Aktuelle Abstracts 16.10.2001

Am J Respir Crit Care Med 2001 Aug 15;164(4):597-601

Marked sympathetic activation in patients with chronic respiratory failure.

Heindl S, Lehnert M, Criee CP, Hasenfuss G, Andreas S
Department of Cardiology and Pneumology, Georg-August-University, Gottingen, Germany.

The autonomic nervous system may be disturbed in chronic respiratory failure. We tested the hypothesis that there is increased sympathetic activity in patients with chronic hypoxemia. Furthermore, we examined the effect of short-term oxygen on muscle sympathetic nerve activity (MSNA) in these patients. We performed microneurography of the peroneal nerve in 11 patients with hypoxemia due to chronic obstructive pulmonary disease (COPD, n = 6) or lung fibrosis (n = 5) and in 11 healthy subjects matched for age and sex. MSNA was measured during normal breathing in all subjects. In eight patients and in seven control subjects, MSNA was also measured during nasal oxygen (4 L/min). MSNA was higher in the patients with chronic respiratory failure compared with the healthy subjects during normal breathing (61 +/- 5 versus 34 +/- 2 bursts/min, mean +/- SEM; p = 0.0002, paired t test). During oxygen administration, MSNA decreased from 63 +/- 6 to 56 +/- 6 bursts/min in the patients (p = 0.0004, ANOVA); there was no change in sympathetic activity in the control subjects. For the first time, there is direct evidence of marked sympathetic activation in patients with chronic respiratory failure. This is partly explained by arterial chemoreflex activation and may play an important role in the pathogenesis of the disease.

PMID: 11520722, UI: 21411260

Am J Respir Crit Care Med 2001 Aug 15;164(4):590-6

The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands.

Feenstra TL, van Genugten ML, Hoogenveen RT, Wouters EF, Rutten-van Molken MP
National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Chronic obstructive pulmonary disease (COPD) causes extensive disability, primarily among the elderly. On the World Health Organization ranking list of disability-adjusted life years (DALYs), COPD rises from the twelfth to the fifth place from 1990 to 2020. The purpose of this study is to single out the impact of changes in demography and in smoking behavior on COPD morbidity, mortality, and health care costs. A dynamic multistate life table model was used to compute projections for the Netherlands. Changes in the size and composition of the population cause COPD prevalence to increase from 21/1,000 in 1994 to 33/1,000 in 2015 for men, and from 10/ 1,000 to 23/1,000 for women. Changes in smoking behavior reduce the projected prevalence to 29/1,000 for men, but increase it to 25/ 1,000 for women. Total life years lost increase more than 60%, and DALYs lost increase 75%. Costs rise 90%; smokers cause approximately 90% of these costs. The model demonstrates the unavoidable increase in the burden of COPD, an increase that is larger for women than for men. The major causes of this increase are past smoking behavior and the aging of the population; changes in smoking behavior will have only a small effect in the nearby future.

PMID: 11520721, UI: 21411259

Am J Respir Crit Care Med 2001 Aug 15;164(4):585-9

Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease.

Baldi S, Miniati M, Bellina CR, Battolla L, Catapano G, Begliomini E, Giustini D, Giuntini C
Istituto di Fisiologia Clinica del CNR, Centro Regionale di Medicina Nucleare, Istituto di Radiologia, Dipartimento Cardio Toracico, Universita degli Studi di Pisa, Pisa, Italy.

We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37 +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/- 24% predicted, and the exponential constant K of pressure-volume curves was 258 +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/- 11% (range 1 to 38%). It showed a highly significant negative correlation with DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no correlation with either Pst(max) or constant K. A significant relationship was found between the natural logarithm of K and the full width at half maximum of the frequency distribution of CT numbers, taken as an index of the heterogeneity of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods of assessing the extent of emphysema by HRCT closely reflect the reduction of CO diffusion constant, but cannot predict the elastic properties of the lung tissue.

Publication Types:
Validation studies
PMID: 11520720, UI: 21411258

Am J Respir Crit Care Med 2001 Aug 15;164(4):580-4

Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease.

Sin DD, Tu JV
The Institute for Clinical Evaluative Sciences and The Department of Medicine, Sunnybrook and Women's College Health Science Center, University of Toronto, Toronto, Ontario, Canada.

There is considerable controversy concerning the utility of inhaled corticosteroids for the long-term treatment of patients with COPD. Recent studies have suggested that although inhaled corticosteroids do not alter the rate of decline in lung function, they may reduce airway hyperresponsiveness, decrease the frequency of exacerbations, and slow the rate of decline in the patients' health status. The relationship between inhaled corticosteroids and subsequent risk of hospitalization or mortality remains unknown. We therefore conducted a population-based cohort study using administrative databases in Ontario, Canada (n = 22,620) to determine the association between inhaled corticosteroid therapy and the combined risk of repeat hospitalization and all-cause mortality in elderly patients with COPD. Patients who received inhaled corticosteroid therapy postdischarge (within 90 d) had 24% fewer repeat hospitalizations for COPD (95% confidence interval [CI], 22 to 35%) and were 29% less likely to experience mortality (95% CI, 22 to 35%) during 1 yr of follow-up after adjustment for various confounding factors. This cohort study has suggested that inhaled corticosteroid therapy is associated with reduced COPD-related morbidity and mortality in elderly patients. Although not definitive, because of the observational nature of these findings, these data provide a compelling rationale for a large randomized trial to determine the effect of inhaled corticosteroids on COPD-related morbidity and mortality.

PMID: 11520719, UI: 21411257

Chest 2001 Sep;120(3):748-56

Inspiratory muscle training in patients with COPD: effect on dyspnea, exercise performance, and quality of life.

Sanchez Riera H, Montemayor Rubio T, Ortega Ruiz F, Cejudo Ramos P, Del Castillo Otero D, Elias Hernandez T, Castillo Gomez J
Pneumology Service, Virgen Del Rocio University Hospital, Sevilla, Spain.

OBJECTIVE: The aim of the study was to assess the effect of target-flow inspiratory muscle training (IMT) on respiratory muscle function, exercise performance, dyspnea, and health-related quality of life (HRQL) in patients with COPD. PATIENTS AND METHODS: Twenty patients with severe COPD were randomly assigned to a training group (group T) or to a control group (group C) following a double-blind procedure. Patients in group T (n = 10) trained with 60 to 70% maximal sustained inspiratory pressure (SIPmax) as a training load, and those in group C (n = 10) received no training. Group T trained at home for 30 min daily, 6 days a week for 6 months. MEASUREMENTS: The measurements performed included spirometry, SIPmax, inspiratory muscle strength, and exercise capacity, which included maximal oxygen uptake (VO(2)), and minute ventilation (VE). Exercise performance was evaluated by the distance walked in the shuttle walking test (SWT). Changes in dyspnea and HRQL also were measured. RESULTS: Results showed significant increases in SIPmax, maximal inspiratory pressure, and SWT only in group T (p < 0.003, p < 0.003, and p < 0.001, respectively), with significant differences after 6 months between the two groups (p < 0.003, p < 0.003, and p < 0.05, respectively). The levels of VO(2) and VE did not change in either group. The values for transitional dyspnea index and HRQL improved in group T at 6 months in comparison with group C (p < 0.003 and p < 0.003, respectively). CONCLUSIONS: We conclude that targeted IMT relieves dyspnea, increases the capacity to walk, and improves HRQL in COPD patients.

Publication Types:
Clinical trial
Randomized controlled trial
PMID: 11555505, UI: 21439041

Chest 2001 Sep;120(3):743-7

Patterns of lung disease in a "normal" smoking population: are emphysema and airflow obstruction found together?

Clark KD, Wardrobe-Wong N, Elliott JJ, Gill PT, Tait NP, Snashall PD
School of Clinical Medical Sciences, University of Newcastle upon Tyne, UK.

STUDY OBJECTIVES: We determined whether emphysema demonstrated on high-resolution CT (HRCT) scanning in apparently well smokers is associated with airflow obstruction. INTERVENTIONS: Lung function testing and limited HRCT scanning. DESIGN: Lung function measurements and scans were analyzed independently of each other. We used analysis of covariance to compare FEV(1) and maximum expiratory flow at 50% of vital capacity (MEF(50)) values after suitable corrections, between subjects with and without parenchymal damage (emphysema and/or reduced carbon monoxide transfer coefficient [KCO]), and to compare indexes of parenchymal damage between subjects with and without airflow obstruction. SETTING: Radiology and lung function departments of a district general hospital. PARTICIPANTS: Eighty current cigarette smokers and 20 lifetime nonsmoking control subjects (aged 35 to 65 years) who volunteered following publicity in local media. In all subjects, FEV(1) was > 1.5 L; no subjects were known to have lung disease. Measurements and results: FEV(1) and MEF(50) were measured spirometrically; static lung volumes were measured by helium dilution and body plethysmography; KCO was measured by a single-breath technique. HRCT scans were analyzed for emphysema by two radiologists. Of smokers, 25% had HRCT emphysema, generally mild; 16.3% and 25% had reduced FEV(1) and MEF(50), respectively; 12.5% had reduced KCO. Smokers with airflow obstruction were not more likely to have parenchymal damage. Smokers with parenchymal damage did not have reduced airway function. Nonsmokers generally had normal airways and parenchyma. CONCLUSIONS: "Normal" smokers with lung damage had either airflow obstruction or parenchymal damage, but not generally both.

PMID: 11555504, UI: 21439040

Chest 2001 Sep;120(3):730-3

Erythromycin and common cold in COPD.

Suzuki T, Yanai M, Yamaya M, Satoh-Nakagawa T, Sekizawa K, Ishida S, Sasaki H
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.

Publication Types:
Clinical trial
Randomized controlled trial
PMID: 11555501, UI: 21439037

Chest 2001 Sep;120(3):725-9

CT assessment of subtypes of pulmonary emphysema in smokers.

Satoh K, Kobayashi T, Misao T, Hitani Y, Yamamoto Y, Nishiyama Y, Ohkawa M
Department of Radiology, Kagawa Medical University, Kagawa, Japan.

OBJECTIVE: To determine the incidence of subtypes of pulmonary emphysema (PE) identified by CT imaging in male patients who have a significant smoking history. Patients and setting: We reviewed 945 subjects (619 men and 326 women) who had undergone CT scanning. However, only the data for male subjects were analyzed due to there being too few female subjects. The male subjects were divided into the following two age groups: group A (age, 50 years). There were two subtypes of PE found: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Based on these subtypes, PE was divided into the following three categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). RESULTS: PE was found in 270 of 516 male smokers (10 of 38 female smokers had PE). Among male subjects, in age group A there were 53 subjects with some degree of PE (category I, 12 subjects [22.6%]; category II, 7 subjects [13.2%]; and category III, 34 subjects [64.2%]). Among men in age group B, there were 217 subjects with some degree of PE (category I, 109 subjects [50.2%]; category II, 23 subjects [10.6%]; and category III, 85 subjects [39.2%]). CONCLUSION: In age group A, men < 50 years of age who were in category III (PSE or PSE-predominant PE) predominated (34 of 53 subjects; 64.2%). In age group B, men > 50 years of age who were in category I (CLE or CLE-predominant PE) predominated (109 of 217 subjects; 50.2%).

PMID: 11555499, UI: 21439035

Thorax 2001 Sep;56(9):721-6

Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations.

Dentener MA, Creutzberg EC, Schols AM, Mantovani A, van't Veer C, Buurman WA, Wouters EF
Department of Pulmonology and Surgery, Maastricht University, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), 6202 AZ Maastricht, The Netherlands.

BACKGROUND: The aim of this study was to test the hypothesis that the chronic inflammatory process present in chronic obstructive pulmonary disease (COPD) is due to a defective endogenous anti-inflammatory mechanism. METHODS: Systemic levels of the anti-inflammatory mediators soluble interleukin 1 receptor II (sIL-1RII), soluble tumour necrosis factor receptor p55 (sTNF-R55) and sTNF-R75, and of C reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were analysed in 55 patients with stable COPD (median forced expiratory volume in one second (FEV(1)) 34% predicted (range 15-78)) and compared with levels in 23 control subjects. In addition, changes in these mediators were studied in 13 patients with COPD (median FEV(1) 34% predicted (range 19-51)) during the first 7 days in hospital with an exacerbation of the disease. RESULTS: Patients with stable COPD were characterised by a systemic inflammatory process indicated by an increased leucocyte count (7.2 (4.7-16.4) v 4.8 (3.5-8.3) x 10(9)/l), raised levels of CRP (11.8 (1.1-75.0) v 4.1 (0.6-75.0) microg/ml) and LBP (45.6 (8.1-200.0) v 27.9 (14.1-71.5) microg/ml), and moderate increases in both sTNF-Rs. In contrast, the sIL-1RII level did not differ between patients and controls (4.53 (2.09-7.60) v 4.63 (3.80-5.93) ng/ml). During treatment of disease exacerbations, systemic levels of both CRP (at day 3) and LBP (at day 7) were significantly reduced compared with day 1, whereas sIL-1RII levels increased. CONCLUSIONS: These data suggest an imbalance in systemic levels of pro- and anti-inflammatory mediators in patients with stable COPD. The increase in the anti-inflammatory mediator sIL-1RII during treatment of exacerbations may contribute to the clinical improvement.

PMID: 11514694, UI: 21406233

Thorax 2001 Sep;56(9):713-20

Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease.

Hadcroft J, Calverley PM
Department of Medicine, University of Liverpool, University Hospital Aintree, Liverpool L9 7AL, UK.

BACKGROUND: Bronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung mechanics-measurement of end expiratory lung volume (EELV) using the inspiratory capacity manoeuvre and application of negative expiratory pressure (NEP) during tidal breathing to detect tidal airflow limitation-do relate to the degree of breathlessness in COPD. Their usefulness as end points in bronchodilator reversibility testing has not been examined. METHODS: We studied 20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men, forced expiratory volume in one second (FEV(1)) 29.5 (1.6)% predicted) with tidal flow limitation as assessed by their maximum flow-volume loop. Spirometric parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were measured seated, before and after nebulised saline, and at intervals after 5 mg nebulised salbutamol and 500 microg nebulised ipratropium bromide. The patients attended twice and the treatment order was randomised. RESULTS: Mean FEV(1), FVC, SVC, and IC were unchanged after saline but the degree of tidal flow limitation varied. FEV(1) improved significantly after salbutamol and ipratropium (0.11 (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with further significant increases after the combination. Tidal volume and mean expiratory flow increased significantly after all bronchodilators but breathlessness fell significantly only after the combination treatment. The initial NEP score was unrelated to subsequent changes in lung volume. CONCLUSIONS: NEP is not an appropriate measurement of acute bronchodilator responsiveness. Changes in IC were significantly larger than those in FEV(1) and may be more easily detected. However, our data showed no evidence for separation of "reversible" and "irreversible" groups whatever outcome measure was adopted.

PMID: 11514693, UI: 21406232

Thorax 2001 Sep;56(9):708-12

Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome.

Plant PK, Owen JL, Elliott MW
Department of Respiratory Medicine, St James's University Hospital, Leeds LS9 7TF, UK.

BACKGROUND: Non-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation. The second aim was to determine the long term survival of patients treated with and without NIV. METHODS: In this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998. Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic factors were identified using logistic regression analysis. All patients were followed until death or 1 January 1999. RESULTS: At enrolment the H(+) concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and PaCO2 (OR 1.14 per kPa, 95% CI 1.14 to 1.81, p<0.01) were associated with treatment failure. Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80). After 4 hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to 0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84 to 0.99, p=0.04) were associated with success. Median length of survival was 16.8 months in those treated with NIV and 13.4 months in those receiving standard treatment (p=0.12). The trend in improved survival was attributable to prevention of death during the index admission. CONCLUSION: Initial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation. NIV reduces this risk and progress should be monitored using change in respiratory rate and pH. The long term survival after NIV is sufficiently good to render treatment appropriate.

Publication Types:
Clinical trial
Multicenter study
Randomized controlled trial
PMID: 11514692, UI: 21406231

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