Lili Guan

Effectiveness of neuromuscular electrical stimulation for the rehabilitation of moderate-to-severe COPD: a meta-analysis.

Purpose Patients with COPD often experience skeletal muscle dysfunction. For those who are unable or unwilling to undertake physical training, neuromuscular electrical stimulation (NMES) may provide an alternative method of rehabilitation. The purpose of this meta-analysis was to investigate the controversial topic of whether this therapy is effective in patients with moderate-to-severe COPD. Patients and methods We pooled data from nine trials published between January 9, 2002 and January 4, 2016 across PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, and relevant websites for randomized controlled trials. In these trials, patients with moderate-to-severe COPD were randomly allocated to receive NMES. Primary outcomes were quadricep strength and exercise capacity. The secondary outcome was health-related quality of life. Results We extracted data from 276 patients. NMES contributed to statistically improved quadricep strength (standardized mean difference 1.12, 95% confidence interval [CI] 0.64–1.59, I2=54%; P<0.00001) and exercise capacity, including longer exercise distance (weighted mean difference 51.53, 95% CI 20.13–82.93, I2=90%; P=0.001), and longer exercise endurance (standardized mean difference 1.11, 95% CI 0.14–2.08, I2=85%; P=0.02). There was no significant difference in St George’s Respiratory Questionnaire scores (weighted mean difference −0.07, 95% CI −2.44 to 2.30, I2=56%; P=0.95). Conclusion NMES appears an effectual means of enhancing quadricep strength and exercise capacity in moderate-to-severe COPD patients. Further research is demanded to clarify its effect on other outcomes and determine the optimal parameters for an NMES program.

Home noninvasive positive pressure ventilation with built-in software in stable hypercapnic COPD: a short-term prospective, multicenter, randomized, controlled trial

Background The benefits of noninvasive positive pressure ventilation (NPPV) in patients with hypercapnic COPD are controversial. It is presumed that methodology and appropriate use of NIV ventilator might be crucial for the outcomes. With the new built-in software, the performance of NIV can be monitored at home, which can guarantee the compliance and appropriate use. This study investigated effects of home use of NIV in hypercapnia in COPD patients using the NIV ventilator with built-in software for monitoring. Methods The current multicenter prospective, randomized, controlled trial enrolled patients with stable GOLD stages III and IV hypercapnic COPD. Patients were randomly assigned via a computer-generated randomization sequence, with a block size of four patients, to continue optimized treatment (control group) or to receive additional NPPV (intervention group) for 3 months. The primary outcome was arterial carbon dioxide pressure (PaCO2). Data were derived from built-in software and analyzed every 4 weeks. Analysis was carried out with the intention to treat. This study is registered with ClinicalTrials.gov, number NCT02499718. Results Patients were recruited from 20 respiratory units in China from October 1, 2015, and recruitment was terminated with a record of the vital statistics on May 31, 2016. A total of 115 patients were randomly assigned to the NPPV group (n=57) or the control group (n=58). Patients complied well with NPPV therapy (mean [± standard deviation] day use 5.6±1.4 h). The mean estimation of leaks was 37.99±13.71 L/min. The changes in PaCO2 (−10.41±0.97 vs −4.32±0.68 mmHg, P=0.03) and 6-min walk distance (6MWD) (38.2% vs 18.2%, P=0.02) were statistically significant in the NPPV group versus the control group. COPD assessment test (CAT) showed a positive trend (P=0.06) in favor of the NPPV group. Pulmonary function and dyspnea were not different between groups. Conclusion Ventilators equipped with built-in software provided methodology for monitoring NIV use at home, which could facilitate the improvement of compliance and quality control of NIV use. It was shown that three months use of NIV at home could reduce the PaCO2 and improve exercise tolerance (6MWD) in chronic hypercapnic COPD patients.

Correlation and compatibility between surface respiratory electromyography and transesophageal diaphragmatic electromyography measurements during treadmill exercise in stable patients with COPD.

Purpose To evaluate the compatibility and correlation between noninvasive surface respiratory electromyography and invasive transesophageal diaphragmatic electromyography measurements as facilitating indicators of neural respiratory drive (NRD) evaluation during treadmill exercise. Patients and methods Transesophageal diaphragmatic electromyogram activity (EMGdi,es) and surface inspiratory electromyogram (EMG) activity, including surface diaphragmatic EMG activity (EMGdi,sur), surface parasternal intercostal muscle EMG activity (EMGpara), and surface sternocleidomastoid EMG activity (EMGsc), were detected simultaneously during increasing exercise capacity in 20 stable patients with COPD. EMGdi,es, EMGdi,sur, EMGpara, and EMGsc were quantified using the root mean square (RMS) and were represented as RMSdi,es, RMSdi,sur, RMSpara, and RMSsc, respectively. Results There was a significant association between EMGdi,es and EMGdi,sur (r=0.966, p<0.01), EMGpara (r=0.967, p<0.01), and EMGsc (r=0.956, p<0.01) in the COPD patients during exercise. Bland-Altman plots showed that the lowest mean bias value was between EMGdi,es and EMGpara compared with the bias values between EMGdi,es and the other two EMG parameters. In comparing the estimation of EMGdi,es, we observed the lowest bias values (−1%) and the lowest limits of agreement values (−10% to −12%). Intraclass correlation coefficient (ICC) between EMGdi,es and EMGdi,sur was 0.978 (p<0.01), between EMGdi,es and EMGpara was 0.980 (p<0.01), and between EMGdi,es and EMGsc was 0.868 (p<0.01). Conclusion RMSdi,sur, RMSpara, and RMSsc could provide useful physiological markers of NRD in COPD. RMSpara shows the best compatibility and correlation with transesophageal diaphragmatic electromyography during treadmill exercise in stable patients with COPD.

Transdiaphragmatic pressure and neural respiratory drive measured during inspiratory muscle training in stable patients with chronic obstructive pulmonary disease

Purpose Inspiratory muscle training (IMT) is a rehabilitation therapy for stable patients with COPD. However, its therapeutic effect remains undefined due to the unclear nature of diaphragmatic mobilization during IMT. Diaphragmatic mobilization, represented by transdiaphragmatic pressure (Pdi), and neural respiratory drive, expressed as the corrected root mean square (RMS) of the diaphragmatic electromyogram (EMGdi), both provide vital information to select the proper IMT device and loads in COPD, therefore contributing to the curative effect of IMT. Pdi and RMS of EMGdi (RMSdi%) were measured and compared during inspiratory resistive training and threshold load training in stable patients with COPD. Patients and methods Pdi and neural respiratory drive were measured continuously during inspiratory resistive training and threshold load training in 12 stable patients with COPD (forced expiratory volume in 1 s ± SD was 26.1%±10.2% predicted). Results Pdi was significantly higher during high-intensity threshold load training (91.46±17.24 cmH2O) than during inspiratory resistive training (27.24±6.13 cmH2O) in stable patients with COPD, with P<0.01 for each. Significant difference was also found in RMSdi% between high-intensity threshold load training and inspiratory resistive training (69.98%±16.78% vs 17.26%±14.65%, P<0.01). Conclusion We concluded that threshold load training shows greater mobilization of Pdi and neural respiratory drive than inspiratory resistive training in stable patients with COPD.

The Chinese version of the Severe Respiratory Insufficiency questionnaire for patients with chronic hypercapnic chronic obstructive pulmonary disease receiving non-invasive positive pressure ventilation

Objectives The Severe Respiratory Insufficiency (SRI) questionnaire is the best assessment tool for health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) receiving non-invasive positive pressure ventilation (NIPPV). This study aimed to translate the SRI Questionnaire into Chinese and to validate it. Design Prospective validation study. Setting and participants A total of 149 participants with chronic hypercapnic COPD receiving NIPPV completed the study. Methods The SRI questionnaire was translated into Chinese using translation and back-translation. Reliability was gauged using Cronbach’s α coefficient. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess construct validity. Content validity was confirmed by evaluating the relationship between the score of each item and the total score of the relevant subscale. Results Cronbach’s α coefficients for each subscale and summary scale were above 0.7. Using EFA, one factor was extracted from the anxiety and summary scales and two factors were extracted from the remaining six subscales. Based on the EFA results, subsequent CFA revealed a good model fit for each subscale, but the extracted factors of each subscale were correlated. Content validity was confirmed by the good relationship between the score of each item and the total score of the relevant subscale. Conclusion The Chinese version of the SRI questionnaire is valid and reliable for patients with chronic hypercapnic COPD receiving NIPPV in China. Trial registration number NCT02499718.

Author Correction: High-pressure versus low-pressure home non-invasive positive pressure ventilation with built-in software in patients with stable hypercapnic COPD: a pilot study

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Correlation of surface respiratory electromyography with esophageal diaphragm electromyography

OBJECTIVES To assess the correlation between surface respiratory electromyography(sEMG) and esophageal diaphragm electromyography(EMGdi) at different levels of neural respiratory drive (NRD). DESIGN Randomised parallel design controlled trial. SETTING The First Affiliated Hospital of Guangzhou Medical University. PARTICIPANTS 15 healthy subjects and 1 severe to very severe stable COPD patients were studied. INTERVENTIONS 15 healthy subjects performed incremental inspiratory threshold loading (ILT) and 15 stable COPD patients underwent noninvasive positive pressure ventilation (NPPV).The correlation between EMGdi and sEMG at different NRD levels was analyzed. EMGdi was performed with a multi-pair esophageal electrode catheter; sEMG were was performed by surface diaphragm EMG(located in right anterior axillary line and left anterior axillary line respectively expressed as sEMGdi(r) andsEMGdi(l))、surface parasternal EMG(sEMGpara),and surface sternocleidomastoid EMG(sEMGsc).Signals were normalized using the peak EMG expressed as EMG%max. PRIMARY AND SECONDARY OUTCOME MEASURES The mean ± standard deviation resting EMGdi%max was higher in patients with COPD than in healthy subjects (57.26%±15.45% vs13.64% ±4.96%, respectively; p < 0.001).During ILT and NPPV, EMGdi was correlated with sEMGdi (r), sEMGdi (1), sEMGpara and sEMGsc (r = 0.90, 0.87, 0.90, 0.90 and r = 0.92, 0.83, 0.92 and 0.71, respectively; all P < 0.001). CONCLUSION A strong relationship is present between NRD measured by EMGdi%max and NRD measured by sEMG%max. sEMG%max serves as a non-invasive marker of NRD.

Methacholine induces extracellular matrix production by human airway smooth muscle cells through β-catenin signaling

Altered extracellular matrix (ECM) production by airway smooth muscle cells (ASMCs) is an important feature of airway remodeling. Muscarinic receptor agonists contribute to ECM production in vivo, but the mechanisms involved remain unclear. This study attempted to investigate the role of methacholine in promoting ECM production by human ASMCs (HASMCs) and the underlying mechanism. We found that methacholine induced the expression of collagen I protein and multiple ECM genes. β-catenin signaling was activated in this process upon GSK3β phosphorylation, leading to upregulation of total and active β-catenin. Silencing β-catenin by specific small interfering RNA (siRNA) or with the β-catenin inhibitor, PKF115-584, decreased collagen I expression. Conversely, overexpression of active β-catenin by adenoviruses carrying the S33Y-β-catenin mutant increased the methacholine-induced collagen I expression. Furthermore, methacholine induced TGF-β expression in HASMCs, while pan-TGF-β-neutralizing antibody only partially decreased collagen I expression. These findings suggest that methacholine induced ECM production through β-catenin signaling and partially through TGF-β.

Chinese version of the severe respiratory insufficiency questionnaire for patients with COPD receiving long-term oxygen therapy

Purpose Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients’ symptoms and increase survival. As COPD is incurable, improving patients’ health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods We analyzed reliability using Cronbach’s α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results In total, 161 patients participated in this study. The Cronbach’s α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China.

Tiotropium inhibits methacholine-induced extracellular matrix production via β-catenin signaling in human airway smooth muscle cells

Background Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. Purpose In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Methods Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. Results We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. β-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3β (GSK3β) phosphorylation in this process. Tiotropum inhibited the amount of active β-catenin and its transcription activity. Furthermore, overexpression of active β-catenin by adenoviruses carrying the S33Y mutant resisted the suppressive effect of tiotropium on collagen I protein expression. However, silencing β-catenin by specific small interfering RNA enhanced the negative effect of tiotropium. Conclusion These findings suggest that relaxation of ASMCs by tiotropium can prevent ECM production through β-catenin signaling.