Written by: Elkan Rodricks
Cystic Fibrosis is an inherited genetic disease that targets the respiratory and digestive system, mainly the lungs and the pancreas. The condition is non-communicable and can only be acquired through an autosomal recessive manner, conveying that cystic fibrosis can only develop if a person has possession of mutated versions of both recessive alleles of the gene (the offspring acquires a mutated allele of the gene from both parents). The disease causes the production of thick mucus which can lead to congestion in the respiratory tract and obstruction of pancreatic ducts which could impede the process of digestion. Cystic fibrosis can also affect the reproductive system of males, and cause blockages in sperm ducts, which could lead to male infertility. Although the disease is not communicable, cystic fibrotic patients are not permitted to come in close proximity with one another since this puts them at greater risk of catching a further infection and can lead to an increased rate of deterioration in respiratory function. The disease persists over the patient’s life over a prolonged time period, and since there is no viable cure to eradicate this disease as yet, the life span of those with the hereditary condition is significantly shortened, with the most common cause of death being respiratory failure.
To scrutinize the intricacies of the origination of cystic fibrosis, the condition is caused by the mutation of the cystic fibrosis transmembrane conductance regulator gene, which is abbreviated to the CFTR gene. It has been estimated that there are over 1,700 possible mutations that can occur in the CFTR gene to cause cystic fibrosis, wherein the most recurring mutation is called delta F508, which causes the removal of one amino acid at position 508 in the encoded protein. The mutation consequently causes the gene to code for a dysfunctional version of the CFTR protein and impairs it from performing its traditional functions. The CFTR protein is a form of a transmembrane protein where it acts as a channel across plasma membranes of cells that secrete fluids such as sweat, tears, mucus, saliva, water, etc. The channel is responsible for the transportation of chloride ions in and out of the cells, and this movement assists in controlling water potential in tissues, which is essential for the maintenance of mucus fluidity across organs (namely the lungs and pancreas) and passageways. When the function of these channels is hindered by the production of defective CFTR proteins, it instigates the specialised cells surrounding the lungs and pancreas to discharge thick layers of mucus which can cause chronic respiratory and digestive predicaments. As time passes, the concerned organs become more fragile and susceptible to infection, and eventually lead to the formation of cysts and scarring of tissues which is known as fibrosis, hence where its name is derived from.
Testing for cystic fibrosis in newborns involves undergoing a newborn screening test, where blood is taken from a heel prick and is placed on a unique material called the Guthrie Card. Blood tests are then carried out in order to evaluate the amount present of a particular enzyme called immunoreactive trypsinogen (IRT), which is produced by the pancreas. Key points to note are that healthy newborns have low amounts of the IRT enzyme, whereas those with cystic fibrosis have high amounts of the enzyme, however high levels of IRT can also be caused by other factors such as premature or arduous delivery, making it a necessity for further tests to be carried out to confirm the fibrotic condition. Occasionally, DNA tests are performed to determine whether the newborn has both, one, or no copies of the mutated gene. Following a positive blood test for high levels of IRT, the newborn is then required to undergo a chloride sweat test; the test which essentially affirms or dismisses the presence of cystic fibrosis in the individual. The sweat test entails applying a colourless liquid called pilocarpine, and minor electrical impulses to the surface of a limb in order to activate sweat glands, and the level of chloride in the sweat is then measured. Those with cystic fibrosis are likely to have higher levels of chloride in the sweat, that usually exceed the threshold of 60 mmol/L. Those that have a sweat chloride level ranging from 30-59 mmol/L are potential contractors of the condition and have to be tested further, and those with chloride levels below 30 mmol/L are unlikely to have the disease.
Symptoms of Cystic Fibrosis include:
1) Persistent cough with phlegm
2) Breathing difficulties
3) Wheezing
4) Nasal polyps
5) Lung infection; pneumonia, bronchitis
6) Poor growth
7) Malnutrition
8) Diarrhoea
9) Abnormally high levels of salt in sweat
10) Cystic Fibrosis Related Diabetes (CFRD)
11) Infertility in males
Even though there is no effective cure for this condition discovered yet, there have been advances in medication to combat the disease, and novel practices have shown significant progress in lengthening the life span of a fibrotic patient. Symptoms and medication can vary from the state of each patient since environmental factors (which differ from person to person) can also affect the progression and severity of the condition. The primary complication caused by cystic fibrosis is the production of excess, viscous mucus, which is why airway clearance techniques (ACT) are common methods to remove mucus from the lungs and air passageways. The ACT includes postural drainage and percussion, where the therapist taps the patient in certain areas in order to loosen mucus and allow it to be more easily removed. Inhaled medication is the most common form of medicine that is used to suppress the effect of the condition by dissolving and moving mucus out of the airways, killing pathogens, and stimulating cells to secrete less mucus. Medication can be taken via ingestion, inhalation, or intravenously through the blood, and drugs such as ibuprofen and azithromycin, as well as mucolytics, are components of the standard therapy that are used to treat cystic fibrosis. Nutrient and enzyme supplements are also an essential part of medication for a fibrotic patient, which helps to provide the body with viable digestive enzymes to help in the breakdown of food and allow efficient absorption.
Substantial growth of medicine over the past decade saw the production of CFTR modulators (limited to specific mutations only). This medication assists by targeting the roots of the condition; the dysfunctional CFTR protein, where it helps to transport the protein to the surface of the cell and revitalizes it to form its original function; enabling smooth flow and equal balance of fluids and ions across plasma membranes of cells. Prescription drugs such as Kaftrio, Orkambi, Kalydeco, and the most recent triple therapy Trikafta (elexacaftor, ivacaftor, tezacaftor) are special medication used for distinct mutations only, and each drug has a target population of different age groups. Triple therapy, Trikafta, is used specifically for the mutation delta F508, the most common mutation that affects over 80% of fibrosis patients. The combination modulator operates by the binding of two corrector molecules, elexacaftor and tezacaftor and the potentiator molecule, ivacaftor. This homogenization helps in improving chloride flow through channels, lung function, and causes reduced chloride levels in sweat.
As of 2021, cystic fibrosis affects an estimated 70,000 individuals or 0.0009% of the world’s population, with approximately 1,000 new cases diagnosed annually, classifying it as an extremely rare genetic disease. While novel research is in passage to make further progress towards achieving an efficacious cure, it is seen that there is an upward trend on the number of fibrotic patients surpassing the age of 40 using current medication.
Citations:
Comments