Late Diagnosis Defines a Unique Population of Long-term Survivors of Cystic Fibrosis

Cystic fibrosis (CF) is the most common, lethal, inherited disease in whites, affecting 1 in 2,500 individuals (1). When CF was originally described by D. Andersen in 1936, the affected population was identified as children with severe pancreatic insufficiency, recurrent pulmonary infections, and a life expectancy of less than 2 years. Since then, improvements in treatment have extended the median age of survival to 32.9 years (2, 3). In addition, identification of the CF gene (cystic fibrosis transmembrane conductance regulator [CFTR]) and improved diagnostic testing has expanded the spectrum of recognized disease phenotypes to include milder aspects of CFTR dysfunction (4, 5).

Although certain missense mutations are associated with milder disease, phenotypic variability in CF cannot be explained on the basis of the CFTR genotype alone (6, 7). In this regard, an important study population is the cohort of individuals who survive to older age despite having typical diagnostic features of CF. In the past, individuals who survived to old age, particularly those diagnosed after the third decade of life, were considered curiosities, often the subject of individual case reports in the medical literature (8-11). More recently, several series have described characteristics of adult patients, including those diagnosed after childhood (12-14). Our adult CF center is located at a national respiratory disease referral hospital, the National Jewish Medical and Research Center (Denver, CO), and testing for CF is done routinely in patients with persistent airway infections. We undertook a retrospective chart review to characterize older patients with CF identified or followed up at our center. Fifty-five individuals 40 years or older were identified, falling above the 95th percentile of patients with CF currently under care at 117 CF centers in the United States (3). As a group, extensive heterogeneity in pulmonary disease severity, spectrum of lung infection, pancreatic involvement, and severity of CFTR mutations were observed. However, two discrete populations, differentiated by their age at diagnosis, were present with respect to genotype and phenotype. The series of adult patients with CF described here is considerably older than previously reported cohorts, and the subgroup of patients diagnosed in adulthood were diagnosed 20 to 30 years later than previously reported series of adults diagnosed with CF (12-14). Our analysis demonstrates that, although older patients with CF diagnosed in adulthood often have fairly classic features of CF, they are more frequently women, typically have normal pancreatic function, have less severe pulmonary disease, and have a different spectrum of pulmonary infection. In particular, infection with nontuberculous mycobacteria (NTM) may represent a common mode of presentation in these patients. Components of this report were previously reported as an abstract at the 16th annual North American CF conference (15).

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