Effects of Gender and Age of Diagnosis on Disease Progression in Long-term Cystic Fibrosis Survivors

Am J Respir Crit Care Med. 2010 May 6.

Effects of Gender and Age of Diagnosis on Disease Progression in Long-term Cystic Fibrosis Survivors.

Nick JA, Chacon CS, Brayshaw SJ, Jones MC, Barboa CM, St Clair CG, Young RL, Nichols DP, Janssen JS, Huitt GA, Iseman MD, Daley CL, Taylor-Cousar JL, Accurso FJ, Saavedra MT, Sontag MK.

Department of Medicine, National Jewish Health, Denver, Colorado, United States; Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, United States.
Abstract

RATIONALE: Long-term CF survivors (age >40 years) are a growing population comprised of both patients diagnosed with classic manifestations in childhood, and non-classic phenotypes typically diagnosed as adults. Little is known concerning disease progression and outcomes in these cohorts.

OBJECTIVES: Examine effects of age at diagnosis and gender on disease progression, setting of care, response to treatment, and mortality in long-term CF survivors.

METHODS: Retrospective analysis of the Colorado CF database (1992-2008), CF Foundation Registry (1992-2007), and Multiple Cause of Death Index (1992-2005).

MEASUREMENTS AND MAIN RESULTS: CF patients diagnosed in childhood that survive to age 40 have more severe CFTR genotypes and phenotypes compared to adult diagnosed patients. However, past age 40 the rate of FEV1 decline and death from respiratory complications were not different between these cohorts. Compared to males, childhood diagnosed females were less likely to reach age 40, experienced faster FEV1 declines, and no survival advantage. Females comprised the majority of adult diagnosed patients, and demonstrated equal FEV1 decline and longer survival than males, despite a later age of diagnosis. Most adult diagnosed patients were not followed at CF Centers, and with increasing age a smaller percentage of CF deaths appeared in the CFF Registry. However, newly diagnosed adults demonstrated sustained FEV1 improvement in response to CF Center care.

CONCLUSIONS: For CF patients older than 40, the adult diagnosis correlates with delayed but equally severe pulmonary disease. A gender-associated disadvantage remains for females diagnosed in childhood, but is not present for adult diagnosed females.

Diabetes Care. 2009 Nov 16. [Epub ahead of print]

Diabetes as a Determinant of Mortality in Cystic Fibrosis.

Chamnan P, Shine BS, Haworth CS, Bilton D, Adler AI.

1. MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge.

Background: Diabetes is increasingly common in cystic fibrosis (CF), but little exists describing its influence on mortality. Using national UK data, this study documents diabetes-specific mortality rates, estimates the impact of diabetes on survival, and estimates population attributable fractions.

Methods: This retrospective cohort study identified 8,029 individuals aged 0-65 years from the UK CF Registry (1996-2005). 5,892 patients were included in analyses of mortality rates and 4,234 in analyses of risk factors. We calculated age-adjusted mortality rates using Poisson regression, standardized mortality ratios using the population of England and Wales, and relative risks using proportional hazards modeling.

Findings: During 17,672 person-years of follow-up, 393 subjects died. The age-adjusted mortality rate was 1.8/100 person-years (95% CI 1.6 to 2.0).

The age-adjusted mortality rates per 100 person-years were 2.0 (CI 1.8 to 2.4) in women and 1.6 (95% CI 1.4 to 1.9) in males, and 4.2 (95% CI 3.4-5.1) in individuals with diabetes vs 1.5 (95% CI 1.3 to 1.7) in those without diabetes.

Independent risk factors for death included diabetes (hazard ratio, 95% confidence interval, 1.31 (1.03 to 1.67), female sex (1.71, 1.36 to 2.14) plus poorer pulmonary function, lower body mass index, B. cepacia infection, absence of S. aureus infection, allergic bronchopulmonary aspergillosis, liver disease, prior organ transplantation, and corticosteroid use.

Interpretation: Individuals with CF die earlier with diabetes, which, if delayed or better treated, might reasonably extend survival, and merits testing.

PMID: 19918014 [PubMed - as supplied by publisher]