REALizing and improving management of stable COPD in China: results of a multicentre, prospective, observational study (REAL).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management in China is far from adequate; underdiagnosis and undertreatment are major barriers to optimal care and improved patient outcomes. OBJECTIVE: To generate reliable information on COPD management, outcomes, treatment patterns and adherence, and disease knowledge in China in a real-world setting. DESIGN: A 52-week multicentre, prospective, observational study. METHODS: Outpatients (⩾40 years old) diagnosed with COPD were enrolled from 50 secondary and tertiary hospitals across six geographical regions. Data were collected in routine clinical practice. 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, 79.5% were male and 90% had moderate-to-very-severe airflow limitation. Annual rates of overall and severe exacerbation were 0.56 and 0.31, respectively. During 1 year, 1536 (30.8%) patients experienced ⩾1 exacerbation and 960 (19.3%) patients had ⩾1 exacerbation requiring hospitalization/emergency visit. Mean (SD) COPD assessment test score was 14.6 (7.6) at baseline and 10.6 (6.8) at follow-up; however, 42-55% of patients had persistent dyspnoea, chest tightness and wheezing at 1 year. The most prescribed treatments were inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) (36.0%), ICS/LABA + long-acting muscarinic antagonist (LAMA) (17.7%) and LAMA monotherapy (15.3%). Among patients with high exacerbation risk (GOLD Groups C and D), 10.1% and 13.1%, respectively, did not receive any long-acting inhalers; only 53.8% and 63.6% of Group C and D patients with ⩾1 exacerbation during follow-up were prescribed ICS-containing therapy, respectively. Mean (SD) adherence for long-acting inhalers was 59.0% (34.3%). Mean (SD) score for the COPD questionnaire was 6.7 (2.4). CONCLUSION: These results indicate a high burden of severe exacerbations and symptoms in Chinese outpatients with COPD, and low adherence with treatment guidelines, highlighting the need for more effective management nationwide. REGISTRATION: The trial was registered on 20 March 2017 (ClinicalTrials.gov identifier: NCT03131362).

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

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management in China is inadequate and there is a need to improve care and outcomes for patients nationwide. OBJECTIVES: The REAL study was designed to generate reliable information on COPD management from a representative sample of Chinese patients with COPD. Here, we present study outcomes related to acute exacerbations. DESIGN: A 52-week, multicentre, prospective, observational study. METHODS: Outpatients (aged ⩾ 40 years) enrolled from 25 tertiary and 25 secondary hospitals across six geographic regions in China were followed for 12 months. Risk factors for COPD exacerbation and disease severity by exacerbation were assessed using multivariate Poisson and ordinal logistic regression models, respectively. RESULTS: Between June 2017 and January 2019, 5013 patients were enrolled, with 4978 included in the analysis. Mean (standard deviation) age was 66.2 (8.9) years. More patients presented with exacerbations in secondary versus tertiary hospitals (59.4% versus 40.2%) and in rural versus urban areas (53.2% versus 46.3%). Overall exacerbation rates differed across regions (range: 0.27-0.84). Patients from secondary versus tertiary hospitals had higher rates of overall exacerbation (0.66 versus 0.47), severe exacerbation (0.44 versus 0.18) and exacerbation that resulted in hospitalisation (0.41 versus 0.16). Across regions and hospital tiers, the rates of overall exacerbation and exacerbations that resulted in hospitalisation were highest in patients with very severe COPD (based on the severity of airflow limitation or GOLD 2017 combined assessment). Strong predictors of exacerbation included demographic and clinical characteristics, modified Medical Research Council scores, mucus purulence, exacerbation history and the use of maintenance mucolytic treatment. CONCLUSION: COPD exacerbation rates varied across regions and were higher in secondary compared with tertiary hospitals in China. Understanding the factors associated with COPD exacerbation may facilitate improved management of COPD exacerbations in China. REGISTRATION: The trial was registered on 20 March 2017 (ClinicalTrials.gov: NCT03131362; https://clinicaltrials.gov/ct2/show/NCT03131362). PLAIN LANGUAGE SUMMARY: Exacerbations in patients with chronic obstructive pulmonary disease in ChinaBackground: Chronic obstructive pulmonary disease (COPD) causes progressive and irreversible airflow limitation. As the disease progresses, patients often experience a flare up of symptoms referred to as an exacerbation. There is inadequate management of COPD in China and, therefore, there is a need to improve care and outcomes for patients across the country.Objective: This study aimed to generate reliable information on exacerbations among Chinese patients with COPD to help inform future management strategies.Study design and methods: Patients (aged ⩾ 40 years) were enrolled from 25 secondary and 25 tertiary hospitals across six regions of China. Physicians collected data over 1 year during routine outpatient visits.Results: There were more patients who experienced an exacerbation in secondary versus tertiary hospitals (59% versus 40%) and in rural versus urban areas (53% versus 46%). Patients in different geographic regions experienced varying frequencies of exacerbations over 1 year. Compared with patients from tertiary hospitals, patients from secondary hospitals experienced exacerbations (including exacerbations that were severe and those that resulted in hospitalisation) at a higher frequency over 1 year. Patients with very severe disease experienced exacerbations (including exacerbations that resulted in hospitalisation) at the highest frequency over 1 year, regardless of the patient's geographic region or hospital tier. Patients who had certain characteristics and symptoms, had exacerbation(s) over the previous year, or received medication that aids in the clearance of mucus were more likely to experience exacerbations.Conclusion: The frequency of exacerbations among Chinese patients with COPD varied between patients living in different geographic regions and between patients presenting to different hospital tiers. Understanding the factors related to the occurrence of an exacerbation may help physicians better manage the disease.

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

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 ChinaBackground: 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.

Severity distribution and treatment of chronic obstructive pulmonary disease in China: baseline results of an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) receives low awareness and is undertreated in China. Understanding the burden and treatment of COPD across the nation is important for improving quality of care for this disease. This study aims to reveal the current situation of COPD severity distribution and management across China. METHODS: Baseline data from REALizing and Improving Management of Stable COPD in China, a multicentre, prospective, longitudinal, observational study, were analysed. Patients diagnosed with COPD as per Global Initiative for Chronic Obstructive Lung Disease 2016 (GOLD 2016) criteria were enrolled from 50 randomly selected hospitals (tertiary, 25; secondary, 25) across six geographical regions. Data were collected in routine clinical settings. RESULTS: Between 15 December 2017 and 6 August 2020, 5013 patients were enrolled and 4978 included in the full analysis set. Of these, 2459 (49.4%) reported ≥ 1 exacerbation within 12 months prior to study enrolment, with a mean annual rate of 0.9/patient, including 0.2/patient and 0.5/patient leading to emergency room visits and hospitalisation, respectively. Spirometry graded 458 (10.1%), 1886 (41.7%), 1558 (34.5%), and 616 (13.6%) were GOLD stage I-IV, and 536 (11.4%), 1034 (22.0%), 563 (12.0%), and 2566 (54.6%) were classified as GOLD 2016 Group A-D, respectively, without evident regional variations. Inhaled corticosteroids plus long-acting beta2-agonist (ICS/LABA, 1316 [26.4%]), ICS/LABA plus long-acting muscarinic antagonist (ICS/LABA + LAMA, 871 [17.5%]), and LAMA (754 [15.1%]) were prescribed at high rates across all groups and regions. Medications not recommended by GOLD were commonly prescribed (TCM, 578 [11.6%]; others, 951 [19.1%]), and 681 (13.7%) were not given ICS or long-acting bronchodilators. CONCLUSIONS: Disease burden among Chinese COPD outpatients is high. Improved guideline adherence for COPD treatment is needed. Trial registration ClinicalTrials.gov identifier, NCT03131362.

Current situation of asthma-COPD overlap in Chinese patients older than 40 years with airflow limitation: a multicenter, cross-sectional, non-interventional study.

BACKGROUND AND AIMS: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is poorly recognized in China. Our study determined the distribution of ACO and its clinical characteristics among patients (aged ⩾40 years) with airflow limitation at Chinese tertiary hospitals. METHODS: This cross-sectional, non-interventional study (NCT02600221), conducted between December 2015 and October 2016 in 20 Tier-3 Chinese hospitals, included patients aged ⩾40 years with post-bronchodilator (BD) FEV1/FVC <0.7. The primary variable was distribution of ACO in adults with post-BD forced expiratory volume /forced vital capacity (FEV1/FVC) <0.7 based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015 and 2017 reports. Other variables included determination of characteristics of ACO and its clinical recognition rate. RESULTS: In 2003 patients (mean age 62.30 ± 9.86 years), distribution of ACO, COPD and asthma were 37.40%, 48.50% and 14.10%, respectively. Proportions of patients with A, B, C and D grouping were 11.70%, 31.00%, 6.90% and 50.30% as per GOLD 2017, whereas they were 15.10%, 51.10%, 3.60% and 30.20% as per GOLD 2015. Similar clinical symptoms were reported in all three groups. A higher percentage of ACO patients presented with dyspnea, wheezing and chest tightness. Compared with the COPD group, a greater proportion of ACO patients reported wheezing (74.6% and 65.40%), while a lower proportion in the ACO group reported cough (79.40% versus 82.70%) and expectoration (76.50% versus 81.60%). Blood eosinophil count ⩾0.3 × 109/L was observed in 34.6% of ACO patients. The clinical recognition rate of ACO was 31.4%. CONCLUSION: Despite ACO affecting two-fifths of the study population, the initial diagnosis rate was low at 6% in China, thus warranting concerted efforts to improve ACO diagnosis. CLINICALTRIALS.GOV: [ClinicalTrials.gov identifier: NCT02600221] registered 22 October 2015, https://clinicaltrials.gov/ct2/show/NCT02600221The reviews of this paper are available via the supplemental material section.

REALizing and improving management of stable COPD in China: a multi-center, prospective, observational study to realize the current situation of COPD patients in China (REAL) - rationale, study design, and protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China. METHODS/DESIGN: The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients' usual care visits, and by telephone interview every 3 months. DISCUSSION: Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

Clinical features of pulmonary mucormycosis in patients with different immune status.

BACKGROUND: Pulmonary mucormycosis (PM) is a relatively rare but often fatal and rapidly progressive disease. Most studies of PM are case reports or case series with limited numbers of patients, and focus on immunocompromised patients. We investigated the clinical manifestations, imaging features, treatment, and outcomes of patients with PM with a focus on the difference in clinical manifestations between patients with different immune status. METHODS: Clinical records, laboratory results, and computed tomography scans of 24 patients with proven or probable PM from January 2005 to December 2018 in Peking Union Medical College Hospital were retrospectively analyzed. RESULTS: Ten female and 14 male patients were included (median age, 43.5 years; range, 13-64 years). Common presenting symptoms were fever (70.8%), cough (70.8%), sputum production (54.2%), and hemoptysis (41.7%). Radiological findings included consolidation (83.3%), ground-glass opacities (58.3%), nodules (50.0%), masses (37.5%), cavities (33.3%), mediastinal lymphadenopathy (29.2%), and halo sign (12.5%); one patient had a reversed halo sign. Seven patients (29.2%) had no obvious predisposing risk factors, and 17 (70.8%) had underlying diseases including diabetes, hematological malignancy, and use of immunosuppressants. Compared with immunocompromised patients, immunocompetent patients with PM were younger {23 [13-46] vs. 48 [17-64] years, P=0.023}, comprised a higher proportion of men (100.0% vs. 41.2%, P=0.019), had a longer disease course {34 [8-47] vs. 9 [2-102] weeks, P=0.033}, had a higher eosinophil count [0.66 (0.07-2.00) ×109/L vs. 0.04 (0.00-0.23) ×109/L, P=0.001], and had a lower erythrocyte sedimentation rate {12 [1-88] vs. 74 [9-140] mm/h, P=0.032}. CONCLUSIONS: PM can occur in heterogeneous patients with different immune status, and the clinical phenotype differs between immunocompetent and immunocompromised patients. Because of the lack of specific clinic and imaging manifestations, aggressive performance of invasive procedures to obtain histopathological and microbial evidence is crucial for a definitive diagnosis.

Pulmonary hypertension associated with combined fibrosing mediastinitis and bronchial anthracofibrosis: A retrospective analysis in a single Chinese hospital.

INTRODUCTION: Both fibrosing mediastinitis (FM) and bronchial anthracofibrosis (BAF) are unique diseases. The combined appearance of FM and BAF is extremely rare. OBJECTIVES: The aim of this study was to investigate the clinical features of patients with coexisting FM and BAF. METHOD: Between January 2003 and December 2015, a total of eight patients were diagnosed at the Peking Union Medical College Hospital as having combined FM and BAF. The clinical presentations, radiographic features and bronchoscopic findings of the eight patients were reviewed. RESULTS: The patients were five women and three men with a median age of 64 years (range 56-86 years). Symptoms included dyspnea (eight patients), cough (seven patients), chest pain (two patients), hemoptysis (two patients) and so on. Chest CT of all eight patients showed mediastinal soft-tissue lesions, with multiple narrowed or obliterated lobar or segmental bronchi and arteries. Bronchoscopy showed that all of the patients had multiple stenoses of lobar or segmental bronchi with anthracotic pigmentation on the mucosa. Echocardiography showed that all of the patients had elevated pulmonary arterial systolic pressure (median 81 mm Hg, range 51-107 mm Hg). Each of the eight patients had a history of exposure to, or infection with, tuberculosis, although there was no evidence of active disease. All of the eight patients had long-term exposure to indoor coal or biomass fuel smoke. CONCLUSIONS: FM can coexist with BAF, characterized by prominent pulmonary hypertension. The possible etiological factors are tuberculosis and coal or biomass fuel exposure.

Perception of circadian variation of symptoms in Chinese patients with chronic obstructive pulmonary disease.

BACKGROUND: Although, the variable pattern of asthmatic symptoms is well recognized, little is known about the respiratory symptoms variability in patients of chronic obstructive pulmonary disease (COPD). The present study evaluated the variability of the respiratory symptoms in a day and their influence on the daily activities in a cohort of Chinese COPD patients. METHODS: An observational cross-sectional study was conducted in 11 medical centers of China. Participants were outpatient ≥40 years old with stable COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) <80% predicted. Overall, data of 1,032 eligible patients were valid for final analysis. RESULTS: Mean post bronchodilator FEV1 (predicted %) was 46.5%. Cough, expectoration and dyspnea were the most commonly observed symptoms (73.6%, 68.8% and 61.4%, respectively). Daily symptom variability was experienced by 50.2% of symptomatic patients. The wake up time in the morning was the worst and the most troublesome time during the day (39.3%), followed by the nighttime (21.3%). The morning activities were most affected by COPD symptoms. Multivariate analyses revealed that COPD assessment test (CAT) scores was the only factor correlated with patients' symptom variability [odds ratio (OR) =0.463, P<0.0001]. CONCLUSIONS: Patient-perceived symptoms vary during the day in Chinese COPD patients. They experience the greatest increase in respiratory symptoms early in the morning. This variation should be considered as a potential new target in the long-term COPD management.

Anomalous systemic arterial supply of pulmonary sequestration in adult patients.

OBJECTIVES: This study described the characteristics of the systemic arterial supply of pulmonary sequestration (PS) in an attempt to better distinguish PS from other acquired lesions. METHODS: We identified 25 patients hospitalized at the Peking Union Medical College Hospital during January 2013 to December 2015 with the assistance of medical catalogers. Twenty-three patients with a definite diagnosis of "pulmonary sequestration" clinically or pathologically were included in the study. The medical records, imaging information, and pathological data were reviewed retrospectively. The general characteristics of the patients and the features of the anomalous arteries were summarized. RESULTS: Aberrant arterial supply of PS was found in all 23 (100%) cases. Among them, twenty patients received surgery, including 14 (70%) with aberrant arterial supply found before surgery, and the other 6 (30%) found during surgery. Nineteen (82.6%) patients had a single systematic arterial supply, with a median diameter of 8 mm. More than one arterial supplies were found in four (17.4%) cases. In 21 (91.3%) cases, the anomalous systemic artery originated from the descending thoracic aorta just adjacent to the sequestrated lung which it supplied, without the presence of accompanying bronchi. In twenty (87.0%) patients who received the surgical intervention, samples of 12 (85.7%) were proved to have elastic vessel walls, out of the 14 samples in which the anomalous systemic arteries were available for analysis. CONCLUSIONS: There are no certain pathology diagnostic criteria for the diagnosis of PS. The detecting of the aberrant systematic artery and distinguishing it from the bronchial arteries corresponded to certain lung abnormalities are the keys to the accurate diagnosis of pulmonary sequestration in adult patients. We propose that the characteristic features of the anomalous arteries include: Originating from aorta and its main branches, adjacent to the sequestrated area, directly running into the sequestrated mass without accompanying bronchus branch, being large in diameter, and having elastic vessel wall.

Chronic bronchitis is associated with severe exacerbation and prolonged recovery period in Chinese patients with COPD: a multicenter cross-sectional study.

BACKGROUND: Chronic bronchitis (CB) is closely associated with the frequency and severity of chronic obstructive pulmonary disease (COPD) exacerbation. However, little is known about the impact of CB on COPD exacerbations, severe and non-severe, and on recovery from an exacerbation. METHODS: We conducted a nation-wide multicenter cross-sectional survey in China between September 2007 and December 2008. Eleven hospitals participated in this study. Patients' demographic information, presence of CB, overall numbers of COPD exacerbation and severe exacerbation leading to emergency visit, hospitalization and intensive care unit (ICU) stay in the past year, recovery period following the last exacerbation, and well- or poor-recovery were recorded. RESULTS: A total of 1,101 patients with COPD were enrolled and 890 (80.8%) had CB. Patients with CB reported more history of frequent exacerbations (≥2/patient/year) (59.6% vs. 50.7%, P=0.019) and severe exacerbation (% emergency visit ≥1: 28.0% vs. 16.6%, P=0.001; % hospitalization ≥1: 51.2% vs. 28.0%, P<0.001; %ICU stay ≥1: 6.5% vs. 1.9%, P=0.009). Recovery period following the last exacerbation was longer in patients with CB (19.0±16.2 vs. 15.2±14.7 days, P=0.003) and more patients with CB reported poor recovery (85.8% vs. 78.4%, P=0.003). Multivariate analyses showed that CB was independently associated with severe exacerbation requiring emergency visit (adjusted OR, 1.512, P=0.048) and hospitalization (adjusted OR, 2.031, P<0.001) and prolonged recovery period (adjusted regression coefficient 2.861, P=0.030). CONCLUSIONS: CB is associated with frequent exacerbations of COPD in Chinese population, especially severe exacerbations requiring emergency visit and hospitalization admission. Additionally, CB significantly prolongs recovery period following COPD exacerbation.

Current situation of asthma-COPD overlap syndrome (ACOS) in Chinese patients older than 40 years with airflow limitation: rationale and design for a multicenter, cross-sectional trial (study protocol).

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are the frequently occurring chronic airway diseases, and the overlapping syndrome observed in the majority of patients has been recently defined as asthma-COPD overlap syndrome (ACOS) by the Global Initiative for Chronic Obstructive Lung (GOLD, 2014) and Global initiative for Asthma (GINA, 2015). The proportion, features, and clinical practice of ACOS still remain elusive in China. We are conducting this multicenter, cross-sectional, observational study (NCT02600221) to investigate the distributions of chronic obstructive diseases in patients >40 years of age with chronic airflow limitation in China along with determination of the main clinical practice and features of these diseases. The study will also explore the factors that may influence the exacerbations and severity of ACOS in Chinese patients (>40 years of age). METHODS: A total of 2,000 patients (age, ≥40 years; either sex) who are clinically diagnosed as having asthma, COPD/chronic bronchitis/emphysema, or ACOS for at least 12 months with airflow limitation [post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC): <0.7] will be enrolled from approximately 20 sites in China between December 2015 and December 2016. The proportion of ACOS among patients older than 40 years based on GINA 2015 and GOLD 2014 definitions is the primary variable. Following were the secondary variables: the proportions of COPD and asthma among the patients, distributions of the severity of airflow limitation, distribution of groups according to GOLD 2011 group definition (A, B, C, D), and the distribution of medication by drug class in patients with ACOS, asthma, and COPD. Acute exacerbation history, hospitalization, and severity of ACOS as evaluated using COPD Assessment Test, Asthma Control Questionnaire-5, and Modified British Medical Research Council in patients with ACOS were also assessed. IMPLICATIONS: This will be the first study to disseminate scientific knowledge on the current situation, main clinical practice, and features of ACOS, asthma, and COPD conditions in Chinese patients. The insights will be helpful in designing optimal management strategies for ACOS and redefining the healthcare development programs.

mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis.

The mammalian target of rapamycin (mTOR) signaling pathway in pulmonary fibrosis was investigated in cell and animal models. mTOR overactivation in alveolar epithelial cells (AECs) was achieved in the conditional and inducible Tsc1 knock-down mice SPC-rtTA/TetO-Cre/Tsc1(fx/+) (STT). Doxycycline caused Tsc1 knock-down and consequently mTOR activation in AECs for the STT mice. Mice treated with bleomycin exhibited increased mortality and pulmonary fibrosis compared with control mice. In wild-type C57BL/6J mice, pretreatment with rapamycin attenuated the bleomycin-mediated mortality and fibrosis. Rapamycin-mediated mouse survival benefit was inhibited by chloroquine, an autophagy inhibitor. Autophagosomes were decreased in the lungs after bleomycin exposure. Rapamycin induced the production of autophagosomes and diminished p62. We concluded that mTOR overactivation in AECs and compromised autophagy in the lungs are involved in the pathogenesis of pulmonary fibrosis. The suppression of mTOR and enhancement of autophagy may be used for treatment of pulmonary fibrosis.

[Present status of medical treatment for patients with chronic obstructive pulmonary disease based upon different severity classifications].

OBJECTIVE: To survey the present status of medical treatment for Chinese outpatients with chronic obstructive pulmonary disease (COPD) based upon the guidelines for diagnosing and treating COPD (2007 Revised Edition and 2013 Revised Edition) and explore the impact of new guideline on treatment regimens. METHODS: A retrospective study was conducted at 11 participating hospitals. Stable COPD patients were consecutively recruited from outpatient clinics in China between September 2007 and December 2008 and categorized into the Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-IV classification and A-D groups according to the Chinese guidelines for diagnosing and treating COPD (2007 Revised Edition and 2013 Revised Edition). The authors compared the present status of medical treatment of two guidelines and analyze the impact of new guideline on treatment regimens. RESULTS: Among a total of 749 patients, 79.2% (593/749) patients received medical treatment. The distribution of classification GOLD I-IV was 34 (4.5%), 211 (28.2%), 309 (41.3%) and 195 (26.0%). According to the guideline 2007, the patients on medical under-treatment based upon the guidelines in GOLD I-IV classification were 32.4% (11/34), 53.6% (113/211), 57.6% (178/309) and 55.4% (108/195); those on medical treatment: 23.5% (8/34), 3.8% (8/211), 28.8% (89/309) and 33.3% (65/195); those on medical over-treatment: 44.1% (15/34), 42.7% (90/211), 13.6% (42/309), 11.3% (22/195). The distribution of categories A-D was 93 (12.4%), 45 (6.0%), 196 (26.2%), and 415 (55.4%). According to guideline 2013, the patients on medical under-treatment were 34.4% (32/93), 62.2% (28/45), 67.9% (133/196) and 60.7% (252/415); those on medical treatment: 24.7% (23/93), 4.4% (2/45), 32.1% (63 /196) and 39.3% (163/415); those on medical over-treatment: 40.9% (38/93), 33.3% (15/45), 0 and 0. The concordance analysis comparing the judgments of treatment regimens by these two guideline yielded a weighted Kappa coefficient of 0.534 (P < 0.001), indicating that there was a moderate degree of judgments between two guidelines. Medical treatment regimens recommended by new guideline was different from old guideline in 143 COPD patients. Among them, 24 patients (16.8%) required a step-down therapy while 119 patients (83.2%) a step-up therapy. CONCLUSIONS: There are more outpatients with COPD on medical treatment, but few of them have received standardized treatment. Compared with the old GOLD classification, more patients are recommended for a step-up therapy by new stratification.

[Smoking cessation among rural populations in Beijing].

OBJECTIVE: To survey the smoking cessation among rural populations in Beijing. METHODS: One natural village in Beijing suburb was sampled and all the 1901 villagers were surveyed by face-to-face interview to collect information on smoking status and smoking cessation. The potential factors related with smoking prevalence and smoking cessation were analzyed. RESULTS: The response rate was 91.2%. The ever-smoking rate was 35.8%. Among the 621 ever-smokers, 35.5% had tried or were trying to quit smoking. The vast majority (93.9%) of smoking cessation methods was self-service method. The overall rate of abstinence was 12.4%, and the success rate was higher in those groups of elder age, lower educational level, lower income level, having respiratory symptoms, and/or without nicotine dependence. There were 291 responders (46.9%) had the willingness to quit. Responders at older age, having respiratory symptoms, or with nicotine dependence had higher willingness to quit. CONCLUSIONS: The tobacco control efforts in rural areas should be strengthened. In part of motivated intervention, the advice should be given from the family, friends, doctors to young, asymptomatic smokers.

Expert consensus on acute exacerbation of chronic obstructive pulmonary disease in the People's Republic of China.

Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People's Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD.

Tsc1 deficiency-mediated mTOR hyperactivation in vascular endothelial cells causes angiogenesis defects and embryonic lethality.

This is a study on the role of tuberous sclerosis complex1 (TSC1) mutation and mTOR activation in endothelial cells during angiogenic and embryonic development. Past studies had shown that Tsc1/Tsc2 mutant genes lead to overactivation of mTOR in the regulating pathways in developing fetus. We used conditional Cre-loxp gene knockout approach to delete Tsc1 in mice's endothelial cells in our experimental models. Similarly, activation of mTOR signaling in endothelial cells of these embryos (Tie2-Cre/Tsc1(-/-)) was found. Majority of Tie2-Cre/Tsc1(-/-) embryos died at embryonic day 14.5 in utero. Cardiovascular defects, subcutaneous edema and hemorrhage were present among them. Whole-mount immunostaining in these embryos revealed a disorganized vascular network, defective sprouting of vessels in yolk sac and thickening of the labyrinth layer in the placenta. A thinner ventricular wall with disorganized trabeculae was present in the hearts of Tie2-Cre/Tsc1(-/-) embryos. Endothelial cells in Tsc1-deficient mice showed defective mitochondrial and endoplasmic reticular morphology, but no significant change was observed in cell junctions. The mutant embryos displayed significantly reduced cell proliferation, increased apoptosis and disturbed expression of angiogenic factors. A cohort of mice was treated prenatally with mTOR inhibitor rapamycin. The offspring of these mutant mice survived up to 22 days after birth. It was concluded that physiological TSC1-mTOR signaling in endothelial cells is crucial for vascular development and embryogenesis. We postulated that disruption of normal angiogenic pathways through hyperactive mTOR signaling maybe the mechanism that lead to deranged vascular pathogenesis in the tuberous sclerosis complex.