Aktuelle Studien (09.06.01) aus der Zeitschrift
American Journal of Critical Care Medicine
(Am J Respir Crit Care Med)
|Cassart M, Hamacher J, Verbandt Y, Wildermuth S, Ritscher D, Russi EW, de Francquen P,
Cappello M, Weder W, Estenne M
Department of Radiology, University Hospital, Zurich, Switzerland.
Am J Respir Crit Care Med 2001 Apr;163(5):1171-5
Effects of lung volume reduction surgery for emphysema on diaphragm dimensions and
Part of the functional benefit provided by lung volume reduction surgery (LVRS) may be
related to improvement in respiratory muscle function resulting from changes in diaphragm
dimension and configuration. To study these changes, we obtained 3D reconstructions of the
muscle using spiral computed tomography in 11 patients with severe emphysema before and 3
mo after surgery, and in 11 normal subjects matched for sex, age, height, and weight.
Bilateral LVRS was performed by thoracoscopy in eight patients and by sternotomy in three
patients. Acquisitions were made in the supine posture at relaxed FRC, midinspiratory
capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and a 30
+/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and of the zone
of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%, respectively, but the
surface area of the dome did not change. Compared with the values recorded in the normal
subjects, postoperative values of A(di) and A(ap) at FRC were reduced by 11% (p < 0.05)
and 24% (p < 0.005), respectively. The curvature of the dome increased at TLC in the left
sagittal plane, but was otherwise unaffected by the procedure. We conclude that LVRS
substantially increases A(di) and A(ap), but does not significantly improve diaphragm
configuration at FRC.
Rennard SI, Anderson W, ZuWallack R, Broughton J, Bailey W, Friedman M, Wisniewski M, Rickard K
University of Nebraska Medical Center, Omaha, Nebraska, USA. firstname.lastname@example.org
Am J Respir Crit Care Med 2001 Apr;163(5):1087-92
Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a condition in which continuous
bronchodilation may have clinical advantages. This study evaluated salmeterol, a
beta-agonist bronchodilator with a duration of action substantially longer than that of
short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator,
and placebo in patients with COPD. Four hundred and five patients with COPD received either
salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or
placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were
stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml
improvement) and were randomized within each stratum. Bronchodilator response was measured
over 12 h four times during the treatment period. Salmeterol provided similar maximal
bronchodilatation to ipratropium but had a longer duration of action and a more constant
bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments
were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect
over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol.
The long duration of action of salmeterol offers the advantage of twice daily dosing
compared with the required four times a day dosing with ipratropium.
Poole DC, Kindig CA, Behnke BJ
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5602, USA. email@example.com
Am J Respir Crit Care Med 2001 Apr;163(5):1081-6
Effects of emphysema on diaphragm microvascular oxygen pressure.
Pulmonary emphysema impairs lung and respiratory muscle function leading to restricted
physical capacity and accelerated morbidity and mortality consequent to respiratory muscle
failure. In the absence of direct evidence, an O2 supply-demand imbalance within the
diaphragm and other respiratory muscles in emphysema has been considered the most likely
explanation for this failure. To test this hypothesis, we utilized phosphorescence
quenching techniques to measure mean microvascular PO2 (PO2m) within the medial costal
diaphragm of control (C, n = 10) and emphysematous (E, elastase instilled, n = 7) hamsters.
PO2m and mean arterial pressure (MAP) were measured in the spontaneously breathing
anesthetized hamster at inspired O2 percentages of 10, 21, and 100, and across a range
of mean MAPs from 40 to 115 mm Hg. At each inspired O2, diaphragm PO2m was significantly
(p < 0.05) lower in E animals (10%: C, 19 +/- 3; E, 9 +/- 2; 21%: C, 32 +/- 2; E, 21 +/-
2; 100%: C, 60 +/- 8; E, 36 +/- 9 mm Hg). At 21% inspired O2, the PO2m decrease was
correlated with reduced MAP in both C (r = 0.968) and E (r = 0.976) animals. We conclude
that diaphragmatic PO2m (and therefore microvascular O2 content) is decreased in
emphysematous hamsters reflecting a greater diaphragmatic O2 utilization at rest and a
lower O2 extraction reserve. According to Fick's law, this lower PO2m will mandate an
exaggerated fall in intramyocyte PO2, which is expected to accelerate muscle glycogen
depletion and consequently fatigue. This provides empirical evidence in support of one
possible mechanism for respiratory muscle failure in emphysema.
Ingenito EP, Loring SH, Moy ML, Mentzer SJ, Swanson SJ, Reilly JJ
Division of Pulmonary and Critical Care Medicine and Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. firstname.lastname@example.org
Am J Respir Crit Care Med 2001 Apr;163(5):1074-80
Interpreting improvement in expiratory flows after lung volume reduction surgery in terms of flow limitation theory.
Spirometry and pulmonary mechanics were measured pre- and postoperatively in 37 patients
undergoing bilateral lung volume reduction surgery (LVRS). The relative contributions of
changes in compliance (CL), recoil pressures (PTLC), small airway conductance (Gu), and
airway closing pressures (Ptm') to changes in expiratory flows were examined with a Taylor
series expansion of the Pride- Permutt model of flow limitation. The resulting variational
expression, deltaVmax = GudeltaPel + PeldeltaGu - GudeltaPtm' - Ptm'deltaGu -
deltaGudeltaPtm', was then used to describe how the peak flow rate (Vmax) depends on
preoperative Gu, P TLC, Ptm', and on changes (delta) in these parameters after surgery.
After LVRS, both FEV(1) and Vmax increased significantly ( DeltaFEV(1) = 28 +/- 44%;
DeltaVmax = 78 +/- 132%), and changes in FEV(1) and Vmax correlated closely (r = 0.74, p <
0.001). Among responders (DeltaFEV(1) > or = 12%; n = 19; DeltaFEV(1) = 60 +/- 38%), PTLC
increased (8.8 +/- 2.8 to 12.2 +/- 4.7 cm H2O) and the time constant for expiration (tau =
CL/Gu) decreased (2.67 +/- 0.62 to 2.35 +/- 0.55 s), while Ptm', CL, and Gu did not change.
GudeltaPel, the change in recoil weighted by preoperative conductance upstream of the
flow-limiting site, accounted for 72% of the improvement in Vmax. Among nonresponders (
DeltaFEV(1) = -6 +/- 15%, n = 18), tau increased significantly, contributing to a decline
in FEV(1)/FVC ratio. PeldeltaGu decreased (-0.25 +/- 0.68, p = 0.013), accounting for all
of the decline in Vmax. This analysis suggests that (1) improvement in expiratory flows
after LVRS is largely due to increases in recoil pressure; (2) large improvements in FEV(1)
can occur without changes in Gu or Ptm', arguing that LVRS has little effect on airway
resistance or closure; and (3) large changes in PTLC can occur without changes in CL,
supporting arguments of Fessler and Permutt (Am J Respir Crit Care Med 1998;157:715-722)
that "resizing of the lung to chest wall" is the primary mechanism by which LVRS improves
Ingenito EP, Loring SH, Moy ML, Mentzer SJ, Swanson SJ, Hunsaker A, McKee CC, Reilly JJ
Department of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. email@example.com
Am J Respir Crit Care Med 2001 Apr;163(5):1068-73
Comparison of physiological and radiological screening for lung volume reduction surgery.
Physiological and radiological criteria are both used to identify candidates for LVRS. This study compares the predictive value of these screening techniques among patients with homogeneous (Ho) and heterogeneous (He) emphysema. Preoperative inspiratory lung conductance (G(Li)) during spontaneous breathing and quantitative radioisotope V/Q scan (QVQS) results were available for 48 of 50 patients undergoing bilateral LVRS for emphysema. Ho disease (n = 21) was defined by QVQS as an upper/lower perfusion ratio (ULPR) between 0.75 and1.25. G(Li) correlated with 6-mo improvement in FEV(1) (DeltaFEV(1)-6) (r = 0.53, p < 0.001) for the entire cohort, and for patients with both Ho (n = 21, r = 0.56, p = 0.015) and He disease (n = 27, r = 0.46, p = 0.017). ULPR correlated less well with DeltaFEV(1)-6 (n = 48, r = -0.38; p = 0.008) for the cohort, and was significantly correlated with outcomes only in the subgroup of patients with He disease (r = -0.40, p = 0.04). Multivariate regression demonstrated that by combining G(Li) and ULPR criteria, 33% of the DeltaFEV(1)-6 response could be accounted for. We conclude that both physiological and radiological criteria help identify appropriate candidates for LVRS. G(Li) best identifies patients with Ho emphysema who may benefit from surgery, but would be excluded on the basis of strictly radiological criteria. ULPR helps identify patients with He disease that improves with surgery, despite unfavorable G(Li).
Am J Respir Crit Care Med 2001 Apr;163(5):1047-8
The GOLD standard for chronic obstructive pulmonary disease.
No abstract available
Dowson LJ, Newall C, Guest PJ, Hill SL, Stockley RA
Lung Investigation Unit, Nuffield House, Queen Elizabeth University Hospital, Birmingham, United Kingdom.
Am J Respir Crit Care Med 2001 Mar;163(4):936-41
Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency.
Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.
O'Donnell DE, D'Arsigny C, Webb KA
Respiratory Investigation Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada. firstname.lastname@example.org
Am J Respir Crit Care Med 2001 Mar;163(4):892-8
Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic obstructive pulmonary disease.
We studied interrelationships between exercise endurance, ventilatory demand, operational lung volumes, and dyspnea during acute hyperoxia in ventilatory-limited patients with advanced chronic obstructive pulmonary disease (COPD). Eleven patients with COPD (FEV(1.0) = 31 +/- 3% predicted, mean +/- SEM) and chronic respiratory failure (Pa(O(2)) 52 +/- 2 mm Hg, Pa(CO(2 ))48 +/- 2 mm Hg) breathed room air (RA) or 60% O(2) during two cycle exercise tests at 50% of their maximal exercise capacity, in randomized order. Endurance time (T(lim)), dyspnea intensity (Borg Scale), ventilation (V E), breathing pattern, dynamic inspiratory capacity (IC(dyn)), and gas exchange were compared. Pa(O(2)) at end-exercise was 46 +/- 3 and 245 +/- 10 mm Hg during RA and O(2), respectively. During O(2), T(lim) increased 4.7 +/- 1.4 min (p < 0.001); slopes of Borg, V E, V CO(2), and lactate over time fell (p < 0.05); slopes of Borg-V E, V E-V CO(2), V E-lactate were unchanged. At a standardized time near end-exercise, O(2) reduced dyspnea 2.0 +/- 0.5 Borg units, V CO(2) 0.06 +/- 0.03 L/min, V E 2.8 +/- 1.0 L/min, and breathing frequency 4.4 +/- 1.1 breaths/min (p [ 0.05 each). IC(dyn) and inspiratory reserve volume (IRV) increased throughout exercise with O(2) (p < 0.05). Increased IC(dyn) was explained by the combination of increased resting IRV and decreased exercise breathing frequency (r(2) = 0.83, p < 0.0005). In conclusion, improved exercise endurance during hyperoxia was explained, in part, by a combination of reduced ventilatory demand, improved operational lung volumes, and dyspnea alleviation.
Engelen MP, Wouters EF, Deutz NE, Does JD, Schols AM
Departments of Pulmonology, Maastricht University, Maastricht, The Netherlands. M.Engelen@Pul.Unimaas.NL
Am J Respir Crit Care Med 2001 Mar;163(4):859-64
Effects of exercise on amino acid metabolism in patients with chronic obstructive pulmonary disease.
Depletion of fat-free mass (FFM) significantly contributes to decreased skeletal muscle weakness and impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). FFM wasting suggests disturbances in intermediary metabolism, confirmed by data showing profound alterations in the skeletal muscle amino acid (AA) status in COPD at rest. To unravel whether there is a role for AAs in the mechanisms for skeletal muscle dysfunction in COPD, basic knowledge of AA metabolism in the muscle during exercise is important. We examined the effects of 20 min of exercise on AA metabolism in 14 patients with COPD and eight control subjects. Arterialized venous blood and a quadriceps femoris muscle biopsy were obtained before and immediately after exercise. FFM was not significantly different between the groups. In COPD, a significant reduction of most muscle AAs was present postexercise, whereas several plasma AAs were increased (p < 0.05). Consequently, sum AAs was reduced in muscle (20%; p < 0.01) and increased in plasma (16%, p < 0.05), suggesting an enhanced AA release from muscle in COPD during exercise. In the COPD group, the increase in plasma alanine and glutamine was even higher postexercise (61%, p < 0.01 and 21%, p < 0.01, respectively), suggesting enhanced nitrogen efflux. This study shows that exercise alters amino acid (intermediary) metabolism in patients with COPD and independent of the presence of FFM wasting.
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