Cystic Fibrosis (CF)


Cystic fibrosis (CF) is a progressive hereditary disorder that affects multiple organs.1,2 The inheritance is autosomal recessive. In CF, the secretions of various exocrine glands, such as the sweat glands and glands in the lungs, are abnormally thickened because the movement of chloride to the cell surface is impaired so that the attraction of water to the cell surface is reduced.2,3 Thickened mucus can affect several physiological functions. In the lungs, it blocks the airways, leading to inflammation, infection, and respiratory failure.4

CF affects every racial and ethnic group and is currently estimated to afflict more than 30,000 individuals in the United States and at least 100,000 people worldwide.1,2,5

What Causes Cystic Fibrosis?

CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene.1,6,7 This gene encodes CFTR protein, which is a channel protein located on the apical side of epithelial tissue.7 CFTR protein transports chloride and bicarbonate across the apical surfaces of secretory epithelia in the sweat glands, pulmonary airways, gastrointestinal tract, pancreas, and vas deferens.1 The release of bicarbonate is important physiologically; bicarbonate is involved in the activation of pancreatic enzymes and the correct unfolding of mucins in the airway, which is necessary for protection against bacterial infection.6 Defects of the CFTR protein lead to surface dehydration and the formation of thick, viscous, mucopurulent secretions.1

More than 2000 mutations in the CFTR gene have been described, of which F508del (deletion of three bases coding for phenylalanine at the 508th position) is the most common.6-8 However, not all of these are responsible for the development of CF.7 Mutations in the CFTR gene have been divided into several classes (I-VI), according to their effect on the quantity or function of CFTR protein.5

Symptoms and Complications

The symptoms of CF are caused by abnormally thick mucus and affect predominantly the respiratory and digestive systems. As the mucus blocks the respiratory pathways, persistent cough, bacterial infections (eg, with Pseudomonas aeruginosa), and shortness of breath develop.8 Neutrophil infiltration with elastase release causes chronic lung damage.3,8 The disease also results in poor nutrition and growth because pancreatic obstruction prevents digestive enzymes from entering the intestine.3 Excessive loss of salt in sweat can result in abnormal levels of minerals in the blood, resulting in dehydration, weakness, fatigue, cardiac arrhythmias, and rarely death.8 The liver and reproductive organs may also be affected.3 

Diagnosis

Universal newborn screening (NBS) is essential for an early diagnosis and has been implemented in every state in the United States.2,9 The levels of immunoreactive trypsinogen (IRT) released by the pancreas are measured, and because other factors, such as premature birth, can affect IRT levels, additional testing, such as genetic testing, may be required.9 Women who are pregnant or planning to become pregnant may be carriers.4

Genetic testing identifies mutations in the CFTR gene that cause CF.2 The diagnostic process also includes a sweat test, as the concentrations of sodium chloride in the sweat of persons with CF (>60 mmol/L, diagnostic; 40-60 mmol/L, intermediate) may be higher than those of people without the disease.2,10 

Read more about cystic fibrosis diagnosis

Treatment

Even though no cure for CF is available, several therapeutic approaches can help reduce potential complications and increase the patient’s quality of life.9 Treatment is focused on improving respiration and digestion by reducing the thickness and quantity of secretions to prevent blockage and infection. Patients with severe CF may require a lung transplant.3

Chest physical therapy (postural drainage and percussion techniques) and inhalation therapy with hypertonic saline may help to clear the airways and thin the mucus, while antibiotics such as azithromycin play an important role in treating lung infection and decreasing inflammation.3,5 The administration of a bronchodilator such as albuterol may clear the airways in some cases.3 Supplementation with pancreatic enzymes and fat-soluble vitamins can increase the absorption of nutrients and improve nutrient balance.2,5,9

Drugs targeting CFTR protein defects are currently available to treat CF. CFTR modulators such as ivacaftor and lumacaftor/ivacaftor can help to restore CFTR protein function and improve mucociliary clearance.5 However, these drugs are effective only in people with specific mutations.2,5

Read more about cystic fibrosis treatment

References

1. Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet. 2021;397(10290):2195-2211. doi:10.1016/S0140-6736(20)32542-3

2. About cystic fibrosis. Cystic Fibrosis Foundation. Accessed January 5, 2022.

3. Cystic fibrosis. National Organization for Rare Disorders. Accessed January 5, 2022.

4. Cystic fibrosis. Centers for Disease Control and Prevention. Accessed January 5, 2022.

5. Chen Q, Shen Y, Zheng J. A review of cystic fibrosis: basic and clinical aspects. Animal Model Exp Med. 2021;4(3):220-232. doi:10.1002/ame2.12180

6. De Boeck K. Cystic fibrosis in the year 2020: a disease with a new face. Acta Paediatr. 2020;109(5):893-899. doi:10.1111/apa.15155

7. Almughem FA, Aldossary AM, Tawfik EA, et al. Cystic fibrosis: overview of the current development trends and innovative therapeutic strategies. Pharmaceutics. 2020;12(7):616. doi:10.3390/pharmaceutics12070616

8. Rafeeq MM, Murad HAS. Cystic fibrosis: current therapeutic targets and future approaches. J Transl Med. 2017;15(1):84. doi:10.1186/s12967-017-1193-9

9. Cystic fibrosis. Diagnosis. Mayo Clinic. Accessed January 5, 2022.

10. Davies JC, Alton EW, Bush A. Cystic fibrosis. BMJ. 2007;335(7632):1255-1259. doi:10.1136/bmj.39391.713229.AD

Reviewed by Debjyoti Talukdar, MD, on 1/9/2022.

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