Explaining the Sex Effect on Survival in Cystic Fibrosis: a Joint Modeling Study of UK Registry Data

Overview

Journal Epidemiology

Specialty Public Health

Date 2020 Aug 26

PMID 32841985

Citations 2

Authors

David Taylor-Robinson

Daniela K Schluter

Peter J Diggle

Jessica K Barrett

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study.

Palma M, Keogh R, Carr S, Szczesniak R, Taylor-Robinson D, Wood A J Cyst Fibros. 2024; 23(5):936-942.

PMID: 38969604 PMC: 11409769. DOI: 10.1016/j.jcf.2024.05.013.

Ancel J, Launois C, Perotin J, Ravoninjatovo B, Mulette P, Hagenburg J Healthcare (Basel). 2022; 10(7).

PMID: 35885877 PMC: 9325027. DOI: 10.3390/healthcare10071351.

References

Barrett J, Diggle P, Henderson R, Taylor-Robinson D . Joint modelling of repeated measurements and time-to-event outcomes: flexible model specification and exact likelihood inference. J R Stat Soc Series B Stat Methodol. 2015; 77(1):131-148. PMC: 4384944. DOI: 10.1111/rssb.12060. View

Taylor-Robinson D, Whitehead M, Diderichsen F, Olesen H, Pressler T, Smyth R . Understanding the natural progression in %FEV1 decline in patients with cystic fibrosis: a longitudinal study. Thorax. 2012; 67(10):860-6. PMC: 3446776. DOI: 10.1136/thoraxjnl-2011-200953. View

Schluchter M, Piccorelli A . Shared parameter models for joint analysis of longitudinal and survival data with left truncation due to delayed entry - Applications to cystic fibrosis. Stat Methods Med Res. 2018; 28(5):1489-1507. PMC: 6456442. DOI: 10.1177/0962280218764193. View

Rosenfeld M, Emerson J, McNamara S, Thompson V, Ramsey B, Morgan W . Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort. J Cyst Fibros. 2012; 11(5):446-53. PMC: 4786375. DOI: 10.1016/j.jcf.2012.04.003. View

Kerem E, Reisman J, Corey M, Canny G, Levison H . Prediction of mortality in patients with cystic fibrosis. N Engl J Med. 1992; 326(18):1187-91. DOI: 10.1056/NEJM199204303261804. View

Barr H, Britton J, Smyth A, Fogarty A . Association between socioeconomic status, sex, and age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional study. BMJ. 2011; 343:d4662. PMC: 3160750. DOI: 10.1136/bmj.d4662. View

Keogh R, Seaman S, Barrett J, Taylor-Robinson D, Szczesniak R . Dynamic Prediction of Survival in Cystic Fibrosis: A Landmarking Analysis Using UK Patient Registry Data. Epidemiology. 2018; 30(1):29-37. PMC: 6276867. DOI: 10.1097/EDE.0000000000000920. View

Baron R, Kenny D . The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986; 51(6):1173-82. DOI: 10.1037//0022-3514.51.6.1173. View

Keogh R, Szczesniak R, Taylor-Robinson D, Bilton D . Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data. J Cyst Fibros. 2018; 17(2):218-227. PMC: 5885983. DOI: 10.1016/j.jcf.2017.11.019. View

10.

OConnor G, Quinton H, Kahn R, Robichaud P, Maddock J, Lever T . Case-mix adjustment for evaluation of mortality in cystic fibrosis. Pediatr Pulmonol. 2002; 33(2):99-105. DOI: 10.1002/ppul.10042. View

11.

Verma N, Bush A, Buchdahl R . Is there still a gender gap in cystic fibrosis?. Chest. 2005; 128(4):2824-34. DOI: 10.1378/chest.128.4.2824. View

12.

Rosenfeld M, Davis R, Fitzsimmons S, Pepe M, Ramsey B . Gender gap in cystic fibrosis mortality. Am J Epidemiol. 1997; 145(9):794-803. DOI: 10.1093/oxfordjournals.aje.a009172. View

13.

Quanjer P, Stanojevic S, Cole T, Baur X, Hall G, Culver B . Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012; 40(6):1324-43. PMC: 3786581. DOI: 10.1183/09031936.00080312. View

14.

Salvatore D, Buzzetti R, Baldo E, Furnari M, Lucidi V, Manunza D . An overview of international literature from cystic fibrosis registries. Part 4: update 2011. J Cyst Fibros. 2012; 11(6):480-93. DOI: 10.1016/j.jcf.2012.07.005. View

15.

McIntyre K . Gender and survival in cystic fibrosis. Curr Opin Pulm Med. 2013; 19(6):692-7. DOI: 10.1097/MCP.0b013e328365af49. View

16.

Stephenson A, Hux J, Tullis E, Austin P, Corey M, Ray J . Higher risk of hospitalization among females with cystic fibrosis. J Cyst Fibros. 2010; 10(2):93-9. DOI: 10.1016/j.jcf.2010.10.005. View

17.

Konstan M, Wagener J, VanDevanter D, Pasta D, Yegin A, Rasouliyan L . Risk factors for rate of decline in FEV1 in adults with cystic fibrosis. J Cyst Fibros. 2012; 11(5):405-11. PMC: 4086189. DOI: 10.1016/j.jcf.2012.03.009. View

18.

Taylor-Robinson D, Smyth R, Diggle P, Whitehead M . The effect of social deprivation on clinical outcomes and the use of treatments in the UK cystic fibrosis population: a longitudinal study. Lancet Respir Med. 2014; 1(2):121-8. PMC: 3878382. DOI: 10.1016/S2213-2600(13)70002-X. View

19.

Vandenbranden S, McMullen A, Schechter M, Pasta D, Michaelis R, Konstan M . Lung function decline from adolescence to young adulthood in cystic fibrosis. Pediatr Pulmonol. 2012; 47(2):135-43. PMC: 4219484. DOI: 10.1002/ppul.21526. View

20.

Konstan M, Morgan W, Butler S, Pasta D, Craib M, Silva S . Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr. 2007; 151(2):134-9, 139.e1. DOI: 10.1016/j.jpeds.2007.03.006. View