IS IT REALLY USEFUL TO REPEAT OUTPATIENT PULMONARY REHABILITATION PROGRAMS IN PATIENTS WITH CHRONIC AIRWAY OBSTRUCTION?
Foglio K; Bianchi L; Ambrosino N Chest. 2001;119:1696-1704.
Background.
Pulmonary rehabilitation has been shown to produce benefits that last 12 to 18 months. There is a need to develop strategies to extend the benefit period and incorporate rehabilitation principles into longer-term disease management plans for patients with chronic lung diseases.
Purpose.
Evaluate the effects of administering repeat pulmonary rehabilitation programs at yearly intervals on clinical and physiological outcomes.
Methods.
Sixty-one patients with chronic obstructive pulmonary disease were recruited for a clinical trial after completing an initial 8-week outpatient pulmonary rehabilitation program (PRP1) and randomly assigned to two groups. Group 1 completed a repeat rehabilitation program (PRP2) after 1 year. After 2 years, both groups underwent rehabilitation again (PRP3). Outcome measures included measures of pulmonary function, maximal cycle ergometry exercise, 6-minute walk test, dyspnea, health-related quality of life (HRQL) and the frequency of hospitalizations and exacerbations.
Results.
Complete data were obtained from 36 patients (17 in group 1, 19 in group 2). The two groups were similar before and after the initial PRP and at randomization. Pulmonary function did not change over time in either group. After PRP2, exercise tolerance, dyspnea, and HRQL improved in group 1. Nevertheless, after the second year, the two groups did not differ significantly in any measure of symptoms or function. Hospitalizations and exacerbations decreased significantly in both groups after PRP1. However, only group 1 experienced a further reduction in exacerbations over the second year of follow-up. Both groups improved after PRP3.
Conclusion.
In patients with COPD, PRP produces benefits in HRQL and a decreased number of hospitalizations and exacerbations that persist for up to 2 years. Successive, yearly interventions led to short-term gains but did not result in additive long-term physiologic benefits. Further reduction in yearly exacerbations seemed to be the main benefit of an additional PRP.
Comment.
This study evaluates an important new paradigm for pulmonary rehabilitation with repeat treatment in an attempt to sustain longer-term benefits. This treatment model is certainly consistent with a disease management program for a chronic condition and warrants further study. Unfortunately, the results of this study are limited by the small sample size and number of patients lost to follow-up. As a result, there was not sufficient statistical power to fully evaluate some encouraging trends in the data.
PATIENTS AT HIGH RISK OF DEATH AFTER LUNG-VOLUME-REDUCTION SURGERY
National Emphysema Treatment Trial Research Group N Engl J Med. 2001;345:1075-1083.
Background.
Lung volume reduction surgery (LVRS) is a proposed treatment for emphysema, but optimal selection criteria have not been defined. The National Emphysema Treatment Trial (NETT) is a randomized, multicenter clinical trial comparing LVRS with medical treatment.
Purpose.
Describe changes in patient selection criteria for the NETT study due to identification of a high-risk sub-group of patients with advanced emphysema and high surgical mortality from LVRS.
Methods.
All patients in NETT undergo extensive evaluation and pulmonary rehabilitation before random assignment to LVRS or continued medical treatment. Outcomes are assessed regularly with a variety of measures of physiologic function, symptoms, quality of life, and resource utilization. Results are monitored by an independent data and safety monitoring board.
Results.
A total of 1033 patients had been randomized by June 2001. For 69 patients with a forced expiratory volume in 1 second (FEV1) <= 20% predicted and either (1) a homogeneous distribution of emphysema on computed tomography or (2) a carbon monoxide diffusing capacity <= 20% predicted, the 30-day mortality rate after surgery was 16% (95% confidence interval, 8.2-26.7%), as compared with a rate of 0% among 70 medically treated patients (P < .001). Among these high-risk patients, the overall mortality rate was higher in surgical patients than medical patients (0.43 deaths per person-year versus 0.11 deaths per person-year; relative risk, 3.9; 95% confidence interval, 1.9-9.0). Compared with medically treated patients, survivors of surgery had small improvements at 6 months in the maximal workload (P = .06), the distance walked in 6 minutes (P = .03), and FEV1 (P < .001), but a similar health-related quality of life. The results of the analysis of functional outcomes for all patients, which accounted for deaths and missing data, did not favor either treatment.
Conclusions.
Caution is warranted in the use of LVRS in patients with emphysema who have a low FEV1 and either homogeneous emphysema or a very low carbon monoxide diffusing capacity. These patients are at high risk for death after surgery and also are unlikely to benefit from the surgery.
Comment.
These first published results from NETT substantiate the importance of a study like this in helping to systematically identify appropriate selection criteria for a new surgical procedure. The results of the main trial are not yet known. In the meantime, these data help to identify characteristics of a high-risk sub-group of patients in whom the risks of surgery do not appear to outweigh potential benefits.
SIMVASTATIN AND NIACIN, ANTIOXIDANT VITAMINS, OR THE COMBINATION FOR THE PREVENTION OF CORONARY DISEASE.
Brown BG; Zhao XQ; Chait A; Fisher LD; Cheung MC; Morse JS; Dowdy AA; Marino K; Bolson EL; Alaupovic P; Frohlich J; Albers JJ N Engl J Med. 2001;345(22):1583-92.
Background.
Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. The authors studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of high-density lipoprotein (HDL).
Methods.
In a 3-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal low-density lipoprotein cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants, or placebos. End points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization).
Results.
The mean levels of low-density lipoprotein and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42% and +26%, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9% with placebos, 1.8% with antioxidants (P = .16 for the comparison with the placebo group), and 0.7% with simvastatin-niacin plus antioxidants (P = .004) and regressed by 0.4% with simvastatin-niacin alone (P < .001). The frequency of the clinical end point was 24% with placebos; 3% with simvastatin-niacin alone; 21% in the antioxidant-therapy group; and 14% in the simvastatin-niacin-plus-antioxidants group.
Conclusions.
Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in coronary patients must be questioned. This study provides important additional information about the ineffectiveness of antioxidant vitamins for prevention or reversal of atherosclerosis. In addition to this study, the Heart Protection Study reported in abstract form in November 2001, also failed to show any benefit of antioxidant vitamin supplements on prevention of atherosclerotic clinical events in a very large trial (more than 20,000 men and women) of high-risk people. Many of our patients take antioxidant vitamins, often without informing their healthcare providers. Not only have the accumulated data suggested that antioxidant vitamins are unhelpful in this context, the new findings suggest that they may actually cause harm.
EFFECTS OF ENDURANCE EXERCISE TRAINING ON PLASMA HIGH-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS DEPEND ON LEVELS OF TRIGLYCERIDES: EVIDENCE FROM MEN OF THE HEALTH, RISK FACTORS, EXERCISE TRAINING AND GENETICS (HERITAGE) FAMILY STUDY.
Couillard C; Despres JP; Lamarche B; Bergeron J; Gagnon J; Leon AS; Rao DC; Skinner JS; Wilmore JH; Bouchard C Arterioscler Thromb Vasc Biol. 2001;21(7):1226-32.
Background.
High-density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations.
Objective.
The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study.
Results.
At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the HDL-raising effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P < .005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs (approximately -15.0%, P < .005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (-6.0%, P < .005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P < .01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol.
Conclusion.
Results of this study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity. These data should be helpful in identifying patients most likely to benefit from exercise training as a means of modifying low levels of HDL-cholesterol. Although it is disappointing that isolated low HDL-cholesterol did not respond well to exercise training, the majority of coronary patients have low-HDL in combination with high triglycerides and abdominal obesity. Thus, the majority of our patients can expect to receive a beneficial change in HDL-cholesterol in conjunction with aerobic training.
RESISTANCE TRAINING TO COUNTERACT THE CATABOLISM OF A LOW-PROTEIN DIET IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY
Castendada C; Gordon PL; Uhlin KL; Levey AS; Kehayias JJ; Dwyer JT; Fielding RA; Roubenoff R; Singh MF Ann Intern Med. 2001;135:965-976.
Background.
Chronic renal insufficiency leads to muscle wasting and the problem may be exacerbated by low protein diets prescribed to delay disease progression. These outcomes contribute to decreased functional capacity and excess morbidity and mortality. It is recognized that resistance training increases muscle mass and improves both functional status and quality of life.
Objective.
The purpose of this randomized, controlled investigation was to determine whether resistance training would preserve lean body mass in patients with moderate chronic renal insufficiency, who were consuming a low protein diet to slow the progression of real failure.
Methods.
Twenty-six patients, mean age 64.5 years, with moderate renal insufficiency including 17 men and 9 women, were randomly assigned to a low-protein diet (0.6 g/kg of body weight per day.) Fourteen subjects also were assigned to a resistance training program with the remaining 12 to the low-protein diet alone. Subjects received dietary instruction, and adherence was monitored using dietary records and regular meetings with a dietitian, along with urine collections for every 3-day dietary record. Protein intake was estimated using urea nitrogen levels calculated from urine collections. Muscle strength was determined before training and after 12 weeks of resistance training using 1 repetition maximum testing (chest and leg press, latissimus pull-down, knee extension, and knee flexion). Initial workload during training was adjusted to reflect 80% of 1 repetition maximum, three sets of eight repetitions for each station. Data collection included measurements of total body potassium (a measure of body cell mass that has been linked to functional status, prognosis, and survival), mid-thigh muscle area, and type I and type II muscle-fiber cross sectional area.
Results.
Patients in both groups maintained an appropriate protein intake (.64 g/kg/day). Total body potassium and both type I and type II muscle fiber cross-sectional areas increased in patients who participated in the resistance training program compared to those subjects not involved in resistance training. Additionally, resistance training was associated with maintenance of body weight compared to controls. Muscle strength improved by 32% in the resistance training group and decreased by 13% in controls.
Conclusions.
Resistance training was safe and effective in its purpose, that is, in improving muscle cellular function, muscle mass, and overall body muscle strength and function capacity. The data support the usefulness of resistance training. If nutritional status cannot be improved by increasing protein intake, or a low-protein diet is used to limit the progression of the disease, then such training appears to be an important adjunct to therapy and improving function capacity.
Comment.
This investigation provides further evidence, albeit in a relatively small sample size, that resistance training is and should be an essential component of the exercise regimen. One should be cautioned, however, that although there were no reports of injury or other associated problems with the resistance training protocol, others have reported potential adverse musculoskeletal responses, particularly in this age group. One should be mindful of the need to initiate and progress cautiously when undertaking these activities.
ORAL CONTRACEPTIVES AND THE RISK OF MYOCARDIAL INFARCTION
Tanis BC; van den Bosch MAAJ; Kemmeren JM; Cats VM; Helmerhorst FM; Algra A; van der Graaf Y; Rosoendaal FR N Engl J Med. 2001;345:1787-1793.
Background.
An association between the use of oral contraceptives and risk of myocardial infarction (MI) has been reported. However, findings have been inconsistent and may be affected by a variety of factors including type and dose of oral contraceptives and presence of other cardiovascular risk factors.
Objective.
The purpose of this investigation was to assess the impact on MI risk of oral contraceptives (particularly third-generation oral contraceptives, desogestrel or gestodene, versus second-generation oral contraceptives, levonorgestrel), dose of estrogen, and cardiovascular risk factor profile, with comparisons to a control group.
Methods.
Subjects were 248 women, ages 18 and 49 years, who were hospitalized from a first MI between 1990 and 1995 and 925 age-matched women without history of MI. Data collected included demographics; use and type of oral contraceptives; reproductive history; height and weight (body mass index); and the presence of hypertension, diabetes, hypercholesterolemia, cigarette smoking, obesity, alcohol consumption, and family history of arterial disease. Statistical analysis included adjustment for age, area of residence, and each cardiovascular risk factor listed previously.
Results.
Patients had a higher prevalence of hypertension (24% versus 6%), diabetes (6% versus 1%), hypercholesterolemia (11% versus 3%), and current smoking (84% versus 43%). Patients also had a lower level of education than controls. The risk of MI among users of any type of oral contraceptive was twice that of non-users. The risk of MI was more than twice (2.4 odds ratio) in those who used second-generation oral contraceptives compared to controls and a 1.3 odds ratio in those using third-generation oral contraceptives compared to controls. Oral contraceptive dosage did not appear to impact results. Among women who used oral contraceptives, risk of MI was highest among those who smoked (13.6 odds ratio), had diabetes (17.4 odds ratio), and hypercholesterolemia (24.7 odds ratio).
Conclusions.
The risk of MI among those studied was greatest among women using second-generation oral contraceptives compared to third-generation oral contraceptives. Presence of other cardiovascular disease risk factors in women using oral contraceptives dramatically increased risk, particularly smoking, diabetes, and hypercholesterolemia. Although the absolute risk of MI in users of oral contraceptives is small, it has an important potential effect on women's health because it is estimated that as many as 35% to 45% of women of reproductive age use these agents. Additionally, as absolute risk of MI increases with age and more than 25% of women age 35 years or greater still use oral contraceptives, these findings are particularly meaningful.
Comment.
In addition to their findings and important conclusions, the authors underscore the importance of cardiovascular risk factor screening and efforts to modify behavior, particularly habitual smoking, in both primary and secondary prevention patients who use oral contraceptives.