• cystic fibrosis
• cystic fibrosis transmembrane conduction regulator (CFTR) gene
• bronchiectasis

Over 1000 different mutations of the cystic fibrosis transmembrane conduction regulator (CFTR) gene have so far been identified. These mutations have been associated with a spectrum of clinical phenotypes ranging from classic cystic fibrosis (CF) presenting in early childhood to CFTR related conditions that may present in adulthood such as congenital bilateral absence of the vas deferens, chronic pancreatitis, and rhinosinusitis. In addition, the 5T variant in the polythimidine tract is felt to be important in atypical CF as it significantly reduces the amount of normal CFTR transcript because intron 8 is inefficiently spliced.¹

Bronchiectasis in adults is most commonly idiopathic² and is a significant cause of chronic morbidity. The chief manifestation of CF is bronchiectasis, and the role of CFTR mutations in adult bronchiectasis is still not well defined. Several small studies have suggested that there is an increased prevalence of CFTR mutations in diffuse adult bronchiectasis,^3–5 and one large study found that there was a marginally higher prevalence of mutations in adult bronchiectasis.⁶ Most of these studies have had little information on the patients’ clinical status and family history of disease and have not assessed the 5T mutation.

A joint project was undertaken between Monash Medical Centre (MMC) and the Murdoch Children’s Research Institute to assess the role of CFTR mutations in adult bronchiectasis. A sequential series of 100 adults with bronchiectasis confirmed on high resolution computed tomographic (CT) scanning was studied. The patients were screened for the 10 most common mutations in the local population (ΔF508, Δ1507, V520F, G542X, G551D, R553X, R117H, 621+1G→T, A455E and N1303K) responsible for 82% of cases of CF and the 5T mutation by previously published methods.^7,8 Ethical approval for the project was obtained from the ethics committee at MMC.

The group comprised 36 men and 64 women of mean (SD) age 61 (13) years. Most of the patients were white (n = 95), predominantly from a northern European background (n = 84). The main symptom was chronic mucopurulent sputum production which was present in 98 of the 100 subjects and, in most cases (n = 78), this had started in childhood. Chronic rhinosinusitis was also common (n = 75). Lung function tests showed moderate airway obstruction in the cohort. Most patients (n = 86) had multilobar disease on CT scanning, predominantly in the lower zone. The mean (SD) number of lobes with bronchiectatic changes on the CT scan was 2.5 (0.98). Nine of the patients had Pseudomonas aeruginosa isolated from their sputum and one of these isolates was a mucoid strain. The most common pathogen was Haemophilus influenzae (37%) followed by Streptococcus pneumoniae (10%). Screening for underlying causes of bronchiectasis showed that most patients (n = 84) had idiopathic disease. All subjects were asked about the presence of chronic respiratory illness in first degree relatives. There was not a high incidence of familial chest disease. No relative had a diagnosis of CF and only one had a history of bronchiectasis.

The patients did not have a high prevalence of features in addition to bronchiectasis and rhinosinusitis which are known to be associated with CF (none had pancreatitis, one had unexplained infertility, and three had predominantly upper zone bronchiectasis).

Screening of the cohort showed that none of the subjects was homozygous and four were heterogeneous for CFTR mutations (table 1). Three of the subjects had mutations of the most common CFTR mutation (ΔF 508) which is responsible for 67.5% of CFTR mutations in the local population and the other subject had the second most common mutation (G551D, 4.7%). Sweat tests on the heterozygote subjects showed normal chloride levels.

The prevalence of CFTR mutations in normal predominantly white populations based on several studies is approximately 1/25.^9,10 The expected level of heterozygotes in this group which had been screened for 82% of mutations was 3–4 subjects. Thus, in this group of subjects with bronchiectasis the number of carriers was the same as would be predicted in a normal population (95% confidence intervals (CI) 1.1 to 9.9). Similarly, the incidence of the 5T mutation was 7% which is similar to the incidence in a normal population⁸ (95% CI 2.9 to 13.9).

These findings suggest that CFTR mutations do not have a major role in the pathogenesis of adult bronchiectasis and further investigation is needed to establish the predisposing factors involved in the development of this condition.