Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study.

BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China.

INTRODUCTION: The presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD. METHOD AND ANALYSIS: A randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40-80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV1), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis. DISCUSSION: Currently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I-II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IIR-17012604 . Registered on 07 September 2017.

Development of a new method for the isolation and culture of pulmonary arterial endothelial cells from rat pulmonary arteries.

Pulmonary endothelial dysfunction plays an integral role in the pathogenesis and development of pulmonary hypertension. It is difficult and inconvenient to obtain pulmonary arterial endothelial cells (PAECs) from humans and large animals. Some methods for the isolation of PAECs from rats require complex equipment and expensive reagents. In this study, we describe a new method of obtaining cultures of PAECs isolated from rat pulmonary arteries with Chinese acupuncture needles. We acquired PAECs in 5 steps. These were: the isolation of pulmonary arteries, exposure of endothelium, enzymatic digestion, concentration of resuspended pellets and incubation. PAECs were characterized by morphological activity and by immunostaining for von Willebrand factor, CD31 and CD34, but not for α-smooth muscle actin, smooth muscle myosin heavy chain or CD90/Thy-1. Furthermore, transmission electron microscopy was carried out, confirming the presence of Weibel-Palade bodies that are characteristic ultrastructures of vascular endothelial cells. In conclusion, we established a simple and economical technique to isolate and culture PAECs from rat pulmonary arteries. These PAECs exhibit features consistent with vascular endothelial cells, and they could subsequently be used to study pathophysiological mechanisms involving the pulmonary arterial endothelium.

Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey.

RATIONALE: The prevalence of chronic obstructive pulmonary disease (COPD) in China is largely unknown. OBJECTIVES: To obtain the COPD prevalence in China through a large-population, spirometry-based, cross-sectional survey of COPD. METHODS: Urban and rural population-based cluster samples were randomly selected from seven provinces/cities. All residents 40 years of age or older in the selected clusters were interviewed with a standardized questionnaire revised from the international BOLD (Burden of Obstructive Lung Diseases) study. Spirometry was performed on all eligible participants. Patients with airflow limitation (FEV(1)/FVC < 0.70) were further examined by post-bronchodilator spirometry, chest radiograph, and electrocardiogram. Post-bronchodilator FEV(1)/FVC of less than 70% was defined as the diagnostic criterion of COPD. MEASUREMENTS AND MAIN RESULTS: Among 25,627 sampling subjects, 20,245 participants completed the questionnaire and spirometry (response rate, 79.0%). The overall prevalence of COPD was 8.2% (men, 12.4%; women, 5.1%). The prevalence of COPD was significantly higher in rural residents, elderly patients, smokers, in those with lower body mass index, less education, and poor ventilation in the kitchen, in those who were exposed to occupational dusts or biomass fuels, and in those with pulmonary problems in childhood and family history of pulmonary diseases. Among the patients who had COPD, 35.3% were asymptomatic; only 35.1% reported lifetime diagnosis of bronchitis, emphysema, or other COPD; and only 6.5% have been tested with spirometry. CONCLUSIONS: COPD is prevalent in individuals 40 years of age or older in China.