Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry

Garvin J Leung; Ting J Cho; Thomas Kovesi; Jemila S Hamid; Dhenuka Radhakrishnan

doi:10.1016/j.jcf.2019.06.007

Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry

J Cyst Fibros. 2020 Mar;19(2):255-261. doi: 10.1016/j.jcf.2019.06.007. Epub 2019 Jun 26.

Authors

Garvin J Leung¹, Ting J Cho², Thomas Kovesi³, Jemila S Hamid⁴, Dhenuka Radhakrishnan⁵

Affiliations

¹ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: garvin.leung@uottawa.ca.
² Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada.
³ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada; Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Electronic address: kovesi@cheo.on.ca.
⁴ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada. Electronic address: JeHamid@cheo.on.ca.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 5B2, Canada; Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Electronic address: dradhakrishnan@cheo.on.ca.

PMID: 31253541
DOI: 10.1016/j.jcf.2019.06.007

Abstract

Background: This study aimed to improve our understanding of the natural history of cystic fibrosis (CF) by comparing lung function and body mass index z-score (zBMI) between patients with different genotypes and identify a genotype with outcomes most comparable to homozygous ΔF508 patients.

Methods: Data was obtained from the Canadian CF Registry between January 1st 2007-January 1st 2016. Patients were categorized into one of five groups based on their genotype. A mixed-effects model was conducted with adjustments for age, sex, age of diagnosis, and baseline clinical measures.

Results: Among 2612 patients, those with non-mild forms of CF, and particularly adult patients with the same functional allele classification were found to have a lung function trajectory comparable to individuals with the homozygous ∆F508 genotype (annual change in percent predicted forced expiratory volume in 1 s of -0.83, 95% CI: -0.93, -0.73). The rates of zBMI change over the study period were not significantly different between the genotype groups.

Conclusion: This population-based study of Canadian CF patients provides adjusted rates of lung function decline and zBMI over ten years. The finding that there are different genotypes with comparable rates of lung function decline to patients of the homozygous ∆F508 group supports the use of multiple comparison groups to assess the long-term efficacy of emerging CF therapies.

Keywords: Body mass index; Cystic fibrosis; Epidemiology; Lung function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Body Mass Index
Canada / epidemiology
Child
Chloride Channel Agonists / therapeutic use
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Cystic Fibrosis* / diagnosis
Cystic Fibrosis* / drug therapy
Cystic Fibrosis* / epidemiology
Cystic Fibrosis* / physiopathology
Female
Genetic Association Studies
Homozygote
Humans
Male
Mutation
Nutritional Status*
Patient Acuity
Registries / statistics & numerical data
Respiratory Function Tests* / methods
Respiratory Function Tests* / statistics & numerical data
Severity of Illness Index
Treatment Outcome

Substances

Chloride Channel Agonists
Cystic Fibrosis Transmembrane Conductance Regulator