Effect of add-on therapy of tiotropium in COPD treated with theophylline

Background

Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators.

Objective

We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients.

Methods

In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD.

Results

Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV₁) 1.5 L [62.5% predicted]). FEV₁ in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 ± 0.13 L, p < 0.001) and 8 weeks (1.60 ± 0.13 L, p < 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV₁.

Conclusion

Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.     

Reliability of the Brazilian Portuguese version of the fatigue severity scale and its correlation with pulmonary function,dyspnea, and functional capacity in patients with COPD

OBJECTIVE:

To describe the intra-rater and inter-rater reliability of the Brazilian Portuguese version of the fatigue severity scale (FSS) in patients with COPD and to identify the presence of its association with parameters of pulmonary function, dyspnea, and functional capacity.

METHODS:

This was an observational cross-sectional study involving 50 patients with COPD, who completed the FSS in interviews with two researchers in two visits. The FSS scores were correlated with those of the Medical Research Council (MRC) scale, as well as with FEV₁, FVC, and six-minute walk distance (6MWD).

RESULTS:

The mean age of the patients was 69.4 ± 8.23 years, whereas the mean FEV₁ was 46.5 ± 20.4% of the predicted value. The scale was reliable, with an intraclass correlation coefficient of 0.90 (95% CI, 0.81-0.94; p < 0.01). The FSS scores showed significant correlations with those of MRC scale (r = 0.70; p < 0.01), as well as with 6MWD (r = –0.77; p < 0.01), FEV₁ (r = –0.38; p < 0.01), FVC (r = –0.35; p < 0.01), and stage of the disease in accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria (r = 0.37; p < 0.01).

CONCLUSIONS:

The Brazilian Portuguese version of the FSS proved reliable for use in COPD patients in Brazil and showed significant correlations with sensation of dyspnea, functional capacity, pulmonary function, and stage of the disease.     

Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model

Objective

To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator-induced lung injury (VILI).

Methods

Male, adult pathogen-free Sprague-Dawley rats weighing 300-350 g were used in this study. Animals were tracheotomized and allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF-κΒ of alveolar macrophages’ expression under the different ventilation conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL-1β were assessed as well.

Results

Rats subjected to high tidal volume showed significantly greater pulmonary permeability and lung inflammatory than the control rats. Alveolar macrophages from rats subjected to high tidal volume also showed significantly higher protein expression of TLR2 (0.59±0.049 vs. 0.35±0.036 and 0.36±0.031, both P<0.001), TLR4 (0.845±0.0395 vs. 0.401±0.026 and 0.403±0.020, both P<0.001), TLR9 (0.727±0.074 vs. 0.383±0.039 and 0.367±0.043, both P<0.001), MyD-88 (1.01±0.060 vs. 0.485±0.045 and 0.507±0.046, both P<0.001) and NF-κΒ (0.776±0.067 vs. 0.448±0.043 and 0.481±0.047, both P<0.001), as well as significantly higher concentrations of IL-6 (7.32±0.24 vs. 2.42±0.13 and 2.44±0.32, both P<0.001) and IL-1β (139.95±9.37 vs. 53.63±5.26 and 53.55±6.63, both P<0.001) than the control and low tidal volume group.

Conclusions

The overexpression of TLR2, TLR4, and TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a role in VILI.     

Evaluation of von Willebrand factor in COPD patients

OBJECTIVE:

To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers.

METHODS:

The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9). During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic.

RESULTS:

Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01). Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05). In all three groups, there was a negative correlation between FEV₁ (% of predicted) and relative serum vWF activity (r² = −0.13; p = 0.009).

CONCLUSIONS:

Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.     

Effects of bronchoscopic lung volume reduction using transbronchial infusion of autologous blood and thrombin in patients with severe chronic obstructive pulmonary disease

Background

Existing medical treatments have limitations in the management of very severe chronic obstructive pulmonary disease (COPD).

Methods

We performed bronchoscopic lung volume reduction (BLVR) using transbronchial infusion of autologous blood and thrombin (BLVR with blood) in three patients with very severe COPD whose dyspnea could not be relieved by maximum medical management. Two patients underwent BLVR with blood in the left and right lungs at intervals of a half-year or a year, and one patient underwent this procedure in only the right lung. We assessed the changes in pulmonary function, exercise capacity and quality of life before and after BLVR with blood in a total of five procedures.

Results

The subjects were 58- to 74-year-old males. Their forced expiratory volume in one second (FEV₁) percent predicted ranged from 14.8% to 23.4%. BLVR with blood achieved significant improvements as follows (values before → after the procedure, mean ± standard deviation): FEV₁ 0.45r the L → 0.76r the L (P=0.004), inspiratory capacity 1.50cityo L → 2.05±.05c L (P=0.015), 3-minute walk test 46.8nuteo m → 89.6±34.5 m (P=0.004). Lung function peaked several months after BLVR with blood and returned to nearly the baseline level in 6 months, but exercise capacity was better than that at baseline for at least 12 months. St. George’s Respiratory Questionnaire (SGRQ), measured in two patients before and 12 months after the procedure, showed remarkable improvements (−15.6 and −11.9 units).

Conclusions

BLVR with blood is an effective palliative treatment for very severe COPD.     

Effects of transdermal tulobuterol on dyspnea and respiratory function during exercise in patients with chronic obstructive pulmonary disease

Background

Poor exercise tolerability is a major barrier to improving the quality of life of patients with chronic obstructive pulmonary disease (COPD). Although COPD is often treated with long-acting β₂ adrenergic agonists, few studies have examined their effects on exercise tolerability.

Methods

In this study, Japanese COPD patients were treated with 2 mg transdermal tulobuterol, a long-acting β₂ agonist, once daily for 4 weeks. Spirometry and exercise tests were conducted at baseline and at the end of treatment. The patients conducted constant load (30 W for 5 min) and incremental load (starting at 10 W and increasing by 10 W every 1 min for 5 min to a maximum load of 50 W) exercise tests on a cycle ergometer.

Results

Thirteen patients with stable COPD participated in this study (mean age ± standard deviation (SD), 69.5±9.7 years; smoking history 55.9±27.8 pack-years). Resting spirometric parameters were unchanged at the end of treatment. The maximum Borg scale for dyspnea and the Borg scale slope (BSS) decreased significantly from baseline to the end of treatment. The threshold load of dyspnea (TLD) increased slightly, although not significantly, in the constant load test but not in the incremental load test. There were no changes in respiratory parameters during exercise after treatment.

Conclusions

In conclusion, we found that treatment with transdermal tulobuterol for 4 weeks improved self-assessed dyspnea in Japanese COPD patients during constant and incremental exercise tests. This improvement in dyspnea may encourage patients to perform daily life activities or regular physical activity.     

Higher level of heme oxygenase-1 in patients with stroke than TIA

Background

There is a reverse relationship between serum bilirubin level and incidence of stroke, heme oxygenase-1 (HO-1) can catalyze heme into bilirubin, it is unknown the association of HO-1 level with risk of stroke.

Methods

Sixty patients with stroke and fifty patients with transient ischemic attack (TIA) were recruited. Serum level of HO-1, total and direct bilirubin, alanine transaminase, live function, lipid profile and infection status of patients were measured.

Results

Significant differences were found between two groups in terms of serum levels of HO-1 (163.6±58.7 vs. 141.2±49.7, P=0.032), total bilirubin (10.1±4.6 vs. 15.8±2.7, P<0.001), direct bilirubin (3.2±2.1 vs. 5.9±1.2, P<0.001), fasting glucose (6.7±3.1 vs. 4.9±1.3, P<0.001), cholesterol (4.4±1.1 vs. 3.9±0.8, P=0.005) and diastolic blood pressure (DBP) (84.9±9.4 vs. 81.3±9.2, P=0.046). In multivariate analysis, serum direct bilirubin (OR, 2.83; P<0.001), total bilirubin (OR, 1.82, P=0.001), DBP (OR, 0.88, P=0.041), and fasting glucose (OR, 0.34, P<0.001) were independent predictors of stroke.

Conclusions

Serum HO-1 level is higher in patients with stroke than TIA, but the bilirubin level is lower in patients with stroke than TIA and is an independent predictor of stroke. Further studies are warranted to clarify the underlying link among HO-1, bilirubin and stroke.     

Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in rats

Objective

We hypothesized that pretreatment with sivelestat therapy could attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat model.

Methods

The neutrophil elastase inhibitor was administered intraperitoneally 30 min before and at the initiation of ventilation. The rats were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV) early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI scores were investigated.

Results

The ratio of wet-to-dry weight, BALF neutrophil and protein, tissue MDA and VILI scores were significantly increased in the VILI group compared to the sham group [3.85±0.32 vs. 9.05±1.02, P<0.001; (0.89±0.93)×10⁴ vs. (7.67±1.41)×10⁴ cells/mL, P<0.001; 2.34±0.47 vs. 23.01±3.96 mg/mL, P<0.001; 14.43±1.01 vs. 36.56±5.45 nmol/mg protein, P<0.001; 3.78±0.67 vs. 7.00±1.41, P<0.001]. This increase was attenuated in the early sivelestat group compared with the sivelestat group [wet-to-dry ratio: 6.76±2.01 vs. 7.39±0.32, P=0.032; BALF neutrophil: (5.56±1.13)×10⁴ vs. (3.89±1.05)×10⁴ cells/mL, P=0.021; BALF protein: 15.57±2.32 vs. 18.38±2.00 mg/mL, P=0.024; tissue MDA: 29.16±3.01 vs. 26.31±2.58, P=0.049; VILI scores: 6.33±1.41 vs. 5.00±0.50, P=0.024].

Conclusions

Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.     

A modified nebulization modality versus classical ultrasonic nebulization and oxygen-driven nebulization in facilitating airway clearance in patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial

Background

Ultrasonic nebulization (UN) and oxygen-driven nebulization (ON), two commonly used modalities for nebulization inhalation, are not ideally suitable for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

A total of 91 patients with AECOPD were randomized to three groups given different nebulization modalities: ON, UN, and ultrasonic nebulization with warming and oxygen (UNWO). The sputum clearance, lung function, changes in physiological measures such as peripheral oxygen saturation (SpO₂) and tolerance to these nebulization modalities were recorded and compared among the three groups.

Results

The time to the first expectoration was shorter and the sputum volume was larger after UN and UNWO than after ON (both P<0.01). Compared with pre-nebulization, SpO₂ significantly increased (P<0.01) and the dyspnea decreased significantly (P<0.05) after UNWO. The SpO₂ and dyspnea post-UNWO were significantly better than those post-UN (P<0.01, P<0.05), but not statistically different from those post-ON (both P>0.05). UNWO demonstrated significantly greater comfort and longer duration of nebulization than UN (P<0.01, P<0.05), but no significant differences in these respects from ON (both P>0.05). Forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) decreased significantly after UNWO (P<0.05, P<0.01, and P<0.01, respectively).

Conclusions

UNWO may promote expectoration of sputum with fewer adverse reactions and a higher level of comfort than simple UN and ON. Therefore, it can be used as an adjuvant therapy for AECOPD patients.     

Antimicrobial peptide LL-37 circulating levels in chronic obstructive pulmonary disease patients with high risk of frequent exacerbations

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) increase the decline in lung function, deterioration in health status and risk of death. The assessment of exacerbation risk is important in the grading of COPD. The most common cause of COPD exacerbation is respiratory tract infection. The only known human cathelicidin antimicrobial peptide, LL-37, play an important role in innate defense against infection. Its gene expression is regulated by the bioactive form of vitamin D. The objective of the present study was to explore the relationship between LL-37 plasma levels, vitamin D status and exacerbation risk in patients with COPD.

Methods

COPD patients and normal subjects were recruited from Beijing Hospital for this study. COPD patients were divided into low risk group and high risk group according to the criteria of GOLD strategy. The plasma concentrations of LL-37 were measured by ELISA technique to explore the difference in LL-37 levels between groups. The plasma levels of 25-hydroxy vitamin D [25(OH)D] were analyzed using electrochemiluminescence immunoassay (ECLIA).

Results

A total of 84 COPD patients and 51 normal subjects (control group) were recruited. COPD patients were divided into low risk group (37 cases) and high risk group (47 cases), depending on forced expiratory volume in one second (FEV₁)%pred and exacerbation frequency in the previous year. The plasma concentrations of LL-37 in control group, low risk group and high risk group were 20.7±5.8, 19.5±4.1 and 17.9±3.9 µg/L respectively. The plasma concentration of LL-37 was significantly lower in high risk group than in control group (P=0.006). But there was no significant difference between low risk group and high risk group (P=0.152). The plasma concentrations of 25(OH)D in control group, low risk group and high risk group were 18.1±9.4, 13.1±6.9 and 9.3±5.8 ng/mL respectively. The plasma concentration of 25(OH)D was significantly higher in control group than in low risk group (P=0.004) or high risk group (P<0.001). The plasma concentration of 25(OH)D was significantly lower in high risk group than in low risk group (P=0.031). Hospitalization frequency for COPD exacerbations was negative correlated with plasma levels of LL-37 (r=−0.290, P=0.048) and 25(OH)D (r=−0.341, P=0.020) in high risk group. There was not significant correlation between LL-37 and 25(OH)D in COPD patients (r=0.115, P=0.303).

Conclusions

The plasma levels of LL-37 and 25(OH)D were lower in COPD patients with high risk of frequent exacerbations than normal subjects. Low plasma levels of LL-37 and 25(OH)D might be predictors of exacerbation risk in COPD patients.     

Efficacy and safety of endobronchial valves for advanced emphysema: a meta analysis

Objective

A meta-analysis was undertaken to evaluate the efficacy and safety of bronchoscopic lung volume reduction with endobronchial valves (EBV) for advanced emphysema.

Methods

A systematic search was performed from PubMed, EMBASE, CNKI, Cochrane Library database. Randomized control clinical trials on treatment of emphysema for 3-12 months with the EBV compared with standard medications and sham EBV were reviewed. Inclusion criteria were applied to select patients with advanced emphysema treated with EBV. The primary outcome was the percentage of the forced expiratory volume in the first second (FEV₁%). Secondary outcomes included St George’s Respiratory Questionnaire (SGRQ) score, the distance of the 6-minute walk (6MWD) test, the Modified Medical Research Council (MMRC) dyspnoea score, cycle ergometry workload, and the rate of the six major complications at 3 or 12 months. Fixed- or random-effects models were used and weighted mean differences (WMD), relative risks (RR) and 95% confidence intervals (CI) were calculated.

Results

Three trials (565 patients) were considered in the meta-analysis. EBV patients yielded greater increases in FEV₁% than standard medications (WMD =6.71; 95% CI, 3.31 to 10.10; P=0.0001), EBV patients also demonstrated a significant change for SGRQ score (WMD =−3.64; 95% CI, −5.93 to −1.34; P=0.002), MMRC dyspnoea score (WMD =−0.26; 95% CI, −0.44 to -0.08; P=0.004), and cycle ergometry workload (WMD =4.18; 95% CI, 2.14 to 6.22; P<0.0001). A similar level was evident for 6MWD (WMD =11.66; 95% CI, −3.31 to 26.64; P=0.13). EBV may increase the rate of hemoptysis (RR =5.15; 95% CI, 1.16 to 22.86; P=0.03), but didn’t increase the adverse events including mortality, respiratory failure, empyema, pneumonia, pneumothrax. The overall rates for complications compared EBV with standard medications and sham EBV was not significant (RR =2.03; 95% CI, 0.98 to 4.21; P=0.06).

Conclusions

EBV lung volume reduction for advanced emphysema showed superior efficacy and a good safety and tolerability compared with standard medications and sham EBV, further more randomized controlled trial (RCT) studies are needed to pay more attention to the long-term efficacy and safety of bronchoscopic lung volume reduction with EBV in advanced emphysema.     

What is the difference between FEV1 change in percentage predicted value and change over baseline in the assessment of bronchodilator responsiveness in patients with COPD?

Background

Several criteria are clinically applied in the assessment of significant bronchodilator responsiveness in chronic obstructive pulmonary disease (COPD). The present study aimed to investigate the differences in various degree of severity of COPD among these criteria.

Methods

After 400 micrograms of salbutamol administered via spacer by metered dose inhaler (MDI), forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) changes (including percentage change, absolute change and absolute change in percentage predicted value) were retrospectively analysed in 933 stable patients with mild-to-very-severe COPD. Significant bronchodilator responsiveness was assessed using American Thoracic Society and European Respiratory Society (ATS-ERS) criterion based on FEV₁ or/and FVC (both ≥12% increase over baseline and ≥200 mL) and FEV₁ percentage predicted criterion (≥10% absolute increase in percentage predicted FEV₁) in different grades of COPD.

Results

Of the patients [age 66.8 years, baseline FEV₁ 974 mL (39.3% predicted) and FVC 2,242 mL], mean improvements were 126 mL in FEV₁ and 265 mL in FVC; 21.4% and 45.3% met ATS-ERS criterion based on FEV₁ and FVC, respectively; and 13.5% met FEV₁ percentage predicted criterion. The responsive ratios of ATS-ERS criterion based on FEV₁ to FEV₁ percentage predicted criterion in grade I, II, III and IV of COPD were 0.95^:1.26^:2.53^:6.00, respectively (P<0.01 in grade II and P<0.001 in grade III). As the degree of severity increased, the mean improvement of FEV₁ was reduced; on the contrary, that of FVC was increased.

Conclusions

Compared with FEV₁ percentage predicted criterion, ATS-ERS criterion based on FEV₁ as well as FVC, the later in particular, detected a larger percentage of patients with significant responsiveness. The increasing difference was relevant as a function of the severity of airflow obstruction.KEY WORDS : Airflow obstruction, bronchodilator responsiveness, chronic obstructive pulmonary disease (COPD), forced vital capacity (FVC), forced expiratory volume in one second (FEV₁)     

Glutathione and nitrite levels in induced sputum at COPD patients and healthy smokers

Objectives

The role of oxidative stress at the pathogenesis of chronic obstructive pulmonary disease (COPD) is known. The aim of this study is to investigate the oxidative stress with sputum induction that is a simple method in COPD patients and healthy smokers.

Methods

Sputum induction was performed in 21 COPD patients (10 stable, 11 acute exacerbations), nine healthy smokers, and ten healthy non-smokers. Glutathione, NO₂^– levels, and cell counts at sputum, and plasma NO₂^– contents were evaluated in all subjects.

Results

Mean sputum glutathione and NO₂^– levels were significantly higher in acute exacerbations with COPD patients than healthy smokers (P=0.007 and P<0.001 respectively), and non-smokers (P<0.001 and P<0.001 respectively). On the other hand, sputum glutathione and NO₂^– levels did not show significant differences between stable and acute exacerbations with COPD patients. Although, sputum glutathione levels were higher in stable COPD patients than healthy smokers’, no statistically significant difference was established. In addition, sputum glutathione levels were significantly higher in healthy smokers than non-smokers (P<0.001).

Conclusions

As a result, we can say that oxidative stress increases not only in COPD patients but also in healthy smokers. In addition, sputum induction that is a simple method can be used to demonstrate to show oxidative stress.     

A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV₁) than those patients who have stopped smoking.

OBJECTIVES:

To assess the effect of tiotropium on pre-dose (trough) FEV₁ in patients with COPD followed in Canada.

METHODS:

A total of 913 patients were randomly assigned to receive either tiotropium 18 μg once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV₁, FEV₆ and forced vital capacity), symptoms, health-related quality of life (St George’s Respiratory Questionnaire) and exacerbations were examined.

RESULTS:

Tiotropium improved trough FEV₁ in both current and ex-smokers compared with placebo. Baseline FEV₁ in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14±0.04 L (P<0.001) in the smoker group and 0.08±0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV₆ compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George’s Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005).

CONCLUSIONS:

Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.     

Postoperative outcome after coronary artery bypass grafting in chronic obstructive pulmonary disease

BACKGROUND:

It is uncertain if the presence and severity of airflow obstruction in chronic obstructive pulmonary disease (COPD) is predictive of surgical morbidity and mortality after coronary artery bypass grafting (CABG).

METHODS:

Retrospective study of patients who underwent CABG between 1998 and 2003 in a university-affiliated hospital for whom a preoperative spirometry was available. COPD was diagnosed in smokers or ex-smokers 50 years of age or older in the presence of irreversible airflow obstruction. Patients were divided into three groups depending on the spirometry: controls (forced expiratory volume in 1 s [FEV₁] 80% or more, FEV₁/forced vital capacity [FVC] greater than 0.7), mild to moderate COPD (FEV₁ 50% or more and FEV₁/FVC 0.7 or less) and severe COPD (FEV₁ less than 50% and FEV₁/FVC 0.7 or less).

RESULTS:

Among the 411 files studied, 322 (249 men, 68±8 years of age) were retained (controls, n=101; mild to moderate COPD, n=153; severe COPD, n=68). The mortality rate (3.0%, 2.6% and 0%, respectively) was comparable among the three groups. Patients with severe COPD had a slightly longer hospital stay than controls (mean difference 0.7±1.4 days, P<0.05). Pulmonary infections were more frequent in severe COPD (26.5%) compared with mild to moderate COPD (12.4%) and controls (12.9%), P<0.05. Atrial fibrillation tended to be more frequent in severe COPD than in the other two groups.

CONCLUSION:

Mortality rate associated with CABG surgery is not influenced by the presence and severity of airflow obstruction in patients with COPD. The incidence of pulmonary infections and length of hospital stay were increased in patients with severe COPD.     

Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension

Objective

To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs.

Methods

AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated.

Results

A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG.

Conclusions

AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD.     

Effects of yoga training in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Introduction

Currently, several studies have assessed the effect of yoga training on the management of chronic obstructive pulmonary disease (COPD), but these studies involved a wide variation of sample and convey inconclusive results. Hence, the present study was performed a systematic review and meta-analysis to investigate the efficacy of yoga training in COPD patients.

Methods

PubMed, EMBASE, the Cochrane Library, Google Scholar, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcomes were forced expiratory volume in one second (FEV₁), FEV₁% predicted (% pred). Secondary outcomes included 6-min walking distance (6 MWD), arterial oxygen tension (PaO₂), and arterial carbon dioxide tension (PaCO₂). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I² test.

Results

Five randomized controlled trials (RCTs) involving 233 patients fulfilled the inclusion criteria. Yoga training significantly improved FEV₁ (WMD: 123.57 mL, 95% CI: 4.12-243, P=0.04), FEV₁% pred (WMD: 3.90%, 95% CI: 2.27-5.54, P<0.00001), and 6 MWD (WMD: 38.84 m, 95% CI: 15.52-62.16, P=0.001). However, yoga training had no significant effects on PaO₂ (WMD: 1.29 mmHg, 95% CI: –1.21-3.78, P=0.31) and PaCO₂ (WMD: –0.76 mmHg, 95% CI: –2.06-0.53, P=0.25).

Conclusions

The current limited evidence suggested that yoga training has a positive effect on improving lung function and exercise capacity and could be used as an adjunct pulmonary rehabilitation program in COPD patients. However, further studies are needed to substantiate our preliminary findings and to investigate the long-term effects of yoga training.     

Systemic inflammation after inspiratory loading in chronic obstructive pulmonary disease

Objective

Patients with chronic obstructive pulmonary disease (COPD) present systemic inflammation. Strenuous resistive breathing induces systemic inflammation in healthy subjects. We hypothesized that the increased respiratory load that characterizes COPD can contribute to systemic inflammation in these patients.

Patients and methods

To test this hypothesis, we compared leukocyte numbers and levels of circulating cytokines (tumor necrosis factor alpha [TNFα], interleukin-1β [IL-1β], IL-6, IL-8, and IL-10), before and 1 hour after maximal incremental inspiratory loading in 13 patients with stable COPD (forced expiratory volume in one second [FEV₁] 29 ± 2.5% ref) and in 8 healthy sedentary subjects (FEV₁ 98 ± 5% ref).

Results

We found that: (1) at baseline, patients with COPD showed higher leukocyte counts and IL-8 levels than controls (p < 0.01); and, (2) one hour after maximal inspiratory loading these values were unchanged, except for IL-10, which increased in controls (p < 0.05) but not in patients with COPD.

Conclusions

This study confirms the presence of systemic inflammation in COPD, shows that maximal inspiratory loading does not increase the levels of pro-inflammatory cytokines (IL-1β, IL-8) in COPD patients or controls, but suggests that the former may be unable to mount an appropriate systemic anti-inflammatory response to exercise.     

Obesity and chronic obstructive pulmonary disease: Is fatter really better?

BACKGROUND:

Overweight/obesity is associated with longer survival in chronically ill patients, a phenomenon referred to as the ‘obesity paradox’.

OBJECTIVE:

To investigate whether the obesity paradox in patients with chronic obstructive pulmonary disease (COPD) is due to fat accumulation or confounding factors.

METHODS:

A total of 190 patients with stable COPD who underwent a mean (± SD) follow-up period of 72±34 months were enrolled. Anthropometry, pulmonary function tests, midthigh muscle cross-sectional area obtained using computed tomography (MTCSA_CT), arterial blood gas and exercise testing data were measured at baseline. Patients were categorized into two subgroups according to body mass index (BMI) <25 kg/m² or ≥25 kg/m² (normal and overweight/obese, respectively).

RESULTS:

Seventy-two patients (38%) died during the follow-up period. Survival tended to be better in the overweight/obese patients but this difference did not reach statistical significance. Overweight/obese patients had better lung function and a larger MTCSA_CT than those with normal BMI (P<0.001). Overweight/obese patients also had a significantly higher peak work rate than patients with normal BMI (P<0.001). PaO₂ and PaCO₂ were not significantly different in the two groups. When adjusted for PaCO₂, peak work rate and MTCSA_CT, the tendency for improved survival in overweight/obese patients disappeared. In fact, when these variables were considered in the survival analysis, patients with lower BMI tended to have better survival.

CONCLUSION:

These results suggest that important confounders, such as hypercapnia, exercise capacity and muscle mass, should be considered when interpreting the association between increased BMI and survival in patients with COPD.     

Initial synchronized intermittent mandatory ventilation versus assist/control ventilation in treatment of moderate acute respiratory distress syndrome: a prospective randomized controlled trial

Background

Assist/control (A/C) ventilation may induce delirium in patients with acute respiratory distress syndrome (ARDS). We conducted a trial to determine whether initial synchronized intermittent mandatory ventilation with pressure support (SIMV + PS) could improve clinical outcomes in these patients.

Methods

Intubated patients with moderate ARDS were enrolled and we compared SIMV + PS with A/C. Identical sedation, analgesia and ventilation strategies were performed. The co-primary outcomes were early (≤72 h) partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) and incidence of delirium. The secondary outcomes were all-cause in-hospital mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, and duration of mechanical ventilation and hospital stay.

Results

We screened 2,684 patients and 40 patients were enrolled in our study. In SIMV + PS, early (≤72 h) PaO₂/FiO₂ was greater improved than that at baseline and that in A/C (P<0.05) with lower positive end-expiratory pressure (PEEP) (8.7±3.0 vs. 10.3±3.2, P<0.001) and FiO₂ (58%±18% vs. 67%±19%, P<0.001). We found more SIMV + PS success (defined as SIMV + PS successfully applied without switching to A/C) (100.0% vs. 16.7%, P<0.001), less male (46.3% vs. 85.7%, P=0.015) and pulmonary etiology of ARDS (53.8% vs. 92.9%, P=0.015), and lower PEEP (9.1±3.1 vs. 10.3±3.3, P=0.004) and FiO₂ (58%±19% vs. 71%±19%, P<0.001) in survival patients. However, there were no significant differences in incidence of delirium and mortality, dosages of analgesics and sedatives, incidence of patient-ventilator asynchrony, duration of mechanical ventilation and hospital stay (P>0.05).

Conclusions

In patients with moderate ARDS, SIMV + PS can safely and effectively improve oxygenation, but does not decrease mortality, incidence of delirium and patient-ventilator asynchrony, dosages of analgesics and sedatives, and duration of mechanical ventilation and hospital stay.