberculous mycobacteria
• Improving pre & post-transplant care for CF
• Studies of outcomes and interventions for MRSA infection
• Evaluating sex difference in exacerbation treatment and outcomes
• Evaluation of a continuous sweat chloride monitor
• Comparative effectiveness research of CF Guideline care
• http://www.hopkinscf.org/about-us/adult-clinic/clinic-staff-adult/
• https://www.cff.org

Michael P Boyle MD

Expertise: Pulmonology

Primary Location: Johns Hopkins Outpatient Center, Baltimore, MD

Rebecca Dezube MD

• Vice Chair for Inpatient Operations at JHH, Department of Medicine
• Assistant Professor of Medicine

Noah Lechtzin MD

• Director, Adult Cystic Fibrosis Program
• Associate Professor of Medicine

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Dr. Jennifer Taylor-Cousar is passionate about bringing attention to health inequities in cystic fibrosis. By partnering with the CF Foundation, other organizations, and the CF community, she believes we can work together to create equitable health outcomes for everyone with CF. 

How did you get involved with cystic fibrosis as a clinician?

I went to medical school with the plan to become a neonatologist because I loved working with children, but I was scientifically and clinically intrigued by lung disease. As an intern and resident, I had the opportunity to work with people with CF, first in the hospital and then in clinic. The resilience of the people with CF and their families drew me to want to establish the long-term care relationships that are an essential aspect of improving the quality and quantity of people’s lives.

When did you first notice health inequity in the CF community? What red flags did you see?

In medical school, like others, I learned that CF was a disease that occurred in people who are white . However, as a resident, I took care of people who were Black with CF. At that time, I did not understand how underlying structural racism and bias led to that conflicting information. Investigators like Dr. Susanna McColley and Dr. Michael Schechter began publishing manuscripts regarding health disparities in CF in the 1990s, but these disparities were not a central focus or discussed in front of large audiences at conferences. As a faculty member and CF Center director, it was incredibly disheartening to continue to see people from ethnically and racially marginalized groups present to me with many years of unnecessary suffering that could have been prevented with a correct diagnosis. It is also heartbreaking to hear the stories of the mental trauma caused by biased comments made to people who were seeking diagnosis (e.g., assumptions that failure to thrive was caused by parental neglect or pancreatitis was caused by alcoholism rather than the correct diagnosis of CF).  

How have you advocated for health equity in cystic fibrosis?

In Bijal Trivedi’s Breath from Salt , she referenced Dr. Dorothy Andersen’s seminal manuscript that described cystic fibrosis of the pancreas. Motivated by that reference, I re-read Dr. Andersen’s paper and understood that we have known since the beginning that CF affects people of all races and ethnicities. This knowledge motivated me to push harder to find ways to re-educate people and bring the discussion of health inequity to the forefront. 

I have advocated for health equity by serving on committees for the CF Foundation including the Racial Justice Working Group and co-chairing the Health Equity Team Science Award study section. But I have also brought a health-equity lens to the other Foundation committees on which I serve, including the Clinical Research Executive Committee, Clinical Research Advisory Board and the Sexual Health, Reproduction, and Gender Research Working Group, and as the Adult Care Advisor to the CF Foundation’s Board of Trustees. Additionally, I have partnered with a number of organizations to create enduring materials about health inequity including the CF Foundation, the American Board of Pediatrics, Cystic Fibrosis Research Incorporated, and the National Organization of African Americans with CF (NOAACF). I also partnered with NOAACF to create a symptom self-screening tool that could enable people to advocate for themselves to be tested for CF. Finally, I give lectures at local, regional, national, and international conferences to raise awareness of health inequities in CF and motivate others to get involved to change the systems that lead to these inequities.

What motivates you to combat health inequity? What keeps you going when you’re feeling discouraged?

As a Black woman, I have personally experienced the bias and inequities that exist in our health care system and have had to intervene for close friends and family members whose lives were put at risk by these biases and inequities. I also deeply care about my patients and the experiences that they have endured, and I want it to be better so that other people are not subjected to the same approaches. The knowledge that other healthcare systems have much better health outcomes than those in the U.S. motivates me to believe in and continue to fight for health equity. 

When I am feeling discouraged, I think about the steps forward we have made in the last few years, such as:

• Increasing inclusion of the voices and perspectives of people from ethnically and racially marginalized groups in all the spaces in which we work with the CF community
• Expanding the number of variants included on newborn screen panels in some states that make it more likely that infants from ethnically and racially marginalized groups will also have the opportunity to benefit from an early diagnosis of CF
• Expanding modulator eligibility to variants more often found in individuals with CF who identify as Black, indigenous, and people of color

What would you say to someone who is interested in fighting for health equity in cystic fibrosis?

We need you! Dr. Martin Luther King, Jr. said, “Of all the forms of inequality, injustice in health is the most shocking and inhuman.” While health disparities are often viewed as a problem only for those affected, it is one in which we all must be invested in order to improve health outcomes. Our mission at the CF Foundation is “Until It’s Done” and that means until it’s done for everyone with CF.  

Interested in sharing your story? The   CF Community Blog   wants to hear from you.

This site contains general information about cystic fibrosis, as well as personal insight from the CF community. Opinions and experiences shared by members of our community, including but not limited to people with CF and their families, belong solely to the blog post author and do not represent those of the Cystic Fibrosis Foundation, unless explicitly stated. In addition, the site is not intended as a substitute for treatment advice from a medical professional. Consult your doctor before making any changes to your treatment.

Jennifer is a professor of adult and pediatric pulmonary medicine at National Jewish Health, where she serves as the medical director of Clinical Research Services. She oversees the care of children with pulmonary disease and adults with cystic fibrosis. Jennifer is also co-director of the Adult CF Program and director of the CF Therapeutics Development Network research that is conducted at National Jewish Health. She has been site primary investigator on more than 40 studies and global site investigator on three studies. Her investigator-initiated research focuses on the development and evaluation of novel therapies for the treatment of CF. Jennifer is the chair of the Cystic Fibrosis Foundation's Women's Health Research Working Group. She received her undergraduate degree in human biology from Stanford University in 1993. She completed her doctorate in medicine in 1998, combined residency in internal medicine and pediatrics in 2002, and her combined fellowship in adult and pediatric pulmonary medicine in 2006 at Duke University Medical Center. She obtained her master's in clinical science at the University of Colorado in 2015.

Organization Tips for Parents of Children With CF Blog | 5 min read

Giving Myself Permission to Forget Blog | 5 min read

Living in the In-Between Blog | 6 min read

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UB Contributing to Dramatic Results in CF Care, Research

( EDITOR’S NOTE:  This is the first installment in a three-part series recognizing Cystic Fibrosis Awareness Month. For the next two Wednesdays in May, stay tuned for more stories on UB’s research and clinical care efforts in the area of cystic fibrosis.)

By Dirk Hoffman

Published May 8, 2024

One of the most dramatic success stories in modern medicine is the treatment of cystic fibrosis (CF), where therapeutic breakthroughs have dramatically reduced patients’ symptoms and increased their life expectancies.

Researchers and clinicians at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo have played key roles in developing game-changing discoveries such as cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies that are designed to correct the malfunctioning protein made by the CFTR gene. Their efforts are continuing on a daily basis as they seek to develop more novel and improved therapies.

Cystic fibrosis is a progressive, genetic disease that affects the lungs, pancreas and other organs.

There are close to 40,000 children and adults living with cystic fibrosis in the United States (and an estimated 105,000 people have been diagnosed with CF across 94 countries), according to the Cystic Fibrosis Foundation.

During the 1950s, a child with CF rarely lived long enough to attend elementary school. Today, many people with CF are achieving their dreams of pursuing careers, getting married and having children, and living into retirement.

Four Jacobs School faculty members involved with CF recently sat for a roundtable discussion on the state of the disease, new therapeutics and clinical guidelines, and some of the new challenges facing the population.

The faculty members are:

• Carla A. Frederick, MD , associate professor of medicine . She is an adult pulmonologist who takes care of individuals with CF at the Cystic Fibrosis Center of Western New York. She co-directs the CF research program at the center through the Cystic Fibrosis Foundation’s Therapeutics Development Network (TDN). She sees patients through UBMD Internal Medicine .
• Danielle M. Goetz, MD , clinical associate professor of pediatrics . She is a pediatric pulmonologist at Oishei Children’s Hospital and UBMD Pediatrics and director of the Cystic Fibrosis Center of Western New York. She co-directs the CF research program at the center through the Cystic Fibrosis Foundation’s TDN. At the national level, she is serving on the position paper for the new CF Care Model for the CF Foundation and is a leader for the Foundation’s Quality Improvement Network’s mental health lab.
• Ryan C. Hunter, PhD , associate professor of microbiology and immunology . His lab is a group of microbiologists who focus on the bacterial infections that impact the lungs of individuals with cystic fibrosis. The researchers think about how these bacteria are behaving at the site of infection within the lungs of the patient and try to come up with new therapeutic strategies moving forward that can be used to better combat these infections.
• Beth A. Smith, MD , clinical professor of psychiatry and pediatrics and interim chair of psychiatry and division chief for child and adolescent psychiatry . On the national level, she serves as chair of the Cystic Fibrosis Foundation’s Mental Health Advisory Committee, whose goal is the integration of mental health care into routine CF care. Smith also serves on the CF Foundation’s North American Planning Committee as its pyschosocial chair, and on its Clinical Research Advisory Board. Her research is focused on mental health and cystic fibrosis, specifically around anxiety, depression and its effect on disease outcomes, as well as appearance. Smith is also involved in multiple intervention trials, specifically for depression and anxiety, including randomized, controlled trials for CF-specific cognitive behavioral therapy.

Danielle M. Goetz, MD, examines Muhammad Rafay at the UBMD Pediatric Outpatient Center at Conventus. The baby’s family resettled in Buffalo from Pakistan. The New York State newborn screening program revealed the baby has two copies of a CF mutation that is more common in Pakistan.

What is the current state of cystic fibrosis and the research and clinical care surrounding it?

Goetz: It is an exciting time because for those of us who have been involved with CF for many years, we have seen a lot of changes such as a lot of treatments that we did not have previously — mostly the CFTR modulators (the most famous one is elexecaftor-tezacaftor-ivacaftor, or Trikafta) approved for people as young as age 2 as of 2021.

These therapies are helping people live longer lives; they help their pulmonary function and their weight gain. Their overall quality of life improves.

Frederick: When I first started in medicine, I saw so many young patients that did not have a very long life expectancy.

Now, it is almost like a mid-career change for me. Earlier in my career, I was caring for adults who were inevitably getting sicker and who were going for lung transplants, on oxygen, and would need to apply for disability.

Now, in addition to routine daily care, the most common issues adults with CF face are things like thinking about careers, figuring out what they are going do with their life that they never thought they would have to do before — having kids, having grandchildren.

In Buffalo, we have a high percentage of people who have access to CFTR modulator therapy. We currently have 116 adult patients and 68 pediatric patients. It has completely flipped from when we started. There used to be more pediatric patients than adult patients.

Smith: As the life expectancy has increased, it has caused some good challenges. Patients with CF did not plan to live that long. They did not plan for college or a career.

Now some of them are old enough to retire so there are a lot of issues around future planning. They are dealing with conditions such as osteoporosis and dementia — comorbidities that people did not live long enough to have.

Hunter: From a research perspective, it is an exciting time as well. We are most interested in the bacterial infections of the lungs and the nature of those are changing. With these modulator therapies, lung function is improving.

The pathogens are still hanging around, but lung function is getting better. It’s interesting to think about what airway infections are going to look like, moving forward. We are shaping our research in that direction, just trying to think about what lung infection might become, but also some of the comorbidities as well.

For instance, there is an increased risk in colorectal cancer in the aging CF population so my lab is also now thinking about gut microbes and what kind of role they might play in gastrointestinal manifestations of the disease.

CF as a disease ties in really well, timing-wise, with UB’s commitment to aging research. I think it is a great case study of what the aging population is facing.

Tap infographics to enlarge.

Can you speak to the importance of multidisciplinary teams at the CF centers?

Goetz: I think they are a key to the outcomes we have had, even prior to the modulators. The concept of a multidisciplinary care network idea started in the 1960s. In 1997, it became more standardized as there was a guidebook made by the CF Foundation and others.

Key team members are respiratory therapists, dietitians, social workers/mental health providers, physicians and nurses, along with other subspecialists.

Having that team has helped us in our assessment and treatment of the patients. We are assessing the whole person and making sure we are addressing all aspects of care. Each person focuses on and becomes experts in the area of the daily treatments that patients with CF have to undergo.

It is a collaborative effort. We do a lot of pre-visit planning, prior to the clinic visits and try to include the patients in that.

Carla A. Frederick, MD, is an adult pulmonologist who takes cares of individuals with CF at the Cystic Fibrosis Center of Western New York.

What are some of the common comorbidities among patients with CF?

Frederick: Traditionally, pulmonary disease — and nutritional deficits with the inability to absorb fat nutrients — those two areas have treatments for them that CF centers have provided for a number of years.

Also, more commonly as individuals age, CF-related diabetes is one that over half of individuals with CF have some form of, that might move on a spectrum throughout their life

Some individuals have had many treatments over time, that could be toxic to their kidneys so chronic renal disease can develop in some.

Cancer is another big one that is emerging in understanding, and there is not a way where we can just implement screening like the general population. Some of these cancers in the GI form come faster than you would have predicted.

Also, we are in a culture where we always think of mental health, anxiety and depression as something that comes along with chronic illness, especially this one. This is not something that is simply related to feeling down when their heath is worse off, it can also occur when they are feeling better. There are a lot of people who have guilt associated with surviving longer than siblings or friends with CF, or when someone improved on CFTR modulator therapy some feel like their own identity is lost when this new, healthier person evolves.

Hunter: Chronic sinus infection is another one. About 95 percent of patients with CF have them. Maybe not lethal directly, but it is a risk factor for lower airway infection.

How are new therapies and better outcomes affecting the mental well-being of patients with CF?

Smith: It depends on where you are on the lifespan. The children that are born now are going to have a much different mental health trajectory than those who were raised thinking they are going to die earlier than they are.

When the life expectancy changed, it also stirred up a lot of trauma. We are doing a study right now, hearing personal narratives from patients with CF across the lifespan. In the over 50 age group, medical traumatic stress and procedure anxiety is ubiquitous.

These are individuals who have had many, many procedures throughout their life and many traumatic medical procedures and the trauma from them has been layered throughout their lifespan. I feel the interventions we are providing now earlier and earlier are going to result in a much different trajectory.

Is the isolation that patients with CF often feel still a legitimate concern?

Smith: There is often talk about a lack of understanding. During the COVID-19 pandemic, some positives came out of it in that people understood the idea of isolation, of that worry of getting an infection that can potentially kill you.

We all got a taste of that. In some ways, it gave credibility to everything that patients with CF have been going through across their lifespan.

Frederick: The reasons for these isolation guidelines is because of the fear for cross-contaminating different individuals with CF with different strains of bacteria that could become harmful.

Hopefully, future research will lead to relaxing those guidelines because quality of life is important. Separating people in time and space and touch is kind of cruel in this lifelong illness where finding someone who truly understands one’s point of view is difficult.

Beth A. Smith, MD, is involved in a number of  mental health clinical trials that involve cystic fibrosis-specific cognitive behavioral intervention for depression and anxiety and the development of a CF-specific general mental health screener.

What are some of the ongoing clinical trials happening at UB?

Goetz: In children, we are doing observational studies on preschoolers who are on Trikafta, and seeing what happens to their growth parameters and pulmonary function.

We are also doing surveys on personal experience with Trikafta in adolescents. We received a grant from the CF Foundation for all the newborn screening programs at the CF centers in New York state to assure all people with CF and their families have genetic counseling from a genetic counselor trained in CF. This is important due to the increasing complexity of CF genetics and to address unique CF mutations in diverse populations.

Frederick: We are involved in a rollover study from a head-to-head trial between current modulator therapy (elexacaftor/tezacaftor/ivacaftor) versus a once-a day alternative.

It is in the rollover phase where everyone is getting the once-a-day alternative therapy.

Taking a pill twice a day versus once-a-day may seem simple, but it isn’t. There is not a one-size-fits-all. Some people may feel that the current therapy is not good enough because “xyz” side effects happen — weight gain, mental health side effects such as anxiety, etc. Some simply do not have as strong of an improvement as desired.

These therapies are life-changing so more personalized medicine is in the works elsewhere to help make that therapy really great for everybody.

We participated in all the trials coming up to this present modulator therapy.

We dosed the first person with ivacaftor in the world here in Western New York and she just had her second baby a couple of months ago.

We have had a long history of recruiting people with CF to participate and families at first didn’t know what they were getting into, but now enter those trials with hope and excitement.

Smith: In addition to the medication trials, we’ve had a few mental health trials. We worked hard on a randomized, controlled trial of a cystic fibrosis-specific cognitive behavioral intervention for depression and anxiety. We are now in the adolescent pilot phase of the study. Buffalo is also involved in a national randomized, controlled implementation trial. We are implementing different models of how to disseminate this cognitive behavioral therapy that is specific to CF and we are studying it in a randomized way.

Buffalo is also the lead site in a multisite project to develop a CF-specific general mental health screener to pick up on other important and impactful mental health conditions in addition to depression and general anxiety for adults with CF.  

We also have the longest longitudinal database for depression and anxiety screening and are looking at the longitudinal trajectories of depression and anxiety in patients with CF 12 years and older and associations to important health outcomes.

Ryan C. Hunter, PhD, serves on the Cystic Fibrosis Foundation’s basic science grant review committee, which helps the CF Foundation establish its priorities and decide what to fund.

Can you talk about your roles on a national level within the Cystic Fibrosis Foundation?

Smith: I am the founding chair of its mental health advisory committee. It came about after the international guidelines for mental health screening and treatment in CF, where I led the screening portion. The Foundation wanted to figure out how to disseminate and implement these guidelines in the care centers across the U.S. With our initiatives, currently over 95% of individuals with CF 12 and older are screened annually across U.S. CF Centers.

We’ve taken that show on the road and worked to help implement the mental health in CF guidelines in Australia and across Europe. We have international membership on our committee and many of the resources we have created have been translated into 50+ languages.

In some countries without a lot of mental health infrastructure, when individuals are screened for depression and anxiety, that may be one of the only resources they are given.

Frederick: We are also involved in the Success With Therapy Research Consortium that is a branch of the Foundation’s research efforts to help partner with people with CF and their families to see how we can help improve health and self-management.

In a randomized, controlled trial, we are measuring everything and all visits are structured. But in the real world, when things like parenting or having a job, or having a friend come into the mix, does using this therapy still work? We perform some observational research to study these things.

We are involved in a lot of survey studies of qualitative research. Nutrition is a huge topic. In the new era of widely available modulator therapy, what does the world of nutrition look like? There is a study where we are learning about attitudes toward nutrition.

It seems like it would be a no-brainer to take this modulator therapy, but there are lots of other variables, so we are participating in a survey study with all sorts of different parameters for people to see what kind of modifiable or non-modifiable factors are affecting the week they take modulator therapy.

These studies are a really nice way we round out our center. We have mental health; we have care, and we have clinical research, and we have this other consortium where we partner with people with CF to see if we are really on the right track to help their lives be better.

Goetz: We are working with the CF Learning Network, which is the Quality Improvement Network for the CF Foundation. At our center, we do QI projects on all sorts of topics.

They asked me to be co-director of the laboratory on mental health to help design QI projects that the whole network can use. I am also serving on the CF Foundation committee, writing a position paper on the new CF Care Model in 2023-2024.

I have also served on the Foundation’s Therapeutics Development Network (TDN) steering committee. We get to look at all the protocols and see what is coming down the pipeline. We get to help shape what TDN is looking at for the sites.

Right now, they are doing gene editing and mRNA studies, so we are in a regional network of the TDN. We meet with other centers like Pittsburgh, West Virginia, Rochester and Syracuse.

They know there may not be a lot of subjects in Buffalo or each individual center who are eligible for genetic therapy, but we may be able to refer people to other centers within the network. The TDN is dividing the centers into geographic regions so people may more easily participate in studies.

Hunter:  I serve on the basic science grant review committee. Twice a year, a bunch of mostly basic researchers get together and we review applications. They are mostly U.S.-based, but they do accept international.

About 20-to-30 of us get together to review the science, to help the CF Foundation establish its priorities and decide what to fund. We try to make recommendations on which science is the strongest and which proposals are most worthy of being supported by the Foundation.

Is there something about Buffalo or UB’s collaborative spirit that helps your efforts?

Smith: When I first got involved with Drucy (Drucy S. Borowitz, MD, who served as the Cystic Fibrosis Center director at the former Woman and Children’s Hospital of Buffalo for more than 25 years) and some of the other pulmonologists, they were excited to have a child and adolescent psychiatrist who was interested in chronic illness and recognized the need for that.

They were doing collaborative care before it was called collaborative care. I was brought in as another specialist and wound up spending my career in CF because of the multidisciplinary nature and the spirit of collaboration.

Goetz: I became the CF center director in 2014, so we did a year where Dr. Borowitz and I were co-directors before that. She mentored me and we transitioned, but then she was still here until she went to the CF Foundation. Even while working at the CF Foundation, Dr. Borowitz was always there as our mentor. She was always in our corner, always available.

Smith: We would be putting in grants or writing a paper that got rejected for the second time, and Drucy would just take her proverbial red pen and very magically make edits. She was such a great mentor.

Goetz: We are trying to carry on the tradition she started.

Smith: Buffalo is a small center and yet we are involved in so many of these groundbreaking CF research projects. We have such a cohort.

I think it is due to Dr. Borowitz and her culture that patients and their families are very giving of themselves to our studies. Our rates of participation in studies are higher than most centers. Although we are small, we are mighty.

And the individuals are a part of this team of researchers. We have patient advisers on every one of our grants. And all of the educational materials are co-written with individuals with CF.

It has been just a great experience because many of them have said “I never thought I was going to be a researcher” or “I never thought I was going to be an author.”

Goetz: We are working on a CF Foundation position paper that I am helping to write in a group that includes patients and parents. It is asking the question if we need to change the care model now that we have modulators.

Patients and families should be a part of those discussions because they are the ones living it.

Smith: Their lived experience puts everything that we do into context. They are able to look at what we are producing and give us that feedback.

There is so much resilience in this population. Their survival stories are now thriving stories.

( Next Week:  A look at the career of Drucy S. Borowitz, MD, a leader in cystic fibrosis care and research, who changed the course of the disease in Western New York.)

Upcoming Events

Superbugs Pose a Deadly Threat to Cystic Fibrosis Patients

— a little-known microbe claimed mallory smith's life but did not quell her light.

by Claire Panosian Dunavan , MD , Contributing Writer, MedPage Today May 14, 2024

Claire Panosian Dunavan is a professor of medicine and infectious diseases at the David Geffen School of Medicine at UCLA and a past-president of the American Society of Tropical Medicine and Hygiene.

"What is my life?! Sometimes my life is so awful it's surreal." -- March 2014 entry in the book Diary of a Dying Girl by Mallory Smith.

Daily battles with sticky secretions, steatorrhea, and constipation. Respiratory treatments, mucolytics, endless antibiotics. Sudden gushes of hemoptysis. A vibrant life repeatedly interrupted by ever-lengthening hospitalizations.

Then, in November 2017, everything ended 2 months after Mallory Smith received new lungs at the University of Pittsburgh, the only medical center in the country that would operate on a cystic fibrosis (CF) patient chronically colonized with Burkholderia cepacia .

Although some may find its name unfamiliar, today, this water- and soil-borne microbe is arguably the world's worst superbug in a modern CF sufferer.

So, what actually killed Smith following her long-awaited transplant? A virulent, necrotizing pneumonia fueled not only by B. cepacia 's antimicrobial resistance (AMR) but its ability to trigger a massive release of inflammatory cytokines. As a final, desperate countermeasure, 24 hours before succumbing to " cepacia syndrome ," Smith even received special viruses called bacteriophage meant to destroy her invaders.

But, for Smith, the sci-fi weapons arrived too late.

And yet, what a luminous life she lived for 25 years, cherishing family and friends, attending and graduating from Stanford, surfing in Hawaii, savoring romance, and chronicling every step of her journey on her laptop.

Only after Smith died did Diane Shader Smith read her daughter's intensely personal journal, then select excerpts that became Salt in My Soul , a posthumously published memoir. Then, just last week, Random House followed up with Diary of a Dying Girl so readers could take one more look at Smith's short-but-extraordinary life.

Cystic Fibrosis, Then and Now

When considering the years that have passed since CF's first description by Dorothy Andersen, MD, it's hard to imagine another once-uniformly fatal genetic disease that has changed as much.

In the mid-1950s, affected infants often died before their first birthday, sometimes from malnutrition, sometimes from other complications stemming from faulty transport of chloride and water in their lungs, gut, and other organs. But by the 1980s and 1990s, CF youngsters were surviving far longer -- so much so that many in their 20s and 30s were cycling in and out of adult hospital beds with fevers and thick globs of sputum that often grew highly resistant strains of Staph aureus or Pseudomonas aeruginosa .

Today, 56 years is the predicted life expectancy of a baby with CF born from 2018 through 2022, according to the Cystic Fibrosis Foundation. Moreover, half of all currently affected 3-year-olds are likely to live into their 60s.

What accounts for this remarkable shift?

In addition to antibiotics, nutritional strategies, and daily respiratory care, what tops the list are new, effective CF transmembrane conductance regulator (CFTR) modulator therapies designed to correct the malfunctioning protein made by the CFTR gene. The first of these new medications, ivacaftor (Kalydeco) , was approved in 2012. Then came new combinations -- tezacaftor-ivacaftor (Symdeko) , lumacaftor-ivacaftor (Orkambi) , and elexacaftor-tezacaftor-ivacaftor (Trikafta) -- that expanded treatment to other genetic variants to reach a broader group of patients with CF.

The recent 80% drop in CF lung transplants in the U.S. is further proof of the modulators' impact. Yet, despite their miraculous benefits, superbugs still pose deadly threats in the mucus-filled airways of advanced CF patients.

Superbug vs Superphage

In a moment we will segue to AMR writ large and the growing evidence that bacteriophage might soon eradicate certain deadly microbes in anyone from a CF sufferer to a war-wounded soldier to you or me. After all, there's no guarantee any of us won't someday acquire a dangerous drug-resistant pathogen.

But first, consider these thought-provoking facts about global AMR:

• Between 2000 and 2015, global antibiotic use increased by 65%
• In 2019, AMR contributed to roughly 5 million deaths worldwide
• WHO now includes AMR among its top 10 global health threats; without major interventions, AMR's death toll will likely double by 2050

One obvious battle-plan is to develop new antibiotics while curbing the excess antibiotic use that has long fueled AMR. That's an ongoing global challenge.

But another hope for patients in truly desperate straits is to find and receive viruses that destroy superbugs. This strategy has recently caught fire thanks, in part, to the power of one man's personal story.

I'm referring to The Perfect Predator , an electrifying book in which epidemiologist Steffanie Strathdee, PhD, describes how bacteriophages saved her husband's life after he traveled to Egypt and developed gallstone pancreatitis and a football-sized pseudocyst awash in multi-drug resistant Acinetobacter baumannii . Tom Patterson, PhD, was initially medevaced to Germany, and then spent months septic and (often) comatose in the ICU at the University of California San Diego.

Meanwhile, Strathdee and her medical colleagues called multiple phage researchers until a viral match was found at Texas A&M, was approved for experimental use, then administered. Twenty-four hours later, Patterson emerged from the jaws of death.

Today, Strathdee (recognized as one of Time magazine's 50 most influential people in healthcare in 2018) is the director of the Center for Innovative Phage Applications and Therapeutics (IPATH), the first dedicated phage therapy center in North America. In a recent paper , she highlighted a recent uptick in clinical trials of bacteriophage. And, according to her review of case reports published from 1999 through 2022, phage-based treatments have now been used to treat antibiotic-resistant infections involving skin, burn wounds, the prostate, the urinary tract, the abdomen, bones, heart valves, lungs, blood, and implanted devices.

Strathdee has made an impact outside of the research world too. At the request of Shader Smith, Strathdee authored the epilogue of Smith's memoir, Salt in My Soul .

The Ongoing Fight Against AMR

It's fair to say that Smith and Shader Smith are now known to almost everyone in the U.S.'s close-knit community of CF patients, family members, and healthcare professionals -- Smith for her amazing grit and commitment to "living happy," and Shader Smith for her passion to spur greater awareness of the global AMR threat.

One of many AMR-impacted CF patients Shader Smith has personally touched is a 25-year-old woman from Ohio with B. cepacia . Thanks to Shader Smith, Jennifer Nelson is currently receiving high-quality care at the University of Pittsburgh Medical Center and one day hopes to receive a lung transplant preceded by bacteriophage therapy.

Last month, I spoke with the former ballerina and competitive ice skater. All in all, Nelson said, her childhood was "pretty normal" until her teens, when her disease worsened and required more antibiotics, then took another downhill turn in her early 20s. Today, Nelson has 22,000 followers on Instagram, but she also has an ileostomy, requires parenteral nutrition, and sometimes uses oxygen for the simplest of physical tasks. Meanwhile, her B. cepacia isolate has become almost fully antibiotic-resistant.

Nonetheless, Nelson continues to believe that even in the worst situations, something good can emerge or lies hidden within.

"Having a mindset like that," she continued, "when things are really awful, I've trained myself to think: what can this teach me? And then I search for that little 1% slice that could be positive."

Shader Smith also continues to find higher purpose following Smith's final battle. On May 7, 2024, she officially launched an initiative endorsed by CDC, WHO, and the European Centre for Disease Prevention and Control, among others, meant to raise awareness and shape new AMR policies through collective storytelling. For more, go to globalamrdiary.org .

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Cystic Fibrosis-Related Diabetes Research Overview

Pediatric endocrinologist Malinda Wu discusses ongoing research at Johns Hopkins on cystic fibrosis-related diabetes during the 2023 North American Cystic Fibrosis Conference. Cystic fibrosis is most commonly known for causing lung disease, but it affects most organs in the body, including exocrine and endocrine functions of the pancreas. CF-related diabetes is associated with worse lung function, worse nutritional status and decreased survival. Prompt treatment with insulin can reverse these outcomes, which makes it important to detect cystic fibrosis-related diabetes early.

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Malinda Wu, MD, MSCR

Pediatric Endocrinology

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Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies

Affiliations.

• 1 Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
• 2 Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
• 3 Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH Aachen University Hospital, Aachen, Germany.
• 4 Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: [email protected].
• PMID: 37236017
• DOI: 10.1016/j.mam.2023.101191

Fibrosis, or tissue scarring, develops as a pathological deviation from the physiological wound healing response and can occur in various organs such as the heart, lung, liver, kidney, skin, and bone marrow. Organ fibrosis significantly contributes to global morbidity and mortality. A broad spectrum of etiologies can cause fibrosis, including acute and chronic ischemia, hypertension, chronic viral infection (e.g., viral hepatitis), environmental exposure (e.g., pneumoconiosis, alcohol, nutrition, smoking) and genetic diseases (e.g., cystic fibrosis, alpha-1-antitrypsin deficiency). Common mechanisms across organs and disease etiologies involve a sustained injury to parenchymal cells that triggers a wound healing response, which becomes deregulated in the disease process. A transformation of resting fibroblasts into myofibroblasts with excessive extracellular matrix production constitutes the hallmark of disease, however, multiple other cell types such as immune cells, predominantly monocytes/macrophages, endothelial cells, and parenchymal cells form a complex network of profibrotic cellular crosstalk. Across organs, leading mediators include growth factors like transforming growth factor-β and platelet-derived growth factor, cytokines like interleukin-10, interleukin-13, interleukin-17, and danger-associated molecular patterns. More recently, insights into fibrosis regression and resolution of chronic conditions have deepened our understanding of beneficial, protective effects of immune cells, soluble mediators and intracellular signaling. Further in-depth insights into the mechanisms of fibrogenesis can provide the rationale for therapeutic interventions and the development of targeted antifibrotic agents. This review gives insight into shared responses and cellular mechanisms across organs and etiologies, aiming to paint a comprehensive picture of fibrotic diseases in both experimental settings and in human pathology.

Keywords: EMT; Fibroblast; Mechanism; Myofibroblast; TGF-beta.

Copyright © 2023 Elsevier Ltd. All rights reserved.

Publication types

• Research Support, Non-U.S. Gov't
• Cytokines / metabolism
• Endothelial Cells* / metabolism
• Fibroblasts / metabolism
• Myofibroblasts* / metabolism