Elsevier

Annals of Epidemiology

Volume 20, Issue 3, March 2010, Pages 223-232
Annals of Epidemiology

Predictors of Mortality in Elderly Subjects with Obstructive Airway Disease: The PILE Score

https://doi.org/10.1016/j.annepidem.2009.11.005Get rights and content

Purpose

To identify significant covariates in addition to spirometry that predict mortality in elderly subjects with obstructive airway disease (OAD).

Methods

Two hundred sixty-eight (268) participants with OAD from the Health, Aging and Body Composition study, a community-based observational cohort of well-functioning elderly aged 70-79 years, were followed on average for 6.1 years. Covariates related to pulmonary and physical function, comorbidity, demographics, and three inflammatory markers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein) were evaluated for their association with all-cause mortality (31%) by means of Kaplan Meier analysis and Cox proportional hazards modeling.

Results

Percent predicted forced expiratory volume in one second (PPFEV1; hazard ratio [HR] = 2.03, p < 0.0001), knee extensor strength (HR = 1.36, p = 0.0002), interleukin-6 (HR = 1.37, p = 0.0002) and 400 m corridor walk time (HR = 1.24, p = 0.008) significantly predicted mortality. A multidimensional index, the PILE score, was constructed from PPFEV1, interleukin-6, and knee extensor strength. Each one-point increase in PILE score (range: 1-10) was associated with a 30% increase in mortality (95% confidence interval: 0.16-0.47) after adjusting for age, race, gender, smoking, and comorbidity, resulting in a 10.4-fold higher risk of death between the highest and lowest risk category.

Conclusions

Subjects with OAD have a wide gradient of risk for mortality that can potentially be incorporated in clinical decision making.

Introduction

Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the United States (1). Percent predicted forced expiratory volume in 1 second (PPFEV1) is the major prognostic variable used to grade disease severity and predict risk of death in COPD patients, but it fails to capture important systemic manifestations of the disease 2, 3. Thus it has only limited predictive power for mortality in COPD patients. Celli et al. (4) introduced a multidimensional index, the BODE index, that includes not only PPFEV1 (as a measure of airway obstruction, O), but also three other markers of disease severity: body mass index (B), dyspnea (D), and exercise capacity (E). The BODE index was shown to be better than PPFEV1 alone at predicting all-cause and respiratory mortality among patients with COPD. The BODE index highlights that the prognostic assessment of COPD patients should include factors other than lung function 4, 5.

Since then, several composite indices have been reported to predict mortality in COPD patients. These include the CPI (COPD Prognostic Index) (6), the DOSE index (Dyspnea, airflow Obstruction, Smoking status, Exacerbation frequency) (7), and the ADO index (Age, Dyspnea, airflow Obstruction) (8). The CPI was developed from a data set of more than 8,000 patients and was shown to predict COPD exacerbations and hospital episodes in addition to mortality. This index, however, is difficult to construct in routine clinical settings as it comprises seven variables. Moreover, the CPI does not include variables which capture the systemic manifestations of COPD, such as loss in endurance and strength. The DOSE index has the advantage of being simple and not requiring any specialized test or equipment other than a spirometer to capture its variables. The DOSE index, however, also does not fully capture the systemic manifestations of COPD and was not compared to the already established BODE index. The ADO index has only three variables and thus is easy to construct; it was compared with the BODE index and was found to be superior in predicting mortality in COPD patients in two different European cohorts, but the authors caution that different protocols were used for assessing the respective variables. In summary, it is important to note that (a) all the above indices were developed in COPD patients and (b) none of them included markers of systemic inflammation.

The Health, Aging and Body Composition Study (Health ABC) is a prospective community-based observational cohort study in well-functioning elderly (9). In this article we explore the validity of the BODE index in Health ABC participants with obstructive airway disease (OAD), examine the role of other covariates associated with airway obstruction in predicting mortality, and develop a multivariate model (the PILE score) to predict all-cause mortality in this population.

Section snippets

Study Population

Health ABC is a longitudinal study of 3,075 well-functioning individuals (50% men; 40% black), 70 to 79 years of age, residing in Pittsburgh, Pennsylvania and Memphis, Tennessee (10). Participants were included if they reported no difficulty walking a quarter mile, climbing 10 steps without resting, or performing basic activities of daily living. Exclusion criteria included any life-threatening condition, participation in any research study involving medications or modification of eating or

Results

Survivors and non-survivors differed significantly in PPFEV1, IL-6 concentration, knee extensor strength, and LDCW (Table 1). There was also a significant gender difference, with 41% deaths in men compared to only 18% deaths in women.

Kaplan-Meier and univariate Cox proportional hazards analysis both indicate that all-cause mortality in the study participants was significantly predicted by PPFEV1 (HR = 2.03, p < 0.0001), knee extensor strength (HR = 1.36, p = 0.0002), IL-6 concentration (HR =

Discussion

PPFEV1 is an important health indicator that has been associated with disease progression and mortality in pulmonary and extrapulmonary conditions 25, 26, 27, 28. It has been recognized, however, that a single measurement of PPFEV1 incompletely reflects the complex clinical consequences of COPD and its systemic manifestations 4, 16. In the present analysis, we used mortality over a 6-year period among Health ABC participants with OAD to investigate non-spirometric predictors of mortality

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