Cystic fibrosis (CF, from "cystic" i.e. cyst formation, and "fibrosis" i.e. scarring, within the pancreas" aka mucoviscidosis) affects mostly the lungs, but also the pancreas (i.e. GI organ which secretes digestive enzymes, and endocrine gland producing GI hormones), liver (i.e. produces bile, detoxifying enzymes, stores glycogen), kidneys (i.e. detoxifies blood into urine), and intestine.

• It is autosomal recessive, meaning healthy people have 2 working copies, carriers have 1 working copy, Pt's w/ CF have 0 working copies
• Caused by one of many different mutations in the gene, CFTR (cystic fibrosis transmembrane conductance regulator), found at 7q31.2 (i.e. on chromosome 7), required to regulate the components of sweat, digestive fluids, and mucus
• The mutation is a ΔF508 (Δ=deletion) of 3 nucleotides, resulting in loss of the amino acid phenylalanine at the 508th position on the protein. This accounts for 68% of cases worldwide, and 90% in the USA. However, there are >1500 other mutations that can produce CF
• CFTR is responsible for a chloride ion channel, important in creating sweat, digestive juices, and mucus. Thus, the lack of it will cause abnormal transport of sodium and chloride, across the epithelium (i.e. cell layer covering membranes over organs), causing thick, viscous secretions

Different people have different degrees of Sx, including:

• Difficulty breathing, the most serious Sx, resulting from frequent lung infections
• Sinus infections
• Poor growth → due to reduced digestive enzymes, due to pancreas
• Steatorrhea (fatty stool)
• Clubbing of the fingers and toes
• Infertility in males (97%), due to:
  • Congenital absence of the vas deferens, which normally connects the testes to the ejaculatory ducts of the penis, most commonly
  • Azoospermia (no sperm)
  • Teratospermia
  • Oligoasthenospermia (few sperm with por motility)
• Infertility in females (20%), due to thickened cervical mucus or malnutrition. Malnutrition can disrupt ovulation and cause amenorrhea 

• Newborn screening (10% are Dx this way), which measures for raised blood concentration of immunoreactive trypsinogen. However, there can be false positives, thus sometimes only done in some jurisdictions after Sx (e.g. respiratory or GI manifestations). It is followed by screening for common CF gene mutations, followed by a weat test to confirm the Dx
• Genetic testing, by mutations in the CFTR gene. However, CF can result from >1,000 different mutations, and it isn't possible to test for each one. Most commerical tests look for 32 or fewer different mutations
• In early childhood, by sweat test, which involves measuring concentration of salt excreted in sweat, which is elevated in CF, when a drug that stimulates sweating, pilocarpine, is applied. The deliver the drug through skin, iontophoresis is used, where 1 electrode is placed onto the applied drug, and an electric current is passed to a seprate electrode on the skin. The resultant sweat is then colleted on filter paper, or in a capilary tube, and analyzed for abnormal amounts of sodium and chloride. Patients with CF have increased amounts of sodium and chloride in their sweat
• Prenatal tests, including:
  • Testing for the CFTR gene mutations in the parents, in 1 or both parents, to determine risk child will be born with CF
  • During pregnancy, CVS or amniocentesis can be performed, although both have risks of fetal death, the risk in amniocentesis being less
  • Pre-implantation Dx, provides net economic benefits up to 40yo maternal age, after which natural conception, prenatal testing, and abortion has higher economic benefit

• Lung infection Tx w/ antibiotics. Sometimes, azithromycin is used long term
• Inhaled hypertonic saline
• Salbutamol
• Lung transplantation, is often necessary as CF worsens
• Pancreatic enzyme replacement (e.g. Creon), particularly in the young
• Fat-soluble fat vitamin supplementation, particularly in the young
• DMD's, overcoming a nonsense mutation (premature stop codon) to synthesize a full-length CFTR protein. including:
  • Ivacaftor (Kalydeco) targets the G551D mutation (glycine in 551 is substituted with aspartic acid)
  • Lumacraftor targets F508del (phenylalanine in 508 is missing)
• Airway clearance techniques, e.g. chest physiotherapy, used by many although not well supported by evidence

• No cure
• Average life expectancy is 42-50 years in the developed world
• Lung problems are repsonsible for death of 80% of people with CF

• Most common in Northern Europeans (1 in 25 are carriers), and rarest in Africans and Asians
• 1st recognized by Dorothy Andersen in 1938
• Screening of infants at birth takes place in some areas of the world
• The term cystic fibrosis, comes from the characteristic fibrosis and cysts that form within the PANCREAS