A 19-year-old boy has a history of repeated chest infections. He had problems with a cough
and sputum production in the first 2 years of life and was labelled as bronchitic. Over the next
14 years he was often ‘chesty’ and had spent 4–5 weeks a year away from school. Over the past
2 years he has developed more problems and was admitted to hospital on three occasions with
cough and purulent sputum. On the first two occasions, Haemophilus influenzae was grown
on culture of the sputum, and on the last occasion 2 months previously Pseudomonas aeruginosa
was isolated from the sputum at the time of admission to hospital. He is still coughing up
sputum. Although he has largely recovered from the infection, his mother is worried and asked
for a further sputum to be sent off. The report has come back from the microbiology laboratory
showing that there is a scanty growth of Pseudomonas on culture of the sputum.
There is no family history of any chest disease. Routine questioning shows that his appetite
is reasonable, micturition is normal and his bowels tend to be irregular.
On examination he is thin, weighing 48 kg and 1.6 m (5 ft 6 in) tall.
• The only finding in the chest is of a few inspiratory crackles over the upper zones of
both lungs. Cardiovascular and abdominal examination is normal.
The chest X-ray shows abnormal shadowing throughout both lungs, more marked in both
upper lobes with some ring shadows and tubular shadows representing thickened bronchial
walls. These findings would be compatible with a diagnosis of bronchiectasis. The pulmonary
arteries are prominent, suggesting a degree of pulmonary hypertension. The distribution
is typical of that found in cystic fibrosis where the changes are most evident in the
upper lobes. Most other forms of bronchiectasis are more likely to occur in the lower lobes
where drainage by gravity is less effective. High-resolution computed tomography (CT) of
the lungs is the best way to diagnose bronchiectasis and to define its extent and distribution.
In younger and milder cases of cystic fibrosis, the predominant organisms in the sputum
are Haemophilus influenzae and Staphylococcus aureus. Later, as more lung damage
occurs, Pseudomonas aeruginosa is a common pathogen. Once present in the lungs in cystic
fibrosis, it is difficult or impossible to remove it completely.
Cystic fibrosis should always be considered when there is a story of repeated chest infections
in a young person. Although it presents most often below the age of 20 years, diagnosis
may be delayed until the 20s, 30s or even 40s in milder cases. Associated problems
occur in the pancreas (malabsorption, diabetes), sinuses and liver. It has become evident
that some patients are affected more mildly, especially those with the less common genetic
variants. These milder cases may only be affected by the chest problems of cystic fibrosis
and have little or no malabsorption from the pancreatic insufficiency.
The common diagnostic test for cystic fibrosis is to measure the electrolytes in the sweat,
where there is an abnormally high concentration of sodium and chloride. At the age of
19 years, the sweat test may be less reliable. It is more specific if repeated after the administration
of fludrocortisone. An alternative would be to have the potential difference across
the nasal epithelium measured at a centre with a special interest in cystic fibrosis. Cystic
fibrosis has an autosomal recessive inheritance with the commonest genetic abnormality
F508 found in 85 per cent of cases. The gene is responsible for the protein controlling
chloride transport across the cell membrane. The commoner genetic abnormalities can be
identified and the current battery of genetic tests identifies well over 95 per cent of cases.
However, the absence of F508 and other common abnormalities would not rule out cystic
fibrosis related to the less common genetic variants.
In later stages, lung transplantation can be considered. Since the identification of the
genetic abnormality, trials of gene-replacement therapy have begun