Cystic Fibrosis (CF) is an inherited condition impacting the exocrine glands, which produce mucus, sweat, saliva, and digestive enzymes. The disorder stems from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to a faulty or absent protein that regulates the movement of salt and water across cell membranes. While CF is typically identified in infancy through newborn screening programs, milder or atypical forms often escape early detection. These less severe presentations mean diagnosis may not occur until adolescence or adulthood, requiring specific diagnostic protocols tailored to the adult patient population.
Indicators Leading to Adult Testing
The clinical indicators prompting a cystic fibrosis evaluation in an adult differ significantly from the severe, multi-system failure seen in pediatric cases. Adults who receive a late diagnosis often have localized or less pronounced symptoms. A primary reason for testing is chronic respiratory disease, particularly bronchiectasis, which involves the permanent widening of the airways and recurrent infections. This manifestation often includes chronic cough, persistent production of sputum, and repeated bouts of pneumonia that fail to resolve completely.
Gastrointestinal issues also serve as a strong indicator, especially chronic or recurrent pancreatitis. Unexplained malnutrition or difficulty maintaining weight, despite adequate caloric intake, can also raise suspicion for CF-related digestive malabsorption.
In men, the most common single indicator leading to an adult CF diagnosis is infertility caused by congenital bilateral absence of the vas deferens (CBAVD). This condition means the tubes that transport sperm are missing or blocked, and it is present in the vast majority of men with CF. A final reason for testing is a known family history of cystic fibrosis, which prompts screening for carrier status or milder forms of the disease in relatives.
The Standard Diagnostic Procedure
The gold standard for diagnosing cystic fibrosis in adults remains the Sweat Chloride Test (SCT), a non-invasive and highly reliable measure of CFTR protein function in the sweat glands. The test is based on the observation that a malfunctioning CFTR protein fails to reabsorb chloride from the sweat as it moves through the sweat duct, resulting in a significantly elevated chloride concentration. Because of the technical rigor required, the test should be performed at a laboratory accredited by a recognized foundation or organization.
The procedure begins with quantitative pilocarpine iontophoresis to stimulate localized sweat production. A small, painless electrical current is applied for about five minutes after applying the chemical pilocarpine to the skin. Pilocarpine acts as a stimulant to the sweat glands, ensuring a sufficient volume of sweat is produced for accurate analysis.
After the stimulation phase, the technician collects the sweat sample using a specialized device, such as a Macroduct coil or a collection patch, for a period not exceeding 30 minutes. A minimum sample volume or weight is required to prevent an inconclusive result. Once collected, the sample is analyzed in the laboratory to determine the exact concentration of chloride, typically measured in millimoles per liter (mmol/L).
The interpretation of the results relies on standardized concentration thresholds. A sweat chloride value of less than 30 mmol/L indicates that cystic fibrosis is unlikely. A result of 60 mmol/L or greater is considered diagnostic for cystic fibrosis, though a positive result should be confirmed by a second test or genetic analysis.
Results falling between 30 and 59 mmol/L are classified as intermediate or borderline, suggesting the diagnosis is possible but not confirmed. This range necessitates further investigation, such as full genetic sequencing, because individuals with milder forms of CF may present with intermediate sweat chloride levels. The interpretation must always be considered alongside the patient’s specific clinical symptoms and medical history.
Confirmatory Genetic Analysis and Advanced Testing
Genetic analysis of the CFTR gene is frequently the next step following a positive or intermediate sweat chloride test result, or when clinical suspicion remains high despite a normal sweat test. This testing confirms the diagnosis by identifying specific mutations in the CFTR gene. Identifying the exact mutations is crucial, as it confirms the diagnosis and informs potential treatment strategies, particularly the use of newer mutation-specific therapies.
Genetic testing typically involves analyzing a blood or cheek swab sample for the presence of known CFTR mutations. While over 2,000 different mutations have been documented, standard genetic panels screen for the most common variants. For adults with atypical symptoms or intermediate test results, an expanded panel or full gene sequencing may be necessary to detect rarer mutations that cause milder disease.
A definitive genetic diagnosis requires the identification of two disease-causing CFTR mutations, one inherited from each parent. If only one mutation is found and the sweat test was intermediate, the diagnosis remains uncertain, or the individual may be a carrier. In cases where standard diagnostic tools are inconclusive, but the clinical picture strongly suggests functional CFTR dysfunction, specialized physiological measures can be employed.
The Nasal Potential Difference (NPD) measurement is used in specialized CF centers to directly assess the function of ion channels in the epithelial lining of the nasal airway. This procedure involves measuring the small electrical voltage across the nasal lining, which is generated by the transport of ions like sodium and chloride. Because the CFTR protein regulates this ion flow, the electrical response in a person with CF is distinctly abnormal.
The NPD test involves perfusing the nasal lining with a series of specialized salt solutions, including one containing the sodium channel blocker amiloride, to measure the change in the electrical potential. This response provides a functional readout of the CFTR protein’s ability to transport chloride ions in the airway cells. The NPD measurement is especially valuable for diagnosing individuals with atypical CF or those with inconclusive sweat test and genetic results.