Long-Term Ozone Exposure and Small Airway Dysfunction: The China Pulmonary Health (CPH) Study.

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.

Associations of residential greenness with lung function and chronic obstructive pulmonary disease in China.

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.

Development and Validation of a Screening Questionnaire of COPD from a Large Epidemiological Study in China.

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

MRI features of and factors related to ankle injuries in asymptomatic amateur marathon runners.

OBJECTIVE: To analyze the MRI manifestations of and factors related to ankle injuries in asymptomatic amateur marathon runners. MATERIALS AND METHODS: A total of 113 amateur marathon runners without any ankle joint symptoms were recruited. Each participant was asked to complete a questionnaire at the beginning of the study and underwent MRI of the ankle. The MRI manifestations of ankle injuries were summarized, and binary logistic regression analysis was applied to analyze the factors related to ankle injuries. RESULTS: The main MRI features were bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. Others included Achilles tendinopathy, cyst-like lesions, osteochondral lesions, and subcutaneous soft tissue edema. The risk factor for bone marrow edema-like signal intensity in amateur marathon runners was a rearfoot strike pattern (p = 0.028, OR = 1.172); the risk factors for peritendinous effusion were a higher weekly running distance (p = 0.013, OR = 1.685) and increased running years (p = 0.039, OR = 1.113), whereas a rearfoot strike pattern (p = 0.005, OR = 0.831) was a protective factor for peritendinous effusion; the risk factor for Achilles tendinopathy was increased age (p = 0.008, OR = 1.412); the risk factors for anterior talofibular ligament injury were a rearfoot strike pattern (p = 0.017, OR = 1.346) and higher weekly running distance (p = 0.022, OR = 1.171); and the factors for calcaneofibular ligament injury were a higher weekly running distance (p = 0.029, OR = 1.570) and rearfoot strike pattern (p = 0.035, OR = 1.463). CONCLUSION: The main MRI features of asymptomatic amateur marathon runners are bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. In addition, increased age, increased running years, higher weekly running distance, and different foot strike patterns are risk factors for ankle injuries.

Prevalence, risk factors, and management of asthma in China: a national cross-sectional study.

BACKGROUND: Asthma is a common chronic airway disease worldwide. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of asthma. We therefore aimed to estimate the national prevalence of asthma in a representative sample of the Chinese population. METHODS: A representative sample of 57 779 adults aged 20 years or older was recruited for the national cross-sectional China Pulmonary Health (CPH) study using a multi-stage stratified sampling method with parameters derived from the 2010 census. Ten Chinese provinces, representative of all socioeconomic settings, from six geographical regions were selected, and all assessments were done in local health centres. Exclusion criteria were temporary residence, inability to take a spirometry test, hospital treatment of cardiovascular conditions or tuberculosis, and pregnancy and breastfeeding. Asthma was determined on the basis of a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. All participants were assessed with a standard asthma questionnaire and were classed as having or not having airflow limitation through pulmonary function tests before and after the use of a bronchodilator (400 µg of salbutamol). Risk factors for asthma were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was assessed by the self-reported history of physician diagnosis, treatments, and hospital visits in people with asthma. FINDINGS: Between June 22, 2012, and May 25, 2015, 57 779 participants were recruited into the CPH study. 50 991 (21 446 men and 29 545 women) completed the questionnaire survey and had reliable post-bronchodilator pulmonary function test results and were thus included in the final analysis. The overall prevalence of asthma in our sample was 4·2% (95% CI 3·1-5·6), representing 45·7 million Chinese adults. The prevalence of asthma with airflow limitation was 1·1% (0·9-1·4), representing 13·1 million adults. Cigarette smoking (odds ratio [OR] 1·89, 95% CI 1·26-2·84; p=0·004), allergic rhinitis (3·06, 2·26-4·15; p<0·0001), childhood pneumonia or bronchitis (2·43, 1·44-4·10; p=0·002), parental history of respiratory disease (1·44, 1·02-2·04; p=0·040), and low education attainment (p=0·045) were associated with prevalent asthma. In 2032 people with asthma, only 28·8% (95% CI 19·7-40·0) reported ever being diagnosed by a physician, 23·4% (13·9-36·6) had a previous pulmonary function test, and 5·6% (3·1-9·9) had been treated with inhaled corticosteroids. Furthermore, 15·5% (11·4-20·8) people with asthma reported at least one emergency room visit and 7·2% (4·9-10·5) at least one hospital admission due to exacerbation of respiratory symptoms within the preceding year. INTERPRETATION: Asthma is prevalent but largely undiagnosed and undertreated in China. It is crucial to increase the awareness of asthma and disseminate standardised treatment in clinical settings to reduce the disease burden. FUNDING: National Key R&D Program of China, Ministry of Science and Technology of China; the Special Research Foundation for Public Welfare of Health, Ministry of Health of China; the Chinese National Research Program for Key Issues in Air Pollution Control; and the National Natural Science Foundation of China.

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.

Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study.

BACKGROUND: Although exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China. METHODS: The CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. FINDINGS: Between June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5-9·9), accounting for 99·9 (95% CI 76·3-135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2-13·8) than in women (5·4%, 4·6-6·2; p<0·0001 for sex difference) and in people aged 40 years or older (13·7%, 12·1-15·5) than in those aged 20-39 years (2·1%, 1·4-3·2; p<0·0001 for age difference). Only 12·0% (95% CI 8·1-17·4) of people with COPD reported a previous pulmonary function test. Risk factors for COPD included smoking exposure of 20 pack-years or more (odds ratio [OR] 1·95, 95% CI 1·53-2·47), exposure to annual mean particulate matter with a diameter less than 2·5 µm of 50-74 µg/m3 (1·85, 1·23-2·77) or 75 µg/m3 or higher (2·00, 1·36-2·92), underweight (body-mass index <18·5 kg/m2; 1·43, 1·03-1·97), sometimes childhood chronic cough (1·48, 1·14-1·93) or frequent cough (2·57, 2·01-3·29), and parental history of respiratory diseases (1·40, 1·23-1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64-0·90) and college or higher education (0·47, 0·33-0·66). INTERPRETATION: Spirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality. FUNDING: Ministry of Health and Ministry of Science and Technology of China.

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis.

AIM: To character the specific metabolomics profiles in the sera of Chinese patients with mild persistent asthma and to explore potential metabolic biomarkers. METHODS: Seventeen Chinese patients with mild persistent asthma and age- and sex-matched healthy controls were enrolled. Serum samples were collected, and serum metabolites were analyzed using GC-MS coupled with a series of multivariate statistical analyses. RESULTS: Clear intergroup separations existed between the asthmatic patients and control subjects. A list of differential metabolites and several top altered metabolic pathways were identified. The levels of succinate (an intermediate in tricarboxylic acid cycle) and inosine were highly upregulated in the asthmatic patients, suggesting a greater effort to breathe during exacerbation and hypoxic stress due to asthma. Other differential metabolites, such as 3,4-dihydroxybenzoic acid and phenylalanine, were also identified. Furthermore, the differential metabolites possessed higher values of area under the ROC curve (AUC), suggesting an excellent clinical ability for the prediction of asthma. CONCLUSION: Metabolic activity is significantly altered in the sera of Chinese patients with mild persistent asthma. The data might be helpful for identifying novel biomarkers and therapeutic targets for asthma.

Bacterial infection, airway and systemic inflammation and clinical outcomes before and after treatment of AECOPD, a longitudinal and cross-sectional study.

Abstract Bacterial infection is a major cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), which are associated with significantly increased airway and systemic inflammation. However, the relationship among bacteriology, the resolution of inflammation and clinical outcomes is largely unknown. In this study, we recruited consecutive patients hospitalized for AECOPD with purulent sputum. We measured the airway and systemic inflammation levels, the COPD assessment test (CAT) score and adverse outcomes between patients with and without potentially pathogenic microorganisms (PPM). Among sputum samples collected from the 135 episodes of AECOPD, 42 (31.1%) were PPM-positive at admission. Compared with those in the PPM-negative group, more patients in the PPM-positive group had ≥2 exacerbations in previous year and Anthonisen type I at admission and higher drop in sputum neutrophil, serum hs-CRP and CAT value from exacerbation to the subsequent baseline. No significant differences in the adverse outcomes between the two groups were observed. Among the 38 PPM-positive patients who survived and were discharged from hospital, 19 remained PPM-positive (bacterial persistence group) and 19 PPM-negative (bacterial clearance group). Both inflammation indices and CAT score decreased compared to admission in the two groups, regardless of the bacteriology at discharge. Our data suggest uncultivated bacteria and/or virus might also play important roles in causing inflammation and AECOPD.

[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.

Correlation between levels of exhaled hydrogen sulfide and airway inflammatory phenotype in patients with chronic persistent asthma.

BACKGROUND AND OBJECTIVE: Endogenous hydrogen sulfide (H2 S) may be a biomarker of asthma severity and activity. However, the relationship between exhaled H2 S and airway inflammation phenotypes in asthma remains unclear. This study examined associations between endogenous H2 S and chronic airway inflammatory phenotypes in patients with chronic persistent asthma. METHODS: One hundred forty-eight patients (47 males, 101 females, 47.4 ± 15.3 years old) with chronic persistent asthma were enrolled. Induced sputum cells were examined, and patients were grouped according to sputum inflammatory cell composition. Baseline demographics, Asthma Control Test (ACT) scores, spirometry data and H2S levels in exhaled air and plasma were obtained for all patients. RESULTS: The eosinophilic, neutrophilic, mixed granulocytic and paucigranulocytic inflammation groups included 57 (38.5%), 28 (18.9%), 23 (15.5%) and 40 (27%) subjects, respectively. The paucigranulocytic group had the best lung function, and patients with eosinophilic inflammation had lower ACT scores than patients with paucigranulocytic findings. In the eosinophilic group, lower exhaled H2S were found and exhaled H2 S levels were negatively correlated with sputum eosinophil counts (R = -0.428, P < 0.01). Exhaled H2 S levels were positively correlated with percent of predicted forced expiratory volume in 1 s (R = 0.567, P < 0.01) and ACT score (R = 0.519, P < 0.01). CONCLUSIONS: Exhaled H2 S may be a useful marker of airway inflammation in asthma.

Effect of once-daily indacaterol in a predominantly Chinese population with chronic obstructive pulmonary disease: a 26-week Asia-Pacific study.

BACKGROUND AND OBJECTIVE: This study, in a predominantly Chinese population, investigated the efficacy and safety of a once-daily (o.d.) inhaled ultra-long-acting ß2 -agonist indacaterol for the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: This is a 26-week, double-blind study on randomized patients who received indacaterol 150 µg or 300 µg or placebo o.d. The primary variable was trough forced expiratory volume in 1 s (FEV1 , average of 23 h 10 min and 23 h 45 min post-dose values) at Week 12. Health status (St George's Respiratory Questionnaire, SGRQ), dyspnoea (transition dyspnoea index, TDI) and safety were evaluated over 26 weeks. RESULTS: Of the 563 patients randomized, 561 (89.8% Chinese) received treatment and 482 completed. At Week 12, trough FEV1 improved significantly for indacaterol 150 and 300 µg versus placebo (1.32, 1.29 vs 1.17; P < 0.001 for both comparisons), with differences exceeding the pre-specified minimal clinically important difference of 0.12 L. At Week 26, TDI score was superior to placebo for indacaterol 150 and 300 µg (0.82, 1.15; P < 0.01), as was the percentage of patients with a clinically relevant improvement (≥1 point) (74.1%, 78.6% vs 55.5%; P < 0.05). Both doses provided ≥4-point improvements from baseline in SGRQ score at Week 26 that were numerically greater than placebo (unadjusted means: -9.6, -8.8 vs -7.0), with a similar pattern in percentage of patients with clinically relevant improvements in SGRQ score (65.0%, 61.5% vs 60.6%). Incidences of adverse events were comparable across treatment groups. CONCLUSIONS: Indacaterol delivered effective bronchodilation with significant improvements in breathlessness and health status in this predominantly Chinese population.

Time course of inflammation resolution in patients with frequent exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: When exacerbation of chronic obstructive pulmonary disease (AECOPD) occurs frequently, patients have high levels of airway and systemic inflammation and a poor quality of life. This study compared the nature and course of systemic and airway inflammation during AECOPD between patients who experienced frequent exacerbations and those with non-frequent exacerbations. MATERIAL AND METHODS: Consecutive hospitalized patients with AECOPD were recruited and divided into 2 groups according to the frequency of AECOPD they had experienced in the previous year. Frequent exacerbators (defined as 2 or more AECOPD in the previous year) and non-frequent exacerbators (defined as zero or 1 AECOPD in the previous year). Inflammatory (interleukin 6, interleukin 8, myeloperoxidase, and C-reactive protein) and clinical (dyspnea, COPD assessment test (CAT), and peak expiratory flow) indices were assessed on the day of admission before starting therapy, day 7 of treatment, the day of planned discharge (day 10-14), and 8 weeks after discharge. RESULTS: We analyzed data from 135 patients; 78 (57.8%) were non-frequent exacerbators and 57 (42.2%) were frequent exacerbators. In both groups, the inflammatory and clinical indices at day 7, the day of planned discharge (day 10-14), and 8 weeks were significantly improved compared to those at admission. Frequent exacerbators had a smaller reduction in their inflammatory indices and CAT scores between exacerbation onset and all the other time points compared with infrequent exacerbators. CONCLUSIONS: Frequent exacerbators have a reduced response to treatment of AECOPD in terms of inflammatory indices and quality of life.

[A cross-sectional survey of familial aggregation of chronic obstructive pulmonary disease: in seven provinces/cities in China].

OBJECTIVE: To investigate the familial aggregation in chronic obstructive pulmonary disease (COPD). METHODS: Based on a cross-sectional survey in seven provinces/cities in China (Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shaanxi) from 2002 to 2004, the familial aggregation of COPD was investigated with multi-stage cluster random sampling method.One urban and one rural area were selected as samples from each of seven provinces/cities. All residents equal or older than 40 years old received questionnaires and pulmonary function tests. Questionnaires included risk factors of COPD, respiratory symptoms, quality of life, diagnosis and prevention conditions of COPD. Bronchodilator tests, physical examination, X-ray and electrocardiograph (ECG) were conducted in those subjects.In pulmonary function tests, the ratio of the first second forced expiratory volume (FEV1) /forced vital capacity (FVC) less than 70% fulfill the diagnostic criteria of COPD.If any of siblings and parents had chronic bronchitis, emphysema, asthma or COPD, it should be considered as a positive family history of COPD-related disease.Otherwise, it was negative. RESULTS: FEV1 was lower in the subjects with a family history of COPD-related diseases than in those without [(2.24 ± 0.70) L vs (2.28 ± 0.73) L]. The prevalence of COPD in the population with history of COPD-related diseases was 12.1% (540/4 481), which was significantly higher than that without [7.2% (1 128/15 764), χ(2) = 110.599, P < 0.001]. After adjusted for potential confounder, the population with a family history of COPD-related diseases still had much higher incidence of COPD [OR = 2.18 (95%CI 1.94-2.46)]. Furthermore, the population having two or more first-degree relatives with COPD-related diseases, exhibited the highest likelihood of COPD [OR = 2.48 (95%CI 2.00-3.08)]. The population having only one first-degree relative with COPD-related diseases showed an increased risk of COPD with an OR = 2.10 (95%CI 1.84-2.40) compared with those without any one. Those whose father, mother or siblings had COPD-related diseases were similarly likely to have COPD, with an OR of 1.54 (95%CI 1.32-1.80), 1.83 (95%CI 1.56-2.15) and 1.81 (95%CI 1.48-2.23), respectively. CONCLUSIONS: There is a familial aggregation in COPD. The more relatives have COPD-related diseases in the family, the greater risk of COPD the subject will have.

[Bacteriology in acute exacerbation in patients hospitalized frequently for acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To analyze the distribution of pathogens and bacterial drug resistance for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in patients hospitalized frequently for AECOPD versus those with infrequent admissions. METHODS: A total of 172 patients admitted into Peking University Third Hospital for AECOPD from January 2007 to December 2008 were recruited. According to the frequency of AECOPD-related hospitalization during the previous year, they were divided into two groups of frequently hospitalized ( ≥ 2 hospitalizations due to AECOPD during the previous year) and infrequently hospitalized (<2 hospitalizations due to AECOPD during the previous year). The distribution and drug resistance of pathogenic bacteria were compared between two groups. RESULTS: At the time of acute exacerbation, the frequently hospitalized patients had significantly higher rates of non-fermentative gram-negative bacteria (18.8% (9/48) vs 4.8% (6/124), χ² = 6.756, P = 0.009), enterobacteriaceae (18.8% (9/48) vs 7.3% (9/124), χ² = 4.877, P = 0.027) versus those infrequently hospitalized ones. The frequently hospitalized patients had more multidrug resistant bacteria isolated from sputum versus those infrequently hospitalized ones (25.0% (12/48) than 8.1% (10/124), χ² = 8.898, P = 0.003). CONCLUSION: The distribution and drug resistance of pathogenic bacteria are associated with the frequency of AECOPD-related hospitalization during the previous year.

Heterogeneities and impact profiles of early chronic obstructive pulmonary disease status: findings from the China Pulmonary Health Study.

Background: The prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet. Methods: Data were obtained from the China Pulmonary Health study (2012-2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria. Findings: The age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3-6.9), 7.2% (5.9-8.8), 1.1% (0.7-1.8), and 3.1% (2.5-3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents' events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment. Interpretation: Significant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population. Funding: Chinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

The relationship between particulate matter (PM10) and hospitalizations and mortality of chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Numerous studies have reported variable associations between ambient particulate matter (PM) and chronic obstructive pulmonary disease (COPD) hospitalizations and mortality. OBJECTIVE: To conduct a systematic study assessing the associations between hospitalizations and mortality from COPD and ambient PM10 (particulate matter with aerodynamic diameters ≤ 10 µm, PM10). METHODS: Systematic searches were conducted in 6 common electronic databases. A meta-analysis was performed to estimate the odds ratio (OR) to evaluate the relationship between PM10 and COPD hospitalizations and mortality. Publication bias and heterogeneity of samples were tested by Begg funnel plot and Egger test, respectively. Study findings were analyzed using random-effect model and fixed-effect model. RESULTS: The search yielded 31 studies suitable for the meta-analysis during the period from Jan 1, 2000 to Oct 31, 2011. A 10 µg/m(3) increase in PM10 was associated with a 2.7% (95%CI = 1.9%-3.6%) increase in COPD hospitalizations with an OR of 1.027 (95%CI: 1.019-1.036), and a 1.1% (95%CI: 0.8%-1.4%) increase in COPD mortality with an OR of 1.011 (95%CI: 1.008-1.014). CONCLUSIONS: Ambient PM10 is associated with increased COPD hospitalizations and mortality. Further research is needed to elucidate whether this association is causal and to clarify its mechanisms.

High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

[The prevalence and risk factors of bronchiectasis in residents aged 40 years old and above in seven cities in China].

OBJECTIVE: To investigate the prevalence and risk factors of bronchiectasis in urban city of China. METHODS: A cross-sectional survey was conducted in 17 urban areas in Beijing, Shanghai, Tianjin, Chongqing cities, and Guangdong, Liaoning, Shanxi provinces. In this study, urban population-based cluster samples were randomly selected from each city/province. In the selected city communities, all residents at least 40 years old were recruited, interviewed with questionnaires and tested with spirometry. Each participant was asked whether he/she was ever diagnosed as bronchiectasis by physician, whether had symptoms of respiratory diseases and possible risk factors, etc. RESULT: Data of 10 811 participants was enrolled for analysis, with a response rate of 75.4% (10 811/14 337). The overall prevalence of physician-diagnosed bronchiectasis was 1.2% (135/10 811), with 1.5% (65/4382) in male and 1.1% (70/6429) in female, without statistical difference in gender (χ² = 3.289, P = 0.070). Prevalence of bronchiectasis increased with age (χ² = 31.029, P < 0.001). There were no statistical significances in crude prevalences of bronchiectasis among cities (χ² = 10.572, P = 0.103), while there was a significant difference among cities after adjustment with confounders (Wald value = 22.116, P = 0.001), by using logistic regression analysis. Logistic regression analysis showed, bronchiectasis was significantly associated with elder ( ≥ 70 years vs 40-49 years; OR = 4.11, 95% CI 2.29-7.36), the family history of respiratory diseases (having two subjects with respiratory diseases in family vs no suffered relatives; OR = 2.04, 95% CI 1.06-3.94), respiratory infection during childhood (suffering two kinds of respiratory diseases vs never; OR = 4.89, 95% CI 2.03-11.81), exposure to coal (OR = 2.30, 95% CI 1.17-4.52), chronic pharyngitis (OR = 3.96, 95% CI 1.38-11.40) and pulmonary tuberculosis (OR = 3.07, 95% CI 1.89-4.98), heart diseases (OR = 1.64, 95% CI 1.11-2.42) and lung cancer(OR = 18.61, 95% CI 7.67-45.18). CONCLUSION: The prevalence of bronchiectasis in population aged 40 years old and above in urban area in China is high and associated with multiple factors such as age, family history of respiratory diseases, respiratory infection during childhood, exposure to coal, chronic pharyngitis, pulmonary tuberculosis, heart diseases, lung cancer and so on.