Improved clinical and radiographic outcomes after treatment with ivacaftor in a young adult with cystic fibrosis with the P67L CFTR mutation.
The underlying cause of cystic fibrosis (CF) is the loss of epithelial chloride and bicarbonate transport due to mutations in the CF transmembrane conductance regulator (CFTR) gene encoding the CFTR protein. Ivacaftor is a gene-specific CFTR potentiator that augments in vivo chloride transport in CFTR mutations affecting channel gating. Originally approved for the G511D CFTR mutation, ivacaftor is now approved for eight additional alleles exhibiting gating defects and has also been tested in R117H, a CFTR mutation with residual function that exhibits abnormal gating. P67L is a class 4 conductance (nongating) mutation exhibiting residual CFTR function. We report marked clinical improvement, normalization of spirometry, and dramatic reduction in radiographic structural airway changes after > 1 year of treatment with ivacaftor in a young adult with the compound heterozygous genotype P67L/F508del CFTR. The case suggests that ivacaftor may have a potential benefit for patients with CF with nongating mutations.
Division of Pediatric Pulmonology, Miller School of Medicine, University of Miami, Miami, FL.
Shatha
S
Yousef
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
George M
GM
Solomon
Departments of Radiology and Pediatrics, Cincinnati Children's Hospital and the University of Cincinnati College of Medicine, Cincinnati, OH.
Alan
A
Brody
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. Electronic address: smrowe@uab.edu.
Steven M
SM
Rowe
Division of Pediatric Pulmonology, Miller School of Medicine, University of Miami, Miami, FL.
Andrew A
AA
Colin
D000293:Adolescent; D000627:Aminophenols / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D015363:Quinolones / Q000627:therapeutic use*; D013902:Radiography, Thoracic; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000627:Aminophenols; C505032:CFTR protein, human; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor