CF step 1

Cystic fibrosis (CF) is an autosomal recessive inherited disease caused by a mutation in the gene coding for a complex chloride channel. It results in thick, viscous secretions that affect the lungs, pancreas, liver, and reproductive system.

CF is caused by mutations in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. It is located on chromosome 7.

The most common mutation is delta F508 (deletion of the three bases coding for phenylalanine, which is the 508th amino acid in the CFTR protein).

The CFTR protein normally functions as a cAMP-activated chloride channel on the epithelial cells of the respiratory tract, pancreas, sweat/salivary glands, intestines, and reproductive system.

The defective CFTR channel in CF results in decreased chloride secretion and increased reabsorption of sodium and water by epithelial cells. This leads to dehydration at the cell surface and abnormally thick secretions. These secretions are more difficult to clear, and are more prone to harborinfectious organisms.

Common infection-causing pathogens in the lungs of cystic fibrosis patients include:

  • Haemophilus influenzae - common in early childhood
  • Staphylococcus aureus - common in early childhood
  • Pseudomonas aeruginosa- more prevalent later in life
  • Burkholderia cepacia

In the gastrointestinal tract, abnormal bile and pancreatic secretions cause maldigestion and malabsorption, including fat soluble vitamin deficiencies (A, D, E, and K).

More than 95% of men with cystic fibrosis are infertile because of problems with sperm transport, though they are able to produce normal sperm. It is very common in men with CF to have congenital bilateral absence of the vas deferens.

CF is the most common life-shortening autosomal recessive disease in Caucasians, and occurs once in every 2000 to 3000 live births. The disease is most common in the Caucasian population, followed by the Hispanic population.

Symptoms of cystic fibrosis usually begin to present in early childhood and commonly include meconium ileus, respiratory symptoms, and failure to thrive.

Respiratory symptoms of CF may include persistent, productive cough and wheezing. If the disease progresses untreated, patients may experience increased cough, tachypnea, dyspnea, increased sputum production, malaise, anorexia, and weight loss.

The majority of cystic fibrosis patients develop sinus disease, including pan-opacification of the paranasal sinuses, and, less commonly, nasal polyposis.

Symptoms of CF-related pancreatic insufficiency may include steatorrhea and failure to thrive or poor weight gain.

Meconium ileus, distal intestinal obstruction, rectal prolapse, and duodenal ulcers are among the GI manifestations of cystic fibrosis.

The majority of cystic fibrosis cases in the United States are now detected through newborn screening. All infants undergo initial screening, commonly using a serum immunoreactive trypsin (IRT) assay.

Infants with positive newborn screening should undergo sweat chloride testing to confirm the diagnosis. Patients with cystic fibrosis will have elevated sweat chloride > 60 mEq/L. Abnormal sweat chloride testing is sufficient to diagnose CF in infants and is the diagnostic test of choice for non-infant patients.

In adults and older children, two criteria must be met for the diagnosis of CF: Clinical symptoms consistent with CF in at least one organ system AND evidence of CFTR dysfunction (elevated sweat chloride, presence of two disease-causing mutations in CFTR, or abnormal nasal potential difference.)

Cystic fibrosis may be suspected on prenatal ultrasound if there is evidence of meconium peritonitis, bowel dilation, or absent gallbladder.

Findings consistent with cystic fibrosis on physical exam include wheezing, increased anteroposterior diameter of the thorax, digital clubbing, and poor weight gain/failure to thrive.

While chest x-ray is not used for diagnosis, the chest x-rays of cystic fibrosis patients may show hyperinflation, bronchiectasis, cyst formation, and flattening of the diaphragms.

The complications of cystic fibrosis are many and varied. Respiratory complicationsare the major contributors to morbidity and mortality in CF.

Common pulmonary cystic fibrosis complications are hemoptysis (frequent coughing and inflammation leads to the erosion of the walls of bronchial arteries), bronchiectasis, and pneumothorax.

Progressive obstructive lung disease and hypoxia can eventually lead to chronic pulmonary hypertensionand then to right heart failure in CF patients.

Patients may also develop pancreatitis or diabetes due to pancreatic damage caused by thick, abnormal secretion.

Treatment of CF varies based on the specific mutation and severity of disease, but typically includes:

  • Short-acting inhaled beta-2 agonists
  • Inhalation of hypertonic saline
  • Prophylactic antibiotics
  • Chest physiotherapy
  • Dornase alfa
  • A high protein/high calorie diet
  • Pancreatic enzyme replacement therapy

Cystic fibrosis lung disease exacerbations are typically treated with aggressive chest physiotherapy and additional antibiotics.

Cystic fibrosis patients with severe disease may be lung transplant candidates.