Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

Carlo Castellani, MD; Barry Linnane, MB, BCh, BAO, DCH, MRCPI, MRCPCH, MD; Iwona Pranke, PhD; Federico Cresta, MD; Isabelle Sermet-Gaudelus, MD, PhD; Daniel Peckham, MD


Semin Respir Crit Care Med. 2019;40(6):701-714. 

In This Article

Sweat Testing as a Part of CF NBS

Essentially all CF NBS programs employ an initial IRT assay (tier 1), followed by methods to improve specificity (tier 2 ± tiers 3 and 4), culminating in referral of an infant identified as being at increased risk of CF for clinical assessment and diagnostic testing. Even in the era of molecular medicine, the sweat test remains the gold standard diagnostic test.[8,93,94] It is sometimes suggested that it is unnecessary in infants with two disease causing mutations identified; however, there remain strong arguments to confirm this life-long condition, with significant morbidity and mortality, with a physiological test demonstrating CFTR dysfunction.[8,68,93,108,109]

Sweat testing infants at this age are challenging. Guidelines suggest it should be possible to collect sweat from infants over 36-weeks corrected gestational age and >2-kg weight.[8] It is suggested the quantity not sufficient (QNS) rate should be less than 10%.[8,110] In practice, this can be challenging with QNS rates in infants ≤3 months old varying from 0 to 40%.[110] However, it is critical that QNS rate is kept to the minimal achievable as an unavailable sweat test result significantly delays the entire clinical assessment and diagnostic process with potential negative consequences, including the psychological well-being of the parents.[16,111] With quality improvement measures it should be possible to achieve low QNS rates.[110] When an adequate volume of sweat is obtained from an infant, a sweat chloride value ≥60 mmol/L is consistent with the diagnosis, a value <30 mmol/L indicates CF is unlikely, and a value 30 to 59 mmol/L is equivocal and requires further assessment.[8,94]

The sweat test has equal, if not greater, importance for the infant identified through the CF NBS program as being at increased risk of CF, but with only one mutation identified. The majority of these infants would be found to have a normal sweat test, and hence be "diagnosed" as unaffected carriers of a single CF mutation. These families are exposed to a significant psychological stress, which can have short, and indeed long-term implications.[16,70,98,111] How a CF NBS program manages the critical time around communication of a positive NBS result, the performance of the sweat test, and the communication of the results, may ultimately dictate the net benefit of the program to the population as a whole. The logistics can be challenging. The initial contact with the family should be by someone well informed regarding CF, and the CF NBS program. There should be minimal delay between the communication of the CF NBS program results and the performance of the diagnostic sweat test (ideally the following day) and usually happening within 2 to 4 weeks of life.[8,94] The results of the sweat test should be provided the same day to the parents, in person, by someone experienced in the care of children with CF. If the infant is found to have CF they should be linked immediately with a specialist CF center.[21,22,28] If the infant is found to be an unaffected carrier, the benign nature of this result must be communicated with clarity to the family, and follow-up with genetic counselling offered.[17]