What is Cystic Fibrosis?
Cystic fibrosis is a disease that has affected children worldwide since ancient times, often resulting in a shorter life span. In medieval Europe, these children were thought to be cursed by witches, destined for an early death. A popular belief at the time was, “A child who tastes salty from a forehead kiss has been cursed and will soon meet their end.” This saying came from the fact that salty skin was an early warning sign of this mysterious, untreatable disease.
Up until modern times, understanding of cystic fibrosis remained limited. Finally, in 1949, a group of scientists led by Lowe suggested that the disease was caused by a genetic mutation. They noted that patients with cystic fibrosis had sweat that was more salty than usual, indicating a possible issue with how salt levels were controlled in their sweat glands. A scientist named Quinton suggested that patients’ sweat ducts didn’t properly handle the element chloride. Further research led to the theory that a malfunctioning chloride channel could explain the lung and systemic organ failure typically seen in cystic fibrosis patients.
Nowadays, we know that cystic fibrosis is a genetic disorder that primarily affects people with Northern European ancestry, occurring in about 1 in 3500 people. It affects the function of exocrine glands, which produce and secrete substances like sweat and digestive enzymes. As a result, individuals often suffer from repetitive lung infections and problems with digestion. The most common cause of death for those with cystic fibrosis is advanced lung disease.
What Causes Cystic Fibrosis?
Cystic Fibrosis (CF) is a disease caused by a change in a specific gene found on chromosome 7. This gene is responsible for creating a protein known as CFTR, which acts like a gate for chloride. This gate is controlled by a molecule called cAMP. In CF patients, both copies of the gene are changed, leading to the disease.
There are over 2000 different types of changes that can occur in the CFTR gene, contributing to this condition. These different changes, also called mutations, fall into five categories:
1. The protein isn’t made correctly
2. The protein isn’t processed correctly
3. There are problems with the regulation of the protein
4. The chloride gateway controlled by the protein doesn’t function properly
5. The protein gets replaced too quickly
Risk Factors and Frequency for Cystic Fibrosis
The most typical change in the genes causing Cystic Fibrosis, known as a mutation, is delta F508. This mutation is found in 70% of white American patients and makes up two-thirds of all global cases. This type of mutation causes the CFTR protein to fold abnormally, leading to its early destruction within a part of the cell called the Golgi apparatus. The consequence of the delta F508 mutation is typically a less effective pancreas and a higher risk of a condition called meconium ileus.
- The delta F508 mutation is the most common mutation causing Cystic Fibrosis.
- It’s found in 70% of white Americans with the disease and two-thirds of cases worldwide.
- The mutation causes the CFTR protein to fold incorrectly, resulting in its early breakdown within a cell component known as the Golgi apparatus.
- The delta F508 mutation typically leads to a condition where the pancreas doesn’t function properly and increases the likelihood of meconium ileus, a intestinal blockage in newborns.
Signs and Symptoms of Cystic Fibrosis
Cystic fibrosis (CF) is a health condition that can show different symptoms based on the age of the patient.
Newborns with CF can have symptoms such as meconium ileus (a blockage in the baby’s intestines), prolonged neonatal jaundice, or early lung infection. Infants and children with CF may have issues like poor growth and weight gain, anemia, undescended testicles in boys, repeated lung infections, and intestinal obstruction. The median age of diagnosis is between 6 to 8 months, even though the signs may not appear until later.
Adults with CF often have a worsening of previous symptoms. Lung issues include chronic bronchitis, abnormal lung function tests, bronchiectasis, specific types of asthma, allergic bronchopulmonary aspergillosis, and Pseudomonas aeruginosa infections. Sinus conditions include chronic rhinosinusitis, chronic post-nasal drip, nasal polyposis, and panopacification of the paranasal sinuses. Pancreatic manifestations include pancreatic insufficiency, recurrent pancreatitis, and early-onset diabetes.
- Hepatobiliary conditions (affecting liver, gall bladder, or bile ducts) such as focal biliary cirrhosis, gallstones, liver cirrhosis, portal hypertension, and variceal bleeding.
- Musculoskeletal conditions like kyphoscoliosis (curvature of the spine), osteopenia/osteoporosis (weak or brittle bones), and joint diseases.
- Hematologic manifestations (related to blood) such as iron-deficiency anemia or a chronic disease leading to an enlarged spleen.
- Nephrogenic manifestations (related to kidneys) such as nephrolithiasis (kidney stones), nephrocalcinosis (calcium deposits in kidneys), hyperoxaluria (excess oxalate in urine), and hypocitraturia (low citrate in urine).
- Dermatologic manifestations (skin conditions) like “salty sweat,” digital clubbing (rounded fingertips and nails), and cyanosis (bluish skin). Other skin conditions due to malabsorption may include acrodermatitis enteropathica (zinc deficiency) and scaly dermatitis (fatty acid deficiency).
- Male fertility can also be impacted due to absent vas deferens, while females may have reduced fertility due to thickened cervical mucus.
Testing for Cystic Fibrosis
In the United States, all newborn babies are tested for Cystic Fibrosis (CF) as part of the standard screening process. Sometimes CF is identified before birth during an ultrasound scan. Signs during an ultrasound might include meconium peritonitis (a severe bowel infection), bowel dilation (an enlarged bowel), or an absent gallbladder. These observations often lead to further CF testing during pregnancy.
To diagnose CF, doctors look for certain signs and conditions:
Possible Signs of Cystic Fibrosis
1. A sibling has cystic fibrosis
2. A positive newborn CF screening result
3. Symptoms related to CF in one or more body systems, which could include:
– Chronic lung disease
– Digestive or nutrition problems
– Conditions caused by loss of salts
– Infertility in men due to blocked sperm ducts
Evidence of Dysfunction in the CFTR Gene:
1. An elevated level of chloride in sweat, observed in two separate occasions
2. Two disease-causing mutations in the CFTR gene
3. Abnormal nasal potential difference, a test that measures how the cells in the nose transport salt and water.
The path to a CF diagnosis typically begins with a sweat chloride test, which measures the amount of salt in sweat. If this test is normal but symptoms persist, doctors will usually repeat the test. If the test is abnormal, they move on to DNA testing to look for mutations in the CFTR gene. Finding two such mutations confirms a CF diagnosis.
Additionally, doctors use a blood test to measure immunoreactive trypsinogen (IRT), a pancreatic enzyme. This test is especially useful for newborns with meconium ileus, a type of bowel obstruction that is often a sign of CF, and monitoring IRT levels can help assess the severity of CF over time. If IRT levels fall below a certain point, it could indicate a need for pancreatic enzyme replacement therapy.
Depending on the patient’s symptoms, doctors might order other diagnostic tests, such as X-rays of the chest, sinuses, or abdomen, or a bronchial lavage (a procedure that involves washing out the lungs and testing the fluid). The latter often shows elevated neutrophils (a type of white blood cell) and positive microbiology for several types of bacteria.
One of the main tools for evaluating and monitoring CF is pulmonary function testing, which measures lung function. One such test, spirometry, measures the amount of air a patient can exhale after a deep breath in. Results from spirometry can indicate various types of lung disorders, including ones that are characteristic of CF.
Treatment Options for Cystic Fibrosis
Cystic fibrosis is a serious disease that can significantly affect a person’s quality of life, especially if it’s not well-managed. That’s why it’s really important to aim for the best possible day-to-day health to avoid sudden flare-ups. This generally involves taking good care of your lungs by treating any breathing infections quickly and making sure your airways are always clear of mucus. It also means maintaining a good nutrition level with the help of enzyme supplements and multivitamins, and managing any other health problems that might pop up. It’s best to handle cystic fibrosis with a team of experienced specialists.
Failing lungs are usually what lead to most deaths in cystic fibrosis patients. So, if you have cystic fibrosis, it’s crucial to be always alert to any signs of lung illness getting worse, like feeling breathless, tired, or feverish, or coughing a lot. If you start noticing these signs or see a drop in your lung function test results, you should go to a hospital familiar with cystic fibrosis treatment right away.
When treating lung illness, the two main goals are to get rid of the infection and improve oxygen intake. Usually, a bacterium named P. aeruginosa is what causes these lung infections. Doctors prescribe antibiotics to eliminate it, but may adjust the prescription based on a lab test of your mucus. For mild flare-ups, taking oral antibiotics might be enough, but more severe cases require intravenous medication. In addition, you might be given inhalers, oxygen and anti-inflammatory medications to ease your breathing.
Chronic, routine treatment for people with cystic fibrosis includes vitamin supplements that are absorbed with fat (A, D, E, K), drugs like mucolytics, bronchodilators, antibiotics, and anti-inflammatory agents.
There are also new types of medications that work by correcting the gene mutation which causes cystic fibrosis. Each of these drugs targets a specific mutation. They’ve shown to have considerable benefits on lung function and body weight, if tolerated. Your dosing would depend on your age and weight.
Even with these medical breakthroughs, lung function deterioration due to cystic fibrosis is unavoidable and could eventually lead to premature lung failure. In such cases, doctors may consider a lung transplant. This decision involves considering a list of different conditions related to how well the lungs are functioning, your overall health, frequency of flare-ups, ability to recover from flare-ups, and your nutritional status among others. A lung transplant is not a cure for cystic fibrosis, but it can extend life and provide significant relief from symptoms.
Furthermore, those living with cystic fibrosis are advised to maintain a high-calorie, high-fat diet with additional fat-soluble vitamins to combat the malabsorption of nutrients caused by the disease. This, along with regular exercise, can support lung function and help maintain a healthy weight. For those not meeting their nutritional needs through food alone, tube feeding and, in severe cases, intravenous nutrition may be considered – though the latter can increase the risk of sepsis and should be used sparingly.
What else can Cystic Fibrosis be?
- Asthma – a condition that makes it hard to breathe due to swelling in the airways
- Bronchiolitis – a lung infection mostly affecting babies and young children
- Bronchiectasis – a condition that causes mucus to gather in the lungs leading to frequent infections
- Celiac disease – an autoimmune condition where the body reacts to gluten, a protein found in wheat, barley, and rye
- Nutritional considerations in failure to thrive – concerns about a child’s diet when they are not gaining weight or growing as expected
- Pediatric Aspergillosis – a rare fungus infection that can affect a child’s lungs or other parts of their body
- Primary ciliary dyskinesia – a condition causing issues with the tiny, hair-like structures that move mucus and dirt out of the lungs
- Sinusitis – an infection causing inflammation of the sinuses, often resulting in a blocked nose, pain, and a high temperature.
What to expect with Cystic Fibrosis
Patients with Cystic Fibrosis (CF) are expected to live into their forties before they may need a lung transplant. After the lung transplant, the average lifespan is around 8.5 years.
