Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease

Skeletal muscle dysfunction contributes to poor exercise performance in patients with chronic obstructive pulmonary disease (COPD). Increased oxygen radicals and nitric oxide (NO) have been proposed as mechanisms. In this study, we assessed the levels of protein oxidation (carbonyl formation), lipid peroxidation (4-hydroxy-2-nonenal formation), catalase and Mn-superoxide dismutase (Mn-SOD) expressions, nitric oxide synthases (NOSs), and protein tyrosine nitration in quadriceps muscles of 12 patients with patients with COPD and 6 control subjects. Lipid peroxidation was elevated in muscles of patients with patients with COPD as compared with control subjects, but protein oxidation was not. Muscle Mn-SOD but not catalase protein expression was significantly higher (200%) in patients with patients with COPDas compared with control subjects. Expression of neuronal NOS and endothelial NOS isoforms did not differ between control subjects and patients with COPD, whereas no inducible NOS protein expression was detected in limb muscles of the two groups of subjects. In patients with COPD, neuronal NOS expression correlated negatively with the degree of the airway obstruction (%FEV1 predicted). 3-Nitrotyrosine levels were significantly elevated in muscles of patients with COPDas compared with control subjects, and correlated positively with nNOS protein levels. These results indicate the development of both oxidative and nitrosative stresses in the quadriceps of patients with COPD, suggesting their involvement in muscle dysfunction.     

Injury of peripheral muscles in smokers with chronic obstructive pulmonary disease

Muscle injury has clinical relevance in diseased individuals because it is associated with muscle dysfunction in terms of decreased strength and/or endurance. This study was aimed at answering three questions: whether the presence of chronic obstructive pulmonary disease (COPD) is associated with peripheral muscle injury; whether muscle injury is associated with some of the relevant functional impairment in the muscles; and whether muscle injury can be solely justified by deconditioning. Twenty-one male COPD patients were eligible for the study. Seven healthy volunteers recruited from the general population were included as controls. Function of the quadriceps muscle was assessed through specific single-leg exercise (strength and endurance). Cellular (light microscopy) and subcellular (electron microscopy) techniques were used to evaluate muscle injury on biopsies from the vastus lateralis muscle. Signs of injury were found in muscles from both control and COPD patients, not only in cases showing severe airflow obstruction but also in the mild or moderate stages of the disease. Current smoking and presence of COPD were significantly associated with increased injury of the muscle as assessed by light and electron microscopy techniques. The authors conclude that peripheral muscle injury is evident in mild, moderate, and severe stages of COPD even in the absence of respiratory failure, hypercapnia, chronic steroid treatment, low body weight, or some coexisting disease. These findings support the theory that systemic factors with deleterious effect are acting on peripheral muscles of smokers with COPD, increasing the susceptibility of the muscle fibers to membrane and sarcomere injury.     

Corticospinal control of respiratory muscles in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) face an increased respiratory load and in consequence have an elevated respiratory drive. We used transcranial magnetic stimulation (TMS) to investigate associated changes in corticospinal excitability both at rest and during voluntary facilitation at different levels of inspiratory effort. Diaphragm and abdominal motor thresholds were significantly lower in COPD than healthy controls, but the quadriceps response was the same. In patients there was a significant increase in diaphragm response from rest during 20% inspiratory efforts but no further increase with greater efforts. In controls there was a further stepwise increase at 40% and 60% of inspiratory effort. The cortical silent period was significantly shorter in COPD. Using paired stimulation to study intracortical inhibitory and excitatory circuits we found significantly less excitability of intracortical facilitatory circuits in patients at long (>7 ms) interstimulus intervals. These results suggest that there is a ceiling effect in motor control output to the respiratory muscles of patients with COPD.     

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease

Aim: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. Methods: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. Results: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent K_m for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 μm , P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts (P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O₂ kg^?1 min^?1 (P < 0.05) only in the COPD group. Conclusion: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power.     

Electromyographic fatigue thresholds of the superficial muscles of the quadriceps femoris

The purpose of this investigation was to compare the thresholds of neuromuscular fatigue determined simultaneously from the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) muscles using the electromyographic fatigue threshold (EMG_FT) test, Eight adult volunteers [mean (SD) age, 33 (10) years] served as subjects for this investigation. The results of a one-way repeated measured ANOVA indicated that there was a significant (P < 0.05) difference among the mean EMG_FT values for the VL [248(31)W], VM [223(43)W] and RF [220(30)W] muscles. Tukey post-hoc comparisons indicated that the EMG_FT for the RF was significantly (P < 0.05) lower than that of the VL. These findings suggested that during cycle ergometry there is a dissociation in neuromuscular fatigue characteristics of the superficial muscles of the quadriceps femoris group.     

Right ventricular function in patients with chronic obstructive pulmonary disease

Summary Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3±6%). During exercise a significant (p<0.001) decrease of RVEF to 38.8±6.7% occurred. The pumonary artery mean pressures were 19.9±3.8 at rest. During exercise a significant (p<0.001) increase to 41±9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (>35 mm Hg) and lower ejection fractions (<35% RVEF). Radionuclide venticulography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.Abbreviations CI Cardiac index (l/min/m²) - CO Cardiac output (l/min) - COPD Chronic obstructive pulmonary disease - FEV₁ Forced expiratory volume in the first second (ml) - HR Heart rate (B/min) - PAd Pulmonary artery diastolic pressure (mm Hg) - PAP Pulmonary artery mean pressure (mm Hg) - PAs Pulmonary artery peak pressure (mm Hg) - PVR Pulmonary vascular resistance (dyn·s·cm^–5) - PwP Pulmonary capillary wedge pressure (mm Hg) - RAP Right arterial pressure (mm Hg) - Raw Airway resistance (cm H₂/l/s) - RNV Radionuclide ventriculogram - RV Residual volume (l) - RVEF Right ventricular ejection fraction (%) - RVEDVI Right ventricular enddiastolic volume index (ml/m²) - RVEDVI SVI RVEF (ml/m²) - RVESVI Right ventricular endsystolic index (m²/m²) - SVI Stroke volume index (ml/m²) - TLC Total lung capacity (l) - VC Vital capacity (l)     

Neuromuscular transmission in hypoxemic patients with chronic obstructive pulmonary disease

Many studies have focused on the systemic effects of chronic obstructive pulmonary disease (COPD), but none has examined neuromuscular junction transmission (NMT). We evaluated NMT dysfunction using single-fiber electromyography (SFEMG) in patients with COPD. Twenty patients with COPD and 20 age-matched healthy controls were included in the study. All patients and controls underwent SFEMG. Abnormal NMT was found in seven of 20 patients (35%), but in none of the control subjects. The COPD patients were subgrouped according to the presence of hypoxemia. The patients with normoxemia were classified as Group 1, and the patients with hypoxemia were classified as Group 2. Abnormal NMT was found in six patients in Group 2 and in one in Group 1. While there was significant difference in terms of abnormal NMT between Group 2 and the controls, there was none between Group 1 and the controls. Our results show that NMT abnormalities can be present in hypoxemic patients with COPD.     

Analysis of microbiota in stable patients with chronic obstructive pulmonary disease

To identify the bacterial diversity (microbiota) in expectorated sputum, a pyrosequencing method that investigates complex microbial communities of expectorated sputum was done in 19 stable chronic obstructive pulmonary disease patients (mean (SD) FEV1: 47 (18%) of predicted value). Using conventional culture, 3 phyla and 20 bacterial genera were identified, whereas the pyrosequencing approach detected 9 phyla and 43 genera (p < 0.001). In sputum the prevalent genera with pyrosequencing approach were Streptococcus, Actinomyces, Neisseria, Haemophilus, Rothia, Fusobacterium, Gemella, Granulicatella, Porphyromonas, Prevotella and Veillonella. Enterobacteriaceae, detected frequently in conventional culture, were not significantly detected with pyrosequencing methods. In addition, we found that important pathogens such as Haemophilus and Moraxella were detected more frequently with the new genetic procedures. The presence of Enterobacteriaceae is probably overestimated with conventional culture, whereas other difficult cultivable pathogens are underestimated. These studies open a new perspective for evaluating the role of bacterial colonization in chronic obstructive pulmonary disease pathogenesis and progression.     

The safety of ECT in patients with chronic obstructive pulmonary disease

BACKGROUND: Electroconvulsive therapy (ECT) involves the administration of general anesthesia and assisted ventilation while the patient is apneic. OBJECTIVE: Care must be taken to screen for significant pulmonary dysfunction before treatment. Very little has been written about the safety and management strategy of ECT patients with chronic obstructive pulmonary disease (COPD). METHOD: In this retrospective chart review, authors describe their experience with patients in recent years who had this disorder and were treated with ECT. RESULTS: Authors list recommendations for the pre-ECT work up and anesthetic management during and after the treatments. CONCLUSION: Recent guidelines recommend administration of patients' prescribed inhalers on the morning of ECT treatment. Also, caution is recommended when using ECT in patients taking theophylline because this drug has been associated with prolonged seizures and status epilepticus in these patients.     

Chronic Chlamydia pneumonia infection in patients with chronic obstructive pulmonary disease

The aim of our study was to evaluate the frequency of Chlamydia pneumoniae infection (especially chronic infection) in COPD patients. Microimmunofluorescence method has been applied Chlamydia pneumoniae Micro-IF test (Labsystems) has been used. The levels of specific IgG, IgA and IgM have been estimated in patients' serum. According to serologic criteria, 64.1% of COPD patients and 20.5% of healthy controls appeared to be chronically infected with Chlamydia pneumoniae (p < 0.001). Taking in account COPD severity, persistent Chlamydia pneumoniae infection has been present in 68.2%, 57.1%, and 50% of patients with severe, moderate and mild COPD, respectively. Our study has revealed that chronic Chlamydia pneumoniae infection occurs more frequently in COPD patients than in healthy controls and in patients with severe COPD than in ones with mild and moderate disease. It is possible that persistent Chlamydia pneumoniae infection can initiate or amplify inflammatory reactions in the respiratory tract. The results suggest a need to diagnose chronic Chlamydia pneumoniae infection in COPD patients and, if confirmed, to take an attempt of antimicrobial therapy.     

运动锻炼对慢性阻塞性肺疾病患者肺康复的干预效果

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种具有气流受限特征,可以预防和治疗的慢性疾病。该疾病患病率和病死率较高,且严重影响患者的生命质量,给患者家庭和社会带来沉重的经济负担。运动锻炼可以改善COPD患者的呼吸困难和疲劳状况,提高运动能力、肌肉力量和生活质量,还能减少住院率。研究表明,不同类型的运动锻炼对COPD的干预效果存在差异,如步行锻炼可以改善COPD患者的身体功能和运动耐受性,传统抗阻运动锻炼可以改善COPD患者的上下肢肌肉强度和运动能力。本文综述了不同类型的有氧运动和抗阻运动对不同病程COPD患者的干预效果,强调了运动处方个性化的重要性,并讨论了运动风险和规避方法,为慢阻肺患者的运动康复提供指导性建议。     

Characteristics of impaired gas exchange in patients with chronic obstructive pulmonary disease

Eleven patients with chronic obstructive pulmonary disease (COPD), placed in a supine position, were given a mixture of 0.1% CO and 21% O2 in N2 as inspired gas and normal saline containing the six inert gases including SF6, ethane, cyclopropane, halothane, diethyl ether and acetone via the antecubital vein. After the steady state was established, the expired gas was collected and both arterial and mixed venous blood were simultaneously sampled through the catheter inserted either into the femoral or pulmonary artery. Assuming that mass transfer efficiency of a given indicator gas at each gas exchange unit would be limited by the ratio of ventilation to perfusion (VA/Q) and by that of diffusive conductance to perfusion (G/Q), the data were analyzed by means of a lung model with 20 units along the VA/Q and G/Q axes, respectively. By application of the method of weighted least-squares combined with the idea of constrained optimization, the data were transformed into a virtually continuous distribution of Q against VA/Q and G/Q axes. Analytical results revealed that: 1) patients with advanced COPD show widening of VA/Q distribution accompanied with a significant contribution of either high VA/Q (emphysematous change) or low VA/Q area (peripheral airway involvement). and 2) their Q distributions along the G/Q axis are unimodal but have an area with a relatively low G/Q, indicating a small but appreciable contribution of diffusion limitation to their hypoxemia. In conclusion, the findings consistently suggest that inhomogeneity of G/Q may partly be responsible for the impaired gas exchange in the cases of COPD.     

Preoperative pulmonary rehabilitation in patients with non-small cell lung cancer and chronic obstructive pulmonary disease

Introduction

The aim of this study was to assess the effects of preoperative pulmonary rehabilitation (PPR) on preoperative clinical status changes in patients with chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC), and net effects of PPR and cancer resection on residual pulmonary function and functional capacity.

Material and methods

This prospective single group study included 83 COPD patients (62 ±8 years, 85% males, FEV₁ = 1844 ±618 ml, Tiffeneau index = 54 ±9%) with NSCLC, on 2–4-week PPR, before resection. Pulmonary function, and functional and symptom status were evaluated by spirometry, 6-minute walking distance (6MWD) and Borg scale, on admission, after PPR and after surgery.

Results

Following PPR significant improvement was registered in the majority of spirometry parameters (FEV₁ by 374 ml, p < 0.001; VLC by 407 ml, p < 0.001; FEF₅₀ by 3%, p = 0.003), 6MWD (for 56 m, p < 0.001) and dyspnoeal symptoms (by 1.0 Borg unit, p < 0.001). A positive correlation was identified between preoperative increments of FEV₁ and 6MWD (r _s = 0.503, p = 0.001). Negative correlations were found between basal FEV₁ and its percentage increment (r _s = –0.479, p = 0.001) and between basal 6MWD and its percentage change (r _s = –0.603, p < 0.001) during PPR. Compared to basal values, after resection a significant reduction of most spirometry parameters and 6MWD were recorded, while Tiffeneau index, FEF₂₅ and dyspnoea severity remained stable (p = NS).

Conclusions

Preoperative pulmonary rehabilitation significantly enhances clinical status of COPD patients before NSCLC resection. Preoperative increase of exercise tolerance was the result of pulmonary function improvement during PPR. The beneficial effects of PPR were most emphasized in patients with initially the worst pulmonary function and the weakest functional capacity.     

Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease

AIMS: To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD). METHODS AND RESULTS: Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid-Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05). CONCLUSIONS: COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD.     

Potential drug-drug interactions in hospitalized patients with chronic heart failure and chronic obstructive pulmonary disease

Introduction

Polypharmacy is common in patients with chronic heart failure (HF) and/or chronic obstructive pulmonary disease (COPD), but little is known about the prevalence and significance of drug-drug interactions (DDIs). This study evaluates DDIs in hospitalized patients.

Material and methods

We retrospectively screened medical charts over a 6-month period for diagnosis of chronic HF and/or COPD. Potential DDIs were evaluated using Lexi-Interact software.

Results

Seven hundred and seventy-eight patients were included in the study (median age 75 years, 61% men). The median number of drugs on admission and discharge was 6 (interquartile range (IQR) 4–9) and 7 (IQR 5–), respectively (p = 0.10). We recorded 6.5 ±5.7 potential DDIs per patient on admission and 7.2 ±5.6 on discharge (p = 0.2). From admission to discharge, type-C and type-X potential DDIs increased (p < 0.05 for both). Type X interactions were rare (< 1%), with the combination of a β-blocker and a β₂ agonist being the most common (64%). There were significantly more type-C and type-D potential DDIs in patients with chronic HF as compared to patients with COPD (p < 0.001). Patients with concomitant chronic HF and COPD had more type-C and type-X potential DDIs when compared to those with individual disease (p < 0.005). An aldosterone antagonist and ACE inhibitor/ARB were prescribed to 3% of chronic HF patients with estimated glomerular filtration rate < 30 ml/(min × 1.73 m²).

Conclusions

The DDIs are common in patients with chronic HF and/or COPD, but only a few appear to be of clinical significance. The increase in potential DDIs from admission to discharge may reflect better guideline implementation rather than poor clinical practice.     

Total inspiratory and expiratory impedance in patients with severe chronic obstructive pulmonary disease

OBJECTIVES:

Several studies have confirmed the high potential of the forced oscillation technique for the assessment of respiratory modifications related to chronic obstructive pulmonary disease. However, most of these studies did not employ within-breath analyses of the respiratory system. The aim of this study is to analyze respiratory impedance alterations in different phases of the respiratory cycle of chronic obstructive pulmonary disease patients and to evaluate their clinical use.

METHODS:

39 individuals were evaluated, including 20 controls and 19 individuals with chronic obstructive pulmonary disease who experienced severe airway obstruction. We evaluated the mean respiratory impedance (Zm) as well as values for inspiration (Zi) and expiration cycles (Ze), at the beginning of inspiration (Zbi) and expiration (Zbe). The peak-to-peak impedance (Zpp), and the impedance change (ΔZrs) were also analyzed. The clinical usefulness was evaluated by investigating the sensibility, specificity and the area under the receiver operating characteristic curve.

RESULTS:

The respiratory impedance increased in individuals with chronic obstructive pulmonary disease in all of the studied parameters (Zm, Zi, Ze, Zbi, Zbe, ΔZrs and Zpp). These changes were inversely associated with spirometric parameters. Higher impedances were observed in the expiratory phase of individuals with chronic obstructive pulmonary disease. All of the studied parameters, except for ΔZrs (area under the receiver operating characteristic <0.8), exhibited high accuracy for clinical use (area under the receiver operating characteristic >0.90; Sensibility ≥ 0.85; Sp ≥ 0.85).

CONCLUSIONS:

The respiratory alterations in severe chronic obstructive pulmonary disease may be identified by the increase in respiratory system impedance, which is more evident in the expiratory phase. These results confirm the potential of within-breath analysis of respiratory impedance for the assessment of respiratory modifications related to chronic obstructive pulmonary disease.