Disease presents without warning and some forms milder than others. A sweat chloride concentration of 80 mmol/l is diagnostic. A person with CF cannot contract cholera, because the toxin cannot open the chloride channels in the small intestine. With improved supportive care, the median survival in the UK is now more than 50 years.
Curbed flows of chloride
Lung’s massed mucus, thick and dried
Bad bugs stick and thrive
Body’s small tubes have it worst
Baby gut often blocked first Link to author
- Inherited Defect of the Cystic fibrosis transmembrane conductance regulator (CFTR)
- Leads to the production of thick viscid mucus and secondary infection
- CF is inherited as an AR and there are at least 800 gene mutations
- Mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene on 7q31.2.
- Genotype is a poor guide to disease severity even within families possibly due to unknown modifier genes
- Over 70% are due to the delta F508 mutation on chromosome 7q which codes for the CFTR
- Incidence in the UK is 1 in 2500 and life expectancy for teenagers is 40-50 years old
Gene Mutations and effects
- Positive test results in people with no symptoms, for example infant screening (blood spot immunoreactive trypsin test) followed by sweat and gene tests for confirmation or
- clinical manifestations, supported by sweat or gene test results for confirmation or
- Clinical manifestations alone, in the rare case of people with symptoms who have normal sweat or gene test results.
- Failure to thrive and Malabsorption
- Meconium ileus - intestinal obstruction at birth
- Meconium ileus equivalent later
- Gallstone ileus and gallstone related disease
- Pancreatic insufficiency - steatorrhoea, weight loss
- Increased incidence of cholecystitis and gallstones
- Fatty liver and focal biliary cirrhosis
- Secondary Diabetes develops in 25% of patients
- Rectal prolapse
- Normal lungs become progressively damaged
- Recurrent chest symptoms - infections, bronchiectasis
- Pneumothorax - seen mainly in adults
- Massive haemoptysis, Bronchitis, bronchiolitis, Bronchiectasis
- Eventual Respiratory failure, Rhinitis and nasal polyps
- Overtime increasing Pseudomonas infection
- Respiratory infections: Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa
- Finger clubbing and Nasal polyps and sinusitis
- Circulating immune complexes and amyloidosis
- Male infertility - Failure to develop epididymis and vas deferens
- Osteoporosis and rickets
- Infant's sweat tastes salty - may be noted by parent
Carriers of CF enjoy the mixed blessing of a balanced polymorphism. They do not have enough abnormal chloride channels to cause the laboured breathing and clogged pancreas of cystic fibrosis, but they do have enough of a defect to prevent cholera from taking hold. During the devastating cholera epidemics that have peppered history, individuals carrying mutant CF alleles had a selective advantage, and they disproportionately transmitted those alleles to future generations. However, because CF arose in Western Europe and cholera in Africa, perhaps an initial increase in CF heterozygosity was a response to a different diarrheal infection
- As part of Guthrie screen in newborn measure raised blood concentration of immunoreactive trypsinogen. This will need a sweat test if positive
- Sweat test: CF is diagnosed by clinical suspicion followed by a sweat test using Pilocarpine iontophoresis. If the sweat [Cl] or [Na] > 60 mmol/l then the test is considered positive. Two reliable positive sweat tests with a chloride concentration > 60 mmol/l is considered to be diagnostic
- DNA analysis may be done but with a large number of mutations is not needed
- Pancreatic insufficiency - faecal elastase, ? faecal fats, ? glucose with secondary diabetes
- USS testes may show an absent vas deferens and epididymis
- Establish baseline respiratory function testing
- Being underweight
- Meconium ileus (affects 1 in 7 newborn babies)
- Fat-soluble vitamin deficiencies (including vitamins A, D, E and K)
- Distal intestinal obstruction syndrome
- Muscle pains and arthralgia
- Male infertility caused by obstructive azoospermia (almost all males with cystic fibrosis are infertile)
- Reduced female fertility
- Upper airway complications, including nasal polyps and sinusitis (prevalence increases with age)
- Chronic liver disease (the prevalence increases with age until early adulthood)
- Urinary stress incontinence
- Cystic-fibrosis-related diabetes (uncommon in children under 10 years, but the prevalence increases with age and it affects up to 1 in 2 adults)
- Reduced bone mineral density (including osteoporosis).
- Cystic-fibrosis-related arthritis
- Delayed puberty (associated with severe cystic fibrosis)
- Renal calculi (incidence increases with age and 1 in 20 adults are affected).
- Focus is now on issues with long term survival. Progressively restricted exercise tolerance affects employment and patients need particular support managing the
slow decline in function and well-being that occurs throughout their
- Fertility: males are usually infertile but can parent through the use of intracytoplasmic sperm injection. Various male fertility measures can be used to assist conception such as testicular sperm extraction (TEST), and intracytoplasmic sperm injection.
- Females with CF who have good nutritional status and reasonable health status have normal fertility and genetic counselling should be offered early. For those that do not wish to conceive need good contraceptive advice. The OCP is contraindicated with pulmonary hypertension.
- New Drugs: Lumacaftor and ivacaftor, have recently been licensed;
they can partially rectify functional defects in the CTFR and have
- Good nutritional status is linked with a better overall prognosis. Aided by pancreatic enzyme supplements.
- Pulmonary infections - mostly pseudomonas causes most of the morbidity and mortality but also Burkholderia cepacia, Staphylococcus aureus
- Aerolised DNAse I (Dornase alpha) appears to reduce chest infections. May be combined with hypertonic saline.
- Antibiotic prophylaxis and particular care in early and appropriate management of pseudomonas infections. Many patients take one or more antibiotics long term.
- Insulin for those who develop secondary diabetes if needed
- Genetic counselling is possible and one parent is tested for CFTR gene mutation and if positive the other parent can be tested
- Severe chest disease - single lung or heart-lung transplantation have been done in those with end-stage disease
- Avoidance of other sufferers to avoid exposure to Burkholderia cepacia
- Gene therapy has been explored as a potential cure for cystic fibrosis by attempting to place a normal copy of the CFTR gene into affected cells