Cystic Fibrosis Explained: Causes, Symptoms, Diagnosis, Treatment, Complications, and What’s New in Research and Care

Cystic fibrosis (CF) is a genetic disorder that causes thick, sticky mucus to build up in organs like the lungs and pancreas. This often leads to breathing problems and digestive enzyme deficiencies. It could also involve other organs like the liver, intestine, and kidneys. Lung involvement takes place in about 90% of patients who scale past the neonatal period. Thanks to better therapies and early detection, many individuals with CF now live into adulthood, with increasing survival rates and improved quality of life.

Cystic Fibrosis

Cystic Fibrosis Credit: BruceBlaus

CF is the most prevalent genetic illness that shortens the life expectancy of White people. The highest prevalence of the disease happens in North America, Europe, and Australia. There are approximately 40,000 cases of CF in the US and 162,428 globally. Worldwide, approximately 3 in 100 white people are carriers, and 3 in 10,000 white people develop CF. Roughly 1 in 30 Caucasians are carriers.

While some cystic fibrosis patients experience grave symptoms or potentially fatal complications, others have little or no symptoms at all. Although there isn’t a cure for the disease yet, there are therapies that can help control the illness, ease symptoms, and lower the chance of complications. A person’s life expectancy and quality of life are increased as a result. Nowadays, almost half of CF patients are 18 years of age or older due to advancements in medical care and medications.

Causes

Cystic fibrosis is a hereditary condition that can be passed down from generation to generation due to a mutated gene. It is caused by a defect in the CFTR gene, which produces a protein that regulates the flow of fluid across membranes in the body. If the protein does not function effectively, it can lead to the accumulation of thick sticky secretions in the lungs and various other organs.

Symptoms

The organs most commonly affected are the lungs, pancreas, liver, gallbladder, intestines, and reproductive organs. Therefore symptoms can vary with the organ and age of the person.

In newborns and children, about 10% have meconium ileus, which causes vomiting, abdominal swelling, and lack of bowel movement. Meconium ileus is when meconium (a baby’s first poo) accumulates and blocks the small intestine. This could be complicated by perforation, which can lead to shock and death.

The lack of pancreatic enzymes causes other symptoms like poor weight gain and failure to thrive. This happens due to the inability to digest nutrients, and the stools are usually oily, bulky, and foul-smelling.

Symptoms in Older Children and Adults

In older children and adults, symptoms include: fever, frequent coughing, difficulty in breathing, wheezing, constipation, vomiting, abdominal pain, change in bowel habits, excessive sweating, slowed growth, and delayed puberty.

They usually present for the first time with recurrent cough and breathing difficulties due to lung infections and sinusitis. Coughing is associated with vomiting and sleep disturbances. As the disease worsens, tolerance for physical activities reduces as lung infections become more frequent. The chest appears barrel-shaped, and there is the presence of cyanosis and finger clubbing. Lung destruction from recurrent infections occurs slowly.

These respiratory symptoms are often the first sign of CF in people not diagnosed at birth. Over time, repeated infections can permanently damage the lungs.

Indigestion is also common amongst them because of the deficient pancreatic enzymes. They also have increased loss of salt and water when sweating, leading to dehydration. Salt crystals or even a salty taste may be noticed by parents on their children’s skin.

Diagnosis

Early diagnosis of CF allows medical professionals to work with parents to learn how to maintain their child’s health and postpone or avoid major, lifelong health issues associated with the condition. The diagnosis of CF includes newborn screening, sweat test, genetic testing, and carrier screening. Others include blood tests, pulmonary function tests, X-rays, and CT scans.

Newborn screening

This is done during the first few days of life. It involves measuring the level of a pancreatic enzyme called trypsin. This is done by collecting a drop of blood via a heel prick. If the enzyme level is high, it is indicative of CF, and a confirmatory sweat or genetic test is done. Newborn screening has greatly improved early detection. However, not all cases are caught in infancy, especially milder forms.

About 10% of individuals with CF are not diagnosed until they are in their early adolescent or adult years.

Genetic test

Testing for the presence of a defective CFTR gene is helpful in the diagnosis of CF. Finding two abnormal genes is indicative of CF. This is also done for people who show unusual symptoms or people who have siblings who have been diagnosed with CF.

Sweat test

This is done by measuring the amount of salt in sweat, it is done on an outpatient basis. Sweat is collected from the skin, and an estimation of the salt level is carried out. A high salt level is indicative of CF. Apart from being a confirmatory test after newborn screening, it is carried out on infants, children, and older people who have exhibited uncommon symptoms.

Carrier screening

This test is done for intending couples and parents. This aids in revealing who has the defective gene. If both parents are carriers, each pregnancy has a 25% chance of producing a child with CF,  a 50% chance of producing a carrier, and a 25% chance of producing a child with no defective gene.

Other tests include blood tests to determine the levels of blood sugar and insulin, which could be high and low, respectively. Also, pancreatic and liver enzymes and vitamins A, D, E, and K analysis reveal a low level.

Pulmonary function tests, chest X-rays, and CT scans reveal the state of the lungs and sinuses.

Treatment

Multidisciplinary Care and Support

The treatment of CF should be multidisciplinary and holistic to ensure a better quality of life. A coordinated care team including pulmonologists, nutritionists, physiotherapists, and social workers is essential in managing this lifelong condition. Adolescents require direction, education, and support as they transition to adulthood and become responsible for themselves. Adults also require support as they deal with life’s activities and deteriorating health.

Immunization

CF patients need to be immunized. This will help prevent the emergence of some respiratory infections that can be life-threatening to them. They should be immunized against infections like Pertussis, Haemophilus influenzae, influenza, pneumococcus, measles, varicella, and COVID-19.

Airway Clearance and Physical Therapy

Techniques that clear the airway include chest percussion, postural drainage, hand vibration over the chest wall, and encouragement to cough. Regular aerobic exercise can help. Nebulization with a saline solution has proven to help improve lung function and reduce the occurrence of infections.

Medications for Respiratory Management

Drug options are: bronchodilators like salbutamol, which widen narrowed airways. Corticosteroids such as prednisolone, help in reducing inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and diclofenac also aid in reducing inflammation.

Antibiotics are employed to treat infections. They are essential due to the frequent respiratory tract infections CF patients come down with. They include penicillin, cephalosporins, and so on.

CFTR Modulators

Drugs like CTFR modulators help control the function of the protein produced by the CTRF gene. They come in four combinations: ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor. All are used to treat the various variants of the disease.

Digestive and Nutritional Support

Stool softeners like docusate sodium help in softening bulky stool, newborns often require intestinal surgery. The diet should be modified to provide enough calories and proteins for growth, vitamin supplements could also be administered. Pancreatic enzyme supplements have proven to be beneficial.

Diabetes Management

Insulin is beneficial for individuals who have developed type 2 diabetes. Diet modification and regular monitoring are also necessary.

Advanced Interventions

Liver and lung transplants may be required in severe cases.

Complications

The complications of CF include night blindness, osteoporosis, anemia, bleeding disorders, osteopenia, rectal prolapse, pneumothorax, heart failure, type 2 diabetes, liver cirrhosis, gallstones, and infertility.

Night blindness, anemia, osteoporosis, bleeding disorders, and osteopenia happen due to inadequate digestion of vitamins A, D, E, and K. Rectal prolapse may occur in infants and toddlers.

The tiny air sacs in the lungs may rupture, leading to pneumothorax, which is the leakage of air into the chest. This could lead to lung collapse.

Diabetes could develop due to the inability of the pancreas to produce insulin.

Liver cirrhosis occurs in about 3 to 4% of people with CF. The secretions could cause inflammation, which ends up in liver scarring. It may also cause portal hypertension and esophageal varices.

Gallstones develop in about 10% of people. This is due to the accumulation of bile. Surgical removal might be needed.

People with CF often suffer from reproductive mishaps and infertility. This could be psychologically draining, especially for married people. They suffer from low sperm counts and thick cervical secretions, which decrease fertility. Nevertheless, women with CF have carried babies to term unless symptoms were severe at the time. Other than that, neither men nor women have impaired sexual functions.

Related Reading:

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New Study Shows That Vitamins A, E and D Can Reduce Respiratory Infections

Current management trends

Research has revealed that the defective CFTR gene could be repaired by genetic engineering. The course of treatment is tailored based on the genetic identity of each patient.

It is proposed that if the expression of ENaC (Epithelial sodium channel) in affected patients is inhibited, it could lead to reduced mucus accumulation in glands. This is a promising strategy for the treatment of CF.

Emerging Treatments and Therapies for Cystic Fibrosis

Research into cystic fibrosis (CF) has advanced significantly in recent years, offering new hope for patients, especially those who don’t benefit from current CFTR modulators. Below is an overview of promising therapies that are newly approved or currently under investigation.

Recently Approved Therapy

  • Alyflek (vanzacaftor/tezacaftor/deutivacaftor):
    Approved by the FDA in December 2024, Alyflek is a next-generation, once-daily CFTR modulator. It is indicated for people aged six and older with at least one F508del mutation or another responsive CFTR mutation. This therapy improves lung function and overall clinical outcomes while simplifying dosing regimens (Cystic Fibrosis Foundation, 2024).
  • RCT2100 (inhaled mRNA therapy):
    In March 2025, the FDA granted orphan drug designation to RCT2100, an inhaled mRNA-based therapy for patients who do not benefit from existing CFTR modulators. Early clinical testing is underway.

Therapies in Development

  • VX-522 (mRNA-based CFTR therapy):
    Developed by Vertex Pharmaceuticals in partnership with Moderna, VX-522 uses mRNA technology to deliver functional CFTR protein to cells. It is intended for patients who cannot benefit from existing CFTR modulators. A Phase 1/2 trial is ongoing, with early data expected in 2025 (Vertex Pharmaceuticals, 2024).
  • BI 3720931 (inhaled gene therapy):
    Trials are underway in the UK and Europe for BI 3720931, an inhaled gene therapy that may benefit patients regardless of mutation type. The study includes 36 participants and aims to reduce lung exacerbations and improve function (Radcliffe Department of Medicine, 2024).
  • Sionna Therapeutics NBD1 stabilizers:
    Sionna is developing small molecules that target and stabilize the NBD1 region of the CFTR protein, which is commonly misfolded due to the F508del mutation. This class of drugs could complement existing modulators and improve protein function (Labiotech.eu, 2024).
  • 4D-710 (aerosolized gene therapy):
    4D Molecular Therapeutics is evaluating 4D-710, a gene therapy delivered by aerosol. Early trial data show successful lung delivery and CFTR expression in CF patients (4D Molecular Therapeutics, 2024).

Novel Approaches

Bacteria-sniffing dogs:
A team at Imperial College London is exploring the use of trained dogs to detect bacterial

Clinical opinion

Control of infection is a key aspect in the management of cystic fibrosis. The main risk in the home environment is the contamination of airway clearance and nebulization equipment. Therefore, I advise that proper cleaning and sterilization of equipment should be done regularly. If doing this becomes cumbersome, I suggest that involving family and friends could be helpful. This will help reduce the physical and emotional burden.

Bottom Line

Cystic fibrosis is no longer the childhood death sentence it once was. Advances in CFTR modulators, early diagnosis, and gene therapy have transformed the outlook but it’s not a solved problem.

While many newer treatments focus on patients with the F508del mutation, others with rare or ultra-rare variants remain underserved. Therapies like RCT2100 and VX-522 offer hope, but they’re still in early trials. For these patients, “standard care” still means constant airway clearance, repeated antibiotics, and unpredictable infections. That’s a major quality-of-life burden.

There’s also the question of access. High costs and insurance hurdles make some breakthrough drugs unreachable, especially outside the U.S. And despite a pipeline full of promising options, there’s no guarantee they’ll work for every genetic profile — or even get approved.

The future of CF care depends not just on innovation, but on equity, affordability, and long-term safety data. Until then, managing CF remains a full-time job and one that requires more than medications. It demands system-level support, patient advocacy, and a commitment to making every mutation matter.

References

Generic Error Page | American Lung Association. (n.d.). Retrieved October 28, 2023, from https://www.lung.org/lung-health-diseases/lung-disease-lookup/cystic-fibrosis/learn-about-cystic-fibrosis

Rosenstein, B. J. (2023, October 13). Cystic Fibrosis (CF). MSD Manual Consumer Version. Retrieved October 28, 2023, from https://www.msdmanuals.com/home/children-s-health-issues/cystic-fibrosis/cystic-fibrosis-cf

Almughem, F. A., Aldossary, A. M., Tawfik, E. A., Alomary, M. N., Alharbi, W. S., Alshahrani, M. Y., & Alshehri, A. A. (2020, July 2). Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies. Pharmaceutics. Retrieved October 28, 2023, from https://doi.org/10.3390/pharmaceutics12070616