2017年囊性纤维化诊断指南

Consensus recommendations for diagnosis of CF

1 Sweat chloride testing should be performed according to approved procedural guidelines published in established, international protocols such as the CLSI 2009 Guidelines. 100%

2 Newborns with a positive CF newborn screen, to increase the likelihood of collecting an adequate sweat specimen, should have the test performed bilaterally and when the infant weighs >2 kg, and is at least 36 wk of corrected gestational age. 87%

3 Newborns greater than 36 wk gestation and >2 kg body weight with a positive CF newborn screen, or positive prenatal genetic test, should have sweat chloride testing performed as soon as possible after 10 d of age, ideally by the end of the neonatal period (4 wk of age).93%

4 In infants with presumptive CF identified through NBS, CF treatment should not be delayed while efforts to establish a diagnosis of CF are initiated. 83%

5 Sweat chloride analysis should be performed within a few hours of sweat collection and the results and interpretations should be reported to clinicians and parents or patients, as soon as possible and certainly on the same day. 90%

6 In individuals presenting with a positive newborn screen, clinical features consistent with CF, or a positive family history, a diagnosis of CF can be made if the sweat chloride value is ≥60 mmol/L. 93%

7 Individuals who are screen-positive and meet sweat chloride criteria for CF diagnosis should undergo CFTR genetic testing if the CFTR genotype was not available through the screening process or is incomplete. 100%

8 In individuals with a positive newborn screen, a sweat chloride <30 mmol/L indicates that CF is unlikely. 82%

9 Individuals with clinical features that may be consistent with CF who have a sweat chloride <30 mmol/L indicates that CF is less likely. It may, however, be considered if evolving clinical criteria and/or CFTR genotyping support CF and not an alternative diagnosis. 80%

10 Individuals presenting with a positive newborn screen, symptoms of CF, or a positive family history, and sweat chloride values in the intermediate range (30-59 mmol/L) on two separate occasions may have CF. They should be considered for extended CFTR gene analysis and/or CFTR functional analysis. 90%

11 The latest classifications identified in the CFTR2 project (http://www.cftr2.org/index.php) should be used to aid with CF diagnosis:
• CF-causing mutation: individuals with 2 copies on separate alleles will likely have CF (clinical sweat confirmation needed)
• Mutation of varying clinical consequence (MVCC): a mutation that in combination with a CF-causing mutation or another MVCC mutation may result in CF
• Uncharacterized mutation/mutation of UNK: mutation that has not been evaluated by CFTR2 and may be disease causing or of variable clinical consequence or benign
• Non-CF-causing mutation: individuals with 1 or more are unlikely to have CF (as a result of that allele) 100%

12 In individuals presenting with a positive newborn screen, symptoms of CF, or a positive family history, the identification of 2 CF-causing mutations (defined by CFTR2) is consistent with a diagnosis of CF. Sweat chloride testing is necessary, though, to confirm the diagnosis.87%

13 The absence of detection of 2 CF-causing CFTR mutations does not exclude a diagnosis of CF. 93%

14 If further CF functional testing is needed (NPD and ICM), it should be performed in a validated reference center with trained staff certified by the CF Foundation TDN or ECFS Clinical Trial Network. 100%

15 In individuals with a positive newborn screen but variable or uncharacterized CFTR mutations (<2 CF-causing mutations), the diagnosis of CF can be made by demonstrating CFTR dysfunction (a sweat chloride ≥ 60 mmol/L or CF-typical NPD or ICM).93%

16 The term CRMS is used in the US for healthcare delivery purposes and CFSPID is used in other countries, but these both describe an inconclusive diagnosis following NBS. 96%

17 The term CRMS/CFSPID is reserved for individuals who screen positive without clinical features consistent with a diagnosis of CF.83%

18 The definition of CRMS/CFSPID is an infant with a positive NBS test for CF and either:
• A sweat chloride value <30 mmol/L and 2 CFTR mutations, at least 1 of which has unclear phenotypic consequences OR
• An intermediate sweat chloride value (30-59 mmol/L) and 1 or 0 CF-causing mutations 86%

19 Children designated as CRMS/CFSPID should undergo at least one repeat sweat chloride test at CF centers with suitable expertise, such as an accredited CF center.86%

20 Children designated as CRMS/CFSPID should have clinical evaluation performed by CF providers to identify the minority that may develop clinical symptoms. 83%

21 Children designated as CRMS/CFSPID can be considered for extended CFTR gene analysis (sequencing and or deletion duplication testing), as well as CFTR functional analysis (NPD/ICM) testing to further define their likelihood of developing CF. 80%

22 The decision to reclassify children designated as CRMS/CFSPID as CF is an integrated decision that should take into account functional assessment of CFTR (sweat chloride, and possibly NPD/ICM), CFTR genetic analysis, and clinical assessment by the CF clinicians caring for the patient.90%

23 Genetic counseling should be offered to families of individuals followed for CRMS/CFSPID, including a discussion of the risk in future pregnancies.100%

24 Research Recommendation: Infants with a designation of CRMS/CFSPID (by definition) do not have clinical features consistent with a diagnosis of CF and further research is needed to determine the prognosis and best practices for frequency and
duration of follow-up.96%

25 For individuals presenting with CF symptoms, the same diagnostic criteria recommended for the screened population for sweat chloride testing, CFTR genetic analysis, and CFTR functional testing should be used to confirm a CF diagnosis.93%

26 The diagnosis of CFTR-related disorder has been defined as a monosymptomatic clinical entity (CBAVD/pancreatitis/bronchiectasis) associated with CFTR dysfunction that does not fulfill the diagnostic criteria for CF.86%

27 Clinicians should avoid the use of terms like classic/nonclassic CF, typical/atypical CF, delayed CF, because these terms have no harmonized definition and could be confusing for families or caregivers.83%