Increased pulse pressure is associated with reduced baroreflex sensitivity

Although pulse pressure (PP), heart rate variability (HRV) and baroreflex sensitivity (BRS) have been shown to predict cardiovascular events and mortality in various populations, their relationships have not been clarified. We examined these associations in two separate population-based samples of healthy middle-aged subjects. In population 1, data were obtained from 149 subjects (71 men and 78 women) aged 35-64 (mean 47.7) years, and in population 2, from 214 subjects (88 men and 126 women) aged 40-62 (mean 50.5) years. Increased 24-h ambulatory PP was related to decreased cross-spectral BRS independent of age and gender (beta=-0.28, P<0.001 for population 1; beta=-0.22, P=0.003 for population 2). This association remained significant when 24-h ambulatory diastolic blood pressure, body mass index, smoking and alcohol intake were added as covariates in the multivariate analysis. Increased ambulatory PP was also associated with increased beat-to-beat systolic arterial pressure variability. Associations between ambulatory PP and HRV were not significant after controlling for age and gender. Our results suggest that elevated PP does not affect overall HRV, but it interferes with baroreflex-mediated control of the heart rate. This association may be due to a common denominator, such as arterial stiffness, for PP and BRS.     

Increased effective lung volume following lung volume reduction surgery in emphysema

STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) for emphysema has a variable effect on spirometry with improvement linked to increases in lung elastic recoil. The mechanism by which recoil increases following LVRS has not been described completely. This study examines preoperative and postoperative pulmonary function to describe a mechanism for changes in airflow obstruction. DESIGN: Change in pulmonary function following LVRS. Setting : Public teaching hospital in Australia. PATIENTS: Patients with severe emphysema and pulmonary function measurements made before and after LVRS. MEASUREMENTS: Routine pulmonary function testing performed with ventilated lung alveolar volume (VA) derived from the gas transfer measurement used as a proxy for the effective lung volume. RESULTS: Pulmonary function tests from 36 consecutive patients with measurements made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD, 1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by 0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in those patients whose VAs did not increase (n = 7) was not significant. CONCLUSIONS: The increase in VA reflects an increase of functional or ventilating lung volume and is associated with an improvement in spirometry following LVRS.     

Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema

Endobronchial valve placement improves pulmonary function in some patients with chronic obstructive pulmonary disease, but its effects on exercise physiology have not been investigated. In 19 patients with a mean (SD) FEV(1) of 28.4 (11.9)% predicted, studied before and 4 weeks after unilateral valve insertion, functional residual capacity decreased from 7.1 (1.5) to 6.6 (1.7) L (p = 0.03) and diffusing capacity rose from 3.3 (1.1) to 3.7 (1.2) mmol . minute(-1) . kPa(-1) (p = 0.03). Cycle endurance time at 80% of peak workload increased from 227 (129) to 315 (195) seconds (p = 0.03). This was associated with a reduction in end-expiratory lung volume at peak exercise from 7.6 (1.6) to 7.2 (1.7) L (p = 0.03). Using stepwise logistic regression analysis, a model containing changes in transfer factor and resting inspiratory capacity explained 81% of the variation in change in exercise time (p < 0.0001). The same variables were retained if the five patients with radiologic atelectasis were excluded from analysis. In a subgroup of patients in whom invasive measurements were performed, improvement in exercise capacity was associated with a reduction in lung compliance (r(2) = 0.43; p = 0.03) and isotime esophageal pressure-time product (r(2) = 0.47; p = 0.03). Endobronchial valve placement can improve lung volumes and gas transfer in patients with chronic obstructive pulmonary disease and prolong exercise time by reducing dynamic hyperinflation.     

Weight gain after lung volume reduction surgery is not correlated with improvement in pulmonary mechanics

STUDY OBJECTIVES: Malnutrition and low body weight are common in patients with emphysema. Previous work has demonstrated correlation between severity of airflow obstruction and body weight. Lung volume reduction surgery (LVRS) is a recent advance in the treatment of patients with severe emphysema that results in improved pulmonary function. We formed the hypothesis that improved lung mechanics after LVRS would result in body weight gain. DESIGN: Retrospective chart review. PATIENTS: All patients who underwent bilateral LVRS for severe emphysema at the University of Michigan between January 1995 and April 1996 were eligible for the study. MEASUREMENTS AND RESULTS: Pulmonary function and body weight were measured preoperatively and at 3, 6, and 12 months postoperatively for patients who underwent bilateral LVRS between January 1995 and April 1996. The average weight gain in 38 patients returning for 12 months of follow-up was 3.8 +/- 0.9 kg, or 6.2% of the preoperative weight. Women gained significantly more weight than men (9.2 vs 2.2%, respectively) at 1 year. Interestingly, there was no correlation between change in weight and postoperative change in FEV(1), FVC, residual volume (RV), total lung capacity (TLC), or RV/TLC at 12 months. However, there was a statistically significant correlation between weight gained and improvement in diffusion of carbon monoxide measured 12 months postoperatively. CONCLUSIONS: This study shows that patients with severe emphysema gain weight after LVRS. These changes were independent of changes in pulmonary mechanics but may be a result of improved gas exchange. These findings provide further information about benefits of LVRS in patients with advance emphysema that are beyond simple changes in pulmonary function.     

Successful lung volume reduction surgery in a child with severe airflow obstruction and hyperinflation due to constrictive bronchiolitis

Lung volume reduction surgery (LVRS) may improve pulmonary function in patients with severe emphysema. However, its effects in other types of obstructive lung disease are unknown. To delay the need for lung transplantation, we performed LVRS in a 14-year-old boy with disabling airflow obstruction/hyperinflation secondary to postinfectious bronchiolitis nonresponsive to medical therapy. Within days after LVRS, a major improvement of symptoms and lung function occurred and persisted for > 1 year. Our observation suggests that LVRS may be a novel treatment option in selected patients with extreme hyperinflation even if the underlying disease is not emphysema.     

The BODE index after lung volume reduction surgery correlates with survival

STUDY OBJECTIVE: A recently introduced, multidimensional index called BODE (body mass index [BMI], degree of airflow obstruction assessed by spirometry, grade of dyspnea, and exercise capacity), quantified by 6-min walking distance (6MWD), has excellent predictive power with respect to outcome in COPD. We investigated whether the BODE index is able to predict survival after lung volume reduction surgery (LVRS). DESIGN: Retrospective study. SETTING: Tertiary university hospital. PATIENTS: One hundred eight-six COPD patients (76 women) with severe emphysema (mean +/- SD age, 64 +/- 8 years; mean FEV(1), 28 +/- 8% of predicted). INTERVENTION: Bilateral thoracoscopic LVRS. MEASUREMENTS AND RESULTS: BMI, pulmonary function, 6MWD, and the modified Medical Research Council dyspnea score were assessed before and 3 months after LVRS, and the BODE index was calculated. The patients were followed up with respect to survival for a median time of 40 months (range, 3 to 116 months) after surgery. The mean BODE index decreased from 7.2 +/- 1.6 preoperatively to 4.0 +/- 2.0 at 3 months after LVRS (p < 0.001). The postoperative but not the preoperative BODE correlated with survival, although preoperative patient characteristics were comparable between short-term (< 5 years) and long-term (> 5 years) survivors. A decrease to a lower BODE score class was associated with a reduced mortality (hazard ratio, 0.497, 95% confidence interval, 0.375 to 0.659; p < 0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger (0.74) than that for the FEV(1) (0.63), the degree of dyspnea (0.64), or the 6MWD (0.62). CONCLUSIONS: The postoperative BODE index is a powerful predictor of survival in COPD patients after LVRS.     

Diaphragmatic shape change after lung volume reduction surgery.

Diaphragmatic shape in normal patients was significantly different from shape in emphysema patients. Postoperative diaphragmatic shape in patients with good clinical outcome differed from preoperative shape and was similar to shape in normal patients. In patients with poor clinical outcome, surgery appeared to have little effect on diaphragm shape.     

Short- and long-term results after lung volume reduction surgery

Lung volume reduction surgery (LVRS) is a palliative surgical procedure for patients with severe emphysema. Resection of nonfunctional emphysematous lung tissue has been reported to relieve breathlessness and to improve quality of life for many patients by improving lung elastic recoil, respiratory muscle function, and ventilation-perfusion matching. However, the risks and benefits of LVRS remain controversial, as mainly short-term data are available for carefully selected groups of LVRS patients and no prospective, randomized trials for LVRS with pulmonary rehabilitation versus optimal medical therapy plus pulmonary rehabilitation have been reported. Bilateral staple resection for LVRS appears to be superior to use of a laser or unilateral approach in the short term, but relatively little data exist on long-term outcomes. Additional clinical investigation is required to determine whether LVRS should be a widely accepted therapy for severe emphysema.     

Outcomes of COPD lung transplant recipients after lung volume reduction surgery

STUDY OBJECTIVES: We sought to assess the outcomes of COPD lung transplant recipients who had previously undergone lung volume reduction surgery (LVRS), and to compare these patients to those COPD lung recipients who had not previously undergone LVRS. DESIGN: Retrospective analysis of the United Network for Organ Sharing transplant database over the period between October 25, 1999, and December 31, 2002. PATIENTS: All COPD patients who were listed and underwent transplantation during the time period were analyzed and categorized according to who did and did not have a history of LVRS. The two groups were compared for demographics, severity of illness, and various measures of outcomes after transplantation, including survival. RESULTS: There were 791 COPD patients who underwent transplantation, of whom 50 had a history of LVRS. The two groups had similar demographics and severity of disease. There was no difference in the need for reoperation, hospital length of stay, or survival between the groups. CONCLUSION: A history of LVRS does not impact on outcomes after lung transplantation and should not influence a patient's candidacy for transplantation. Similarly, a patient's potential need for lung transplantation should not impact on the decision-making process for undergoing LVRS.     

Diaphragm length and neural drive after lung volume reduction surgery

RATIONALE: Patients with chronic obstructive pulmonary disease have shorter inspiratory muscles and higher motor unit firing rates during quiet breathing than do age-matched healthy subjects. Lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease improves lung function, exercise capacity, and quality of life. OBJECTIVES: We studied the effect of LVRS on length and motor unit firing rates of diaphragm and scalene muscles. METHODS: Diaphragm length was estimated by ultrasound and magnetometers, and firing rates were recorded with needle electrodes in patients (five females and seven males) with severe chronic obstructive pulmonary disease, before and after surgery. MEASUREMENTS AND MAIN RESULTS: Pre-LVRS total lung capacity was 135 +/- 10% predicted (mean +/- SD), and FEV1 was 30 +/- 12% predicted. After surgery, median firing frequency of diaphragmatic motor units fell from 17.3 +/- 4.2 to 14.5 +/- 3.4 Hz (p < 0.001), and scalene motor unit firing rates were reduced from 15.3 +/- 6.9 to 13.4 +/- 3.8 Hz (p < 0.001). Tidal volume and diaphragm length change during quiet breathing did not change, but at end expiration, the zone of apposition length of diaphragm against the rib cage (L(Zapp)) increased (30 +/- 28%, p = 0.004). Improvements in quality-of-life measures and exercise performance after surgery were related to increased forced vital capacity and L(Zapp). CONCLUSIONS: Increased diaphragm length resulted in lower motor unit firing rates and reduced breathing effort, and this is likely to contribute to improved quality of life and exercise performance after LVRS.     

Improved quality of life after lung volume reduction surgery.

Lung volume reduction surgery (LVRS) improves dyspnoea, pulmonary function, and physical performance in patients with severe pulmonary emphysema. This study investigated the impact of LVRS on health-related quality of life (HRQL) over a 2-yr period following surgery. Thirty-nine consecutive patients were prospectively assessed before LVRS, and followed over 24 months postoperatively. The assessments included pulmonary function, dyspnoea (Medical Research Council (MRC) dyspnoea score), 6-min walking distance (6MWD) and HRQL using the Short Form 36-item questionnaire (SF-36). Several domains of SF-36 improved considerably over 2 yrs after surgery: Physical Functioning: 39 +/- 4 (mean +/- SEM) versus 16 +/- 2 (p<0.01); Vitality: 51 +/- 3 versus 32 +/- 3 (p<0.01); Social Functioning: 72 +/- 4 versus 51 +/- 5 (p<0.01). Also, improvements in pulmonary function (forced expiratory volume in one second (FEV1): 27 +/- 1% predicted, residual volume (RV)/total lung capacity (TLC): 0.65 +/- 0.01), 6 MWD (274 +/- 16 m) and dyspnoea (MRC: 3.9 +/- 01) were sustained for up to 2 yrs after LVRS (FEV1 36 +/- 2% pred, RV/TLC: 0.58 +/- 0.02; 6 MWD: 342 +/- 19 m; MRC: 2.0 +/- 0.2; p<0.05). In patients with severe emphysema, lung volume reduction surgery had positive effects on health-related quality of life and pulmonary function over 2 yrs.     

Neural drive to the diaphragm after lung volume reduction surgery

STUDY OBJECTIVES: The aim of this study was to investigate prospectively the changes in neural drive to the diaphragm in the first year after lung volume reduction surgery (LVRS) in patients with COPD. PATIENTS AND METHODS: In 14 patients with severe emphysema (mean +/- SD; age, 53.7 +/- 8.3 years; FEV(1), 0.64 +/- 0. 18 L; residual volume [RV], 5.33 +/- 1.25 L; PaO(2), 62.3 +/- 9.0 mm Hg; PaCO(2), 39.0 +/- 6.0 mm Hg), we assessed lung function, arterial blood gases, maximal exercise capacity (Wmax), and oxygen uptake (f1.gif" BORDER="0">O(2)max); intrinsic positive end-expiratory pressure (PEEPi); diaphragmatic strength (transdiaphragmatic pressure, Pdisniff) and endurance capacity (tlim); central diaphragmatic drive assessed by root mean square analysis of the esophageal electromyogram (rmsdia); and isotime dyspnea during loaded breathing tests (BS). RESULTS: Despite a significant increase (expressed as a percentage of baseline) in FEV(1) (40.6%) and a decrease in RV (30.0%) and PEEPi (75.7%) 1 month after LVRS, the improvements in Wmax (31.2%) and f1.gif" BORDER="0">O(2)max (13.7%); Pdisniff (25.4%) and tlim (64.9%); rmsdia (34.6%); and BS (21.7%) did not reach statistical significance (p < 0.05) until 6 months after LVRS. Arterial blood gases did not change significantly. Significant correlations were found between decrease in rmsdia and changes in PEEPi (r = 0.69), Wmax (r = -0.56), Pdisniff (r = -0.65), tlim (r = -0.59), and BS (r = 0.71) 6 months after LVRS. CONCLUSIONS: Our results show that LVRS is able to increase the efficacy of the respiratory pump and by this way reduce ventilatory drive and respiratory effort sensation.     

Development of a giant bulla after lung volume reduction surgery

Lung volume reduction surgery (LVRS) is being evaluated in the treatment of emphysema. The proposed mechanisms of improvement are increased elastic recoil of the lung and improved mechanical efficiency of the muscles of respiration. We report a unique patient with emphysema who developed a giant bulla 3 years subsequent to LVRS. The patient underwent extensive evaluation, including measurements of lung mechanics. Bullectomy was performed, but it was unsuccessful. Although the mechanisms behind the development of giant bullous disease remain speculative, heterogeneous improvement in elastic recoil following LVRS may be one of the responsible mechanisms.     

Cost-effectiveness of lung volume reduction surgery

Lung volume reduction surgery (LVRS) is a costly procedure that can improve quality and quantity of life. Given the prevalence of emphysema, the costs involved with its management, and resource constraints on all health care delivery systems, evaluating the cost-effectiveness of LVRS is important. In this article, we describe the purposes and principles of cost-effectiveness analysis and how those principles were applied in evaluating LVRS. We present the results of the cost-effectiveness analysis that was conducted alongside the National Emphysema Treatment Trial and other economic studies of LVRS and discuss how these should be interpreted in the context of current reimbursement guidelines.     

News on lung volume reduction surgery

Lung volume reduction surgery (LVRS) is an established therapeutic option for patients with advanced pulmonary emphysema after all conservative measures, including comprehensive pulmonary rehabilitation, have been exhausted. LVRS improves pulmonary function, shortness of breath, exercise capacity and hence quality of life in some 80% of cases for up to four years. Even patients with homogeneous types of pulmonary emphysema improve if those with extremely low FEV1 and/or very low diffusion capacity are excluded. At experienced centres perioperative mortality is less than 2% in appropriately selected patients, and current results suggest that the five-year survival in COPD patients may even be improved by this palliative surgical intervention. In patients under 60 LVRS may serve as a bridging procedure to lung transplantation. Bronchoscopic creation of extraanatomic bronchopulmonary passages--endoscopic LVRS--is a novel approach now under investigation.     

Successful lung transplantation following lung volume reduction surgery

BACKGROUND: Lung volume reduction surgery (LVRS) is an accepted treatment modality for patients with advanced emphysema. Recently, successful lung transplantation (LTX) has been reported following LVRS. We assess the pulmonary functions in lung transplant recipients after LVRS. METHODS: 8 patients - 5 males and 3 women--aged 53-66 years with advanced emphysema underwent LVRS. Following clinical deterioration and decline of pulmonary function, patients underwent single LTX. Post transplantation follow-up included pulmonary function, 6 minute walk distance (6 MWD) and recording perioperative complications. RESULTS: Median forced expiratory in one second (FEV 1) before and after LVRS were 24 % with 31 % predicted, respectively. All but one showed improvement in lung function and 6 MWD following LVRS. Median maximal 6 MWD before and after LVRS was 222 and 316 meters, respectively. Median time from LVRS to LTX was 46 months (range 10-83). All patients survived and were discharged after LTX. Median FEV1 before and after LTX was 23 % with 57 % predicted, respectively. Median 6MWD before and after LTX was 240 and 462 meters, respectively. NYHA classes improved from 3-4 to 1-2 in 7 surviving patients. At transplantation, bleeding due to pleural adhesions was observed in 4 patients; two required blood transfusions. One patient developed acute respiratory distress syndrome and one had unilateral vocal cord paralysis. At nine-month follow-up, 7 patients are doing remarkably well, while one patient died 6 months after LTX due to bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: LVRS is a therapeutic option in patients with end-stage emphysema. When emphysema deteriorates, LTX can be successfully performed with significant improvement of quality of life without significant additional risk.