Can an adult be diagnosed with new onset cystic fibrosis?

Can Adults Be Diagnosed with New Onset Cystic Fibrosis?

Yes, adults can absolutely be diagnosed with cystic fibrosis for the first time, and this occurs with increasing frequency as clinicians recognize the wide disease spectrum and milder phenotypes that may not manifest until adulthood. 1, 2

Understanding Adult-Diagnosed Cystic Fibrosis

Cystic fibrosis is not exclusively a childhood diagnosis. While newborn screening identifies most cases early, a significant subset of patients—particularly those with milder, atypical presentations—escape detection until adulthood. 1, 3

Key Clinical Presentations in Adults

Adults diagnosed with CF typically present with:

• Chronic respiratory symptoms with recurrent or chronic airway infections, often previously misdiagnosed as asthma, chronic bronchitis, or emphysema 2, 3
• Bronchiectasis of unclear etiology with infection by typical CF pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, or nontuberculous mycobacteria) 3
• Congenital bilateral absence of the vas deferens (CBAVD) in men, which may be the presenting feature 4, 3
• Recurrent or chronic pancreatitis without other identifiable cause 3, 5
• Single-organ manifestations with subclinical respiratory involvement 2, 3

Notably, pancreatic insufficiency—a hallmark of childhood CF—is much less common in adult-diagnosed patients, though pancreatitis occurs with greater frequency. 3

Diagnostic Approach in Adults

Step 1: Sweat Chloride Testing

The sweat chloride test remains the most reliable and widely available diagnostic test for CF, even in 2016 and beyond. 5

• Sweat chloride >60 mmol/L confirms CF diagnosis when combined with compatible clinical features 5
• Sweat chloride 30-59 mmol/L (intermediate range) requires additional testing 5
• Normal sweat chloride does not exclude CF in adults with milder phenotypes 4

Step 2: CFTR Genetic Testing

• Identification of two known disease-causing CFTR mutations confirms the diagnosis 5
• Complete CFTR gene sequencing may be necessary when initial mutation panels identify only one or no mutations 4, 5
• In one reported case, a 74-year-old woman required complete gene sequencing to identify a rare second mutation after standard panels found only one 4

Step 3: Advanced Functional Testing (When Initial Tests Are Inconclusive)

For patients with intermediate sweat chloride values or fewer than two identified mutations, referral to expert CF centers for bioassays of CFTR function is essential:

• Nasal potential difference measurement 4, 5
• Intestinal current measurement 5

These functional tests can demonstrate CFTR dysfunction even when genetic or sweat testing is inconclusive. 4

Important Diagnostic Considerations

CFTR-Related Disorder (CFTR-RD)

Some patients have symptoms compatible with CF and evidence of CFTR dysfunction (e.g., intermediate sweat chloride) but don't meet full diagnostic criteria (e.g., only one CFTR mutation identified). These patients are classified as having CFTR-RD. 5

Conditions that may fall into this category include:

• Disseminated bronchiectasis
• Congenital bilateral absence of the vas deferens
• Acute or recurrent pancreatitis 5

Prognosis and Disease Severity

Adult-diagnosed CF patients typically have:

• Milder disease compared to those diagnosed in infancy 3
• More favorable prognosis overall 3
• Good response to CF center care 2
• Potential benefit from CFTR modulator therapies, making accurate diagnosis increasingly important 1, 2

However, the extent of bronchiectasis can still be severe despite later diagnosis. 3

Critical Clinical Pitfalls to Avoid

• Don't dismiss CF based on age alone—the diagnosis can be made at any age, including in elderly patients (one case report describes diagnosis at age 74) 4
• Don't rely solely on standard mutation panels—complete CFTR gene sequencing may be necessary to identify rare mutations 4
• Don't accept a normal sweat chloride as definitive exclusion in patients with strong clinical suspicion—advanced functional testing may be required 4
• Don't overlook family screening—when one adult is diagnosed, consider testing symptomatic family members regardless of age 4
• Don't assume single-organ involvement excludes CF—carefully evaluate for subclinical respiratory tract involvement 2, 3

When to Suspect CF in Adults

Maintain high clinical suspicion in adults presenting with:

• Unexplained bronchiectasis with chronic airway infection 2, 3
• Male infertility due to CBAVD 4, 3
• Recurrent pancreatitis without other cause 3, 5
• Chronic respiratory symptoms previously attributed to asthma or COPD that don't respond typically to treatment 3

The increasing availability of genetic testing and greater appreciation of CF's clinical spectrum means more adults will receive this diagnosis. 3 Clinicians across specialties—not just pulmonologists—must remain aware of this possibility to ensure patients receive appropriate CF center care and access to transformative CFTR modulator therapies. 1, 2