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The effect of breathing with a positive expiratory pressure of 5 cm H2O was investigated in eight patients with COPD (mean [SD]FEV1 = 54 [13] percent predicted). Specific work of breathing (Wsp) and myoelectrical activity of the following respiratory muscles were measured at rest: scalene muscle, parasternal muscle, and abdominal muscles. Minute ventilation (VE), end-tidal CO2 (FETCO2), physiologic dead space ventilation (VD/VT), oxygen uptake (VO2), and carbon dioxide output (VCO2) were measured at rest and during an incremental bicycle exercise test. Dyspnea sensation during exercise was quantified using the CR10 Borg-scale. All measurements were performed with and without positive expiratory pressure (PEP). During PEP breathing at rest mean (SEM) Wsp increased from 0.54 (0.13) J/L to 1.08 (0.10) J/L. The SEM VE decreased from 12.4 (1.0) L/min to 10.5 (1.1) L/min, and SEM VD/VT decreased from 0.39 (0.03) to 0.34 (0.03). There was a tendency for an increased phasic respiratory muscle activity during PEP breathing of all three muscles as compared with undisturbed breathing, but the changes were not statistically significant. During the exercise test with PEP, VE, VD/VT, VO2, and VCO2 were significantly lower, and FETCO2 was significantly higher as compared with the values obtained during the exercise test with undisturbed breathing. Dyspnea sensation during the exercise test with PEP, however, was higher than during the test with undisturbed breathing. The PEP breathing at rest may be useful in patients with COPD as it increases the efficiency of ventilation by reducing dead space ventilation. This beneficial effect also occurs during exercise, but here it is accompanied by increased dyspnea sensation.
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PMID:Effects of positive expiratory pressure breathing during exercise in patients with COPD. 813 41

The purpose of this study was to determine whether supplemental oxygen-induced decreases in ventilation (VE) and mouth occlusion pressure (P0.1) in patients with COPD are related to the ventilatory or P0.1 responses to hypoxia (delta VE/delta SaO2, delta P0.1/delta SaO2). We measured these responses in 14 patients with a (mean +/- SD) FEV1 of 0.95 +/- .41 L. The VE and P0.1 were also measured while the patients sequentially breathed either room air or supplemental oxygen (1-2 L/min) for 10 min in a randomized single blind fashion. The mean (+/- SEM) SaO2 increased from 90.8 +/- 0.99 percent to 95.2 +/- 0.46 percent and the VE decreased during oxygen breathing from 12.3 +/- 0.46 to 11.6 +/- 0.47 L/min (p < 0.03). However, the individual changes in VE were not significantly related to the corresponding changes in SaO2 (CHG SaO2), (delta VE/delta SaO2), or (delta VE/SaO2) (CHG SaO2). Similarly, the P0.1 decreased from 2.50 +/- 0.27 to 2.26 +/- 0.20 cm H2O (p < 0.05), but the individual changes in P0.1 were not significantly related to (CHG SaO2), (delta P0.1/delta SaO2), or (delta PO.1/delta SaO2) (CHG SaO2).
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PMID:Does the hypoxic ventilatory response predict the oxygen-induced falls in ventilation in COPD? 844 75

The relative invasiveness of the balloon catheter technique in measuring twitch transdiaphragmatic pressure (Pdit) limits its clinical use. By phrenic stimulation we obtained swings in mouth pressure (Pmt) in six COPD patients (age 50 to 72, FEV1 18 to 48% of predicted) at relaxed FRC (rFRC) and during graded inspiratory efforts (IE; twitch occlusion, TO). At rFRC, Pmt was damped and time lagged relative to the esophageal pressure twitch (Pes(t)), as if pressure had equilibrated through an RC system. Pmt was not correlated with Pdit. Conversely, Pmt and Pes(t) were always well matched during IE [Pmt = 0.971 (SEM +/- 0.028) Pes(t), r > 0.89], possibly in relation to a decrease in upper airway compliance or more uniform pleural pressure swings. Pmt decreased with the level of voluntary diaphragmatic contraction (Pdivol) in proportion to Pdit, reflecting a progressive increase in the level of diaphragm activation. During IE, Pmt was closely related to the voluntary mouth pressure in five subjects but not in the remaining subject, indicating intersubject variability in the level of diaphragmatic recruitment relative to other inspiratory muscles. We submit that measuring Pm during inspiratory efforts upon which bilateral phrenic stimulation is superimposed offers a relatively simple method for the assessment of diaphragm activation, potentially applicable in the clinical field.
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PMID:Assessment of diaphragm function using mouth pressure twitches in chronic obstructive pulmonary disease patients. 846 19

We prospectively investigated the mechanism of airflow limitation before and after targeted emphysematous resection in 12 consecutively studied adult patients 68 +/- 4 yr of age (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic stapling techniques. Lung function, static lung elastic recoil, and airway conductance was measured 2 wk before and 5 to 6 mo after surgery. After surgery, there was a significant (p < 0.01) reduction in TLC (9.3 +/- 0.3 [mean +/- SEM] to 7.7 +/- 0.4 L), functional residual capacity, and residual volume. Airway conductance, FVC, and FEV1 (0.7 +/- 0.1 to 1.2 +/- 0.2 L) all improved significantly (p < 0.01). Lung elastic recoil increased markedly at TLC (from 10.3 +/- 0.5 to 14.6 +/- 1.0 cm H20; p < 0.001) as did maximal expiratory airflow in every patient. Analysis of maximal expiratory flow-static elastic recoil pressure curve indicated that conductance of the S segment (Gs) increased from 0.20 +/- 0.03 (mean +/- SEM) to 0.27 +/- 0.03 L/s/cm H20 (p < 0.01), and the critical transmural pressure (Ptm') decreased from 3.1 +/- 0.2 to 2.4 +/- 0.2 cm H20 (p < 0.02). Mean airway conductance increased from 0.14 to 0.22 L/s/cm H20 (p < 0.01). The improvement in maximal expiratory airflow can be primarily attributed to increased lung elastic recoil and its secondary effect on enlarging airway diameter causing increased airway conductance, increased Gs, and decreased Ptm'.
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PMID:Mechanism of short-term improvement in lung function after emphysema resection. 888 90

Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.
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PMID:Decreased C4 complement component serum levels correlate with the degree of emphysema in patients with chronic bronchitis. 926 67

The aim of this study was to compare the effect of inspiratory pressure support (IPS) on the respiratory CO2 response in 13 stable COPD patients and in 13 normal subjects. Without IPS, the slopes of the ventilatory response to CO2 were lower in the patients than in the normal subjects (mean +/- SEM, 0.82 +/- 0.19 vs. 1.69 +/- 0.31 l.min-1.mmHg-1). When IPS was applied, both groups showed, at any level of end-tidal CO2 pressure, an increase in ventilation due to an increase in tidal volume (VT) associated with a decrease in occlusion pressure (P0.1). In addition, respiratory parameters (VE, VT, P0.1, inspiratory flow) were insensitive to CO2 as long as PETCO2 remained below a threshold which was slightly above the eupneic value. However, above this CO2-threshold, no differences in slopes were observed between the IPS and control conditions in either group, except for a decrease in the P0.1 slope during IPS in the COPD patients. In conclusion, IPS induced similar respiratory changes during CO2 response in stable COPD patients and in normal subjects. Above the eupneic value, IPS did not change the slope of the ventilatory response to CO2.
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PMID:Carbon dioxide respiratory response during positive inspiratory pressure in COPD patients. 927 5

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.
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PMID:Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. 1043 Jul 26

A substantial number of patients with COPD are underweight (UW); they comprise the clinical subtype of "dyspneic" or emphysematous. To determine whether these patients are more dyspneic than normal weight (NW) patients with COPD, we quantitated the severity of dyspnea, using a modified Medical Research Council (MRC) dyspnea scale, in 33 UW and 57 NW patients and compared their pulmonary function tests (PFTs), arterial blood gases (ABGs), and respiratory muscle strength as estimated by maximum static inspiratory (PI(max)) and expiratory (PE(max)) mouth pressures (all as means +/- SEM). Body mass index was 18.7 +/- 1.2 and 24.5 +/- 1.8 kg/m(2) in UW and NW patients, respectively (p < 0.0001). The MRC dyspnea scale was 3. 1 +/- 0.9 in UW and 2.5 +/- 1.2 in NW groups (p = 0.035). All PFT and ABG parameters were similar in the two groups except for DCO (36 +/- 11% in UW and 57 +/- 17% in NW, p < 0.001) and PI(max) (55 +/- 18 mm Hg in UW and 66 +/- 19 mm Hg in NW, p = 0.020). In a stepwise multiple regression model, %DCO and %MVV combined were the best predictors of dyspnea severity (R(2) = 0.30, p = 0.001). We conclude that UW patients with COPD are more dyspneic than NW patients. Although the origin of dyspnea in COPD is multifactorial, changes in DCO and respiratory muscle strength may contribute to its intensity.
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PMID:Influence of body weight on the severity of dyspnea in chronic obstructive pulmonary disease. 1071 38

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.
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PMID:In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation. 1121 7

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.
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PMID:Marked sympathetic activation in patients with chronic respiratory failure. 1152 Jul 22


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