Chronic obstructive pulmonary disease (COPD) represents an increasing burden throughout the world. COPD-related mortality is probably underestimated because of the difficulties associated with identifying the precise cause of death. Respiratory failure is considered the major cause of death in advanced COPD. Comorbidities such as cardiovascular disease and lung cancer are also major causes and, in mild-to-moderate COPD, are the leading causes of mortality.The links between COPD and these conditions are not fully understood. However, a link through the inflammation pathway has been suggested, as persistent low-grade pulmonary and systemic inflammation, both known risk factors for cardiovascular disease and cancer, are present in COPD independent of cigarette smoking.Lung-specific measurements, such as forced expiratory volume in one second (FEV1), predict mortality in COPD and in the general population. However, composite tools, such as health-status measurements (e.g. St George's Respiratory Questionnaire) and the BODE index, which incorporates Body mass index, lung function (airflow Obstruction), Dyspnoea and Exercise capacity, predict mortality better than FEV1 alone. These multidimensional tools may be more valuable because, unlike predictive approaches based on single parameters, they can reflect the range of comorbidities and the complexity of underlying mechanisms associated with COPD.The current paper reviews the role of comorbidities in chronic obstructive pulmonary disease mortality, the putative underlying pathogenic link between chronic obstructive pulmonary disease and comorbid conditions (i.e. inflammation), and the tools used to predict chronic obstructive pulmonary disease mortality.

We recruited 985 patients with COPD but without hypoxemia or other serious disease, treated them in a standard fashion, and followed them closely for nearly 3 yr. At the time of recruitment the patients were carefully characterized as to symptom severity, lung function, exercise tolerance, and quality of life, and studies of lung function were repeated during follow-up. Overall mortality was 23% in 3 yr of follow-up. Patient age and the initial value of the FEV1 were the most accurate predictors of death; when FEV1 before bronchodilator was used, the response to bronchodilators was directly related to survival, but this relationship became nonsignificant when postbronchodilator FEV1 was used as a primary predictor. After adjustment for age and FEV1, mortality was related positively to TLC, resting heart rate, and perceived physical disability, and related negatively to exercise tolerance. These relationships, though significant, were relatively weak. When standardized for age and FEV1, mortality in the present series was less than that of a previous series (4), and the same as that of hypoxemic patients with COPD who received continuous home O2 therapy. Changes in FEV1 with time averaged -44 ml/yr, but the standard deviation was large. Patients with low initial values of FEV1 showed relatively little further decline, probably indicating a survivor effect. In patients with well-preserved initial FEV1, rate of decline correlated negatively with bronchodilator response, symptomatic wheezing, and psychological disturbances.

HRONIC OBSTRUCTIVE PULMOnary disease (COPD) affects more than 5% of the adult population, 1 and it is the only major cause of death in the United States in which morbidity and mortality are increasing. 2 Although COPD is currently the 4th-leading cause of mortality and the 12th-leading cause of disability, by the year 2020 it is estimated that COPD will be the 3rd-leading cause of death and the 5th-leading cause of disability worldwide. 3,4 In 1993, the total economic costs of COPD were estimated to be $24 billion in the United States alone; more than 60% of these costs were direct expenditures related to hospital-based care. 4 While these figures are alarming, they most certainly underestimate the true health burdens of COPD because airflow obstruction is an important contributor to other common causes of morbidity and mortality, including ischemic heart disease, stroke, pneumonia, and lung cancer. [5][6][7][8] Chronic obstructive pulmonary disease is characterized by irreversible airflow obstruction, secondary to airway inflammation and emphysema-Author Affiliations are listed at the end of this article.

Background: Although C-reactive protein (CRP) levels are increased in chronic obstructive pulmonary disease (COPD), it is not certain whether they are associated with adverse clinical outcomes. Methods: Serum CRP levels were measured in 4803 participants in the Lung Health Study with mild to moderate COPD. The risk of all-cause and disease specific causes of mortality was determined as well as cardiovascular event rates, adjusting for important covariates such as age, sex, cigarette smoking, and lung function. Cardiovascular events were defined as death from coronary heart disease or stroke, or nonfatal myocardial infarction or stroke requiring admission to hospital. Results: CRP levels were associated with all-cause, cardiovascular, and cancer specific causes of mortality. Individuals in the highest quintile of CRP had a relative risk (RR) for all-cause mortality of 1.79 (95% confidence interval (CI) 1.25 to 2.56) compared with those in the lowest quintile of CRP. For cardiovascular events and cancer deaths the corresponding RRs were 1.51 (95% CI 1.20 to 1.90) and 1.85 (95% CI 1.10 to 3.13), respectively. CRP levels were also associated with an accelerated decline in forced expiratory volume in 1 second (p,0.001). The discriminative property of CRP was greatest during the first year of measurement and decayed over time. Comparing the highest and lowest CRP quintiles, the RR was 4.03 (95% CI 1.23 to 13.21) for 1 year mortality, 3.30 (95% CI 1.38 to 7.86) for 2 year mortality, and 1.82 (95% CI 1.22 to 2.68) for >5 year mortality. Conclusions: CRP measurements provide incremental prognostic information beyond that achieved by traditional markers of prognosis in patients with mild to moderate COPD, and may enable more accurate detection of patients at a high risk of mortality.

We examined the ventilatory response to moderate (arterial O2 saturation 80%), sustained, isocapnic hypoxia in 20 young adults. During 25 min of hypoxia, inspiratory minute ventilation (VI) showed an initial brisk increase but then declined to a level intermediate between the initial increase and resting room air VI. The intermediate level of VI was a plateau that did not change significantly when hypoxia was extended up to 1 h. The relation between the amount of initial increase and subsequent decrease in ventilation during constant hypoxia was not random; the magnitude of the eventual decline correlated confidently with the degree of initial hyperventilation. Evaluation of breathing pattern revealed that during constant hypoxia there was little alteration in respiratory timing and that the changes in VI were related to significant alterations in tidal volume and mean inspiratory flow (VT/TI). None of the changes was reproduced during a sham control protocol, in which room air was substituted for the period of low fractional concentration of inspired O2. We conclude that ventilatory response to hypoxia in adults is not sustained; it exhibits some biphasic features similar to the neonatal hypoxic response.