Final published version
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Explaining the sex effect on survival in cystic fibrosis
T2 - A joint modeling study of UK registry data
AU - Taylor-Robinson, D.
AU - Schlüter, D.K.
AU - Diggle, P.J.
AU - Barrett, J.K.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Background: Male sex is associated with better lung function and survival in people with cystic fibrosis but it is unclear whether the survival benefit is solely due to the sex-effect on lung function. Methods: This study analyzes data between 1996 and 2015 from the longitudinal registry study of the UK Cystic Fibrosis Registry. We jointly analyze repeated measurements and time-to-event outcomes to assess how much of the sex effect on lung function also explains survival. These novel methods allow examination of association between percent of forced expiratory volume in 1 second (%FEV1) and covariates such as sex and genotype, and survival, in the same modeling framework. We estimate the probability of surviving one more year with a probit model. Results: The dataset includes 81,129 lung function measurements of %FEV1 on 9,741 patients seen between 1996 and 2015 and captures 1,543 deaths. Males compared with females experienced a more gradual decline in %FEV1 (difference 0.11 per year 95% confidence interval [CI] = 0.08, 0.14). After adjusting for confounders, both overall level of %FEV1 and %FEV1 rate of change are associated with the concurrent hazard for death. There was evidence of a male survival advantage (probit coefficient 0.15; 95% CI = 0.10, 0.19) which changed little after adjustment for %FEV1 using conventional approaches but was attenuated by 37% on adjustment for %FEV1 level and slope in the joint model (0.09; 95% CI = 0.06, 0.12). Conclusions: We estimate that about 37% of the association of sex on survival in cystic fibrosis is mediated through lung function.
AB - Background: Male sex is associated with better lung function and survival in people with cystic fibrosis but it is unclear whether the survival benefit is solely due to the sex-effect on lung function. Methods: This study analyzes data between 1996 and 2015 from the longitudinal registry study of the UK Cystic Fibrosis Registry. We jointly analyze repeated measurements and time-to-event outcomes to assess how much of the sex effect on lung function also explains survival. These novel methods allow examination of association between percent of forced expiratory volume in 1 second (%FEV1) and covariates such as sex and genotype, and survival, in the same modeling framework. We estimate the probability of surviving one more year with a probit model. Results: The dataset includes 81,129 lung function measurements of %FEV1 on 9,741 patients seen between 1996 and 2015 and captures 1,543 deaths. Males compared with females experienced a more gradual decline in %FEV1 (difference 0.11 per year 95% confidence interval [CI] = 0.08, 0.14). After adjusting for confounders, both overall level of %FEV1 and %FEV1 rate of change are associated with the concurrent hazard for death. There was evidence of a male survival advantage (probit coefficient 0.15; 95% CI = 0.10, 0.19) which changed little after adjustment for %FEV1 using conventional approaches but was attenuated by 37% on adjustment for %FEV1 level and slope in the joint model (0.09; 95% CI = 0.06, 0.12). Conclusions: We estimate that about 37% of the association of sex on survival in cystic fibrosis is mediated through lung function.
KW - Cystic fibrosis
KW - Joint-modeling
KW - Registry
U2 - 10.1097/EDE.0000000000001248
DO - 10.1097/EDE.0000000000001248
M3 - Journal article
VL - 31
SP - 872
EP - 879
JO - Epidemiology
JF - Epidemiology
SN - 1044-3983
IS - 6
ER -