TABLE 1.

Phenotypic features of cystic fibrosis (CF) disease on cystic fibrosis transmembrane conductance regulator (CFTR) modulators and knowledge gaps

	CF disease on CFTR modulators	Knowledge gaps on CFTR modulators effects
Respiratory disease	Marked reduction of respiratory symptoms Rapid improvement in respiratory function	Long-term progression of lung function Best monitoring methods and frequency
Microbiology and pulmonary exacerbations	Lower frequency of pulmonary exacerbations Reduction but persistence of airway inflammation	Long-term clearance of airway pathogens Long-term effect on airway inflammation Prevention or delay in airway colonisation Best sampling methods Relevance of current guidelines
Exocrine pancreatic insufficiency	Possible reversal of pancreatic insufficiency in young children	Long-term effect on exocrine pancreatic function
Gastrointestinal disease and nutrition	No meaningful change in abdominal symptoms Increased number of overweight pwCF No effect on established biliary complications	Optimal diet and nutrition outcomes Prevention or delay in biliary complications
CF-related diabetes	Possible reduction of insulin requirements Improved diabetes control	Robust longitudinal data to assess improvements Prevention or delay in CF-related diabetes
Fertility	No recovery of fertility in males Improved fertility in females No abnormalities in fetal development to date	Effects on male fertility with very early CFTR modulator treatment Robust longitudinal data to assess mothers and infants when CFTR modulators are used during pregnancy and lactation
Chronic rhinosinusitis	Improvement in symptoms and CT scan findings	Effects of early treatment on nasal polyposis development
Bone disease	Possible improvement in bone mineral density	Robust longitudinal data to assess improvement

CT: computed tomography; pwCF: people with CF.