We will be discussing the basic biological principles of cystic fibrosis, the organs affected, and the various treatment options for this disease. So what do you, a panda, or a neighbor’s pet have in common? You’re all made up of cells. The cells can be thought of as a subunit of life. Inside these cells are a set of instructions called DNA. DNA is made up of the bases: adenine, guanine, cytosine, and thymine. You can think of these bases as instructions that code for genes in your body. For example, the DNA contains instructions for traits such as hair type, eye color, and height.
When a nucleotide base is added, removed, or substituted, it is known as mutation. These mutations can change the DNA code, which may affect the traits that are expressed in your body. Now that we know the fundamental genetic makeup of our body, let’s move to the next big question. What is cystic fibrosis? Cystic fibrosis is a disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulatory gene, known as CFTR for short. This mutation occurs on the chromosome.
This disease is an autosomal recessive disorder which means that the disease is inherited when a child inherits a defective copy of the gene from both parents who are carriers of the gene. A carrier is an individual who has a defective copy and a normal copy of a gene and is unaffected themselves. TheCFTR gene codes for the CFTR protein, which is an important chloride channel. The purpose of the channel is to pump ions in and out of the cell. The symptoms and associated complications of cystic fibrosis are caused by the dysfunction.
CFTR protein channel is found throughout the gastrointestinal tract. Affected individuals have elevated sweat electrolyte levels, pancreatic inefficiencies, and lung infections. These signs are observed in most patients but not all since the severity of the disease can range widely amongst individuals. In Canada, 1 in 3,600 are born with this disease. Studies have shown that cystic fibrosis is more frequent in European Caucasian populations than in any other population around the world.
In addition, in the mid1900s, the median survival age of individuals with this disease was eight years, but today the median survival age has drastically improved to thirty years, mainly due to a better understanding of the disease and improved clinical approaches. Now that we know more about the disease itself let’s talk about what organs are affected and the various treatment options available. Recent studies have shown a higher understanding of the underlying causes of cystic fibrosis at a genetic level.
More than 1,500 genetic mutations have been linked to the onset of this disease. However, the most relevant mutation found in 66% of affected patients is the deletion of the phenylalanine in position 508 on the CFTR gene. This inherited disease mainly infects the lungs, pancreas, liver, intestine, and sinuses. The most prominent organ affected is the lungs. Excess mucus caused infections and eventually permanent lung damage due to trapped bacteria. Normal digestive functions are also altered by this disease, as mucous blocks digestive enzymes from reaching the intestines.
Therefore food, specifically fats, and proteins, is not digested properly in patients. Finally, inflammation and infection of the sinuses is a common effect of this disease, as this disease affects the epithelium found in the upper respiratory tract. With this advanced knowledge of the causes of cystic fibrosis, a number of treatments have been proposed with the intent of these treatments being to prevent and control infections in the lungs by removing mucus and to prevent blockages in the intestines.
A number of treatments for this disease are available including antibiotics for infections of the airways, chest physical therapy, and other specific medications. Antibiotics are generally the primary treatment for people with cystic fibrosis as they most likely will have a lung infection. Based on the type of bacteria and the severity of the patient’s condition, there are different types of antibiotics that are available. Some of which include oral, inhaled, or intravenous antibiotics.
The second type of treatment is chest physical therapy which serves as a way to loosen and remove mucus from the lungs. This should be done 3 to 4 times a day and it involves repeatedly pounding one’s chest and back in order to dislodge the mucus. As it might be physically demanding for some people there are devices such as mechanical precursors or a positive expiratory pump mask which both serve the purpose of clearing mucus from the airways.
Cystic fibrosis can also be treated by medications most notably a group called bronchodilators which help to open the airways by relaxing the surrounding muscles. Finally, as mentioned before, the pancreas and intestines are unable to function officially because of this disease. Digestion of food becomes difficult and eventually, malnutrition becomes a cause of the disease. Prevention of malnutrition has become a greater focal point in recent years as it could help the patient fight a persisting lung infection.
Oral pancreatic enzymes are provided to help digest fats and proteins and supplements of vitamin A, D, E, and K are provided to replenish the fat-soluble vitamins that the intestine can no longer absorb. By implementing these techniques we can hope to continue lessening the incidence of this disease. You walk into a busy restaurant. Instinctively, you take a deep breath to smell the wonderful aromas in the air. You also just inhaled thousands of bacteria and viruses, many of which can cause diseases like colds and pneumonia.
So why don’t we constantly get sick? That’s because we’re protected by an excellent defense system in our airways. Gooey mucus coats the surfaces of your airways, trapping inhaled bacteria and viruses. Cilia, which are small hair-like protrusions on cells, can sweep the mucus up and out of the airways. Together, the mucus and cilia from the mucociliary system, which protects us against the germs we inhale. We can either cough or sneeze the dirty mucus out, or subconsciously swallow it to kill the germs with acid in the stomach.
If something is preventing the mucociliary system from working, it makes sense that we would get sick more often. This is exactly what happens in people with cystic fibrosis. Their mucus becomes so thick and dry that cilia are unable to sweep it out of the airways. This leads to massive infections that eventually are the cause of death for people with cystic fibrosis.CFTR and mucus are also found in the digestive ducts right where the stomach and small intestine connect. These ducts allow bile from the gallbladder and enzymes from the pancreas to enter the small intestine.
These substances are important because they help digest food. Defective CFTR can once again lead to mucus buildup in the ducts, clogging them and preventing the release of those digestive substances. Therefore, another symptom of cystic fibrosis malnutrition as food cannot be broken down properly. Sweat glands also have CFTR, except they allow chloride ions to enter cells, opposite of what happens in the airways and gut. Normally, this reverse direction prevents too much electrolyte loss from sweating.
However, with defective CFTR, chloride ions accumulate in the sweat and combine with sodium ions to produce salt. Abnormally salty sweat is therefore another symptom that can be used to diagnose cystic fibrosis. Therefore, the main symptoms of people suffering from cystic fibrosis are clogged and infected airways, malnutrition from clogged digestive ducts, and very salty sweat. All of these are caused by a genetic mutation in the CFTR gene, leading to defective CFTR.
Because it is a genetic disease, rates of cystic fibrosis differ with ethnicity. This disease affects Caucasians the most, with 1/3000 Caucasians affected, followed by African-Americans and Asians, with over 70,000 people affected worldwide. Advancements in medicine have increased the average lifespan of people with cystic fibrosis from 14 years in the 1980s to 40 years now and growing. Some of these medications include digestive enzymes and vitamin supplements that can treat the effects of malnutrition. Antibiotics can treat infections.
Medication that breaks down mucus or expands the airways can treat blockage of airways. However, these medications only treat the symptoms and not the cause of the disease, which is defective CFTR. New medications are now being researched that can make CFTR functional again, called CFTR potentiators. These have only worked for approximately5% of people with cystic fibrosis that have a certain mutation, but the other 95% is still desperately in need of a cure.