Cystic Fibrosis Flashcards
Definition of cystic fibrosis
A severely life-shortening genetic disease (Autosomal recessive) resulting from abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR)- a chloride channel found in the cells lining the lungs, intestines, pancreatic ducts, sweat glands and reproductive organs.
Prevalence and life-expectancy of CF
The life-expectancy for the condition has increased from a few years to mid-30s.
Prevalence: 1 in 2500 live births and carrier rate of 1 in 25
Pathophysiology of CF
- Caused by a defective CFTR (AMP-dependant chloride channel) due to mutation in the gene on chromosome 7
- The most frequent mutation in the UK is ∆ F508 (~78%)
- Identification of the mutation involved in a family allows prenatal diagnosis and carrier detection in the wider family
- In delta F508- CFTR gets misfolded and cannot migrate to the epithelial surface- meaning less cl- is pumped out
Causes a multi-system disorder:
* In the airways, lack of CFTR function leads to a reduction in airway surface liquid layer and consequently causes impaired ciliary function and retention of thick, mucopurulent secretions which are prone to infection
* Defective CFTR also causes dysregulation of inflammation and defence against infection.
* In the intestine, thick viscid meconium leads to meconium ileus in 10%–20% of infants
* The pancreatic duct also becomes blocked with secretions- leading to pancreatic enzyme deficiency and malabsorption
* Abnormal function of sweat glands leads to excessive concentrations of sodium and chloride in the sweat
Respiratory symptoms of CF
- In a handful of cases, children with CF are identified with recurrent chest infections, faltering growth and malabsorption (most are identified by newborn blood spot screening)
- Early bacterial pathogens include Staphylococcus aureus and Haemophilius influenzae. Subsequently can get P.aureginosa. These infections can be eradicated if treated early, but may become chronic if not and are associated with lung damage and bronchiectasis
- Severe CF lung diseases cause a persistent ‘wet’ cough, productive of purulent sputum. May additionally cause haemoptysis and pneumothorax
- Will be hyperinflation, coarse inspiratory crepitations, expiratory wheeze and finger clubbing O/E
15% of older children and adolescents with CF develop asthma-type symptoms and obstructive patterns on spirometry due to allergic sensitization and exposure to Aspergillus fumigatus
* Patchy chest x-ray changes, acute respiratory symptoms
* A diagnosis of allergic broncho-pulmonary aspergillosis (ABPA) is confirmed if there is elevated and rising specific IgE antibodies to Aspergillus
* Treat with oral steroids and antifungals (itraconozole)
GI symptoms of CF
- Over 90% will have pancreatic exocrine insufficiency resulting in maldigestion and malabsorption
- If untreated this leads to faltering growth + steatorrhea
- Pancreatic insufficiency can be diagnosed with low faecal elastase
- Thick inspissated bowel contents can cause bowel obstruction with vomiting, abdominal distension and failure to open bowels. Leads to meconium ileus in neonates (requires surgery) and distal intestinal obstruction syndrome in older children (give oral gastrograffin)
Other symptoms of CF (non GI, resp)
- CF-related diabetes (CFRD)- due to pancreatic dysfunction (screened annually from the age of 10)- presents differently to DM with gradual reduction in lung function and failure to gain weight
- Liver disease (Regular ursodeoxycholic acid improves bile flow.)
- Males are virtually always infertile due to absence of the vas deferens (can father through intracytoplasmic sperm injection)
Clinical course of CF
- Newborn: diagnosed through screening, meconium ileus (first stool obstructs the intestines)
- Infancy: Prolonged neonatal jaundice, faltering growth, recurrent chest infections, malabsorption and steatorrhea
- Young child: Bronchiectasis, rectal prolapse, nasal polyp, sinusitis
- Older children and adolescent: ABPA, CFRD, Cirrhosis and portal hypertension, distal intestinal obstruction, pneumothorax, infertility in males
Investigations for CF
- Newborn blood spot test (Guthrie heel prick test)- Occurs when the child is 5-8 days old
- The gold standard diagnostic procedure is the sweat test, which confirms the concentration of Cl- in sweat (CL 60-125 mmol/L in CF, 10-140 mmol/L is normal)
o Sweating is stimulated by applying a low-voltage current to pilocarpine applied to the skin
o Sweat is then collected in a capillary tube - Diagnosis may be confirmed by testing for gene abnormalities in the CFTR gene (chr. 7)
How is CF care coordinated
Care for people with cystic fibrosis should be provided by a specialist cystic fibrosis MDT based at a CF centre
Patients should have an annual review of their condition and at least one other review per year by the specialist CF MDT, in addition to reviews by local paediatric teams
* Annual review should involve a pulmonary, liver and psychological assessment. Additionally, their nutrition and exercise should be assessed. Testing for CFRD should be conducted from 10 years old
* Routine reviews should be done more frequently immediately after diagnosis and in early life (weekly in first month of life, 4 weekly between 1 and 12 months, every 6-8 weeks between 1-5 yo, every 8-12 weeks after this)
Members of the CF MDT
Paediatrician, Nurses, PT, Dietician, Pharmacist, Psychologist, Social worker (provides support regarding education, employment, finance)
Respiratory management of CF
- Review children every 8 weeks: clinical assessment + examination, O2 sats, respiratory secretion samples for MC&S, lung function testing with spirometry, lung clearance index
- Additionally at annual review should have a chest x-ray, bloods including WCC, serum IgE, resp secretions and spirometry
General prophylactic management:
* Airway clearance techniques (at least 2x per day)
* Mucoactive agents:
* rhDNase- first line
* rhDNase + hypertonic NaCl if inadequate response to rhDNase
* Mannitol dry powder- if ineligible to prior treatment or inadequate response
- For people with cystic fibrosis and deteriorating lung function or repeated pulmonary exacerbations, offer long-term treatment with azithromycin or oral corticosteroids
- Bilateral lung translantation is the only therapeutic option for end-stage CF lung disease
- lumacaftor–ivacaftor is a new agent being consider for treatment of ∆ F508
Management of Staph. aureus infection in CF
Offer flucloxacillin as prophylaxis (from diagnosis up to 3 years and can be given up to years years)
Management of Pseudomonas aeruginosa infection in CF
- For acute infection: start on a course of oral or IV (IV if clinically unwell) Abx according to trust guidelines, followed by an extended course of oral/ ingaled Abx
- For chronic infection: Colistimethate sodium dry powder for inhalation (DPI)- first line, or Tobramycin DPI- second line
GI management of CF
- The CF specialist dietician should offer advice on optimal nutrition (and at the annual assessment should review- total intake, estimated need and pancreatic enzyme replacement)
- Encourage increased portion size and high-energy foods
- If attempts to increase intake are not effective consider NG tube feeding
- Pancreatic enzyme replacement therapy (e.g Creon)- Insufficiency of pancreatic enzymes can be tested with faecal elastase
- Consider an H2 receptor antagonist or a proton pump inhibitor) for people who have persistent symptoms or signs of malabsorption
Other aspects of management in CF
Distal intestinal obstruction syndrome:
* First line: diatrizoate meglumine and diatrizoate sodium solution (Gastrografin) (orally or via an enteral tube)
Liver disease (the prevalence increases with age until early adulthood)
* If abnormal LFTs then ursodeoxycholic acid first line (stop once LFTs recover)
* If chronic and deteriorating refer to specialist
Consider doing a DEXA for reduced bone mineral density
Advise people with cystic fibrosis and their family members or carers (as appropriate) that regular exercise improves both lung function and overall fitness
Review mental health
- Inform people with cystic fibrosis, their family members or carers (as appropriate) and staff involved in their care about the risk of cross-infection and how to avoid it
- Offer support networks which minimise risk of cross-infection (e.g online support groups)
