Cystic Fibrosis

Indications for Testing

Molecular testing for CF is indicated for the following    :

• Carrier screening in women who are pregnant or planning a pregnancy
• Carrier screening in individuals with a family history of CF or CFTR-related conditions
• Diagnosis in newborns with a positive newborn screening result
• Diagnosis in adult or pediatric patients with signs or symptoms or a family history of CF
• Confirmation of the causative CFTR gene variants in a known affected individual to determine eligibility for CFTR variant-specific treatment

Laboratory testing is also used to monitor complications in patients with an established diagnosis of CF.

Criteria for Diagnosis

The Cystic Fibrosis Foundation  proposes the following diagnostic criteria for CF in an individual with a positive newborn screening test, signs and/or symptoms of CF, or a family history of CF:

• A positive sweat chloride test result ≥60 mmol/L
• Identification of two CF-causing variants on separate chromosomes and a sweat chloride value of ≥30 mmol/L
• Demonstrated CFTR dysfunction (ie, a sweat chloride test result of ≥60 mmol/L or CF-typical nasal potential difference or intestinal current measurement), regardless of whether or not two molecular pathogenic variants can be identified

Laboratory Testing

Carrier Screening

Carrier screening for CF is recommended for all women who are pregnant or planning a pregnancy, individuals with a family history of CF, and men with isolated congenital bilateral absence of the vas deferens.   A panel test for the 23 most common CF-causing variants is recommended for carrier screening  ; each of these variants occurs with a frequency of more than one in 1,000 in a panethnic U.S. population. For more information on the genetics of CF, see the Cystic Fibrosis (CFTR) Expanded Variant Panel Test Fact Sheet.

Newborn Screening

Screening for CF is recommended for all newborns in the U.S.  Screening is performed using a measurement of IRT in blood spots; depending on the results, a reflex test for a panel of common pathogenic CFTR gene variants may be performed.   False-negative results occur at an increased rate in infants with meconium ileus. 

Diagnosis

In individuals with a positive IRT test, positive CFTR genetic test, or suggestive symptoms [see Cystic Fibrosis (CFTR) Expanded Variant Panel Test Fact Sheet], sweat chloride testing is recommended.  A sweat chloride test result of ≥60 mmol/L is diagnostic for CF, and no further testing is required.  A sweat chloride test result of <30 mmol/L suggests that CF is unlikely, and further testing is not indicated unless clinical suspicion persists.  An intermediate sweat chloride test result of 30-59 mmol/L should be clarified with CFTR genetic analysis.  CFTR gene sequencing and deletion/duplication analysis should be performed if one or no pathogenic variants are identified on a CF panel of selected variants.  If CFTR sequencing and deletion/duplication testing fails to identify two causative variants, functional analysis (nasal potential difference and intestinal current measurement) is recommended.  If results are inconclusive, a diagnosis of CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) is appropriate. 

Monitoring

CF has numerous complications that require careful monitoring.