What is cystic fibrosis?
Cystic fibrosis (CF) is a genetic disorder that affects the respiratory, digestive, and reproductive systems. It is caused by a mutation in the CFTR gene, which leads to the production of thick, sticky mucus that clogs the lungs and other organs. Cystic fibrosis is a chronic and progressive disease that affects around 70,000 people worldwide, with the majority of cases occurring in Caucasian populations.
The biology and causes of cystic fibrosis:
Cystic Fibrosis (CF) is a genetic disorder that primarily affects the respiratory, digestive, and reproductive systems. CF is caused by a mutation in a single gene, known as the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7.
The CFTR gene encodes a protein that regulates the movement of salt and water in and out of cells. In people with CF, the CFTR protein is defective and doesn't function properly. This leads to the buildup of thick, sticky mucus in the lungs, pancreas, and other organs, which can block airways and ducts, causing inflammation, infection, and damage to the affected organs.
CF is an autosomal recessive disorder, which means that a person must inherit two copies of the mutated CFTR gene (one from each parent) to develop the disease. If a person inherits only one copy of the mutated gene, they are a carrier of the CF gene and do not develop the disease but can pass the gene on to their children.
There are over 1,700 known mutations in the CFTR gene, but the most common mutation is a deletion of three nucleotides (codons) in the DNA sequence, which results in the loss of a single amino acid (phenylalanine) in the CFTR protein. This mutation is known as F508del and is present in about 70% of people with CF.
Other mutations in the CFTR gene can affect the amount, function, or stability of the CFTR protein, leading to different types and severity of CF. Some mutations can cause a mild form of CF, while others can cause a severe form of CF.
Symptoms:
Cystic fibrosis affects multiple organs and systems, and its symptoms can vary widely among individuals, depending on the severity and type of mutations in the CFTR gene. Here is a list of some of the most common symptoms of CF:
- Shortness of breath, Chronic cough, and wheezing.
- Frequent lung infections, including pneumonia and bronchitis.
- Thick sticky mucus in the lungs, resulting in congestion, inflammation and damage to the lung tissue.
- Digestive problems, such as malabsorption, bloating, diarrhea, and constipation.
- Steatorrhea (fatty stools) and poor weight gain despite a good appetite.
- Liver disease, such as cirrhosis and bile duct obstruction.
- Pancreatic insufficiency, leading to inadequate secretion of digestive enzymes and insulin.
- Nasal polyps and sinusitis.
- Clubbing of the fingers and toes.
- Male infertility due to absence or blockage of the vas deferens.
- Delayed puberty in girls due to thick cervical mucus and hormonal imbalances.
- Increased salt levels in sweat, leading to salty skin and electrolyte imbalances.
- Fatigue, weakness, and decreased exercise tolerance.
It's important to note that not all people with CF experience all of these symptoms, and some symptoms may develop later in life. CF can also affect other parts of the body, such as the eyes, ears, bones, and skin.
Diagnosis:
The diagnosis of cystic fibrosis involves a combination of clinical evaluation, genetic testing, and specialized tests to assess lung function and digestive function.
Clinical Evaluation:
The first step in diagnosing CF is a thorough clinical evaluation by a healthcare provider, such as a pulmonologist or a gastroenterologist. The provider will ask about the patient's symptoms, medical history, family history, and perform a physical examination, including lung function tests and sweat tests.
Genetic Testing:
Genetic testing can identify the presence of CF mutations in the CFTR gene. Testing is typically performed on a blood sample, but may also be done on a saliva sample or a swab of the inside of the cheek.
Sweat Test:
The sweat test specializes in measuring the amount of salt (sodium and chloride) in sweat. People with CF have higher levels of salt in their sweat due to the defective CFTR protein. The sweat test involves applying a small amount of a chemical that stimulates sweating to the skin, and then collecting and analyzing the sweat. The test is painless and takes about 30 minutes to complete.
Lung Function tests:
Lung function tests, such as spirometry and lung volume measurements, can assess how well the lungs are functioning and detect any abnormalities, such as airflow obstruction, reduced lung capacity, or air trapping. These tests involve breathing into a machine that measures various parameters of lung function.
Digestive Function Tests:
CF can affect the digestive system by impairing the secretion of digestive enzymes from the pancreas, leading to malabsorption of nutrients and poor weight gain. Digestive function tests, such as stool analysis and pancreatic function tests, can assess the patient's digestive function and detect any abnormalities, such as steatorrhea (fatty stools) or reduced pancreatic function.
Treatment of cystic fibrosis:
Unfortunately, cystic fibrosis is a progressive incurable disorder. However, there's a bunch of treatments that control the symptoms and cease complications. Indeed, these treatments involve medications, airway clearance techniques, nutritional support and specialized therapies.
Meducations:
- Antibiotics: to treat and prevent lung infections, which are a major cause of morbidity and mortality in CF.
- Bronchodilators: to open up the airways and improve breathing.
- Mucolytics: to thin and loosen the thick, sticky mucus in the lungs, making it easier to clear.
- Anti-inflammatory agents: to reduce inflammation and prevent lung damage.
- CFTR modulators: a new class of drugs that target the underlying genetic defect in CF by correcting or improving the function of the CFTR protein.
Nutritional support:
CF can impair the absorption and digestion of nutrients, leading to malnutrition, poor weight gain, and growth retardation. Nutritional support is an essential part of CF management and includes a high-calorie, high-fat, and high-protein diet, pancreatic enzyme replacement therapy (PERT) to aid digestion and absorption of nutrients, and vitamin and mineral supplementation.
Specialized therapies:
CF can cause complications in other parts of the body, such as the liver, pancreas, and reproductive system. Specialized therapies, such as liver transplant, pancreatic enzyme replacement, and fertility treatments, may be necessary to manage these complications.
Complications of cystic fibrosis:
CF can cause a range of complications, some of which can be life-threatening. The most common complications of CF include:
- Lung Infections: People with CF are at a higher risk of developing recurrent and severe lung infections, such as pneumonia and bronchitis, due to the thick and sticky mucus that accumulates in the lungs. These infections can lead to inflammation, scarring, and lung damage, and can be life-threatening in severe cases.
Respiratory Failure: Over time, the lung damage caused by CF can lead to respiratory failure, which occurs when the lungs are no longer able to provide enough oxygen to the body. Respiratory failure is a serious complication that requires immediate medical attention, and may require mechanical ventilation or oxygen therapy.
Pancreatitis: CF can cause inflammation of the pancreas, a gland that produces enzymes that aid in digestion. Pancreatitis can lead to abdominal pain, nausea, vomiting, and malabsorption of nutrients, and can be a recurring problem for people with CF.
Diabetes: CF can also affect the endocrine system, leading to a form of diabetes called CF-related diabetes (CFRD). CFRD is characterized by high blood sugar levels, and can lead to complications such as nerve damage, kidney disease, and vision problems.
Liver Disease: CF can cause liver disease, including cirrhosis and bile duct obstruction, due to the accumulation of thick mucus in the liver and bile ducts.
Infertility: CF can affect the reproductive system, leading to reduced fertility or infertility in both men and women. Men with CF may have an absence or blockage of the vas deferens, which carries sperm from the testicles to the urethra, while women with CF may experience reduced fertility due to thick cervical mucus and hormonal imbalances.
