Cystic Fibrosis Treatments and Medications

What is cystic fibrosis?

Cystic fibrosis (or mucoviscidosis) is an inherited condition that reduces the water content of secretions within the body, causing thick and sticky mucus which fills up and blocks the lungs and other organs. It is one of the most common heritable genetic disorder in Caucasians in the US.

This is the basic mechanism responsible for cystic-fibrosis-related diseases throughout the body:

• Mucus in the lungs is too sticky to clear out and provides a rich environment for bacteria growth, resulting in chronic lung infections, bronchial damage (bronchiectasis), and scarring (fibrosis). Chronic and progressive lung disease is the primary cause of death in 77% of CF patients.
• Pancrea The pancreas secretes enzymes that digest food, but the secretions back up causing pancreatic insufficiency (87% of patients), insulin-dependent diabetes, and swelling of the pancreas (pancreatitis). Pancreatic insufficiency means patients with CF have difficulty digesting and absorbing nutrients, particularly fats, proteins, and fat-soluble vitamins.
• The liver serves many functions including secreting bile acid to help digestion. Bile acid obstruction is common in CF patients and results in fatty liver, cirrhosis (scarring), and gallbladder stones.
• Digestive system. Sticky mucus in the intestines causes thick stools that block the intestines (meconium ileus). Meconium ileus in a newborn is often the first sign of cystic fibrosis. Gastroesophageal reflux (GER) is also a common complaint and may contribute to lung infections.
• Nose. Thick secretions in the nose can cause nasal polyps as well as chronic swelling of the sinuses and nasal passages (rhinosinusitis).
• Reproductive tract. Nearly all men with cystic fibrosis (97%) will not have sperm in their ejaculate because of obstruction of the vas deferens, the duct that transports sperm to the urethra.
• Bones. Nutritional deficiency as a result of pancreatic insufficiency can result in bone loss, osteoporosis, and joint disease.

There are over 2000 genetic mutations that are responsible for cystic fibrosis. All are related to the CFTR protein. Based on the type of mutation, cystic fibrosis is divided into five classes of decreasing severity.

• Class 1 CF means cells are unable to produce working copies of CFTR proteins.
• Class 2 CF prevents cells from moving CFTR protein from where it’s made in the cell to the cell membrane and then locks it in place.
• Class 3 CF involves fully-formed but completely defective CFTR proteins on the cell membrane.
• Class 4 CF has fully-formed but partly defective CFTR proteins on the cell membrane.
• Class 5 CF has fully-formed and fully working CFTR proteins that are broken down too quickly by the cell.

The first three classes are the most severe cases. Seven in ten CF patients are class 2 CF patients with a single common mutation, the F508 mutation.

The primary goal of treatment is to prevent and treat lung infections, maintain adequate nutrition, and manage other conditions as they arise. Patients born in 2018 can expect to live an average of 47 years, but life expectancy is more than 50 years in other countries.

How is cystic fibrosis diagnosed?

Cystic fibrosis diagnosis begins at birth. All newborns in the United States are screened for cystic fibrosis along with other conditions using a blood test, the Newborn Screening Test. For cystic fibrosis, the test will measure the amount of a certain pancreatic protein called trypsinogen using IRT (immunoreactive trypsinogen test) and, depending on the state, genetic testing.

The average age for diagnosis is 6 months, but nearly all patients are diagnosed before the age of 2. A definitive diagnosis of CF consists of

• Clinical evidence of cystic fibrosis
• Evidence of CFTR dysfunction.

Clinical evidence of CF could be a positive IRT test or a sibling with CF. If not, the doctor will monitor for clinical signs of cystic fibrosis in the infant including intestinal blockage, jaundice, lung problems, or poor weight gain.

Evidence of CFTR protein dysfunction includes the sweat chloride test, a DNA test, or other tests used if the results are ambiguous.

Sweat chloride test

Patients with a defective CFTR protein do not reabsorb salt from the sweat before it leaves the body as other people do, so excessively salty sweat indicates a defective CFTR protein 99% of the time. Sweat chloride tests are accurate and inexpensive, so they are usually the first-line CFTR function test.

DNA test

A sweat test might show higher than normal salt levels, but not high enough for a CF diagnosis. A DNA test will then be used that looks for at least two copies of a cystic fibrosis mutation. There must be one copy on both chromosomes. The disease usually does not manifest if only one mutated gene is present.

CFTR tests

Neither the sweat test nor the DNA test is foolproof. There are over 2000 genetic mutations that cause cystic fibrosis, but DNA testing can only identify about 70 of the most common ones. To resolve questionable cases, one of two tests can measure the activity of the patient’s CFTR proteins by measuring voltage differences in the body’s tissues: the nasal potential difference (NPD) test and the intestinal current measurement (ICM).

Cystic fibrosis treatment options

• Proactive prevention and treatment of lung infections
• Nutritional support
• Other conditions will be treated as they arise.

Most patients will be treated by a team of healthcare professionals at clinics that specialize in cystic fibrosis. This team will include pulmonologists, gastroenterologists, endocrinologists, nutritionists, nurses, and physical therapists.

Airway clearance

The centerpiece of CF treatment is to clear the lungs of mucus to prevent bacterial infection using physical therapy, exercise, and medications. Therapists and patients will regularly perform Airway Clearance Techniques (ACTs) involving inhaled mucus thinners followed by Chest Physical Therapy (CPT), such as striking the chest, coughing, vibration (a cystic fibrosis “vest”), or deep breathing techniques to bring the mucus out of the lungs.

Lung infection

Patients with CF are vulnerable to lung infections. Over time, serial lung infections damage the airways, reduce lung capacity, and eventually progress to lung failure. For this reason, doctors use a low threshold for lung infection diagnosis and hospitalize CF patients at the first sign of an acute infection. Infections are treated aggressively with oral and injected antibiotics, oxygenation, and airway clearance.

Diet

Pancreatic insufficiency means the digestive system is missing pancreatic enzymes that break down and aid the absorption of nutrients such as fat, proteins, and fat-soluble vitamins. CF patients require a high fat, high protein, and high-calorie diet as well as anywhere from 120% to 200% the normal RDA of vitamins and minerals. Oral pancreatic enzymes will be taken at meals to facilitate digestion and absorption.

Symptomatic treatment

Other conditions caused by cystic fibrosis, such as digestive problems, nasal and sinus problems, and liver problems, will be managed as they occur. The most serious are liver damage and cystic-fibrosis-related diabetes, both of which can reduce life expectancy.

CFTR modulator therapies

Mutation-specific medications go to the source of cystic fibrosis and improve CFTR function. For now, however, CFTR modulator therapies only help supplement symptomatic treatment and are not a cure for cystic fibrosis.

Surgery

Despite the best efforts of doctors, lung function will progressively decline and the lungs will eventually fail, requiring a lung transplant. The average life expectancy after lung transplantation is eight to nine years. Some CF patients may require a liver transplant because of progressive damage to the liver.

Cystic fibrosis medications

Most medications for cystic fibrosis treat or manage cystic-fibrosis-related diseases and conditions. They are effective at slowing down progressive damage to the lungs, organs, and other tissues in the body.

Mucus thinners

One of the primary goals of cystic fibrosis treatment is to clear mucus from the lungs using physical therapy combined with mucus thinners taken through an inhaler or nebulizer. Mucolytics, such as dornase alfa, break up substances in the mucus, making it less sticky and easier to expel. Secretolytics, such as inhaled hypertonic saline solution, make mucus more watery by drawing water out of the tissues and into the airways. The effects of mucus thinners are temporary, so cystic fibrosis patients need to perform physical airway clearance to clear the thinned mucus.

Bronchodilators

Bronchodilators, such as albuterol or ipratropium, increase the width of the airways to allow more airflow. These treatments help with breathing difficulties and improve shortness of breath.

Antibiotics

The single greatest threat of cystic fibrosis is serial lung infections that over time steadily damage the lungs. Aggressive antibiotic therapy is used at the first sign of infection and includes penicillins, cephalosporins, azithromycin, tetracyclines, clindamycin, vancomycin, or sulfa drugs, among others.

Pancreatic enzymes

Pancreatic insufficiency means that vital enzymes needed to digest and absorb nutrients are missing from the digestive system. Many CF patients need to take pancreatic enzymes at each meal to increase the digestion of foods and the absorption of fats, proteins, and nutrients by the intestines.

Vitamins

Cystic fibrosis patients need anywhere from 120% to 150% of the recommended daily allowance of vitamins to compensate for their lowered ability to digest and absorb nutrients. Fat-soluble (ADEK) vitamins are particularly important because CF patients often do not have enzymes that help transport fats across the intestinal walls. These vitamins are often taken as CF-specific multivitamins in a water-soluble format.

CFTR modulators

CFTR modulators directly address CFTR protein malfunction. Ivacaftor treats class 3 cystic fibrosis, which is caused by CFTR proteins on the cell membrane staying permanently closed. Ivacaftor is a “potentiator” that activates CFTR proteins and opens the chlorine channel. Lumacaftor, tezacaftor, and elexacaftor treat class 2 cystic fibrosis which is due to the malformation of the CFTR protein. These drugs are “correctors'' and are always combined with ivacaftor. They help fix the protein, move it to the cell membrane, and put it into place. Ivacaftor then activates the protein and opens the chlorine channel. These effects only last for as long as the drugs are in the bloodstream, so they must be taken regularly to be effective.

Other medications

Cystic fibrosis affects systems and organs throughout the body, so many other types of drugs will be relied on to treat symptoms, such as anti-inflammatory medications, prokinetics to treat gastroesophageal reflux, laxatives for intestinal obstruction, bile acids for liver blockage, and insulin for diabetes.

What is the best medication for cystic fibrosis?

Cystic fibrosis is a complex condition that affects organs and tissues throughout the body. Cystic fibrosis care involves a team effort of physicians and other healthcare providers who will find the right combination of medications and therapies suitable to the patient’s situation. Some of the most common drug classes used are represented in the table below.

What are the common side effects of cystic fibrosis medication?

Cystic fibrosis is a lifelong project that involves numerous medications of various types. Side effects will vary based on the medication, but the most serious issues are allergic reactions and drug interactions since more than one drug is often taken at a time. However, this is not a complete list, and you should consult with a healthcare professional for possible side effects and drug interactions based on your specific situation.

CFTR modulators

Headache is the most common side effect of CFTR modulators. Other side effects are breathing problems, nausea, and diarrhea. More seriously, CFTR modulators affect the liver function or increase blood pressure.

Mucus thinners

Inhaled mucus thinners are considered very safe. Side effects tend to result from irritation from the medicine such as sore throat, cough, runny nose, voice changes, or a bad taste in the mouth. The most serious side effects are allergic reactions to the ingredients.

Bronchodilators

Bronchodilators are classified as beta-2 agonists (albuterol) or anticholinergics (ipratropium). Beta-2 agonists tend to cause nervousness, heart palpitations, trembling, and muscle cramps, while the most common side effects of anticholinergics are dryness: dry mouth, dry eyes, or throat irritation. The most serious side effects of bronchodilators are high blood sugar or low potassium, but these effects are rare.

Antibiotics

Antibiotics typically can cause gastrointestinal problems such as an upset stomach, intestinal problems, and loss of appetite. Allergic reactions are common and could be severe. Cystic fibrosis patients often take other medications, so drug interactions are a concern.

Pancreatic enzymes

Pancreatic enzymes are naturally produced by the body, so side effects from oral pancreatic enzymes are fairly mild gastrointestinal complaints, such as gas, nausea, diarrhea, constipation, and bloating.

What is the best home remedy for cystic fibrosis?

Cystic fibrosis is a lifetime project of protecting lung health, maintaining adequate levels of nutrition, and managing other conditions. Home treatment is an essential component of that project.

1. Eat a healthy diet.

Your dietitian will recommend a daily regimen of three regular nutritious meals, regular snacks, CF-specific supplements, and pancreatic enzymes. Often times you will need a high-calorie diet.

2. Drink fluids and take electrolytes.

It is especially important to drink fluids and replace electrolytes, particularly in warm weather.

3. Exercise.

Regular exercise helps strengthen the lungs and loosen mucus. Breathing exercises are also helpful.

4. Improve indoor air quality.

Avoid smoke, invest in an air purifier, and keep surfaces and fabrics clean.

5. Wash hands regularly.

One of the most effective ways to reduce the risk of bacterial lung infections is to regularly wash the hands in soap and water.

Frequently asked questions about cystic fibrosis

Is cystic fibrosis always fatal?

Cystic fibrosis is a lifelong condition that affects organs throughout the body, particularly the lungs. Eventually, most patients will die of complications due to cystic fibrosis, usually end-stage lung disease. However, children born in 2018 can expect to live an average of 47-48 years with treatment. The oldest living patients with cystic fibrosis are in their early 80’s.

Is there a cure coming soon for cystic fibrosis?

There are many promising therapies in research or clinical trials. Some involve gene therapy to correct the CFTR gene mutation. Currently, however, CF treatment largely focuses on conditions caused by cystic fibrosis.

Can cystic fibrosis be prevented?

Cystic fibrosis is an inherited condition that cannot be prevented.

Has anyone been cured of cystic fibrosis?

Cystic fibrosis is a lifelong condition. It cannot be cured, but the symptoms can be managed. Many patients can complete school, have a career, get married, and maintain a fairly good quality of life.

Would a drug to thin mucus cure cystic fibrosis?

Mucus thinners help to clear the airways to prevent infection, but they do not cure cystic fibrosis.

What are the main treatments for cystic fibrosis?

The foundational treatment of cystic fibrosis is to prevent lung infections through airway clearance, clear lung infections when they do occur, and ensure proper nutrition. Other conditions caused by cystic fibrosis are managed as they occur.

What medications do people with cystic fibrosis take?

Medications treat the symptoms of cystic fibrosis, such as mucus-filled lungs, lung infections, pancreatic insufficiency, and other related problems. Some medications, called CFTR modulators, directly treat the cause of cystic fibrosis by correcting or activating CFTR proteins.

What are some of the other problems and treatments related to CF?

The primary conditions that require constant CF treatment are preventing and treating lung infections and pancreatic insufficiency. However, CF affects organs throughout the body and is responsible for other conditions such as cystic-fibrosis-related diabetes (CFRD), liver disease, enlarged spleen, gallbladder stones, nasal and sinus problems, bone loss, and male sterility. These conditions are treated with medications, physical therapy, and, sometimes, surgery, such as nasal polyp removal or liver transplant.

What are the long term effects of cystic fibrosis?

The long-term consequences of cystic fibrosis include progressive lung and liver damage. Most patients will experience end-stage lung disease that will require a lung transplant.

What foods should be avoided with cystic fibrosis?

CF patients require a diet high in protein, fat, calories, and nutrients. There are no specific foods that cystic fibrosis nutritionists say should be avoided outright. However, the dietitian or nutritionist on the care team will recommend a diet tailored to the patient’s unique needs as well as instruct patients to avoid certain foods.

What are some future treatments for cystic fibrosis?

Current medical research is developing gene therapies that can correct the CFTR gene in various tissues in the body, such as the lungs. CFTR modulators continue to be developed that in combination can restore more normal CFTR function throughout the body.

Related resources for cystic fibrosis

• 2018 Patient Registry Annual Data Report
• About Cystic Fibrosis
• Carrier Testing for Cystic Fibrosis
• Cystic Fibrosis
• Cystic Fibrosis–Causes, Symptoms, Diagnosis, Treatment, Pathology
• Cystic Fibrosis: A Guide for Patient and Family
• Cystic Fibrosis-Related Diabetes
• Depression, Anxiety, and Cystic Fibrosis: What the Guidelines Mean for YouHandbook of Pediatric Nutrition