Cystic fibrosis
Cystic fibrosis is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably Pseudomonas aeruginosa and Staphylococcus aureus. CF is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.
Cystic fibrosis is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene encoding the cystic fibrosis transmembrane conductance regulator protein. Those with a single working copy are carriers and otherwise mostly healthy. CFTR is involved in the production of sweat, digestive fluids, and mucus. When the CFTR is not functional, secretions that are usually thin instead become thick. The condition is diagnosed by a sweat test and genetic testing. The sweat test measures sodium concentration, as people with cystic fibrosis have abnormally salty sweat, which can often be tasted by parents kissing their children. Screening of infants at birth takes place in some areas of the world.
There is no known cure for cystic fibrosis. Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes, the antibiotic azithromycin is used long-term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. Airway clearance techniques such as chest physiotherapy may have some short-term benefit, but long-term effects are unclear. The average life expectancy is between 42 and 50 years in the developed world, with a median of 40.7 years, although improving treatments have contributed to a more optimistic recent assessment of the median in the United States as 59 years. Lung problems are responsible for death in 70% of people with cystic fibrosis.
CF is most common among people of Northern European ancestry, for whom it affects about 1 out of 3,000 newborns, and among which around 1 out of 25 people is a carrier. It is least common in Africa and Asia. It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. The name "cystic fibrosis" refers to the characteristic fibrosis and cysts that form within the pancreas.
Signs and symptoms
Cystic fibrosis typically manifests early in life. Newborns and infants with cystic fibrosis tend to have frequent, large, greasy stools and are underweight for their age. Of newborns, 15–20% have their small intestine blocked by meconium, often requiring surgery to correct. Newborns occasionally have neonatal jaundice due to blockage of the bile ducts. Children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child.The primary cause of morbidity and death in people with cystic fibrosis is progressive lung disease, which eventually leads to respiratory failure. This typically begins as a prolonged respiratory infection that continues until treated with antibiotics. Chronic infection of the respiratory tract is nearly universal in people with cystic fibrosis, with Pseudomonas aeruginosa, fungi, and mycobacteria all becoming increasingly common over time. Inflammation of the upper airway results in frequent runny nose and nasal obstruction. Nasal polyps are common, particularly in children and teenagers. As the disease progresses, people tend to have shortness of breath, and a chronic cough that produces sputum. Breathing problems make it increasingly challenging to exercise, and prolonged illness causes those affected to be underweight for their age. In late adolescence or adulthood, people begin to develop severe signs of lung disease: wheezing, digital clubbing, cyanosis, coughing up blood, pulmonary heart disease, and collapsed lung.
In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some CF patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because clotting factors II, VII, IX, and X are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present.
Lungs and sinuses
Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. In later stages, changes in the architecture of the lung, such as pathology in the major airways, further exacerbate difficulties in breathing. Other signs include high blood pressure in the lung, heart failure, difficulties getting enough oxygen to the body, and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators. Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa are the three most common organisms causing lung infections in CF patients. In addition, opportunistic infection due to Burkholderia cepacia complex can occur, especially through transmission from patient to patient.In addition to typical bacterial infections, people with CF more commonly develop other types of lung diseases. Among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus Aspergillus fumigatus causes worsening of breathing problems. Another is infection with Mycobacterium avium complex, a group of bacteria related to tuberculosis, which can cause lung damage and do not respond to common antibiotics.
The mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue due to inflammation from chronic sinus infections. Recurrent sinonasal polyps can occur in 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties.
Cardiorespiratory complications are the most common causes of death in patients at most CF centers in the United States.
Gastrointestinal
Digestive problems are also prevalent in individuals with CF. Approximately 15%-20% of newborns diagnosed with CF experience intestinal blockage, and other digestive issues may arise due to mucus accumulation in the pancreas. Consequently, there is impaired insulin production, leading to cystic fibrosis-related diabetes mellitus. Moreover, enzyme transport disruption from the pancreas to the intestines results in digestive problems such as recurrent diarrhea or weight loss.In cystic fibrosis, there is impaired chloride secretion due to the mutation of CFTR. This disrupts the ionic balance, causes impaired bicarbonate secretion, and alters the pH. The pancreatic enzymes that work in a specific pH range cannot act as the chyme is not neutralized by bicarbonate ions. This causes impairment of the digestion process.
The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. These secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation. The pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis.
In addition, protrusion of internal rectal membranes is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and increased intra–abdominal pressure due to coughing.
Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K.
In addition to the pancreas problems, people with CF experience more heartburn, intestinal blockage by intussusception, and constipation. Older individuals with CF may develop distal intestinal obstruction syndrome, which occurs when feces becomes thick with mucus and can cause bloating, pain, and incomplete or complete bowel obstruction.
Exocrine pancreatic insufficiency occurs in the majority of patients with CF. It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional. It occurs in 10–15% of patients with one "severe" and one "mild" CFTR mutation where little CFTR activity still occurs, or where two "mild" CFTR mutations exist. In these milder cases, a sufficient pancreatic exocrine function is still present so enzyme supplementation is not required. Usually, no other GI complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development. Despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications.
Liver diseases are another common complication in CF patients. The prevalence in studies ranged from 18% at age two to 41% at age 12, with no significant increase thereafter. Another study found that males with CF are more prone to liver diseases compared to females, and those with meconium ileus have an increased risk of liver diseases.
Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Impaired digestion or absorption of lipids can result in steatorrhea. Over time, this can lead to scarring and nodularity. The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting. Liver disease is the third-most common cause of death associated with CF.
Around 5–7% of people experience liver damage severe enough to cause symptoms: typically gallstones causing biliary colic.