Longitudinal Change in the BODE Index Predicts Mortality in Severe Emphysema

Abstract

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. Conclusions:The mBODE demonstrates short-and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Pharmacological actions of statins: potential utility in COPD

“…It has also been proposed that high levels of cytokines (primarily IL-6), inflammatory mediators and/or ROS in the systemic circulation, derived in a large part from the pulmonary circulation (the ''spill over'' effect) [4,7], may lead to muscle wasting and decreased muscle function [17][18][19][20][21][22]. Apoptosis has also been implicated in muscle wasting, as seen in COPD patients [18,19], and may be important in survival [19][20][21][22].…”

“…Apoptosis has also been implicated in muscle wasting, as seen in COPD patients [18,19], and may be important in survival [19][20][21][22]. Collectively, smoking appears to incite an inflammatory response and high oxidant load that, over time, prematurely ages the body [23] through lung destruction (emphysema), poor elastic recoil of tissues (reduced airway compliance), maladaptive or excessive healing (airway fibrosis), and wasting of skeletal and respiratory muscles resulting in poor exercise tolerance.…”

“…This limitation of physical activity is not in keeping with airflow limitation (FEV1) and has been attributed to the combined effects of elevated oxidative stress and IL-6, i.e. another systemic inflammation based comorbidity [7,[17][18][19][20][21][22]. In the only RCT of statin therapy in COPD, statin use was associated with a 54% increase in exercise tolerance [111].…”

“…In particular, if statins reduce the release of IL-8 in the lungs of COPD patients, then attenuation of neutrophilic inflammation could have considerable downstream effects, such as reduced inflammatory cells in the lungs [81] and reduced remodelling of lung tissue to restore elastin content relative to collagen. If statins reduce the oxidant burden in the systemic circulation [87,88] and the catabolic state conferred by IL-6 release, then wasting and respiratory muscle function might be improved [21,22,87,88]. It is interesting to note that the inhibitory effect of statins in hepatocytes in blocking cholesterol synthesis might also block cytokine production (primarily IL-6), underlying the premature aging and associated morbidities from smoking-induced systemic inflammation [21].…”

Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease

“…BODE scores were categorized as class 1 (score: 0 to 2), class 2 (score: 3 to 4), class 3 (score: 5 to 6), or class 4 (score: 7 to 10) (21). Each patient's BODE was classified as being decreased (≥1 point), stable, or increased (≥1 point) based on its absolute change from baseline, as reported by Martinez et al (22). Data on comorbidities were collected from the patients' medical records and quantified according to the Charlson index (23).…”