TY - JOUR
T1 - Understanding the natural progression in %FEV1 decline in patients with cystic fibrosis
T2 - A longitudinal study
AU - Taylor-Robinson, David
AU - Whitehead, Margaret
AU - Diderichsen, Finn
AU - Olesen, Hanne Vebert
AU - Pressler, Tania
AU - Smyth, Rosalind L.
AU - Diggle, Peter
PY - 2012/10
Y1 - 2012/10
N2 - Background: Forced expiratory volume in 1 s as a percentage of predicted (%FEV1) is a key outcome in cystic fibrosis (CF) and other lung diseases. As people with CF survive for longer periods, new methods are required to understand the way %FEV1 changes over time. An up to date approach for longitudinal modelling of %FEV1 is presented and applied to a unique CF dataset to demonstrate its utility at the clinical and population level. Methods and findings: The Danish CF register contains 70 448%FEV1 measures on 479 patients seen monthly between 1969 and 2010. The variability in the data is partitioned into three components (between patient, within patient and measurement error) using the empirical variogram. Then a linear mixed effects model is developed to explore factors influencing %FEV1 in this population. Lung function measures are correlated for over 15 years. A baseline %FEV1 value explains 63% of the variability in %FEV1 at 1 year, 40% at 3 years, and about 30% at 5 years. The model output smooths out the short-term variability in %FEV1 (SD 6.3%), aiding clinical interpretation of changes in %FEV1. At the population level significant effects of birth cohort, pancreatic status and Pseudomonas aeruginosa infection status on %FEV1 are shown over time. Conclusions: This approach provides a more realistic estimate of the %FEV1 trajectory of people with chronic lung disease by acknowledging the imprecision in individual measurements and the correlation structure of repeated measurements on the same individual over time. This method has applications for clinicians in assessing prognosis and the need for treatment intensification, and for use in clinical trials.
AB - Background: Forced expiratory volume in 1 s as a percentage of predicted (%FEV1) is a key outcome in cystic fibrosis (CF) and other lung diseases. As people with CF survive for longer periods, new methods are required to understand the way %FEV1 changes over time. An up to date approach for longitudinal modelling of %FEV1 is presented and applied to a unique CF dataset to demonstrate its utility at the clinical and population level. Methods and findings: The Danish CF register contains 70 448%FEV1 measures on 479 patients seen monthly between 1969 and 2010. The variability in the data is partitioned into three components (between patient, within patient and measurement error) using the empirical variogram. Then a linear mixed effects model is developed to explore factors influencing %FEV1 in this population. Lung function measures are correlated for over 15 years. A baseline %FEV1 value explains 63% of the variability in %FEV1 at 1 year, 40% at 3 years, and about 30% at 5 years. The model output smooths out the short-term variability in %FEV1 (SD 6.3%), aiding clinical interpretation of changes in %FEV1. At the population level significant effects of birth cohort, pancreatic status and Pseudomonas aeruginosa infection status on %FEV1 are shown over time. Conclusions: This approach provides a more realistic estimate of the %FEV1 trajectory of people with chronic lung disease by acknowledging the imprecision in individual measurements and the correlation structure of repeated measurements on the same individual over time. This method has applications for clinicians in assessing prognosis and the need for treatment intensification, and for use in clinical trials.
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U2 - 10.1136/thoraxjnl-2011-200953
DO - 10.1136/thoraxjnl-2011-200953
M3 - Article
C2 - 22555277
AN - SCOPUS:84866120215
SN - 0040-6376
VL - 67
SP - 860
EP - 866
JO - Thorax
JF - Thorax
IS - 10
ER -