At a Glance

Cystic fibrosis (CF) is a heterogeneous disorder. Thus, clinical suspicion may arise in a number of different circumstances. Newborn screening for CF is routinely performed in the United States. Thus, many referrals for diagnostic testing come as result of a positive newborn screen or due to a family history of CF, sometimes in the absence of overt symptoms. Clinical symptoms of CF differ by age. Newborns may present with intestinal obstruction due to meconium ileus. Young children may exhibit failure to thrive and gastrointestinal symptoms suggestive of malabsorption. A variety of respiratory symptoms, ranging from chronic sinusitis or cough to bronchitis or pneumonia, may present at any age. Rarely, adult male patients may present initially with primary infertility.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The sweat chloride test remains the gold standard for CF diagnosis. Sweat production is stimulated by pilocarpine and chloride levels measured in the collected sweat. This is a technically challenging test and should be performed by an experienced technician. Increased sweat chloride (>60 mEq/L) on at least 2 occasions is diagnostic. Chloride levels of 40-60 mEq/L are suggestive, especially in children, and may indicate CF in the appropriate clinical setting.

The diagnosis can be confirmed by genetic testing to detect mutations in the CFTR gene known to cause CF. Although more than 1,000 such mutations have been described, current tests that detect up to 25 common mutations will identify CF with almost 90% sensitivity in Caucasian populations in whom the disease is most common. A person homozygous or compound heterozygous for CFTR mutations is presumed to have the disease. The genetic test is also useful for estimating prognosis and for genetic testing of relatives.

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In indeterminate or borderline cases with a consistent clinical history, transepithelial potential difference (TEPD) studies, which measure voltage across the nasalepithelium, may also be used. CF patients tend to have greater voltage differences than normal controls.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Sweat chloride levels may fluctuate in some patients, particularly adults, including peak values greater than 60 mEq/L. Thus, it is important that sweat chloride be elevated on at least 2 occasions to make the diagnosis. False-positive tests may be seen in individuals with eczema at the testing site or whose skin is contaminated with creams or lotions. Elevated levels may also be seen in individuals with malnutrition, renal insufficiency, nephrogenic diabetes insipidus, hypothyroidism, adrenal insufficiency, glucose-6-phosphatase deficiency, and mucopolysaccharidoses, among others. These conditions should be ruled out by clinical history.

Newborn infants may not produce sufficient sweat for the test, thus, results may not be reliable in the first 2 weeks of life. In addition, CF patients with hypoproteinemic edema may have false-negative sweat chloride tests due to dilution of extracellular fluid.

The genetic tests only detect a subset of mutations, so, depending on the testing panel used, up to 10% of Caucasian CF patients may have negative tests. The percentage of false-negative tests is even higher in other ethnic groups, although the disease is much less common in these populations.

What Lab Results Are Absolutely Confirmatory?

Sweat chloride testing, in conjunction with clinical evaluation, is considered the gold standard for diagnosis.