Long-term outcomes of adolescents/adults with CF screen positive, inconclusive diagnosis

Long-term outcomes for infants labeled as Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) are poorly defined, especially into adolescence and adulthood. This study evaluates the clinical evolution and management of Italian patients initially classified as CFSPID or maintaining this label over time. The aim is to assess the progression toward cystic fibrosis (CF) or CFTR-related disorders (CFTR-RD) and to describe the long-term clinical status, lung function, and therapeutic management of this cohort.

This retrospective, multicenter, observational study included subjects born before 2011 meeting CFSPID criteria at six Italian CF centers. Clinical data were analyzed from the first evaluation until June 30, 2025, focusing on diagnostic evolution, complications, and treatments.

Among 77 subjects (median age 20.9 years), 41.6% eventually received a CF diagnosis at a median age of 8.6 years, primarily due to sweat chloride levels, while 18.2% were reclassified as CFTR-RD. Most patients maintained preserved nutritional status and lung function with few complications. Notably, 40.2% remained asymptomatic with a persistent inconclusive diagnosis. Despite this, 80.6% and 64.5% of persistent CFSPID cases were prescribed airway clearance and salt supplementation, respectively. Two of ten eligible CF patients received triple-combination modulator therapy.

Most adolescents and adults initially identified as CFSPID experience favorable clinical outcomes, regardless of progression to CF or CFTR-RD. However, the frequent prescription of treatments to asymptomatic individuals with inconclusive diagnoses suggests a potential for overtreatment, highlighting the need for more evidence-based management strategies.