Beyond BMI: Nutritional Recovery and Functional Implications of CFTR Modulators in Cystic Fibrosis

Cystic fibrosis (CF) is a multisystem genetic disorder in which malnutrition has historically been a major determinant of disease severity. The advent of CFTR modulators has significantly altered the nutritional and functional profile of CF patients. This systematic review, conducted following PRISMA guidelines and registered on PROSPERO, summarizes studies published from 2012 to 2025 that evaluated the impact of CFTR modulators on nutritional status, body composition, and respiratory function, with a particular focus on the relationship between BMI changes and FEV₁. Seventeen studies including both pediatric and adult populations were identified and analyzed. All studies reported significant increases in BMI following modulator therapy, ranging from +0.9 to +1.6 kg/m² after 6-12 months of elexacaftor/tezacaftor/ivacaftor (ETI), accompanied by improvements in FEV₁ of 7-13 percentage points. Weight gain was primarily due to increases in fat mass (60-75%). Improvements in albumin, prealbumin, and vitamin levels, along with reductions in C-reactive protein (CRP) and fecal calprotectin, reflected systemic metabolic recovery. However, a marked increase in overweight and obesity (up to 40%), together with increased visceral adiposity, has also been observed. Overall, CFTR modulators result in significant nutritional and functional improvements, highlighting the need for strategies that prioritize overall metabolic health rather than weight gain alone.