A 19-year-old boy has a history of repeated chest infections.- Case Study

History
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 sample 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.

Examination
On examination he is thin, weighing 48 kg, and is 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 is shown below:

Questions
• What does the X-ray show?
• What is the most likely diagnosis?
• What investigations should be performed?

Answers And Discussion:



• What does the X-ray show?
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.

• What is the most likely diagnosis?
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, 40s or later 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.

Differential diagnosis
The differential diagnosis in this young man would be other causes of diffuse bronchiectasis, such as agammaglobulinaemia or immotile cilia.
Respiratory function should be measured to see the degree of functional impairment. Bronchiectasis in the upper lobes may occur in tuberculosis or in allergic bronchopulmonary aspergillosis associated with asthma.

• What investigations should be performed?
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 DF508 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 DF508 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.

Management should be at a center with experience in the management of adult cystic fibrosis.
Treatment at such centers for children, adolescents and adults is associated with improved outcomes.

KEY POINTS
• Milder forms of cystic fibrosis may present in adolescence and adulthood.
• Milder forms are often related to less-common genetic abnormalities.
• A high-resolution CT scan is the best way to detect bronchiectasis and to define its extent.
• Management should be at an experienced cystic fibrosis centre.