The factor calculated is percent probability of death from idiopathic pulmonary fibrosis (IPF).
Measured Factor Disease
- Idiopathic pulmonary fibrosis I risk of mortality
Measured Factor Detail
The factor is a predicted risk of mortality calculated through a scoring system. It is based on four risk factors including age, respiratory hospitalization, percent predicted FVC, and 24 week change in percent predicted FVC. The prediction can serve as a guide for clinical management. It may be used in assessing the need for lung trasplantation and intensive treatments.
Sum of individual level of risk factors indicating a percent probability of death.
Measured Factor Low Impact
- A score of 0-4 indicates a one year probability of death <2% I High scores result in higher percent probability of death.
Measured Factor High Impact
- A score of >50 points indicates a one year probability of death >80%.
- Critical Low: 0%
- Critical High: 80%
- Normal: 0% is indicative of least percent risk of mortality. This scoring system is used for patients with IPF.
- Normal Adult Male: 0%
- Normal Adult Female: 0%
- Normal Geriatric Male: 0%
- Normal Geriatric Female: 0%
Result High Conditions
- IPF I Urgency for lung transplant I Death
- The scoring system overestimates mortality risk by less than 2% I There are no specified factors that may result in a false positive.
One limitation of the du Bois score includes the fact that survival is a less clinically useful outcome as opposed to pre-mortality measures such as disease progression. Additionally, it lacks strength in prediction accuracy as it does not consider co-morbidities or acute exacerbations. The du Bois score also does not consider biological variables such as reliable biomarkers of lung disease or damage. In addition, the study upon which the scoring system was established suggests that the generalizability and application of the system to patient populations excluded from the trial population, like patients with severe emphysema, is unknown. It also states that additional research is needed to validate the accuracy and application of the scoring system.
Study Validation 1
A study was conducted to assess the reliability, validity, and responsiveness of FVC as a measure of IPF in addtion to the minimally clinically important difference. FVC is a factor used in determining risk of mortality using the du Bois scoring system. The experiment included 1,156 randomized patients in two clinical trials testing the biologic IFN-y1b. Reliability was measured based on two different FVC readings. Validity was assessed by comparing FVC with other measurements of lung function. Responsiveness was measured through a longitudinal comparision of FVC over 24 weeks in comparison to other measures of function. The result of this study indicate that FVC is a reliable, valid, and responsive measure of lung function for those with IPF. A one year risk of death was observed to be twofold higher in patients with a 24 week decline in FVC between 5-10% (hazard ratio, 2.14; 95% Cl, 1.43-3.20; P<0.001). Some study limitations include a small sample of 91 patients in measuring reliability of percent predicted FVC. Additionally, analysis of responsiveness utilized all randomized patients instead of those in the placebo arm exclusively due to lack of evidence showing treatment effects. The larger sample size also enhances the power of the study. Finally, all patients enrolled in the study had mild to moderate IPF and those who were deemed too ill were excluded.
Study Validation 2
A longitudinal, observational study compared the du Bois scoring system to the GAP index when identifying high risk patients with IPF. The GAP index is a four point scoring system which considers the following four factors: gender, age, predicted FVC, and predicted diffusing capacity of the lung for carbon monoxide (DLCO). The scoring systems were assessed for superiority using area under the receiver operator characterisitic curve (AUC). A small sample of 101 participants was used retrospectively and followed for up to 3 years or until death. AUC calculated for prediction of one year mortality was 0.78 for teh du Bois score and 0.73 for the GAP index. After 3 years, both systems had a calculated AUC of 0.73. The study suggests that there is no significant difference between teh scores for either outcome (P=0.5 and P=0.9) and that both are of equal value when identifying patients with high risk mortality. This study is limited by sample size.
Study Validation 3
A review discusses the proposed clinical prediction models of IPF and the challenges faced in predicting survival. Respiratory failure is the most frequent cause of death for those with IPF. Increasing age and frequent hospitalizations, factors considered in the du Bois scoring system, were both associated with IPF related deaths. However, comorbidities such as ischemic heart diesase, emphysema, infection, and pulmonary embolsim are also causes of mortality. Comorbidities are not considered in the du Bois scoring system. The six to twelve month changes in FVC and difffusing capacity of the lung for carbon monoxide are highly predictive outcomes. The review suggests that while FVC may be the most appropriate tool, prognosis will best be determined using a multidisciplinary approach.
Study Additional 1
This study was aimed to assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. The study concluded that 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF.
Study Additional 2
Forced Vital Capacity relates to mortality in idiopathic pulmonary fibrosis (IPF), a chronic, progressive, and ultimately fatal parenchymal lung disease important both clinically and to the current drug development paradigm. The aim of the study was to validate and further characterize FVC decline, acute exacerbations, and previously identified baseline predictors as they relate to risk of death. A total of 1,132 placebo subjects from six studies used for the clinical development of nintedanib and pirfenidone for the treatment of IPF were included in the present analysis. Deaths were captured as all-cause mortality. A stratified Cox proportional hazards model was used to test the association between baseline predictors, decline in FVC % predicted from baseline, acute exacerbations, and death. The study signifies the importance of baseline FVC, diffusing capacity of the lung for carbon monoxide, age, and smoking status as predictors of mortality and strengthens the association between decline in FVC and exacerbations with death, verifying a decline in FVC as an appropriate endpoint in IPF drug development.
Study Additional 3
Idiopathic pulmonary fibrosis is a diffuse parenchymal lung disease of unknown cause. The natural history of disease can vary considerably, making it difficult to predict the clinical trajectory for an individual patient. Accurate prognostication is desirable for clinical management as well as for cohort enrichment in clinical trials of therapeutics. Clinical and biomarker models of disease behavior have been developed to improve prognostication in idiopathic pulmonary fibrosis, with moderate predictive capabilities. Integrated prediction models that combine both clinical and biomarker variables will improve prognostication for patients and improved cohort enrichment strategies for clinical trials.