BACKGROUNDChronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV 1 ) over time. Yet it is possible that a normal decline in FEV 1 could also lead to COPD in persons whose maximally attained FEV 1 is less than population norms. METHODSWe stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV 1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV 1 over time among the participants according to their FEV 1 at cohort inception and COPD status at study end. RESULTSAmong 657 persons who had an FEV 1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV 1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV 1 before 40 years of age and had a rapid decline in FEV 1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV 1 in early adulthood and a subsequent mean decline in FEV 1 of 27±18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONSOur study suggests that low FEV 1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV 1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.) a bs tr ac t

The new stratification performs well by identifying individuals at risk of exacerbations. Surprisingly, subgroup B, characterized by more severe dyspnea, had significantly poorer survival than group C, in spite of a higher FEV(1) level. This subgroup warrants special attention, as the poor prognosis could be caused by cardiovascular disease or cancer, requiring additional assessment and treatment.

XACERBATIONS OF RESPIRATORY symptoms in chronic obstructive pulmonary disease (COPD) are of major importance because of their profound and longlasting adverse effects on patients. 1,2 Frequent episodes accelerate loss of lung function, 3 affect the quality of life of the patients, 4,5 and are associated with poor survival. 6-8 In general, exacerbations become more frequent with increasing disease severity, but the single best predictor of exacerbations in all grades of COPD is a previous exacerbation, suggesting the existence of a phenotype susceptible to exacerbations independent of degree of airflow limitation. 9 However, when predicting risk of future exacerbations based on previous events, the positive predictive value remains low, 9 indicating that additional determinants of exacerbation susceptibility remain to be identified. Exacerbations are often caused by respiratory tract infections, 10 and during the acute episode, levels of circulating acute phase proteins and inflammatory cells are elevated. 11,12 However, some patients with COPD also have evidence of low-grade systemic inflammation with increased levels of such inflammatory biomarkers during stable conditions, 13 and previous studies have found that elevated levels of inflammatory biomarkers like Creactive protein (CRP), fibrinogen, and For editorial comment see p 2390.

The findings suggest a U-shaped association between all-cause mortality and dose of jogging as calibrated by pace, quantity, and frequency of jogging. Light and moderate joggers have lower mortality than sedentary nonjoggers, whereas strenuous joggers have a mortality rate not statistically different from that of the sedentary group.

Background-Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. Methods and Results-Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (sЈ), early diastolic (eЈ), and late diastolic (aЈ) velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: eЈ/(aЈϫsЈ). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low sЈ (hazard ratio, 1.23 per 1-cm/s decrease; PϽ0.05) and aЈ (hazard ratio, 1.20 per 1-cm/s decrease; Pϭ0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 (PϽ0.005). Conclusions-In