Yahong Chen

Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma

Endogenous hydrogen sulfide (H(2)S) is hypothesized to have an important role in systemic inflammation. We investigated if endogenous H(2)S may be a crucial mediator in airway inflammation and airway remodeling in a rat model of asthma and if endogenous H(2)S may exert its anti-inflammatory effect by inhibiting inducible nitric oxide synthase (iNOS)/NO pathway. Cystathionine-gamma-lyase (CSE; a H(2)S-synthesizing enzyme) was mainly expressed in airway and vascular smooth muscle cells in rat lung tissue. Levels of endogenous H(2)S was decreased in pulmonary tissue in ovalbumin (OVA)-treated rats. Exogenous administration of NaHS alleviated airway inflammation and airway remodeling: peak expiratory flow (PEF) increased, goblet cell hyperplasia and collagen deposition score decreased, with decreased total cells recovered from bronchoalveolar fluid (BALF) and influx of eosinophils and neutrophils. The H(2)S levels of serum and lung tissue were positively correlated with PEF and negatively correlated with the level of eosinophils and neutrophils in BALF, score of lung pathology. NaHS treatment significantly attenuated pulmonary iNOS activation in OVA-treated rats. These results suggest that the CSE/H(2)S pathway plays an anti-inflammatory and anti-remodeling part in asthma pathogenesis and could be a novel target in prevention and treatment of asthma.

Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung

Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure. Serum H₂S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10⁻⁴ mol/L), L-NAME (10⁻⁴ mol/L), or ODQ (1 μmol/L) or denudation of epithelium. Endogenous H₂S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.

Serum hydrogen sulfide as a novel marker predicting bacterial involvement in patients with community-acquired lower respiratory tract infections

Background and objective:  Endogenous hydrogen sulfide (H2S) may be involved in the pathogenesis of systemic inflammation. It was investigated whether serum H2S levels differed among patients with community‐acquired pneumonia, those with exacerbations of COPD or control subjects, and whether H2S may be used as a surrogate marker of the need for antibiotic treatment.

Primary tracheobronchial amyloidosis in China: Analysis of 64 cases and a review of literature

Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease. A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed. The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified. The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time. The results showed that the morbidity associated with primary TBA has increased over recent years. The clinical manifestations were non-specific. Progressive dyspnea, cough and sputum were the most common symptoms. The percentage of patients undergoing computed tomography (CT) scan has increased over the years. The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis. Treatment was reported for a total of 44 cases. Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients. It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries. Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s. Chest CT scan provides important clues for the diagnosis of the disease. The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen. Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.SummaryPrimary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease. A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed. The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified. The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time. The results showed that the morbidity associated with primary TBA has increased over recent years. The clinical manifestations were non-specific. Progressive dyspnea, cough and sputum were the most common symptoms. The percentage of patients undergoing computed tomography (CT) scan has increased over the years. The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis. Treatment was reported for a total of 44 cases. Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients. It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries. Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s. Chest CT scan provides important clues for the diagnosis of the disease. The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen. Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.

Exhaled Hydrogen Sulfide Predicts Airway Inflammation Phenotype in COPD

BACKGROUND: The role of exhaled H2S as a marker of airway inflammation and its relationship with COPD severity remain to be determined. METHODS: Airway inflammation was classified in 77 COPD subjects based on the presence of inflammatory cells in induced sputum. We investigated the association between disease phenotype and exhaled H2S, lung function, and plasma levels of several inflammatory factors, including tumor necrosis factor alpha, interleukin-8, and leukotriene B4. RESULTS: In total, 33.77% of enrolled COPD subjects were diagnosed with eosinophilia. These subjects had a longer disease course, smoked fewer cigarettes, and experienced more frequent exacerbation events before study enrollment. However, they also had worse lung function and larger residual volume, they demonstrated greater changes in FEV1 following bronchodilator inhalation. Although levels of plasma inflammatory factors did not significantly differ between subjects with and without eosinophilia, subjects without eosinophilia had significantly higher levels of exhaled H2S (9.19 ± 2.74 vs 7.24 ± 1.68 parts per billion, P = .01). Furthermore, exhaled H2S levels were negatively correlated with induced sputum eosinophils (r = −0.45, P = .05), and positively correlated with inspiratory capacity in COPD subjects (r = 0.51, P = .026), but did not correlate significantly with plasma inflammatory factors. A cut-off value of 7.10 parts per billion of exhaled H2S predicted a non-eosinophilic phenotype with 68.6% sensitivity and 77.9% specificity. CONCLUSIONS: Exhaled levels of H2S were lower in subjects with eosinophilia. Increased levels of exhaled H2S predicted a non-eosinophilic phenotype in our study population.

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

Endogenous hydrogen sulfide (H2S) may be a biomarker of asthma severity and activity. However, the relationship between exhaled H2S and airway inflammation phenotypes in asthma remains unclear. This study examined associations between endogenous H2S and chronic airway inflammatory phenotypes in patients with chronic persistent asthma.

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.

Imbalance of Endogenous Hydrogen Sulfide and Homocysteine in Chronic Obstructive Pulmonary Disease Combined with Cardiovascular Disease

Background: Considerable studies showed associations between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), we evaluated the role of endogenous hydrogen sulfide (H2S)/homocysteine (Hcy) in patients with COPD combined with CVD. Methods: Fifty one stable patients with COPD were enrolled (25 COPD, 26 COPD + CVD). Lung function, sputum, peripheral blood samples, serum H2S, Hcy, high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) levels were measured. Dyspnea, symptoms and quality of life were quantified by modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT) and St. George’s Respiratory Questionnaire (SGRQ). Results: Compared with COPD group, waist circumference and body mass index (BMI) were higher in COPD + CVD group, mMRC, CAT and activity scores were also higher, high density lipoprotein cholesterol (HDL-C) was lower, total cells, neutrophils (%) in sputum and serum hs-CRP level were higher, whereas macrophages (% ) in sputum was lower. H2S and Hcy levels from COPD + CVD group were higher than those from COPD group, but H2S/Hcy ratio was lower. With increasing COPD severity, H2S level was decreased, however, Hcy level was increased. H2S level was positively correlated with FEV1/FVC, FEV1% predicted, lymphocytes (%) and macrophages (%) in sputum, but negatively correlated with smoking pack-years and neutrophils (%) in sputum. Hcy level was positively correlated with BMI and total cells in sputum. The ratio of H2S/Hcy was also positively correlated with FEV1/FVC, but negatively correlated with total cells in sputum. Conclusion: The imbalance of H2S/Hcy may be involved in the pathogenesis of COPD combined with CVD and provide novel targets for therapy.

Use of glucocorticoids in patients with COPD exacerbations in China: a retrospective observational study

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common in patients with underlying moderate to severe COPD and are associated with increased health and economic burden. International and Chinese guidelines recommend using glucocorticoids for the management of AECOPD because glucocorticoid therapy has been shown to benefit clinical outcomes. However, only scant data are available for current status of glucocorticoid therapy in hospitalized AECOPD patients in China. The aim of the study was to identify current use of glucocorticoids for the treatment of AECOPD in China. Methods: This retrospective, multicenter, noninterventional study evaluated the treatment pattern of AECOPD in patients hospitalized from January 2014 to September 2014 at 43 sites (41 tertiary hospitals and two secondary hospitals) in China. The endpoints of the study were the percentage of patients receiving glucocorticoids by different routes of administration, doses and duration, mortality, and the mean length of hospitalization. Results: A total of 4569 patients (90.17%) received glucocorticoids for AECOPD treatment. A combination of nebulized and systemic route was most frequently used (40.51%), followed by using nebulized route alone (38.00%), systemic route alone (15.45%), and inhaled route other than nebulization (6.04%). Furthermore, the most commonly prescribed glucocorticoids of the nebulized, intravenous, inhaled (other than nebulized) and oral route was budesonide (69.4%), methylprednisolone sodium succinate (45.31%), fluticasone propionate (19.54%), and prednisone acetate (11.90%), respectively. The in-hospital mortality rate was 1.24% and the mean length of hospitalization was 12.22 ± 6.20 days (± SD). Conclusions: Our study was the first study of the treatment pattern of glucocorticoids in the management of hospitalized AECOPD patients in China. Data indicates that there is a gap in the implementation of international guidelines for the treatment of AECOPD in China. Further studies are warranted to clarify the appropriate glucocorticoids strategy for the management of AECOPD to determine the optimal route of administration, dose and duration, and resulting clinical outcomes.

Gender difference on the knowledge, attitude, and practice of COPD diagnosis and treatment: a national, multicenter, cross-sectional survey in China

Purpose To investigate the gender difference in knowledge, attitude, and practice of COPD diagnosis and treatment in China. Patients and methods A nationwide, multicenter, cross-sectional questionnaire study was carried out to investigate patients’ understanding and experience of COPD between September 2007 and December 2008. Results Two thousand and seventy-two patients were recruited from eleven centers. The final effective questionnaires were those of 1,698 cases, of which 32% were female. Women were younger, had higher body mass index, were more never smokers, and had lesser pack-years (all P<0.01). More women had under elementary education level and monthly income <1,000 RMB (about 160 USD) (all P<0.01). Women had higher ratio of FEV1/FVC (54.1±10.9 vs 50.2±11.5), FEV1% (50.0±19.1 vs 45.4±29.0), and lower short form-36 mental component summary (57.5±26.8 vs 61.3±25.0) (all P<0.01). Fewer women reported severe exacerbation (defined as an acute worsening of respiratory symptoms that results in patient’s hospitalization) in the previous year (44.5% vs 51.6%, P<0.05). More women reported that they never heard of COPD before (67.0% vs 59.0%, P<0.01). Less women reported that physician had to tell them they had emphysema (50.5% vs 60.4%) or COPD (31.9% vs 37.9%). Less women had pulmonary function test (PFT) done before (65.2% vs 70.4%, P<0.05). More women reported that they would not repeat PFT annually (91.7% vs 87.6%, P<0.05) and did not know the PFT results (78.6% vs 73.1%, P<0.05). More women reported not having had pulmonary rehabilitation before (87.8% vs 83.6%, P<0.05). Fewer women reported knowing that COPD should be given combined therapy (38.3% vs 44.5%) and long-term treatment (46.1% vs 51.9%) (all P<0.05). Conclusion Male and female patients had different experiences on COPD diagnosis and treatment. Physicians should pay more attention to patients’ education on COPD, especially of women.