How else will clinicians find the present results of Seshadri et al interesting and useful? For some, the findings may sound a note of caution concerning the use of short-acting anticholinergic agents (eg, ipratropium and oxitropium) and long-acting anticholinergic agents (eg, tiotropium). While these agents have much to recommend them43(beneficial effects include improvements in exercise tolerance, quality of life, and spirometry, and reduced exacerbations in COPD patients), there is no published evidence that they improve survival. And one study of 2,382 hospitalized patients found that those treated with ipratropium experienced higher rates of death from asthma (odds ratio [OR], 4.04; 95% CI, 1.47 to 11.13), COPD (OR, 7.75; 95% CI, 2.21 to 27.14), and cardiovascular diseases (OR, 3.55; 95% CI, 1.05 to 11.94) over the 3 years after hospital discharge.44Autopsy results from seven patients with asthma or COPD who had received ipratropium showed that all had mucus plugging of airways, which was widespread in five. In contrast, of eight similar patients who did not receive ipratropium, only two had extensive mucus plugging. On a more positive note, the present findings will encourage some clinicians to make greater use of graded exercise testing in patients with COPD or restrictive disease to gain insight into their prognosis.45 Such testing, with particular attention to HRR and other measures of vagal tone, might help to tailor pulmonary (and cardiovascular) interventions such as the use of pulmonary rehabilitation and optimization of medications.42 The results presented by Seshadri et al could provide a new (as yet unproven) incentive for the greater use of pulmonary rehabilitation38,43 to improve vagal tone. Such was the finding of La Rovere et al.46 In their study of 95 survivors of myocardial infarction, half were randomized to 4 weeks of endurance training, which improved baroreceptor sensitivity by 26%. Those patients who demonstrated this improvement after such training had a lower 10-year cardiac mortality rate (p < 0.04) compared to the nonresponders.