OBJECTIVE: 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.
STUDY DESIGN: 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.
RESULTS: 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.
CONCLUSIONS: 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.