QJM Advance Access originally published online on February 22, 2006
QJM 2006 99(3):196-197; doi:10.1093/qjmed/hcl018
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Correspondence |
Patients with bronchiectasis: look for specific causes
Sir,Over 90% of cases of cystic fibrosis are diagnosed in infancy or childhood, although older patients with phenotypically mild disease are occasionally discovered. We describe a patient with a long history of chronic suppurative lung disease, who was discovered to have cystic fibrosis in her seventh decade.
A 64-year-old non-smoking female Caucasian with radiologically-confirmed bronchiectasis had been regularly followed up for 6 years at our out-patient respiratory clinic. Prior to this, her medical care had been carried out elsewhere. As a child while living in Africa, she reported frequent episodes of ‘chest infections’, and contracted tuberculosis at the age of 21. Years later, the diagnosis of post-tuberculous bronchiectasis was made, based on the clinical history of chronic sputum expectoration and characteristic chest radiograph appearances. Her other past medical history included mild asthma and allergic bronchopulmonary aspergillosis. There was no clinical evidence of exocrine pancreatic insufficiency (normal bowel habit, body mass index 30.1 kg/m2), hepatobiliary disease (normal ultrasonographic appearances), nasal problems or diabetes. There was no family history of chronic lung disease and she had conceived two healthy children—now adults—without difficulty. There were no risk factors for immunodeficiency, and haematological and biochemical laboratory tests (including immunoglobulin levels) were normal. The forced expiratory volume in 1 s was 77% predicted, and forced vital capacity 83% predicted. During the preceding 5 years, the patient had required 2–3 monthly courses of intravenous anti-pseudomonal chemotherapy administered at home by an indwelling subcutaneous vascular access port. During a routine clinic review, the patient mentioned that her great-nephew had recently been diagnosed with cystic fibrosis (mutations Q43X and D1152H). Subsequent genetic testing of our patient revealed her to be a compound heterozygote for two recognized cystic fibrosis alleles: delta F508 and D1152H.
Delta F508 is the most common mutation worldwide and occurs in up to 80% of cystic fibrosis patients in the UK. D1152H is far less common, having first been identified in Ashkenazi Jews and Northern Europeans, with most data on this mutation arising from studies on infertile males.1 The many different phenotypes observed in cystic fibrosis are believed to relate to the effect of the specific mutation on the production of the cystic fibrosis transmembrane conductance regulator protein. Low values of the protein (class I mutations) are associated with severe disease, and intermediate values (class V) with mild disease.2–5 D1152H is a class IV mutation, and is generally associated with late presentation, mild pulmonary disease, pancreatic sufficiency, normal sweat chloride values and advanced survival.4,5
It is not common for cystic fibrosis to be diagnosed after adolescence, let alone beyond 60 years of age. Although the clinical implication in our patient was limited, her family has received appropriate genetic counselling. Moreover, despite the absence of extra-pulmonary symptoms, advanced age and other plausible causes of bronchiectasis being present (previous ‘chest infections’, tuberculosis and allergic bronchopulmonary aspergillosis), the diagnosis of cystic fibrosis was still made in this particular patient.
Department of Respiratory Medicine Aberdeen Royal Infirmary Foresterhill Aberdeen
email: graeme.currie{at}nhs.net
References
1. Chillón M, Casals T, Mercier B, et al. Mutations in the Cystic Fibrosis Gene in Patients with Congenital Absence of the Vas Deferens. N Engl J Med 1995; 332:1475–80.
2. McKone EF, Emerson SS, Edwards KL, Aitken ML. Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet 2003; 361:1671–786.[CrossRef][Web of Science][Medline]
3. Hubert D, Bienvenu T, Desmazes-Dufeu N, et al. Genotype-phenotype relationships in a cohort. Eur Respir J 1996; 9:2207–14.[Abstract]
4. Feldmann D, Rochemaure J, Plouvier E, Magnier C, Chauve C, Aymard P. Mild course of cystic fibrosis in an adult with the D1152H mutation. Clin Chem 1995; 41:1675.
5. Highsmith WE Jr, Friedman KJ, Burch LH, et al. A CFTR mutation (D1152H) in a family with mild lung disease and normal sweat chlorides. Clin Genet 2005; 68:88–90.[Web of Science][Medline]
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