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Cystic Fibrosis (CF)

By

Beryl J. Rosenstein

, MD, Johns Hopkins University School of Medicine

Last full review/revision Apr 2020| Content last modified Apr 2020
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Cystic fibrosis is a hereditary disease that causes certain glands to produce abnormal secretions, resulting in tissue and organ damage, especially in the lungs and the digestive tract.

  • Cystic fibrosis is caused by inherited genetic mutations that cause thick, sticky secretions to clog the lungs and other organs.

  • Typical symptoms include abdominal bloating, loose stools, and poor weight gain as well as coughing, wheezing, and frequent respiratory tract infections throughout life.

  • The diagnosis is based on sweat test results and/or genetic testing.

  • About half of the people with this disease in the United States are adults.

  • Treatments include antibiotics, bronchodilators, drugs to thin lung secretions, airway clearance treatments for respiratory problems, supplements of pancreatic enzymes and vitamins for digestive problems, and drugs to improve the function of the cystic fibrosis protein in people with certain mutations.

  • Some people benefit from liver and lung transplantation.

Cystic fibrosis is the most common inherited disease leading to a shortened life span among white people. In the United States, it occurs in about 1 of 3,300 white infants and in 1 of 15,300 black infants. It is rare in Asians. Because improvements in treatment have extended life expectancy for people with cystic fibrosis, about half of people in the United States with this disease are adults. Cystic fibrosis is equally common among boys and girls.

Cystic Fibrosis: Not Just a Lung Disease

Cystic fibrosis affects the lungs and also several other organs.

In the lungs, thick bronchial secretions block the small airways, which become inflamed. As the disease progresses, the bronchial walls thicken, the airways fill with infected secretions, areas of the lung contract, and lymph nodes enlarge.

In the liver, thick secretions block the bile ducts. Stones may develop in the gallbladder.

In the pancreas, thick secretions may block the gland completely so that digestive enzymes cannot reach the intestine. The pancreas may produce less insulin, so some people develop diabetes (usually in adolescence or adulthood).

In the small intestine, meconium ileus (a type of intestinal blockage) can result from thick secretions and may require surgery in newborns.

The reproductive organs are affected by cystic fibrosis in various ways, usually resulting in infertility in males.

The sweat glands in the skin secrete fluid containing more salt than normal.

Cystic Fibrosis: Not Just a Lung Disease

Causes

Abnormal genes

Cystic fibrosis results when a person inherits two defective copies (mutations) of a particular gene, one from each parent. This gene is called the cystic fibrosis transmembrane conductance regulator (CFTR). Various mutations can affect the CFTR gene. For example, the most common one is called the F508del mutation. The CFTR gene controls the production of a protein that regulates the movement of chloride, bicarbonate, and sodium (salt) across cell membranes. Mutations in the CFTR gene cause the protein to become dysfunctional. If the protein does not work correctly, the movement of chloride, bicarbonate, and sodium is disrupted, leading to thickening and increased stickiness of secretions throughout the body. 

Worldwide, about 3 of 100 white people carry one defective copy of the CFTR gene. People with one defective copy are carriers but they themselves do not get sick. About 3 of 10,000 white people inherit two defective copies of the gene and develop cystic fibrosis.

Abnormal secretions

Cystic fibrosis affects many organs throughout the body and nearly all the glands that secrete fluids into a duct (exocrine glands).

The organs most commonly affected are the

  • Lungs

  • Pancreas

  • Intestines

  • Liver and gallbladder

  • Reproductive organs

The lungs are normal at birth, but problems can develop at any time afterward as thick secretions begin to block the small airways (mucus plugging). The plugging leads to chronic bacterial infections and inflammation that cause permanent damage to the airways (bronchiectasis). These problems make breathing increasingly difficult and reduce the lungs’ ability to transfer oxygen to the blood. People also may have frequent bacterial respiratory infections that affect the sinuses.

In the pancreas, blockage of ducts prevents digestive enzymes from reaching the intestine. A lack of these enzymes leads to poor absorption of fats, proteins, and vitamins (malabsorption). This poor absorption, in turn, can lead to nutritional deficiencies and poor growth. Eventually, the pancreas can become scarred and no longer produce enough insulin, so some people develop diabetes. However, about 5 to 15% of people who have cystic fibrosis and carry certain mutations do not develop pancreatic digestive problems.

The intestines can become blocked by thick secretions. This blockage is common immediately after birth because the contents of the fetus's digestive tract (called meconium) are abnormally thick. Such blockage in the small intestine is called meconium ileus and in the large intestine is called meconium plug syndrome. Older children and adults may also have problems with constipation and blockage of the intestines (distal intestinal obstruction syndrome).

The liver and gallbladder can be blocked by thick secretions, which eventually can cause liver scarring (fibrosis). Gallstones may develop.

The reproductive organs can be blocked by thick secretions, which can cause infertility. Almost all men are infertile, but infertility is much less common in women.

The sweat glands secrete fluid containing more salt than normal, increasing the risk of dehydration.

Symptoms

The symptoms of cystic fibrosis can vary depending on a person's age.

Newborns and young children

About 15 to 20% of newborns who have cystic fibrosis have meconium ileus, which causes vomiting, bloating (distention) of the abdomen, and absence of bowel movements. Meconium ileus is sometimes complicated by perforation of the intestine, a dangerous condition causing infection and peritonitis (inflammation of the tissue lining the abdominal cavity and abdominal organs) and, if untreated, shock and death. Some newborns have a twisting of the intestine on itself (volvulus) or incomplete development of the intestine. Newborns who have meconium ileus almost always develop other symptoms of cystic fibrosis.

The first symptom of cystic fibrosis in an infant who does not have meconium ileus is often a delay in regaining birth weight or poor weight gain at 4 to 6 weeks of age. This poor weight gain is due to poor absorption of nutrients related to inadequate amounts of pancreatic enzymes. The infant has frequent, bulky, foul-smelling, oily stools and may have a bloated (distended) abdomen. Without treatment, weight gain in infants and older children is slow despite a normal or large appetite.

Older children and adults

Unless a diagnosis is made through newborn screening, about half the children with cystic fibrosis are first taken to the doctor because of frequent coughing, wheezing, and respiratory tract infections. Coughing, the most noticeable symptom, is often accompanied by gagging, vomiting, and disturbed sleep. Children may have difficulty breathing, wheezing, or both. As the disease progresses, children develop a declining tolerance for exercise, lung infections tend to occur more frequently, the chest becomes barrel-shaped, and insufficient oxygen may make the fingers clubbed (see Clubbing) and the nail beds bluish. Polyps may form in the nose. The sinuses may fill with thick secretions, leading to chronic or recurring sinus infections.

Older children and adults may have episodes of constipation or develop recurring and sometimes chronic blockage of the intestines. Symptoms include a change in stooling pattern, crampy abdominal pain, a decreased appetite, and sometimes vomiting. Gastroesophageal reflux is relatively common among children and adults.

When a child or adult with cystic fibrosis sweats excessively in hot weather or because of a fever, dehydration may result because of the increased loss of salt and water. Parents may notice the formation of salt crystals or even a salty taste on their child’s skin.

Adolescents often have slowed growth and delayed puberty. As the disease progresses, lung infection becomes a major problem. Recurring lung infections gradually destroy the lungs.

Complications

There are many complications of cystic fibrosis.

Inadequate absorption of the fat-soluble vitamins A, D, E, and K may lead to night blindness, osteopenia (decrease in bone density), osteoporosis, anemia, and bleeding disorders. In about 20% of untreated infants and toddlers, the lining of the rectum protrudes through the anus, a condition called rectal prolapse. Infrequently, infants with cystic fibrosis who have been fed soy formula or hypoallergenic formula may develop anemia and swelling of the extremities, because they are not absorbing enough protein.

Complications of cystic fibrosis in adolescents and adults include rupture of the small air sacs of the lung (alveoli) into the pleural space (the space between the lung and chest wall). This rupture can allow air to enter into the pleural space (pneumothorax), which collapses the lung. Other complications include heart failure and massive or recurring bleeding in the airways.

About 2% of children, 20% of adolescents, and 40 to 50% of adults with cystic fibrosis develop insulin-dependent diabetes because the scarred pancreas can no longer produce enough insulin.

The blockage of bile ducts by thick secretions can lead to inflammation and eventually scarring of the liver (cirrhosis) in about 2 to 3% of people with cystic fibrosis. Cirrhosis may increase the pressure in the veins entering the liver (portal hypertension), leading to enlarged, fragile veins at the lower end of the esophagus (esophageal varices), which can rupture and bleed profusely.

In almost all people with cystic fibrosis, the gallbladder is small, filled with thick bile, and does not function well. About 10% of people develop gallstones, but only a small percentage develops symptoms. Surgical removal of the gallbladder is rarely needed.

People with cystic fibrosis often have impaired reproductive function. Almost all men have a low or absent sperm count (which makes them sterile) because one of the ducts of the testis (the vas deferens) has developed abnormally and blocks the passage of sperm. In women, cervical secretions are too thick, causing somewhat decreased fertility. However, many women with cystic fibrosis have carried pregnancies to term. The outcome of the pregnancy for both the mother and the newborn is related to the mother's health status during pregnancy. Otherwise, sexual function is not impaired in men or women.

Other complications may include arthritis, chronic pain, problems sleeping and obstructive sleep apnea, kidney stones, kidney disease, depression and anxiety, and an increased risk of cancer of the bile ducts, pancreas, and intestines.

Diagnosis

  • Newborn screening test

  • Sweat test

  • Genetic testing

  • Carrier screening

  • Other tests

Newborn screening

Screening tests for cystic fibrosis are done on all newborns in the United States. A drop of blood is collected on a piece of filter paper and the level of trypsin (a digestive enzyme from the pancreas) is measured. If the trypsin level in the blood is high, newborns undergo confirmatory testing, which includes sweat testing and/or genetic testing. Most cases of cystic fibrosis are now identified by newborn screening tests.

If newborn screening was not done, the diagnosis of cystic fibrosis is usually confirmed in infancy or early childhood, but cystic fibrosis goes undetected until adolescence or early adulthood in about 10% of people with the disease.

Sweat test

A sweat test is done in newborns who have a positive newborn screening test and in infants, children, and older people who have symptoms that suggest cystic fibrosis. This test, which is done on an outpatient basis, measures the amount of salt in sweat. The drug pilocarpine is placed on the skin to stimulate sweating, and filter paper or thin tubing is placed against the skin to collect the sweat. The concentration of salt in the sweat is then measured. A salt concentration higher than normal confirms the diagnosis of cystic fibrosis in people who have symptoms of cystic fibrosis or who have a sibling with cystic fibrosis. Although the results of this test are valid any time after a newborn is 48 hours old, collecting a large enough sweat sample from a newborn younger than about 2 weeks old may be difficult.

Genetic testing

Genetic testing for an abnormal CFTR gene can help diagnose cystic fibrosis in a newborn who has a positive newborn screening test result, in a person who shows one or more typical symptoms, or in a person who has a sibling with cystic fibrosis. Finding two abnormal cystic fibrosis genes (mutations) is consistent with the diagnosis of cystic fibrosis. However, a positive sweat test is still needed to confirm the diagnosis. In addition, because typical genetic testing does not look for all of the more than 2,000 different cystic fibrosis mutations, failure to detect two mutations does not guarantee the person does not have cystic fibrosis (although the chance of having cystic fibrosis is very low). The disease can be diagnosed prenatally by doing genetic testing on the fetus using chorionic villus sampling or amniocentesis.

Some infants with a positive newborn screening test for cystic fibrosis can be hard to classify, even after sweat testing and genetic testing. These are infants who have no cystic fibrosis-related symptoms, sweat test results that are in-between the positive and negative ranges, and either no or only one cystic fibrosis gene mutation. Doctors diagnose this group as having CFTR-related metabolic syndrome (CRMS), also called cystic fibrosis screen positive, inconclusive diagnosis (CFSPID). Although most of these infants remain healthy, later in life some develop symptoms related to cystic fibrosis and are diagnosed with cystic fibrosis or a cystic fibrosis–related disorder. Thus, all of these children should be monitored regularly in a cystic fibrosis care center.

Some people, usually adults, develop symptoms that affect only one organ, often with an intermediate sweat test result and without two cystic fibrosis–causing mutations. For example, symptoms may affect only the pancreas (resulting in pancreatitis), the lungs (resulting in bronchiectasis), or the male reproductive organs (resulting in infertility). They are diagnosed with a CFTR-related disorder.

Carrier testing

Carrier testing can be done for people who want to become parents or are looking for prenatal care. In particular, relatives of a person with cystic fibrosis may want to know whether they are at increased risk of having children with the disease, and they should be offered genetic testing and counseling. A blood sample is taken to help determine whether a person has a defective cystic fibrosis gene (mutation).

Unless both potential parents have at least one such mutation, their children will not have cystic fibrosis. If both parents carry a defective cystic fibrosis gene, each pregnancy has a 25% chance of producing a child with cystic fibrosis, a 50% chance of producing a child who is a carrier, and a 25% chance of producing a child with no defective cystic fibrosis genes.

Other tests

Because cystic fibrosis can affect several organs, other tests may be helpful. Pancreatic enzyme levels are usually reduced, and an analysis of the person’s stool may reveal low or undetectable levels of the digestive enzyme elastase (secreted by the pancreas) and high levels of fat.

Blood tests are done to determine whether insulin secretion is reduced and blood sugar levels are high. Blood tests are also done to look for problems with the liver and to measure fat-soluble vitamin levels.

Doctors routinely take samples of material from the throat or coughed up from the lungs and culture it to identify bacteria in the airways and help them decide which antibiotics may be needed.

Pulmonary function tests may show that breathing is compromised and are good indicators of how well the lungs are functioning. These tests are done several times a year and whenever there is a decline in a person's health.

Chest x-rays and computed tomography (CT) of the chest may be helpful to document lung infection and the extent of lung damage. CT of the sinuses is done for people who have serious sinus symptoms, particularly if they have nasal polyps or are being considered for sinus surgery.

Prognosis

The severity of cystic fibrosis varies greatly from person to person regardless of age. The severity is determined largely by how much the lungs are affected. In the United States, people with cystic fibrosis who were born in the year 2017 are predicted to live to about 47 years of age. The outlook for longer survival has improved steadily over the past 50 years, mainly because people are diagnosed earlier and treatments can now postpone some of the changes that occur in the lungs. Long-term survival is significantly better in people who do not develop pancreatic problems.

However, deterioration is inevitable, leading to loss of lung function and eventually death. People with cystic fibrosis usually die of respiratory failure after many years of deteriorating lung function. A small number, however, die of heart failure, liver disease, bleeding into the airways, or complications of surgery including lung and/or liver transplantation. Despite their many problems, people with cystic fibrosis often attend school or work until shortly before death.

Treatment

  • Routine immunizations

  • Antibiotics, inhaled drugs to thin airway secretions, and airway clearance techniques to remove airway secretions

  • Drugs that help prevent airways from narrowing (bronchodilators) and sometimes corticosteroids

  • Pancreatic enzyme and vitamin supplements

  • High-calorie diet

  • In people with specific mutations, CFTR modulators

A person with cystic fibrosis should have a comprehensive program of therapy directed by a doctor experienced with cystic fibrosis care—usually a pediatrician or an internist—along with a team of other doctors, nurses, a dietitian, a respiratory or physical therapist, and ideally a social worker, genetics counselor, pharmacist, and psychologist. The goals of therapy include long-term prevention and treatment of lung and digestive problems and other complications, maintenance of good nutrition, and encouragement of physical activity.

Children with cystic fibrosis need psychologic and social support because they may be unable to participate in normal childhood activities and may feel isolated. Much of the burden of treating a child with cystic fibrosis falls on the parents, who should receive adequate information, training, and support so they can understand the disorder and the reasons for the treatments.

Adolescents need guidance and education as they transition to independence and assume responsibility for their care.

Adults need support as they deal with issues related to employment, relationships, health insurance, and deteriorating health.

Treatments for the lungs

The treatment of lung problems is focused on

  • Preventing airway blockage

  • Controlling infection

The person should receive all routine immunizations, particularly for infections that can cause respiratory problems such as Haemophilus influenzae, influenza, measles, pertussis, pneumococcus, and varicella.

Airway clearance techniques, which include postural drainage, chest percussion, hand vibration over the chest wall, and encouragement of coughing (see Chest Physical Therapy), are started when cystic fibrosis is first diagnosed. Parents of a young child can learn these techniques and carry them out at home every day. Older children and adults can carry out airway clearance techniques independently by using special breathing devices, an inflatable vest that vibrates at a high frequency (a high-frequency oscillation vest), or special breathing maneuvers. Aerobic exercise, done regularly, can also help keep the airways clear.

Bronchodilators are drugs that help prevent the airways from narrowing. People usually take bronchodilators by inhaling them. People with severe lung problems and a low level of oxygen in the blood may need supplemental oxygen therapy. In general, people with chronic respiratory failure do not benefit from using a ventilator (breathing machine). However, occasional, short periods of mechanical ventilation in the hospital may help during an acute infection, after a surgical procedure, or while waiting for a lung transplant.

Drugs that help thin the thick mucus in the airways, such as dornase alfa or hypertonic saline (a highly concentrated salt solution), are widely used. These drugs are inhaled through a nebulizer. They make it easier to cough up sputum, improve lung function, and may also decrease the frequency of serious respiratory tract infections.

Corticosteroids, such as prednisone or dexamethasone, given by mouth can relieve symptoms in infants with severe bronchial inflammation, in people who have narrowed airways that cannot be opened with bronchodilators, and in people who have an allergic lung reaction to a type of fungus (allergic bronchopulmonary aspergillosis). Allergic bronchopulmonary aspergillosis is also treated with an antifungal drug given by mouth.

Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), is sometimes used to slow the deterioration of lung function.

Antibiotics

Antibiotics must be started as early as possible to treat respiratory tract infections. At the first sign of a respiratory tract infection, a sample of coughed-up sputum or a swab of a sample from the back of the throat and tonsils is collected and tested, so that the infecting organism can be identified and the doctor can choose the drugs most likely to control it. Staphylococcus aureus, including methicillin-resistant or methicillin-sensitive strains, and Pseudomonas species are commonly found. Many different antibiotics can be given by mouth to treat staphylococcal infections. To treat a Pseudomonas infection, an antibiotic such as a fluoroquinolone often can be given by mouth (orally), or an antibiotic such as tobramycin or aztreonam can be inhaled through a nebulizer.

However, if the infection is severe, antibiotics given by vein (intravenously) may be needed. For this treatment, tobramycin or another aminoglycoside antibiotic is combined with another antibiotic that specifically targets Pseudomonas. These antibiotics include cephalosporins, penicillins, fluoroquinolones, and monobactams. This treatment often requires hospitalization, but part of the treatment may be given at home. Taking the inhaled form of tobramycin or aztreonam every other month for a long time and also continuously taking an oral form of the antibiotic azithromycin 3 times each week may help control Pseudomonas infection and slow the decline in lung function.

CFTR modulators

CFTR modulators are oral drugs taken chronically that improve the function of the defective protein made by mutations in the CFTR gene.

There are four CFTR modulators or combinations for people who have specific mutations: ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor. These drugs can be used to treat about 90% of people who have cystic fibrosis. Doctors give these drugs to people based on their age and the mutations they have.

Ivacaftor is given to people 6 months of age and older who have at least 1 copy of a specific cystic fibrosis mutation.

The combination of lumacaftor and ivacaftor can be given to people 2 years of age and older who carry 2 copies of the F508del mutation.

The combination of tezacaftor and ivacaftor can be given to people 6 years of age and over who carry 2 copies of the F508del mutation or other specified mutations.

The combination of elexacaftor, tezacaftor, and ivacaftor can be given to people 12 years of age and over who carry at least 1 copy of the F508del mutation.

CFTR modulators can improve lung function, increase weight, decrease the salt concentration in sweat, and decrease the frequency of lung infections. Although all of these drugs can be helpful, only ivacaftor and the combination of elexacaftor, tezacaftor, and ivacaftor are considered to be highly effective therapy.

Doctors are working to develop drugs that will help people with other mutations that cause cystic fibrosis.

Enemas and stool softeners

Newborns who have blocked intestines may be treated with special enema solutions but often require surgery.

Older children and adults who have constipation or partially blocked intestines may be treated with stool softeners, enemas, and special solutions given by mouth or via a small, flexible plastic tube (nasogastric tube) that is passed through the nose or mouth into the stomach.

Diet and supplements

The diet should provide enough calories and protein for normal growth. Because digestion and absorption can be abnormal even when pancreatic enzyme supplements are used, most children need to consume 30 to 50% more calories than the usually recommended amount to ensure adequate growth. The proportion of fat should be normal to high. High-calorie oral supplements can provide extra calories for children and adults.

People who cannot absorb enough nutrients from food may need supplemental feedings given through a tube inserted into the stomach or small intestine.

People with cystic fibrosis should take double the usual recommended daily amount of fat-soluble vitamins (A, D, E, and K) in a special formulation that is more easily absorbed.

Drugs that stimulate the appetite may be helpful. When people exercise, have a fever, or are exposed to hot weather, they should increase their fluid and salt intake.

Pancreatic enzyme supplements

People whose pancreas has been affected by cystic fibrosis must take capsules of pancreatic enzyme supplements with all meals and snacks. For infants, parents open the capsules and mix the contents with an acidic food such as applesauce so that the special coating on the pancreatic enzyme supplement does not dissolve before reaching the intestines. For some people, drugs that reduce stomach acid, such as a histamine-2 blocker or a proton pump inhibitor, can improve the effectiveness of the pancreatic enzymes. Special milk formulas containing protein and fats that are easy to digest may help infants who have pancreatic problems and poor growth.

Insulin

People with cystic fibrosis who have diabetes need to take insulin injections. Oral drugs for diabetes are not adequate treatment.

In addition to insulin, management includes nutrition counseling, a diabetes self-management program, and monitoring for eye and kidney complications. People also need special nutrition counseling because standard dietary recommendations for people with only diabetes or only cystic fibrosis are not adequate.

Surgery

At times, surgery may be needed to treat a collapsed lung, chronic sinus infection, severe chronic infection restricted to one area of the lung, bleeding from blood vessels in the esophagus, gallbladder disease, or obstruction of the intestine. Massive or recurring bleeding in the lung can be treated by a procedure called embolization, which blocks off the bleeding artery.

Liver transplantation has been successful for people who have bleeding resulting from esophageal varices or severe liver damage.

Double lung transplantation for severe lung disease is becoming more routine and more successful with experience and improved techniques. For adults who have cystic fibrosis, average survival after a double lung transplant is about 9 years.

Other treatments

People who have heart failure are given drugs (diuretics) to reduce the amount of fluid they retain. Diuretics help by increasing the amount of water the kidneys can get rid of from the body. People should also limit their intake of table salt and salty foods.

Injections of human growth hormone may improve lung function, increase height and weight, and reduce the rate of hospitalization. However, this drug is costly and inconvenient for people to receive, so doctors do not commonly prescribe it.

Some people with low oxygen levels in their blood may need supplemental oxygen that is usually given through a two-pronged nasal tube (cannula). Some people are treated with a tight-fitting mask placed over the nose or nose and mouth. A mixture of oxygen and air is delivered under pressure through the mask. This technique, called bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP), can help people maintain normal oxygen levels while they sleep.

End-of-life issues

People who have CF and their family members need to have discussions with their doctor and care team about their prognosis and what types of treatment they want to receive. These discussions are especially important for people whose lung function is worsening. People need to be prepared for what is to come and know what treatments may be done to extend life. With advanced CF, people and their families need to discuss the potential benefits and burdens of lung transplantation.

Doctors should give people who have CF the information they need to make care choices and should help people determine how and when to accept dying and how to talk about dying. Most people facing the end of life with CF are older adolescents or adults who are responsible for and usually capable of making their own choices.

When aggressive treatments are no longer helpful, doctors may begin giving people treatments that aim only to relieve symptoms (called palliative care). People usually do best when they make such decisions for end-of-life care well in advance of needing to. Such early discussions are very important because, later on, the illness often prevents people from explaining their wishes. This process of making decisions in advance for end-of-life care is called advance care planning. Such planning should involve the execution of appropriate legal documents that reflect the person's wishes regarding end-of-life care.

More Information

Drugs Mentioned In This Article

Generic Name Select Brand Names
OZURDEX
ZITHROMAX
PULMOZYME
ISOPTO CARPINE, PILOPINE HS, SALAGEN
TOBI, TOBREX
RAYOS
Tezacaftor
ADVIL, MOTRIN IB
KALYDECO
AZACTAM
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