Background: Underdiagnosis and undertreatment pose major barriers to optimal management of chronic obstructive pulmonary disease (COPD) in China. Objective: The REAL trial was performed to generate reliable information on real-world COPD management, outcomes and risk factors among Chinese patients. Here, we present study outcomes related to COPD management. Design: It is a 52-week, prospective, observational, multicentre study. Methods: Outpatients (aged ⩾40 years) enrolled from 50 secondary and tertiary hospitals across six geographic regions of China were followed up for 12 months, with two onsite visits and by telephone every 3 months following baseline. Results: Between June 2017 and January 2019, 5013 patients were enrolled and 4978 included in the analysis. Mean [standard deviation (SD)] age was 66.2 (8.9) years, the majority of patients were male (79.5%) and mean (SD) time since COPD diagnosis was 3.8 (6.2) years. The most common treatments at each study visit were inhaled corticosteroids/long-acting beta-agonists (ICSs/LABAs; 28.3–36.0%), long-acting muscarinic antagonists (LAMAs; 13.0–16.2%) and ICS/LABA + LAMA (17.5–18.7%), but up to 15.8% of patients at each visit received neither ICS nor long-acting bronchodilators. The use of ICS/LABA, LAMA and ICS/LABA + LAMA differed across regions and hospital tiers; up to fivefold, more patients received neither ICS nor long-acting bronchodilators in secondary (17.3–25.4%) versus tertiary hospitals (5.0–5.3%). Overall, rates of nonpharmacological management were low. Direct treatment costs increased with disease severity, but the proportion of direct treatment costs incurred due to maintenance treatment decreased with disease severity. Conclusion: ICS/LABA, LAMA and ICS/LABA + LAMA were the most frequently prescribed maintenance treatments for patients with stable COPD in China, although their use differed between region and hospital tier. There is a clear need for improved COPD management across China, particularly in secondary hospitals. Registration: The trial was registered on 20 March 2017 (ClinicalTrials.gov identifier: NCT03131362; https://clinicaltrials.gov/ct2/show/NCT03131362). Plain language summary Treatment patterns in patients with COPD in China Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by progressive and irreversible airflow limitation. In China, many patients with this disease do not receive a diagnosis or appropriate treatment. Objective: This study aimed to generate reliable information on the treatment patterns among patients with COPD in China to help inform future management strategies. Study design and methods: Patients (aged ⩾40 years) were enrolled from 50 hospitals across 6 regions of China and physicians collected data over the course of 1 year during routine outpatient visits. Results: The majority of patients were receiving long-acting inhaled treatments, which are recommended to prevent worsening of the disease. Up to 16% of patients in this study, however, did not receive any of these recommended treatments. The proportion of patients who received long-acting inhaled treatments differed across regions and hospital tiers; there were about five times more patients in secondary hospitals (about 25%) who did not receive these treatments compared with those in tertiary hospitals (about 5%). Guidelines recommend that pharmacological treatment should be complemented by nondrug treatment, but this was only received by a minority of patients in this study. Patients with higher disease severity incurred greater direct treatment costs compared with those with milder disease. Maintenance treatment costs made up a smaller proportion of overall direct costs for patients with higher disease severity (60–76%) compared with patients with milder disease (81–94%). Conclusion: Long-acting inhaled treatments were the most frequently prescribed maintenance treatments among patients with COPD in China, but their use differed between region and hospital tier. There is a clear need to improve disease management across China, especially in secondary hospitals.

https://doi.org/10.1177/17534666231158283

Treatment patterns in patients with stable COPD in China: analysis of a prospective, 52-week, nationwide, observational cohort study (REAL)

The progression of an abnormal inflammatory response plays a crucial role in the lung function decline of chronic obstructive pulmonary disease (COPD) patients. Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of inflammatory processes in the airways.A total of 102 COPD participants were divided into a mild-to-moderate group (FEV1%pred≥ 50%, n=57) and a severe-to-very-severe group (FEV1%pred<50%, n=45). We measured a series of inflammatory biomarkers in induced sputum and analyzed their association with lung function and SGRQ in COPD patients. To evaluate the relationship between inflammatory biomarkers and the inflammatory phenotype, we also analyzed the correlation between biomarkers and airway eosinophilic phenotype.We found increased mRNA levels of MMP9, LTB4R, and A1AR and decreased levels of CC16 mRNA in induced sputum in the severe-to-very-severe group. After adjustment for age, sex and other biomarkers, CC16 mRNA expression was positively associated with FEV1%pred (r=0.516, p=0.004) and negatively correlated with SGRQ scores (r=-0.3538, p=0.043). As previously known, decreased CC16 was related to the migration and aggregation of eosinophils in airway. It was also found that CC16 had a moderate negative correlation with the eosinophilic inflammation in airway (r=-0.363, p=0.045) in our COPD patients.Low CC16 mRNA expression levels in induced sputum were associated with low FEV1%pred and a high SGRQ score in COPD patients. Sputum CC16 as a potential biomarker for predicting COPD severity in clinical practice might attribute to the involvement of CC16 in airway eosinophilic inflammation. 

CC16 as an Inflammatory Biomarker in Induced Sputum Reflects Chronic Obstructive Pulmonary Disease (COPD) Severity

Objective: Systematic comparison of the efficacy and safety of nebulized corticosteroids and systemic corticosteroids for treating acute exacerbation of chronic obstructive pulmonary disease reported by high-quality, real-world observational studies and randomized controlled trials. Methods: MEDLINE, EMBASE, and Cochrane Library databases were searched from the database creation date to 1 April 2022. Eligible observational studies and randomized controlled trials with changes in lung function and blood gas analysis results as the primary endpoints of interest, and the numbers of deteriorations and adverse events as the secondary endpoints were sought. Results: Of the 2,837 identified studies, 22 were eligible and included in our analysis (N = 5,764 patients). Compared with systemic corticosteroids, nebulized corticosteroids resulted in comparable improvements in predicted FEV1%, FEV1, PaO2, PaCO2, and SaO2 at the treatment endpoint; however, observational studies reported more significant treatment outcomes with nebulized corticosteroids for FEV1 [mean difference, 0.26; 95% confidence interval (CI), 0.17–0.35; p < 0.005]. In terms of adverse reactions, the risks of gastrointestinal symptoms were 11% [Log risk ratio (LogRR) = 0.10; 95% confidence interval, 0.05–0.15; p < 0.005] higher for systemic corticosteroids than for nebulized corticosteroids in randomized controlled trials, while the risks of hyperglycemia were 6% (LogRR = 0.06; 95% CI, 0.01–0.11; p = 0.01) and 13% (LogRR = 0.12; 95% CI, 0.09–0.16; p < 0.005) higher in observational studies and randomized controlled trials, respectively. Conclusion: According to our meta-analysis, either study type supported that nebulized corticosteroids can be used as an alternative to systemic corticosteroids for treating acute exacerbation of the chronic obstructive pulmonary disease. However, more well-designed prospective studies are needed to determine the optimal dose of nebulized corticosteroids and the advantages of sequential therapy.

/pdf/nebulized-corticosteroids-versus-systemic-corticosteroids-22ne7tv0.pdf

Nebulized corticosteroids versus systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis comparing the benefits and harms reported by observational studies and randomized controlled trials

Purpose The progression of an abnormal inflammatory response plays a crucial role in the lung function decline of chronic obstructive pulmonary disease (COPD) patients. Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of inflammatory processes in the airways. Patients and Methods A total of 102 COPD participants were divided into a mild-to-moderate group (FEV1%pred≥ 50%, n=57) and a severe-to-very-severe group (FEV1%pred<50%, n=45). We measured a series of inflammatory biomarkers in induced sputum and analyzed their association with lung function and SGRQ in COPD patients. To evaluate the relationship between inflammatory biomarkers and the inflammatory phenotype, we also analyzed the correlation between biomarkers and airway eosinophilic phenotype. Results We found increased mRNA levels of MMP9, LTB4R, and A1AR and decreased levels of CC16 mRNA in induced sputum in the severe-to-very-severe group. After adjustment for age, sex and other biomarkers, CC16 mRNA expression was positively associated with FEV1%pred (r=0.516, p=0.004) and negatively correlated with SGRQ scores (r=−0.3538, p=0.043). As previously known, decreased CC16 was related to the migration and aggregation of eosinophils in airway. It was also found that CC16 had a moderate negative correlation with the eosinophilic inflammation in airway (r=−0.363, p=0.045) in our COPD patients. Conclusion Low CC16 mRNA expression levels in induced sputum were associated with low FEV1%pred and a high SGRQ score in COPD patients. Sputum CC16 as a potential biomarker for predicting COPD severity in clinical practice might attribute to the involvement of CC16 in airway eosinophilic inflammation.

https://www.dovepress.com/getfile.php?fileID=89277

Background: The Chinese government has promoted the ‘tiered medical services’ policy in which diseases are classified by severity, mode of onset and difficulty of treatment since 2015 to optimize medical resources. We evaluated the diagnosis and treatment of acute exacerbation (AE) of chronic obstructive pulmonary disease (AECOPD) under the tiered system. Methods: We conducted a cross-sectional study. COPD characteristics and treatments were compared among hospitals in different tiers. Associations were examined by univariate and multivariable logistic regression analysis. In addition, multivariate logistic regression was performed to identify the possible influencing factors of antibiotics, glucocorticoids and anticoagulant usages. Results: Eligible COPD patients (n = 432) were consecutively recruited from eight hospitals in different tiers in China. Patients in the countryside preferred the community hospitals, whereas patients in cities preferred second-tier and teaching hospitals when they suffer from AECOPD. It indicates most COPD patients are likely to treat their disease locally. The severity of COPD AE increased with tiers of hospitals (p < 0.001). However, our results clearly show that most community hospitals can only deal with mild exacerbation of COPD. Approximately 90% of AE patients received antibiotics. We speculated that antibiotics abuse might exist in the three tiers of hospitals. Multivariate analysis demonstrated that long-term antibiotics usage (⩾14 days) was associated with moderate exacerbation [odds ratio (OR): 5.295, 95% confidence intervals (CI) 2.248–12.473, p < 0.001], radiographic progression (OR: 2.176, 95% CI: 1.047–4.522, p = 0.037), positive sputum etiology (OR: 3.073, 95% CI: 1.477–6.394, p = 0.003) and increased white blood cells (OR: 2.470, 95% CI: 1.190–5.126, p = 0.015). The proportion of glucocorticoids increased with the hospital hierarchy (18.6% versus 45.6% versus 69.2%, p < 0.001). The proportions of severe cases in the second-tier hospitals were 26.9%; however, non-invasive positive pressure ventilation (NPPV) rate was only 14.7%. Anticoagulant is not commonly used in AECOPD, and the community hospitals had the lowest proportion of anticoagulation regimen (1.7% versus 14.3% versus 20.5%, p = 0.002). Conclusions: The ‘tiered medical services’ policy in AECOPD management has been unsatisfactory in the past years. Irrational treatment strategies in different hospitals were still found when comparing with international guideline. Further reform of the policy is still needed to optimize the management of AECOPD in China.

https://journals.sagepub.com/doi/pdf/10.1177/17534666221075499

Management of acute exacerbation of chronic obstructive pulmonary disease under a tiered medical system in China

Lung cancer is the most frequent type of cancer affecting both men and women globally, and it is associated with a high mortality rate. It is clinically treated with cisplatin, a platinum‐based drug that works by generating DNA lesions, which activates DNA damage response and induces cell death. However, chemoresistance by cancer cells limits the clinical usefulness of cisplatin as an anticancer drug. Here, we uncovered a role of ubiquitin‐specific protease 51 (USP51) in the chemosensitivity of lung cancer cells to cisplatin by regulating DNA damage response. USP51 was more upregulated in lung cancer tissues of chemotherapy‐resistant patients than those of chemotherapy‐sensitive patients with adjacent, nontumor tissues. USP51 overexpression in lung cancer cells in vitro reduced γ‐H2AX formation and promoted checkpoint kinase 1 (CHK1) phosphorylation, whereas USP51 knockdown showed opposite effects, indicating that USP51 played an important role in promoting DNA damage repair. Finally, USP51 knockdown weakened cisplatin resistance in A549/DDP cells and significantly suppressed tumor growth in vivo, suggesting that a USP51 inhibitor combined with cisplatin may be considered as an effective treatment strategy to eliminate drug‐resistant lung cancer cells.

Jinchang Lu

Papers

Management of acute exacerbation of chronic obstructive pulmonary disease under a tiered medical system in China

The role of USP51 in attenuating chemosensitivity of lung cancer cells to cisplatin by regulating DNA damage response