Page 125 - Medicine and Surgery

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Chapter 3: Suppurative lung disorders 121

Geography 15% at birth with meconium ileus due to viscous
More common in Caucasians, uncommon in Orientals meconium
and Afro Caribbeans. 10% with liver disease
10% with rectal prolapse

Aetiology With later disease, patients show use of accessory mus-
The condition is caused by mutations of the cystic fibro- clesofrespiration,abarrel-chestdeformity,clubbingand
sis transmembrane conductance regulator (CFTR) gene cyanosis. Auscultation of the chest shows widespread
carried on the long arm of chromosome 7. coarse crackles.
Seventy per cent of North European patients have the
F508 mutation, which is a specific codon deletion re- Investigations
sulting in deletion of a phenylalanine at position 508 Diagnosis is by the sweat test which is positive if the
within the amino acid sequence of the CFTR protein. Cl is above 60 mmol/L on two sweat tests in at least
Over 1000 other mutations have now been identified. 75 mg of sweat (preferably 100 mg). Testing involves
There is poor correlation between the genetics and the pilocarpin iontophoresis. Occasionally false positives
clinical disease. or negatives occur.
Pre-natal DNA screening by mutation analysis is

Pathophysiology possible for those with a previous sibling with CF.
In normal mucus secreting epithelium the CFTR acts as Widespread pre-natal screening is not yet recom-
an important cAMP-regulated chloride channel to facili- mended.
tate secretion of sodium chloride and hence water, which Chest X-ray is initially normal, later there is gener-
results in low viscosity mucus. The mutation results in alised bronchial wall thickening and hyperinflation.
defective ion transport and nearly all exocrine glands are Sputum culture for chest infection and lung function
involved to a varying extent: testing are useful.
1 In the lungs, which appear to be histologically normal
at birth, increased production of thick viscous mucus Management
plugs airways, leading to inflammation and secondary 1 Non-pharmacological: Postural drainage, other ma-
infection.Bronchiectasis(thickened,dilatedbronchial noeuvres and exercise, close liaison with a physiother-
walls) filled with purulent, thick secretions and ar- apist is essential.
eas of atelectasis develop. There may also be immune- 2 Pharmacological:
mediated damage by an influx of neutrophils releasing Antibiotics used on the basis of regular sputum cul-
proteases. ture (prophylactic flucloxacillin may be used in first
2 Viscous or solid material also obstructs the lumen of 2years of life). Respiratory exacerbations should be
pancreas, small and large intestine, intrahepatic bile treated with high-dose antibiotic courses lasting 2
ducts and gallbladder. weeks. Oral ciprofloxacin is useful for Pseudomonas
3 There is increased Na and Cl concentration in the aeruginosa infections. Regular nebulised gentam-
sweat. icin may be useful.
4 There is also obstruction or maldevelopment of the Bronchodilators may prove useful in those with re-
vas deferens causing most males to be infertile, and versible airways obstruction.
increased viscosity of cervical secretions impairs fer- Agents to reduce the viscosity of the sputum may
tility in some women. be used including acetylcysteine, triphosphate nu-
cleotide and inhaled recombinant human deoxyri-
Clinical features bonuclease (rhDNase).
10% of patients escape detection until adolescence or Malabsorption is treated with pancreatic enzyme
early adulthood. supplements taken with all meals and snacks. Vi-
Presentation: tamin A, D and E supplements are used. NG or
40% with respiratory disease gastrostomy feeding is possible with either whole

25% with failure to thrive and malabsorption or partially digested food.