Review
Chest computed tomography scans should be considered as a routine investigation in cystic fibrosis

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Summary

Cystic fibrosis (CF) patients demonstrate lung inflammation and infection beginning early in life. Both inflammation and infection lead to irreversible structural lung damage, primarily as bronchiectasis and fibrosis. The course of CF varies widely between patients due to genotypic and environmental differences. The primary aim of CF therapy is to prevent or delay structural damage and conserve lung function. Adequate monitoring of CF lung disease is paramount to tailoring treatment to a patient's need. Pulmonary function tests (PFTs) are important in monitoring lung function. PFTs, however, are only an indirect measure of lung structure and are insensitive to localised or early damage. By contrast, computed tomography (CT) is currently the most sensitive tool to monitor lung structure. As up to 50% of patients will have discordant staging of lung disease when PFTs are compared to CT findings, both methods are needed to adequately assess a patient's pulmonary condition and tailor the treatment strategy to the patient's needs.

Introduction

When a child with cystic fibrosis (CF) is born, the lungs have normal structure. Early in life, the lungs become colonised with micro-organisms such as Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa.1, 2 Protective mechanisms within the lung counter with an inflammatory response aimed at eliminating the micro-organisms. Both the micro-organisms and the inflammatory response contribute to structural lung damage and impaired lung function.

An important structural change within the lungs is bronchiectasis – an irreversible and progressive condition that eventually leads to end-stage lung disease (Fig. 1). Ideally, it should be our aim from the time of diagnosis of CF to prevent the development of any irreversible structural damage, such as bronchiectasis, or at least to minimise the progress of the lung disease. The course of disease varies widely between CF patients and cannot be adequately predicted for the individual patient based on the genotype. Hence, therapy must partially be tailored to the individual patient's needs.

The desirability of therapy should be weighed against negative aspects associated with CF therapy, such as interference with regular life, toxicity, and costs. To tailor treatment, the physician needs information that gives a clear picture about the condition of the lungs and of the progression of structural abnormalities.

Pulmonary function tests (PFTs) have been considered the most important tool for monitoring lung function. PFTs, however, are only an indirect measure of lung structure and are insensitive to localised or early damage. Many CF centres therefore add chest radiographs, which monitor lung structure more directly. Unfortunately, chest radiographs are considered to be insensitive to early disease, the quality of the radiographs is variable, and correct interpretation of the nature of the structural abnormalities is difficult. A new technique, computed tomography (CT), emerged in the early 1990s to become the gold standard for diagnosing bronchiectasis.3, 4, 5 It was found to be superior to chest radiography to monitor lung structure in CF patients.6, 7, 8, 9, 10

Clearly, in addition to structural and functional information, other considerations exist for optimal treatment of CF-related lung disease. Sputum cultures, for example, will identify micro-organisms present in the lung. However, this article focuses on the possible role of CT in the monitoring and treatment of CF lung disease. It argues that the information obtained from PFTs is dissociated from that obtained from CT and that both PFTs and CT are therefore needed to adequately assess a patient's pulmonary condition.

Section snippets

Early infection and inflammation

The basic defect in the gene encoding CF transmembrane regulator (CFTR) results in abnormal secretions in the lung that can be detected in sputum and bronchoalveolar lavage (BAL) fluid.2, 11 These abnormalities lead to early and severe inflammation in CF related to bacterial or viral infections.11 As many as 38% of newly diagnosed CF infants have a lower respiratory tract (LRT) infection by the age of 3 months.11 Considerable inflammation was detected in infants with LRT infection. Inflammatory

Structural lung damage

Both chronic bacterial infection and the exaggerated immune response observed in CF are responsible for structural damage in the airways and parenchyma. As a result of the chronic airway inflammation, the sputum of CF patients contains large quantities of aggressive enzymes, such as free neutrophil elastase.14 The chronic airway inflammation leads to changes in the architecture of the lung. Interestingly, CF patients show extreme inhomogeneity of pathological changes within the lung. For

Lung function and structural lung damage

Traditionally, lung function has been considered the gold standard for monitoring disease progression in CF. As CF lung disease begins early in life, much work was undertaken to develop lung function tools that can be used routinely in infancy. Unfortunately, it is technically difficult and time consuming to perform infant pulmonary function tests (iPFTs) in children between 1 and 5 years of age.30 The consistent finding of such studies is decreased expiratory flows,31 which seem to persist.32

Imaging and structural lung disease

Traditionally, chest radiographs were used to evaluate structural lung abnormalities in CF. Some CF centres undertake chest radiographs for each pulmonary exacerbation; others perform a chest radiograph only as part of the annual check-up. Chest radiographs are quick, relatively inexpensive, and require low radiation exposure and thus can be repeated more frequently when needed. They can also be done in unsedated young children. However, chest radiographs as a tool for the assessment of the

Therapy and imaging

Various interventional studies have used CT-related parameters as end points. Most data are available on the effect of RhDNase, which plays an important role in the treatment of CF lung disease. RhDNase reduces the viscosity of the sputum in CF and thus is thought to improve mucociliary clearance.16, 29 RhDNase has been shown to improve mucociliary clearance and quality of life, and to reduce the loss of lung function, inflammation, and exacerbation rate.29, 35, 38 The effect of RhDNase occurs

Risk--benefit of routine HRCT scanning

Using CT in the follow-up of CF-related lung disease exposes patients to more radiation than only chest radiographs. This issue should neither be underestimated nor overestimated. With current CT technology, one CT examination of the lung exposes the patient to an amount of radiation comparable to 1 year of natural background radiation in a low-dose region or 5 transatlantic flights. Extra exposure to radiation increases one's natural life-long risk of cancer. In a computational model we showed

Summary

Chest CT is the gold standard for the diagnosis of bronchiectasis. Bronchiectasis in CF is irreversible and, in most patients, a progressive disease. Longitudinal studies show that PFTs are insensitive to the presence of bronchiectasis. The information obtained from PFTs is dissociated from that obtained from CT in 50% of patients. Hence structure does not predict function and vice versa. The monitoring of CF lung disease with PTFs and chest radiographs alone underestimates the severity of

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