Diagnosis

Diagnostic Approach

A diagnosis of cystic fibrosis is generally pursued in infants and children who present with meconium ileus, recurrent pulmonary infections, failure to thrive or malnutrition, pancreatic insufficiency, and/or a history of cystic fibrosis in the immediate family. Some patients with mild or fewer manifestations present later in life with atypical symptoms.^3,34

Sweat Chloride Test

A sweat test has long been considered the “gold standard” for a diagnosis of CF. A positive pilocarpine iontophoresis sweat test and one or two of the clinical presentations of CF are usually sufficient to confirm a diagnosis.

The pilocarpine-coated electrode discs are placed on the forearm to stimulate sweating. After the discs are removed, a sweat collection apparatus is placed over the area for 20 to 30 minutes. The collected sweat is then computer analysed to determine sodium and chloride content. Normal salt content varies with age. Generally, a positive test has a chloride concentration >60 mEq/L.

The test is conducted by an experience laboratory and is repeated to confirm results.^3,28,35

Molecular Diagnosis

Because of the large number of CF mutations (almost 1000)⁵, DNA analysis is not used as the primary diagnostic test.

One or two percent of patients who present with clinical symptoms have normal chloride sweat test values, and some patients test with borderline values (borderline and normal sweat test results are more common in atypical CF).

In these patients, a full DNA test is often performed to help confirm diagnosis because these patients have an atypical presentation of CF. The most common mutations would be unlikely.

DNA testing is also conducted to detect carriers of CF and for genetic counselling.^1,3,18

Nasal Potential Difference

Patients who are not diagnosed until adulthood often have an atypical phenotype of CF. They may, for example, suffer from respiratory disease, but have normal pancreatic function and exhibit normal sweat chloride levels.³⁴

Although nasal potential difference (NPD) is difficult to perform and only available in a limited number of CF centers, it is a more sensitive measure of chloride ion transport, and as such, is a useful secondary diagnostic test of this patient population. A high-impedance voltmeter captures the bioelectric signal from an electrode at the epithelial surface in the nose, while a reference electrode is place subcutaneously at the interior epithelial surface of the arm.³⁶

The NPD distinguishes the patient with CF on three values:

A greater NPD in CF patients: Healthy individuals have readings of -20 mV and never reach a value of -40 mV; therefore a reading less than -40 mV is considered CF.
A major reduction in potential difference in patients with CF after nasal perfusion of the sodium channel blocker, amiloride.
Perfusion with a beta agonist shows little or no response in the patient with CF reflecting the CFTR chloride secretion defect.³⁶

Other Tests

The procedures we have just discussed comprise the standard practice used to diagnose CF. However, there are other tests that may be helpful to physicians in confirming the patient’s status:

Plasma tests to check for reduced pancreatic enzymes, such as trypsin and chymotrypsin
Testing the patient’s stool for high levels of fat
Pulmonary function tests to show the degree of lung deterioration
Imaging studies that may be helpful in determining the degree of lung or other organ damage

References:
1. Boucher RC. Cystic Fibrosis. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL et al., editors. Harrison's Internal Medicine. 16th ed. New York: McGraw-Hill; 2005. p. 1-9.
3. Welsh M. Cystic Fibrosis. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia: WB Saunders; 2004. p. 1-22.
5. Mason P. Cystic fibrosis-the disease. Hospital Pharmacist 2005;12:201-7.
18. Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. Cystic fibrosis adult care: consensus conference report. Chest 2004 January;125(1 Suppl):1S-39S.
28. Smyth RL. Diagnosis and management of cystic fibrosis. Arch Dis Child Ed Pract 2005;90:1-6.
34. Wilschanski M, Famini H, Strauss-Liviatan H, et al. Nasal potential difference measurements in patients with atypical cystic fibrosis. Eur Respir J 2001;17:1208-15.
35. Lynch A, Diamond D, Leader M. Point-of-need diagnosis of cystic fibrosis using a potentiometric ion-selective electrode array. Analyst 2000;125:2264-7.
36. Domingo-Ribas C, Bosque-Garcia M. Nasal potential difference test to diagnose cystic fibrosis. Arch Bronconeumol 2006;42(1):33-8.