7 Questions on CF: Sweat Tests, Breast Milk, Tobramycin, & More

December 16, 2019
Veronica Hackethal, MD

Try these 7 questions on guideline-oriented cystic fibrosis diagnosis and treatment.

Which test for cystic fibrosis is appriate in a newborn? Should cow's milk be avoided for infants with CF? At what age should screening for colorectal cancer begin in persons with CF? Answers and 4 more questions follow.

Question 1. Which of the following is not a test used for screening for CF in newborns?

A. IRT test

B. Sweat chloride test

C. CFTR genetic testing

D. Both B and C

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Answer: D. Both B and C. In the US, universal screening of newborns for CF began in 2010 in all 50 states and the District of Columbia. While screening method varies by state, both immunoreactivity trypsinogen test (IRT) and IRT-DNA testing are used-in some states together and in some the IRT test alone. The sweat chloride test and CFTR genetic testing are used confirm a positive screening test. Sweat chloride testing is considered the gold standard for confirming a diagnosis of CF.1

Question 2. A newborn has a positive CF screening test, foul smelling stools, and poor weight gain. Her sweat chloride test is 32 mmol/L. Which of the following is true?

A. Results from the sweat chloride test rule out CF

B. Clinical symptoms indicate this baby has CF

C. Clinical symptoms combined with the positive screening results confirm CF

D. Repeat sweat testing should be considered

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Answer: D. Repeat sweat testing should be considered. According to consensus guidelines from the Cystic Fibrosis Foundation (CFF), infants with a positive newborn screen, symptoms of CF, or a positive family history and sweat chloride values between 30-59 mmol/L. may have CF. In such cases, a repeat sweat test should be conducted by age 2 months. If sweat test results remain elevated,  CFTR gene analysis should be considered. A sweat chloride testing result ≥60 mmol/L is suggestive of CF, especially in babies with positive screens and symptoms of CF. Results between 30-59 mmol/L are considered intermediate. Results <30 mmol/L suggests CF is unlikely.2,3

Question 3. Results of the infant’s follow-up sweat test at age 2 months remain slightly elevated slightly elevated at 35 mmol/L. Her parents agree to CFTR gene testing. Results show that she has one CF-causing mutation and one mutation of varying clinical consequence (MVCC). Which of the following is true?

A. Two CF-causing mutations are required to diagnose CF

B. Absence of 2 CF-causing mutations does not rule out CF

C. The MVCC is protective and rules out CF

D. Results confirm CF, no further testing is necessary

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Answer: B. Absence of 2 CF-causing mutations does not rule out CF. CFF consensus guidelines state that an individual who has 2 CF-causing gene mutations on 2 separate alleles likely has CF, but the absence of 2 CF-causing gene mutations does not rule out CF.

Individuals may have a MVCC that can cause CF when combined with a CF-causing mutation or another MVCC.  Individuals may also have an uncharacterized mutation that may be cause disease or be benign.  Individuals with sweat chloride testing and CFTR genetic analysis suggestive of CF should have CFTR physiologic testing to evaluate for CFTR dysfunction. In this example, additional monitoring of this infant may be necessary to confirm or rule out CF.2,3

Question 4. In the first year of life, infants with CF often have lactose intolerance and need more calories than other infants. For this reason, soy-based, fortified formula is recommended over breast milk as the primary source of nutrition for infants with CF.

A. True

B. False 

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Answer: B. False. In the first year of life, breast feeding is recommended as the primary source of nutrition for most infants, including those with CF. Lactose intolerance and cow’s milk allergies are no more common in individuals with CF than the general population. Infants with CF may have additional energy needs, which may require fortifying breast milk or concentrating formula, as well as adding fat and/or carbohydrate to them. Infants with CF may also need supplementation with fluoride, iron, sodium chloride, and other vitamins. 4

Question 5. The Cystic Fibrosis Foundation recommends against use of which of the following chronic medications for the maintenance of lung health in CF?

A. Tobramycin

B. Inhaled corticosteroids

C. Dornase alfa

D. Hypertonic saline

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Answer: B. Inhaled corticosteroids. The CFF recommends against use of inhaled and oral corticosteroids in patients with CF but without asthma or allergic bronchopulmonary aspergillosis (ABPA), based on the potential for harm and high certainty of no benefit.5 The inhaled antibiotic tobramycin is recommended in mild lung disease, and strongly recommended in moderate to severe lung disease. Likewise, the mucolytic dornase alfa is recommended in mild lung disease, and strongly recommended in moderate to severe lung disease, Hypertonic saline is recommended in all lung disease, regardless of severity.5

Question 5. Which of the following patients is a candidate for the CFTR modulator ivacaftor (Kalydeco)?

A. A patient with at least two copies of the G551 CFTR mutation

B. A patient with at least one copy of the G551 CFTR mutation

C. A patient with at least two copies of the F508del CFTR mutation

D. A patient with at least one copy of the F508del CFTR mutation

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Answer: B. A patient with at least one copy of the G551 CFTR mutation. More than 1700 mutations for the CFTR genes have been identified. The G551 mutations is a gating mutation which in effect locks the gate to the chloride channel on the cell surface. That interferes with the flow of chloride through the channel and results in dysregulation of fluids at the cell surface. Ivacaftor binds to the defective protein and helps to open the gate to improve flow of chloride through the channel and improve fluid regulation.5

F508del, the most common CF mutation, interferes with protein processing so that not enough CFTR protein reaches the cell surface, and proteins that do reach the surface cannot open the gate wide enough to let chloride pass through.

Lumacafotor is a medication that has been FDA-approved to treat individuals with two copies of the F508del mutation.6

Question 6. A 30-year-old woman with CF had a lung transplant at age 28 years and is doing well. According to CFF guidelines, at what age should she start screening for colorectal cancer?

A. 20 years

B. 30 years

C. 40 years

D. 45 years

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Answer: B. Age 30 years. According to a recent study, >70% of individuals with CF who undergo lung transplant are aged 18-39 years at the time of transplant (average, 29 years).7 Among individuals with CF, the risk for colorectal cancer is 5-10 times higher than the general population.8 The CFF recommends that screening colonoscopy for colorectal cancer should begin at age 40 in individuals with CF who have not undergone a solid organ transplant. The guidelines further recommend:

  • CF patients who are at least 30-years-old, who have had a solid organ transplant, and who have adequately recovered from their transplant, should start screening for colorectal cancer within 2 years of their transplant-unless they have had a negative colonoscopy within the past 5 years.

  • Re-screening should occur every 5 years in individuals with CF who have had a solid organ transplant, as well as in individuals with CF who have not had a transplant.

  • Re-screening should be done every 3 years in persons with CF who have had adenomatous polyps detected on screening colonoscopy.9

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References:

1. Cystic Fibrosis Foundation. How Babies Are Screened in IRT-Only vs. IRT-DNA States. Accessed December 13 2019 at: https://www.cff.org/What-is-CF/Testing/How-Babies-Are-Screened-in-IRT-Only-vs-IRT-DNA-States/

2. Farrell PM, White TB, Ren CL, et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181S:S4-S15.e1.

3. CFF. Management of CRMS in First 2 Years and Beyond Clinical Care Guidelines. Accessed December 13 2019 at: https://www.cff.org/Care/Clinical-Care-Guidelines/Age-Specific-Clinical-Care-Guidelines/Management-of-CRMS-in-First-2-Years-and-Beyond-Clinical-Care-Guidelines/

4. Borowitz D, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002 Sep;35(3):246-59.

5. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Pulmonary Clinical Practice Guidelines Committee. Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med. 2013;187:680-9.

6. CFF. CFTR modulator therapies. Accessed Dec 13 2019 at: https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Medications/CFTR-Modulator-Therapies/

7. Benden C, Goldfarb SB, Stehlik J. An aging population of patients with cystic fibrosis undergoes lung transplantation: An analysis of the ISHLT Thoracic Transplant Registry. J Heart Lung Transplant. 2019;38:1162-1169. 

8. CFF. About colorectal cancer. Accessed December 15 2019 at: https://www.cff.org/Life-With-CF/Transitions/Colorectal-Cancer-and-CF/About-Colorectal-Cancer/

9. Hadjiliadis D, Khoruts A, Zauber AG, et al. Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations. Gastroenterology. 2018;154:736-745.e14. doi: 10.1053/j.gastro.2017.12.012.