TY - JOUR
T1 - Rate of Lung Function Decline in People with Cystic Fibrosis Having a Residual Function Gene Mutation
AU - Sawicki, Gregory S.
AU - Konstan, Michael W.
AU - McKone, Edward F.
AU - Moss, Richard B.
AU - Lubarsky, Barry
AU - Suthoff, Ellison
AU - Millar, Stefanie J.
AU - Pasta, David J.
AU - Mayer-Hamblett, Nicole
AU - Goss, Christopher H.
AU - Morgan, Wayne J.
AU - Duncan, Margaret E.
AU - Yang, Yoojung
N1 - Funding Information:
Editorial coordination and support were provided by Nathan Blow, PhD. NB is an employee of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. Medical writing and editorial support were provided by Liz Phipps, PhD, CMPP, and Jackie Highland, PhD, of ArticulateScience, LLC, and was funded by Vertex Pharmaceuticals Incorporated. This work resulted from a scientific advisory group formed by Vertex Pharmaceuticals Incorporated and the US Cystic Fibrosis Foundation. All authors had full access to the study data, and the corresponding author had the final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Introduction: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approximately 5% of people with CF have residual function (RF) CFTR mutations that result in partially retained CFTR activity. Published literature on disease trajectory among those with RF mutations is limited. In this retrospective study, we characterized lung function decline across different age groups in CFTR modulator-untreated people with CF heterozygous for F508del and an RF mutation (F/RF). Methods: Rate of decline in percent predicted forced expiratory volume in 1 s (ppFEV1) was analyzed using data from the US CF Foundation Patient Registry (2006–2014) in F/RF (all), F/RF (excluding R117H), and F508del homozygous (F/F) cohorts. Annual rates of ppFEV1 decline were estimated over 2-year periods based on calendar year. Subgroup analyses by age [6–12 (children), 13–17 (adolescents), 18–24 (young adults), and ≥ 25 years (adults)] were performed. Results: The estimated annualized rate of ppFEV1 decline was − 0.70 percentage points per year (95% CI −1.09, −0.30) in the F/RF (all) cohort (N = 1242) versus −1.91 percentage points per year (95% CI −2.01, −1.80) in the F/F cohort (N = 11,916) [difference, 1.29 percentage points per year (95% CI 0.88, 1.70); P < 0.001]. In the F/RF (all) cohort, all age groups demonstrated lung function decline ranging from −0.30 to −1.38. In the F/RF (excluding R117H) cohort, the rate of decline was −1.05 percentage points per year (95% CI −1.51, −0.60) [difference versus F/F cohort, 0.95 percentage points per year (95% CI 0.48, 1.41; P < 0.001); not statistically significant in children and young adults]. Conclusion: Progressive lung function decline was observed in people with F/RF genotypes across all assessed age groups, reinforcing the importance of early intervention and clinical monitoring to preserve lung function in all people with CF.
AB - Introduction: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approximately 5% of people with CF have residual function (RF) CFTR mutations that result in partially retained CFTR activity. Published literature on disease trajectory among those with RF mutations is limited. In this retrospective study, we characterized lung function decline across different age groups in CFTR modulator-untreated people with CF heterozygous for F508del and an RF mutation (F/RF). Methods: Rate of decline in percent predicted forced expiratory volume in 1 s (ppFEV1) was analyzed using data from the US CF Foundation Patient Registry (2006–2014) in F/RF (all), F/RF (excluding R117H), and F508del homozygous (F/F) cohorts. Annual rates of ppFEV1 decline were estimated over 2-year periods based on calendar year. Subgroup analyses by age [6–12 (children), 13–17 (adolescents), 18–24 (young adults), and ≥ 25 years (adults)] were performed. Results: The estimated annualized rate of ppFEV1 decline was − 0.70 percentage points per year (95% CI −1.09, −0.30) in the F/RF (all) cohort (N = 1242) versus −1.91 percentage points per year (95% CI −2.01, −1.80) in the F/F cohort (N = 11,916) [difference, 1.29 percentage points per year (95% CI 0.88, 1.70); P < 0.001]. In the F/RF (all) cohort, all age groups demonstrated lung function decline ranging from −0.30 to −1.38. In the F/RF (excluding R117H) cohort, the rate of decline was −1.05 percentage points per year (95% CI −1.51, −0.60) [difference versus F/F cohort, 0.95 percentage points per year (95% CI 0.48, 1.41; P < 0.001); not statistically significant in children and young adults]. Conclusion: Progressive lung function decline was observed in people with F/RF genotypes across all assessed age groups, reinforcing the importance of early intervention and clinical monitoring to preserve lung function in all people with CF.
KW - Cystic fibrosis
KW - F508del
KW - Lung function
KW - Lung function decline
KW - R117H
KW - Residual function
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U2 - 10.1007/s41030-022-00202-y
DO - 10.1007/s41030-022-00202-y
M3 - Article
AN - SCOPUS:85141136180
SN - 2364-1754
VL - 8
SP - 385
EP - 395
JO - Pulmonary Therapy
JF - Pulmonary Therapy
IS - 4
ER -