Diagnosis of Cystic Fibrosis in Nonscreened Populations

Although the majority of cases of cystic fibrosis (CF) are now diagnosed through newborn screening, there is still a need to standardize the diagnostic criteria for those diagnosed outside of the neonatal period. This is because newborn screening started relatively recently, it is not performed everywhere, and even for individuals who were screened, there is the possibility of a false negative. To limit irreversible organ pathology, a timely diagnosis of CF and institution of CF therapies can greatly benefit these patients.

Experts on CF diagnosis were convened at the 2015 CF Foundation Diagnosis Consensus Conference. The participants reviewed and discussed published works and instructive cases of CF diagnosis in individuals presenting with signs, symptoms, or a family history of CF. Through a modified Delphi methodology, several consensus statements were agreed upon. These consensus statements were updates of prior CF diagnosis conferences and recommendations.

CF diagnosis in individuals outside of newborn screening relies on the clinical evidence and on evidence of CF transmembrane conductance regulator (CFTR) dysfunction. Clinical evidence can include typical organ pathologies seen in CF such as bronchiectasis or pancreatic insufficiency but often represent a broad range of severity including mild cases. CFTR dysfunction can be demonstrated using sweat chloride testing, CFTR molecular genetic analysis, or CFTR physiologic tests. On the basis of the large number of patients with bona fide CF currently followed in registries with sweat chloride levels between 30 and 40 mmol/L, the threshold considered "intermediate" was lowered from 40 mmol/L in the prior diagnostic guidelines to 30 mmol/L. The CF diagnosis was also discussed in the context of CFTR-related disorders in which CFTR dysfunction may be present, but the individual does not meet criteria for CF.

CF diagnosis remains a rare but important condition that can be diagnosed when characteristic clinical features are seen in an individual with demonstrated CFTR dysfunction.