American Journal of Respiratory and Critical Care Medicine
The Pulmonary Medicine Journal Scan is the clinician's guide to the latest clinical research findings in The American Journal of Respiratory and Critical Care Medicine, Annals of Allergy, Asthma, and Immunology, the Journal of Allergy and Clinical Immunology, and other important journals. Short summaries of feature articles include links to the article abstracts when available. (Access to full-text articles usually requires registration at the specific journal's Web site.)
Predictors of Mortality in Patients With Emphysema and Severe Airflow Obstruction
Martinez FJ, Foster G, Curtis JL, et al
American Journal of Respiratory and Critical Care Medicine. 2006:173;1326-1334
The ability to predict mortality of patients with advanced chronic obstructive pulmonary disease (COPD) remains imprecise. There have been multiple factors that have been described as influencing survival, including the forced expiratory volume in one second (FEV1), inspiratory capacity (IC) (and its ratio to the total lung capacity [TLC]), the diffusing capacity (DLco), hypoxemia, hypercapnia, impaired exercise capacity, sex, body mass index, health status, dyspnea, and hospitalizations.
The National Emphysema Treatment Trial (NETT) has facilitated the prospective monitoring of the clinical course of a large group of patients in the placebo arm of the study. This study is a report of the prognosis of 609 of these patients and the factors influencing their survival. It is important to be aware of the inclusion criteria of the NETT and the influence and perhaps bias resulting from this. For example, patients had to have a TLC predicted > 100% and a residual volume (RV) > 150%, as well as an FEV1 between 15% and 45% of predicted. Some of the baseline demographics of the group included a mean age of 66.7 years, an FEV1 of 26.7%, and a DLco of 28.4% with a 6-minute walk distance of 372 meters. The median follow-up time was 3.9 years with an observed mortality rate of 12.7 per 100 person-years. The following factors were associated with survival in univariate analyses: greater age, lower BMI, oxygen utilization, lower hemoglobin, impaired quality-of-life measures, higher dyspnea scores, lower FEV1, higher residual volume, lower IC/TLC ratio, lower DLco% predicted, lower PaO2, higher PaCO2, lower 6-minute walk distance, lower maximal exercise capacity, more lower-lung zone emphysema, and a higher modified BODE index. Multivariate analysis honed this list down to just a few factors that remained predictive of mortality. These included age, oxygen utilization, TLC, RV, maximal wattage during cardiopulmonary exercise testing, the modified BODE index, hemoglobin, DLco% predicted, the difference in upper and lower lungs in % emphysema and the perfusion ratio of upper to lower lung zones. The factors with the highest hazard ratios (HR) were age and difference in % emphysema between the upper and lower lung zones (HRs of 1.64 and 1.74, respectively).
There are a number of interesting take-home messages from this study, of which I will highlight a few. First, the importance of hyperinflation was underscored with a higher RV and a trend to the IC/TLC ratio as predictors of survival on multivariate analysis. The utility of a composite index in the form of the BODE was confirmed (albeit a modified version of this index based on the use of another measure of the "D" [dyspnea] component).
The FEV1 did not withstand the scrutiny of a multivariate analysis as an independent predictor of survival. We have historically relied on the FEV1 as the physiologic "gold standard" of disease severity. There have been a number of recent publications that have cast dispersions on the utility of the FEV1 in this regard, and yet our definition of disease severity still relies on the FEV1. In fairness, the relatively narrow range of the FEV1 included in this study probably had something to do with the performance of this parameter as a predictor of outcomes. This clustering of disease severity also probably explains why overall percentage of emphysema was not predictive of mortality in either univariate or multivariate analysis. However, the distribution of emphysema did pop out as one of the most predictive factors with better outcomes for patients in whom there was greater emphysema in the upper lobes compared with the lower lobes. This raises the issue of whether lung morphology better defines disease severity and subsets of patients who are more likely to respond to various therapies. This is a hot area at the moment as multidetector CT scanning techniques evolve rapidly in their sophistication, resolution, and reconstructive abilities.
References
Oga T, Nishimura K, Tsukino M, et al. Analysis of the factors related to mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:544-549.
Nishimura K, Izumi T, Tsukino M, et al. Dyspnea Is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002;121:1434-1440.
Schols AM, Slangen J, Volovics L, et al. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:1791-1797.
Gray-Donald K, Gibbons L, Shapiro SH, et al. Nutritional status and mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;153:961-966.
Landbo C, Prescott E, Lange P, et al. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1856-1861.
Connors AF, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med. 1996;154:959-967.
Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest. 2003;124:459-467.
Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:1105-1012.
Reilly J. Using computed tomographic scanning to advance understanding of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:450-455.
Abstract
http://www.medscape.com/medline/abstract/16543549