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EPS5.8 Dynamic prediction modeling to identify rapid lung function decline in cystic fibrosis
E-Poster Sessions / Journal of Cystic Fibrosis 16S1 (2017) S1–S62
Season
Spring Summer Autumn Winter
n
ARE FEV1% Mean (SD)
n
Best FEV1% Mean (SD)
1785 1996 2464 1494
73.47 (24.7) 73.34 (24.65) 72.35 (24.68) 73.63 (25.05)
1567 1449 1655 1418
77.70 (24.37) 77.69 (24.15) 78.53 (24.16) 77.35 (23.55)
[Seasonal variation in FEV1% for both ARE and best]
An ANOVA for ARE FEV1% across seasons and for best FEV1% showed no statistical differences. Jan vs July ARE FEV1% 74.36% vs. 72.79% again was not significant. Conclusion: best FEV% was 4.6% higher than Annual Review Encounter FEV1%, this is an important factor to take into account in any future comparisons of UK CF registry data with other countries. Unlike previous data neither ARE nor best FEV1% showed any statistically significance across the two seasonal indices, suggesting that time of year has negligible influence on reporting of FEV1 in the UK. EPS5.8 Dynamic prediction modeling to identify rapid lung function decline in cystic fibrosis R. Szczesniak1, W. Su2, R. Keogh3, J.P. Clancy4. 1Cincinnati Children’s Hospital Medical Centre, Cincinnati, United States; 2University of Cincinnati, Cincinnati, United States; 3London School of Hygiene and Tropical Medicine, London, United Kingdom; 4Cincinnati Children’s Hospital Medical Centre, Cincinnati, United States Objectives: To utilize a modern statistical approach, known as dynamic semiparametric regression, to forecast cystic fibrosis (CF) disease progression for more accurate, individualized prediction of the timing and degree of rapid lung function decline, and to compare model-based predictions with established clinical guidelines. Methods: We performed a longitudinal cohort study of the US CF Patient Registry (2003–2011) using clinical encounter level data from 27,296 “atrisk” patients aged 6 to 83 years with 619,960 FEV1 observations. Agerelated FEV1 progression was estimated using nonlinear components from regression splines, allowing estimation of individual rates of change through derivatives. Rapid decline was defined as rate of change falling below −1.5% predicted/year and compared to the clinical guideline of an absolute drop of at least 10% predicted within the previous year of observation. FEV1 variation was decomposed into distinct components reflecting between-subject variability, heterogeneity within subjects using a modern covariance function to depict the “saw-tooth” variation in longitudinal FEV1, and variation due to measurement error. Pertinent covariates were identified from previous literature. Results: Our model-based approach detected rapid decline an average (SD) of 2 (1.8) years earlier than the conventional approach used at the local CF center. Risk of rapid decline varied by age with periods of highest risk typically occurring between adolescence and early adulthood. Having higher initial FEV1, being male, having higher numbers of pulmonary exacerbations and clinic visits within the prior year, infection with Pa, having CF-related diabetes corresponded to earlier rapid decline (P < 0.001). Conclusion: Decision support tools based on modern statistical approaches are feasible for monitoring real-time lung function decline and improving personalized clinical management of CF patients. EPS5.9 The prevalence of obesity in Irish adults with cystic fibrosis: a registry study A.L. Dudina1, G. Fletcher1, C.G. Gallagher1, E.F. McKone1. 1St. Vincent’s University Hospital, National Referral Center for Adult Cystic Fibrosis, Dublin, Ireland Objectives: Subjects with cystic fibrosis (CF) are often malnourished and require high calorie diets. This diet may lead to an increase in overweight and obese CF subjects which can itself impair lung function [1]. The objectives were – to determine the prevalence of overweight and obesity in
S49
adults patients with CF and the relationship between body mass index (BMI) and lung function in CF adult subjects to determine if the positive relationship between nutritional status and lung function attenuate as obesity develops. Methods: The study was based on a retrospective analysis of the Cystic Fibrosis Patients Registry (CFPR) of Ireland which included 1,292 CF patients between 2009 and 2013. Data in the CFPR included age, gender, height, weight, BMI and lung function measures. BMI was calculated by using weight (in kg)/height (in cm). Four BMI groups were adopted (kg/ m2): underweight - less than 18.5; normal weight between 18.5 and 24.9; overweight - 25–29.9; obese - 30 and above. Results: Analysable data were available for 435 adults. The prevalence of increased BMI (BMI ≥ 25 kg/m2) was 13.8%; of these, 63 were overweight and 13 obese. We examined the association between BMI and predicted FEV1% in each BMI group, followed by adjustment for age and gender. The differences were statistically significant ( p < 0.000). Predicted FEV1% was lowest in the underweight group. Surprisingly, the highest lung function was in the overweight group. There was a statistical trend for lower lung function in the obese CF group. Conclusion: Overweight but not obese CF subjects have the best lung function. More studies need for the possible recognition for being overweight as a protective role for the lung function. Conversely, overweight might reflect milder disease status. The trend towards reduced lung function in the obese subjects requires larger numbers for verification.
Reference [1] Salome CM KG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol. 2010;108:206–11. EPS5.10 Real-world outcomes in patients ( pts) with cystic fibrosis (CF) treated with ivacaftor (IVA): analysis of 2015 US and UK CF registry data L. Bessonova1, N. Volkova1, M. Higgins2, L. Bengtsson1, S. Tian1, C. Simard1, A. Sewall3, S.O. Nyangoma4, A. Elbert5, D. Bilton4,6. 1Vertex Pharmaceuticals Incorporated, Boston, United States; 2Vertex Pharmaceuticals (Europe) Limited, London, United Kingdom; 3Sewall Inc., Bethesda, United States; 4 Imperial College London, London, United Kingdom; 5US CF Foundation, Bethesda, United States; 6UK CF Registry, London, United Kingdom Objectives: Pts treated with IVA in a real-world setting were evaluated using US and UK CF registry data as part of an ongoing, long-term, postapproval observational safety study. Here we present analyses of the 2015 data. Methods: Risks of key clinical outcomes (death, transplantation, hospitalization, and pulmonary exacerbation [PEx]) were compared between all pts in the registries treated with IVA in 2015 and comparator (COMP) pts who never received IVA matched on age, sex, and genotype severity (eg, G551D mutation IVA pts were primarily matched to pts homozygous for F508del ineligible for IVA therapy). Prevalence of CF complications and pulmonary microorganisms were also evaluated. Results: Analyses included 1727 IVA and 7329 COMP pts from the US registry; and 432 IVA and 2201 COMP pts from the UK registry. In the US, risks of death, hospitalization, and PEx were significantly lower in IVA than in COMP pts, and risk of transplantation was numerically lower (Table). Trends were similar in the UK. In both registries, the prevalence of the majority of evaluated CF complications (eg, CF-related diabetes, hepatobiliary, bone/joint, gastrointestinal) and common bacterial pathogens (eg, P. aeruginosa, Aspergillus, S. aureus) tended to be lower in IVA pts. Table.
US CF Registry Outcome
IVA n (%)
COMP n (%)
Relative Risk
UK CF Registry IVA n (%)
(95% CI)
COMP n
Relative Risk
(%)
(95% CI)
Death
5 (0.3)
117 (1.6)
0.18 (0.07, 0.44)
4 (0.9)
27 (1.2)
Transplantation
9 (0.5)
70 (1.0)
0.55 (0.27, 1.09)
0 (0.0)
19 (0.9)
0.75 (0.27, 2.15)
Hospitalization
411 (23.8)
2641 (36.0)
0.66 (0.60, 0.72)
118 (27.3)
967 (43.9)
0.62 (0.53, 0.73)
PEx
413 (23.9)
2523 (34.4)
0.69 (0.63, 0.76)
145 (33.6)
1205 (54.8)
0.61 (0.53, 0.70)
—
Season
Spring Summer Autumn Winter
n
ARE FEV1% Mean (SD)
n
Best FEV1% Mean (SD)
1785 1996 2464 1494
73.47 (24.7) 73.34 (24.65) 72.35 (24.68) 73.63 (25.05)
1567 1449 1655 1418
77.70 (24.37) 77.69 (24.15) 78.53 (24.16) 77.35 (23.55)
[Seasonal variation in FEV1% for both ARE and best]
An ANOVA for ARE FEV1% across seasons and for best FEV1% showed no statistical differences. Jan vs July ARE FEV1% 74.36% vs. 72.79% again was not significant. Conclusion: best FEV% was 4.6% higher than Annual Review Encounter FEV1%, this is an important factor to take into account in any future comparisons of UK CF registry data with other countries. Unlike previous data neither ARE nor best FEV1% showed any statistically significance across the two seasonal indices, suggesting that time of year has negligible influence on reporting of FEV1 in the UK. EPS5.8 Dynamic prediction modeling to identify rapid lung function decline in cystic fibrosis R. Szczesniak1, W. Su2, R. Keogh3, J.P. Clancy4. 1Cincinnati Children’s Hospital Medical Centre, Cincinnati, United States; 2University of Cincinnati, Cincinnati, United States; 3London School of Hygiene and Tropical Medicine, London, United Kingdom; 4Cincinnati Children’s Hospital Medical Centre, Cincinnati, United States Objectives: To utilize a modern statistical approach, known as dynamic semiparametric regression, to forecast cystic fibrosis (CF) disease progression for more accurate, individualized prediction of the timing and degree of rapid lung function decline, and to compare model-based predictions with established clinical guidelines. Methods: We performed a longitudinal cohort study of the US CF Patient Registry (2003–2011) using clinical encounter level data from 27,296 “atrisk” patients aged 6 to 83 years with 619,960 FEV1 observations. Agerelated FEV1 progression was estimated using nonlinear components from regression splines, allowing estimation of individual rates of change through derivatives. Rapid decline was defined as rate of change falling below −1.5% predicted/year and compared to the clinical guideline of an absolute drop of at least 10% predicted within the previous year of observation. FEV1 variation was decomposed into distinct components reflecting between-subject variability, heterogeneity within subjects using a modern covariance function to depict the “saw-tooth” variation in longitudinal FEV1, and variation due to measurement error. Pertinent covariates were identified from previous literature. Results: Our model-based approach detected rapid decline an average (SD) of 2 (1.8) years earlier than the conventional approach used at the local CF center. Risk of rapid decline varied by age with periods of highest risk typically occurring between adolescence and early adulthood. Having higher initial FEV1, being male, having higher numbers of pulmonary exacerbations and clinic visits within the prior year, infection with Pa, having CF-related diabetes corresponded to earlier rapid decline (P < 0.001). Conclusion: Decision support tools based on modern statistical approaches are feasible for monitoring real-time lung function decline and improving personalized clinical management of CF patients. EPS5.9 The prevalence of obesity in Irish adults with cystic fibrosis: a registry study A.L. Dudina1, G. Fletcher1, C.G. Gallagher1, E.F. McKone1. 1St. Vincent’s University Hospital, National Referral Center for Adult Cystic Fibrosis, Dublin, Ireland Objectives: Subjects with cystic fibrosis (CF) are often malnourished and require high calorie diets. This diet may lead to an increase in overweight and obese CF subjects which can itself impair lung function [1]. The objectives were – to determine the prevalence of overweight and obesity in
S49
adults patients with CF and the relationship between body mass index (BMI) and lung function in CF adult subjects to determine if the positive relationship between nutritional status and lung function attenuate as obesity develops. Methods: The study was based on a retrospective analysis of the Cystic Fibrosis Patients Registry (CFPR) of Ireland which included 1,292 CF patients between 2009 and 2013. Data in the CFPR included age, gender, height, weight, BMI and lung function measures. BMI was calculated by using weight (in kg)/height (in cm). Four BMI groups were adopted (kg/ m2): underweight - less than 18.5; normal weight between 18.5 and 24.9; overweight - 25–29.9; obese - 30 and above. Results: Analysable data were available for 435 adults. The prevalence of increased BMI (BMI ≥ 25 kg/m2) was 13.8%; of these, 63 were overweight and 13 obese. We examined the association between BMI and predicted FEV1% in each BMI group, followed by adjustment for age and gender. The differences were statistically significant ( p < 0.000). Predicted FEV1% was lowest in the underweight group. Surprisingly, the highest lung function was in the overweight group. There was a statistical trend for lower lung function in the obese CF group. Conclusion: Overweight but not obese CF subjects have the best lung function. More studies need for the possible recognition for being overweight as a protective role for the lung function. Conversely, overweight might reflect milder disease status. The trend towards reduced lung function in the obese subjects requires larger numbers for verification.
Reference [1] Salome CM KG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol. 2010;108:206–11. EPS5.10 Real-world outcomes in patients ( pts) with cystic fibrosis (CF) treated with ivacaftor (IVA): analysis of 2015 US and UK CF registry data L. Bessonova1, N. Volkova1, M. Higgins2, L. Bengtsson1, S. Tian1, C. Simard1, A. Sewall3, S.O. Nyangoma4, A. Elbert5, D. Bilton4,6. 1Vertex Pharmaceuticals Incorporated, Boston, United States; 2Vertex Pharmaceuticals (Europe) Limited, London, United Kingdom; 3Sewall Inc., Bethesda, United States; 4 Imperial College London, London, United Kingdom; 5US CF Foundation, Bethesda, United States; 6UK CF Registry, London, United Kingdom Objectives: Pts treated with IVA in a real-world setting were evaluated using US and UK CF registry data as part of an ongoing, long-term, postapproval observational safety study. Here we present analyses of the 2015 data. Methods: Risks of key clinical outcomes (death, transplantation, hospitalization, and pulmonary exacerbation [PEx]) were compared between all pts in the registries treated with IVA in 2015 and comparator (COMP) pts who never received IVA matched on age, sex, and genotype severity (eg, G551D mutation IVA pts were primarily matched to pts homozygous for F508del ineligible for IVA therapy). Prevalence of CF complications and pulmonary microorganisms were also evaluated. Results: Analyses included 1727 IVA and 7329 COMP pts from the US registry; and 432 IVA and 2201 COMP pts from the UK registry. In the US, risks of death, hospitalization, and PEx were significantly lower in IVA than in COMP pts, and risk of transplantation was numerically lower (Table). Trends were similar in the UK. In both registries, the prevalence of the majority of evaluated CF complications (eg, CF-related diabetes, hepatobiliary, bone/joint, gastrointestinal) and common bacterial pathogens (eg, P. aeruginosa, Aspergillus, S. aureus) tended to be lower in IVA pts. Table.
US CF Registry Outcome
IVA n (%)
COMP n (%)
Relative Risk
UK CF Registry IVA n (%)
(95% CI)
COMP n
Relative Risk
(%)
(95% CI)
Death
5 (0.3)
117 (1.6)
0.18 (0.07, 0.44)
4 (0.9)
27 (1.2)
Transplantation
9 (0.5)
70 (1.0)
0.55 (0.27, 1.09)
0 (0.0)
19 (0.9)
0.75 (0.27, 2.15)
Hospitalization
411 (23.8)
2641 (36.0)
0.66 (0.60, 0.72)
118 (27.3)
967 (43.9)
0.62 (0.53, 0.73)
PEx
413 (23.9)
2523 (34.4)
0.69 (0.63, 0.76)
145 (33.6)
1205 (54.8)
0.61 (0.53, 0.70)
—