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

## TL;DR

CFTR modulators improve weight and lung function in cystic fibrosis patients, but often lead to unhealthy fat gain.

## Contribution

This systematic review quantifies the impact of CFTR modulators on body composition and metabolic health in cystic fibrosis.

## Key findings

- Patients gained weight mainly through increased fat mass (60-75%) after CFTR modulator therapy.
- Lung function improved with FEV1 increases of 7-13 percentage points following treatment.
- Metabolic markers like albumin and CRP improved, but obesity rates rose to up to 40%.

## Abstract

Cystic fibrosis is a genetic disease that affects multiple organs and often leads to poor growth and nutrition. Recently, new medicines called CFTR modulators have changed the way the disease affects patients. This review looked at studies published between 2012 and 2025 to understand how these treatments influence body weight, body composition, and lung function. We found 17 studies involving children and adults. Most patients gained weight after starting these medicines, mainly due to an increase in fat rather than muscle. Lung function also improved, showing that the body worked better overall. Blood tests and other markers suggested that metabolism and nutrition improved with treatment. However, many patients became overweight or obese, and fat around organs increased. This shows that while CFTR modulators help people grow and breathe better, it is important to focus on gaining healthy body composition rather than just weight. Understanding these changes can help doctors provide better care and guide patients toward healthier outcomes.

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.