Frailty and Clinical Outcomes in Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Frailty represents an increased vulnerability to adverse health outcomes. The frailty phenotype conceptual model (three or more patient attributes of wasting, exhaustion, low activity, slowness, and weakness) is associated with increased morbidity and mortality in geriatric populations.

Objectives: Our objective was to describe the risks associated with frailty in patients with chronic obstructive pulmonary disease.

Methods: Data from the National Emphysema Treatment Trial (NETT) were retrospectively analyzed. The frailty phenotype conceptual model was operationalized as three or more frailty parameters (a body mass index decrease of ≥5% over 12 months, self-reported exhaustion, low 6-minute walk distance, or physical activity or respiratory muscle strength in the lowest quartile). Frail participants were compared with participants with two or fewer frailty parameters. Participants were followed starting 12 months after NETT randomization (to minimize surgical effect) for 24 months. Univariate, multivariate, Kaplan-Meier, and Cox proportional hazard analyses were performed, adjusting for treatment arm, age, modified Medical Research Council dyspnea scale, sex, and baseline forced expiratory volume in 1 second (FEV1). Multiple imputation was used for missing values.

Results: The participants (N = 902) were predominantly white (94.5%) males (59.5%), with a median age of 67 years (interquartile range, 63-70 yr) and a median FEV1% predicted of 26 (interquartile range, 20-33). Six percent of the participants (95% confidence interval [CI], 4.5 to 7.6) were frail. The incidence rate of frailty was 6.4 per 100 person-years. Frail participants reported significantly worse disease-specific and overall quality of life by St. George's Respiratory Questionnaire total score (mean difference of 11.6; 95% CI, 7.6 to 15.6; P < 0.001), mental composite on Medical Outcomes Survey Short Form-36 (mean difference -6.8; 95% CI, -10.0 to -3.6; P < 0.001), and physical composite scores on Medical Outcomes Survey Short Form-36 (mean difference -16.7; 95% CI, -21.3 to -12.1; P = 0.001). Frail participants had an increased rate of hospitalization (adjusted hazard ratio, 1.6; 95% CI, 1.1 to 2.5; P = 0.02) and an adjusted increase in hospital use of 8.0 days (95% CI, 4.4 to 11.6; P < 0.001) compared with nonfrail participants. Frail participants had a higher mortality rate (adjusted hazard ratio, 1.4; 95% CI, 0.97 to 2.0; P = 0.07).

Conclusions: Among adults with chronic obstructive pulmonary disease, our measure of frailty (modified from the Fried frailty phenotype) was associated with incident and longer-duration hospitalization, and with poor quality of life.

Keywords: COPD; frailty; hospitalizations; quality of life; survival.

Figures

Figure 1.

Frailty phenotype in chronic obstructive pulmonary disease (COPD). “Frail” was defined as the presence of three or more of the following parameters: wasting, exhaustion, low physical activity, slowness, or weakness. Participants with one or two parameters present were “prefrail” and those with none were “nonfrail/normal.” Wasting was defined as a decline in body mass index (BMI) of ≥5% over the past year. Exhaustion was defined as feeling worn out “all” or “most” of the time in the past 4 weeks. Low physical activity was defined as 173 cm for men; >159 cm for women). Weakness was defined as a maximal inspiratory pressure (MIP)

Figure 2.

Kaplan-Meier curves for time to death stratified by the frailty phenotype. The curves demonstrate survival of normal (solid green line), prefrail (dashed blue line), and frail (dotted red line) participants. CI = confidence interval; HR = hazard ratio.

Figure 3.

Cumulative incidence of time to first hospitalization stratified by the presence or absence of the frailty phenotype. The curves demonstrate time to first hospitalization for normal (solid green line), prefrail (dashed blue line), and frail (dotted red line) participants. CI = confidence interval; HR = hazard ratio; NE = not evaluable.