The primary finding of this large prospective investigation of over 225,000 women and men followed for nine years is that adiposity as assessed by WC was strongly and consistently related to death from a comprehensive list of death from major specific causes, including deaths from lung cancer and chronic respiratory disease, independent of BMI and other covariates. In contrast, adiposity as assessed by BMI showed inconsistent associations with specific causes of death, displaying positive relations to death from non-lung cancers, cardiovascular disease, and non-cancer/non-cardiovascular diseases, but inverse or null associations with deaths from lung cancer and chronic respiratory disease. This finding indicates that an increased amount of abdominal fat, but not general adiposity, represents a consistent predictor of premature death from major specific causes.
Our results have significant clinical implications because they suggest that WC represents a superior predictor than BMI of risk of deaths from lung cancer and chronic respiratory disease, two major causes of death. For example, obtaining a WC measurement in individuals already at increased risk for respiratory death (e.g., due to smoking or chronic obstructive respiratory disease) provides important information not delivered by BMI on a patient's risk of premature mortality.
Though speculative, one possible biologic reason for the heterogeneous associations of WC and BMI to mortality from lung cancer and chronic respiratory disease is that lung cancer mortality and chronic respiratory disease mortality may involve biologic pathways related to insulin resistance and related metabolic abnormalities, such as excess release of proinflammatory and prothrombotic factors 
, which are more strongly related to abdominal adiposity than to overall excess body weight.
An alternative explanation for the divergent relations of WC and BMI to deaths from lung cancer and chronic respiratory disease is heterogeneity with respect to residual confounding by smoking. Current smoking is related to both lower BMI 
and increased mortality from lung cancer and chronic respiratory disease. By comparison, current smoking is associated with visceral fat accumulation 
and smoking cessation is related to increases in WC 
. Limiting the investigation to participants who never smoked helps resolve the issue of residual confounding by smoking with respect to both BMI and WC but our cohort lacked sufficient numbers of cases of mortality from lung cancer and chronic respiratory disease among persons who never smoked.
To the best of our knowledge, no previous study has examined the association between WC and risk of death from lung cancer. However, our results regarding WC are consistent with previous epidemiologic investigations that have focused on lung cancer incidence. For example, the Iowa Women's Health Study found a positive relation of WC (relative risk comparing extreme categories
1.76; 95 percent confidence interval, 1.14 to 2.73) to lung cancer incidence 
. Similarly, the Women's Health Initiative observed positive relations of WC to lung cancer incidence among current smokers (relative risk
1.56; 95 percent confidence interval, 0.91 to 2.69) and former smokers (relative risk
1.50; 95 percent confidence interval, 0.98 to 2.31) 
Our findings regarding the relation of BMI to lung cancer death are strikingly consistent with recent data from a large pooled analysis of 57 prospective studies 
. In that analysis, each 5kg/m2
increment in BMI was associated with a relative risk of lung cancer death of 0.71 (95 percent confidence interval, 0.63 to 0.79) within the BMI range of 15 to 25 kg/m2
and was associated with a relative risk of lung cancer death of 0.98 (95 percent confidence interval, 0.88 to 1.09) within the BMI range of 25 to 50 kg/m2 
Our results of a monotonically positive relation of WC to respiratory death are comparable to recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study 
. In that study, the relative risk of respiratory death comparing extreme quintiles of WC among women was 2.95 (95 percent confidence interval, 1.52 to 5.70) and the corresponding relative risk among men was 6.56 (95 percent confidence interval, 3.60 to 11.96).
Our results of a J-shaped association between BMI and death from chronic respiratory disease are comparable to the aforementioned pooled analysis of 57 prospective studies 
. Each 5kg/m2
increase in BMI was related to a relative risk of respiratory death of 0.31 (95 percent confidence interval, 0.28 to 0.35) within the BMI range of 15 to 25 kg/m2
and was related to a relative risk of respiratory death of 1.20 (95 percent confidence interval, 1.07 to 1.34) within the BMI range of 25 to 50 kg/m2 
Notable strengths of our study include its prospective design, a large number of deaths from specific causes, a high follow-up rate, and detailed information on potentially confounding factors. Despite a number of advantageous aspects of our study, one potential limitation is a low response rate to the second questionnaire used to obtain WC information, which could have resulted in selection bias if, for example WC was preferentially missing for persons with high mortality risk. A further potential limitation is that WC, weight, and height were assessed using self-report, a method that is known to be imperfect. However, self-reported BMI values and WC measures have been found to be sufficiently precise for use in epidemiologic studies 
. Self-reported height and weight vary systematically with BMI 
, but the importance of such bias is uncertain 
. Taken together, it is improbable that misclassification of self-reported WC, height, and weight fully accounted for our finding of markedly divergent relations of general and abdominal adiposity to risk for deaths from lung cancer and chronic respiratory disease. We did not evaluate the association between WC and mortality from chronic lung disease according to smoking status because that topic is beyond the scope of the present investigation. Future studies should examine that relation.
We conclude that increased abdominal fat, but not general adiposity is associated with elevated risk of a comprehensive list of death from major specific causes, including deaths from lung cancer and chronic respiratory disease. Based on our observational epidemiologic data, deaths from lung cancer and chronic respiratory disease may potentially be added to the list of causes of death directly related to adiposity.