Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma.

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION: Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

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.

[Changes of C3a in induced sputum in patients with asthma].

OBJECTIVE: To investigate the clinical significance of anaphylatoxin C3a in induced sputum in patients with asthma. METHODS: The patients with acute exacerbation of asthma treated at our department between September, 2006 and February, 2007 were included in the study. The demographic data, medical history, levels of lung function and C3a levels in induced sputum were assessed. RESULTS: A total of 33 patients were included in the study. The level of C3a in induced sputum was significantly higher in patients with acute exacerbation of asthma (2.24 ng/ml, range 1.68-5.58 ng/ml) than that in patients with asthma remission (0.7 ng/ml, range 0.24-2.31 ng/ml, P<0.05). Sputum C3a levels in the remission patients were significantly higher than those in the healthy controls (0.12 ng/ml, range 0.07-0.39 ng/ml, P<0.05). The levels of C3a in patients with severe exacerbation (4.69 ng/ml, range 2.69-6.59 ng/ml) were significantly higher than those in patients with mild exacerbation (0.25 ng/ml, range 0.09-0.40 ng/ml) and moderate exacerbation (2.21 ng/ml, range 1.16-3.41 ng/ml) (P<0.01), and were significantly higher in patients with moderate exacerbation than in those in mild exacerbation (P<0.01). The level of C3a in induced sputum was positively correlated with the number of total cell count (r=0.718, P<0.05), eosinophils (r=0.495, P<0.05) and macrophages (r=0.600, P<0.05) in patients with acute exacerbation of asthma. CONCLUSION: Induced sputum C3a level can serve as an important clinical biomarker for clinical asthma management.

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.

Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial.

BACKGROUND: Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. METHODS: In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group. INTERPRETATION: Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). FUNDING: Hainan Zambon Pharmaceutical.

[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.

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.

Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma.

BACKGROUND: Many studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting ß(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775). METHODS: A total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life. RESULTS: Time to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated. CONCLUSIONS: In Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

[Incidence of comorbidities in hospitalized chronic obstructive pulmonary disease patients and correlated risk factors].

OBJECTIVE: To explore the incidence of comorbidities in hospitalized chronic obstructive pulmonary disease (COPD) patients and influencing factors. METHODS: A retrospective review of medical records was performed for 495 hospitalized COPD patients in Peking University Third Hospital from January 2003 to December 2008. Their comorbidities were identified and ranked in prevalence. The risk factors of comorbidities were analyzed by multivariable Logistic regression. RESULTS: The most frequent comorbidities were: hypertension (60.0%), ischemic heart disease (16.0%), malignant tumor (10.9%), diabetes mellitus (10.5%), chronic heart failure (9.9%) and dyslipidemia (9.9%). The percentage of patients with ischemic heart disease in people with FEV(1)% Pred < 30%, 30% ≤ FEV(1)%Pred < 50%, 50% ≤ FEV(1)%Pred < 80% and FEV(1)%Pred ≥ 80% were 9.2%, 12.7%, 21.3% and 16.5% respectively (P = 0.052). The percentage of patients with dyslipidemia in people with FEV(1)%Pred < 30%, 30% ≤ FEV(1)%Pred < 50%, 50% ≤ FEV(1)%Pred < 80%, FEV(1)%Pred ≥ 80% were 5.3%, 5.7%, 10.9% and 20.3% respectively (P = 0.002). The percentage of patients with ischemic heart disease in people with body mass index (BMI) < 18.5, 18.5 - 23.9, 24.0 - 27.9, ≥ 28.0 kg/m(2) were 13.6%, 14.2%, 14.6% and 28.3% respectively (P = 0.051). The percentage of patients with dyslipidemia in people with BMI < 18.5, 18.5 - 23.9, 24.0 - 27.9, ≥ 28.0 kg/m(2) were 5.5%, 5.7%, 14.6% and 25.0% respectively (P = 0.000). The levels of C-reactive protein (CRP) were higher than the 75(th) percentile (OR = 2.371, P = 0.014), and complications with metabolic syndrome (OR = 2.694, P = 0.003) were independent risk factors of ischemic heart disease in COPD patients. CONCLUSIONS: The incidence of comorbidities varies in different COPD populations. Higher levels of CRP and complications with metabolic syndrome are independent risk factors of ischemic heart disease in COPD patients.

Pulmonary embolism in adolescents.

BACKGROUND: Pulmonary embolism (PE) is rare and seldom considered in adolescent patients; however it occurs with a greater frequency than is generally recognized, and it is a potentially fatal condition. The aim of the current study was to understand its epidemiology, clinical features and the cause of delay of its diagnosis in adolescents. METHODS: A retrospective analysis of nine adolescents with acute PE admitted to the Peking University Third Hospital over the past 16-year period was performed. The epidemiology, clinical features and risk factors of the adolescents were described and compared with those of adults and elderly patients. The time to diagnosis and misdiagnosed diseases were analyzed. Pretest probability of PE was assessed retrospectively by the Wells score and revised Geneva score. RESULTS: The incidence of PE was 43.6 per 100 000 hospitalized adolescents in our hospital. The incidence of PE in adolescents was much lower than that in adults and PE is diagnosed in about 1/50 of elderly people. The clinical features in adolescents were similar to those in adults. But fever and chest pain were more common in adolescents (P < 0.05). The major risk factors included surgery, systemic lupus erythematosus (SLE), thrombocytopenia, long-term oral glucocorticoids and trauma. The mean diagnostic time was (7.8 ± 8.4) days. Six cases had a delayed diagnosis. The mean delay time from symptom onset to diagnosis was (11.0 ± 8.8) days. The time of presentation to diagnosis in patients initially admitted to the emergency department was less than one day, and was much shorter than the time in outpatients, (9.4 ± 7.5) days. Most of the patients were initially misdiagnosed with a respiratory tract infection. Most patients' values of Wells score or revised Geneva score were in the moderate or high clinical probability categories; 88% by Well score vs. 100% by revised Geneva score. CONCLUSIONS: PE was seldom considered in the adolescent patients by physicians, especially outpatient physicians, so the diagnosis was often delayed. If adolescent patients complain of dyspnea or chest pain or syncope with/without fever, and they had risk factors such as surgery, thrombocytopenia and trauma, PE should be considered and included in the differential diagnosis.

[Change in airway anaphylatoxin-complement factors C3a of sputum in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the possible role of anaphylatoxin(C3a) in chronic obstructive pulmonary disease (COPD). METHODS: Sixty-four elderly patients with COPD (including 51 males, 13 females, 31 with acute exacerbation of COPD and 33 with stable COPD) and 25 healthy controls were recruited in the study. The levels of C3a in the serum of centrifugated induced sputum and cell differential count in sendiment were determined. RESULTS: The level of C3a [44.2 (13.2-48.5) µg/L] in induced sputum in acute exacerbation of COPD was significantly higher than those in the stable COPD [5.5 (3.6-20.7) µg/L, Z=-2.974, P=0.003] and the controls [1.7 (0.1-5.9) µg/L, Z=-3.145, P=0.002]. The level of C3a in the stable COPD was higher than that in the healthy subjects, but the statistical difference was not significant. The C3a levels in smokers and non-smokers of the healthy controls were 1.97 (0.12-6.27) µg/L and 1.36 (0.09-5.57) µg/L, respectively, and had no difference (P>0.05). The level of C3a in induced sputum was positively correlated with the number of total leukocytes (r=0.543, P<0.05). CONCLUSION: C3a in induced sputum is significantly increased in COPD, and its high level correlates with the advanced stage of the disease, which suggests a possible role of C3a in the pathogenesis of COPD.

[Causes of chronic obstructive pulmonary disease-related death and influencing factors of survival time].

OBJECTIVE: To study the causes of chronic obstructive pulmonary disease (COPD)-related death and influencing factors of survival time from first hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: All patients with a primary or secondary diagnosis of COPD (International Classification of Diseases (ICD)-10 Codes J40-J47) were continuously enrolled at our hospital from January 2006 to December 2008. A retrospective review was performed on the medical records of COPD patients who died during hospitalization. The causes of death were coded and analyzed according to the International Classification of Diseases (ICD)-10. The underlying causes of death were identified and ranked in order of prevalence. The medical records of first hospitalization due to AECOPD were reviewed. Retrospective analysis was performed for the clinical data. And Cox regression analysis was used to select the independent risk factors of influencing the survival time. RESULTS: Sixty-seven patients died during hospitalization. The median FEV(1) (forced expiratory volume in 1 second percentage) was 34%. The causes of death in the COPD inpatients were as follows: respiratory diseases (n = 39), cardio-cerebrovascular diseases (n = 16), malignant tumors (n = 10), diabetes mellitus (n = 1) and suicide (n = 1). Among them, 54 patients had a history of hospitalization due to AECOPD. Thirteen deceased patients were never hospitalized because of AECOPD. The mean interval between the first admission with AECOPD as the primary diagnosis and death was 38 months (range: 1 - 159). The independent risk factors of influencing the survival time were as follows: complications with coronary artery disease & severe pulmonary hypertension, age, body mass index (BMI) and serum level of C-reactive protein (CRP) (all P < 0.05). CONCLUSION: The major cause of death in moderate-severe COPD patients is respiratory disease. complicated with coronary artery disease & severe pulmonary hypertension, age, BMI and serum level of CRP are the independent risk factors of affecting the survival time from first hospitalization due to AECOPD.

Yohimbine protects against endotoxin-induced acute lung injury by blockade of alpha 2A adrenergic receptor in rats.

BACKGROUND: Alpha 2A adrenergic receptor (AR) is a subtype of α2 AR belonging to G protein-coupled receptors, and exerts a variety of biological effects. Recent studies have demonstrated that the α2A AR activation was closely related with inflammatory reaction. The present study aimed to investigate the influence of α2A AR antagonist, yohimbine, on the severity of endotoxin-induced acute lung injury in rats. METHODS: A total of 72 male Sprague-Dawley rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and LPS + yohimbine group. Rats were intratracheally administrated with normal saline or LPS (300 µg), and the rats in the LPS + yohimbine group were treated with additional yohimbine (2 mg/kg, i.p) soon after LPS administration. Six, 24 and 48 hours after treatment, arterial blood gas analysis was carried out, and optical microscopy was performed to evaluate pathological changes in the lung, and lung injury score was assessed. The count of white blood cells in bronchoalveolar lavage fluid (BALF) was determined. The levels of norepinephrine, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 in BALF were measured with enzyme-linked immunosorbent assay. Immunocytochemistry was performed for the detection of α2A AR on inflammatory cells in BALF. RESULTS: When compared with the control group, the oxygenation index in the LPS group was significantly decreased, and white blood cell count, the lung histopathological scores, levels of norepinephrine and IL-6 as well as α2A AR expression on inflammatory cells in the BALF were dramatically increased at different time points, and the concentrations of TNF-α and IL-1ß were also increased except at 48 hours after LPS administration. The oxygenation index decreased while white blood cell count in BALF and the lung histopathological scores were obviously increased in the LPS + yohimbine group. The level of norepinephrine in BALF was increased at each time interval in the LPS + yohimbine group, and so did the levels of TNF-α, IL-1ß and IL-6 at 6 and 48 hours after LPS administration respectively. When compared with the LPS group, the oxygenation index, white blood cell count, the lung histopathological scores and the level of IL-6 in the LPS + yohimbine group were significantly improved at each time interval, and the concentrations of TNF-α and IL-1ß were also lower at 24 hours of LPS administration (all P < 0.05). Correlation analysis indicated the level of norepinephrine was related to the levels of TNF-α, IL-1ß and IL-6 in the BALF and the lung histopathological scores (r = 0.703, r = 0.595, r = 0.487 and r = 0.688, respectively, P < 0.001) and the intensity scores of immunoreactivity to α2A AR on inflammatory cells were also associated with the levels of TNF-α, IL-1ß and IL-6 as well as the lung histopathologial scores (r = 0.803, r = 0.978, r = 0.716 and r = 0.808, respectively, P < 0.001). CONCLUSIONS: Yohimbine can inhibit TNF-α, IL-1ß and IL-6 overproduction and relieve the severity of pulmonary inflammation induced by endotoxin, which is maybe mediated by blockade of α2A AR on inflammatory cells.

[Clinical analysis of diffusive interstitial lung diseases with positive anti-neutrophil cytoplasmic antibody].

OBJECTIVE: To explore the features of pulmonary interstitial pathological changes in diffuse interstitial lung disease (DILD) patients with positive anti-neutrophil cytoplasmic antibody (ANCA), and the similarities as well as differences between ANCA positive patients with non-primary vasculitis and primary systematic vasculitis. METHODS: Clinical data of 122 patients with DILD having ANCA examined from October 1995 to September 2008, were reviewed. Among the ANCA positive patients with non-primary vasculitis (Group A), those with primary systematic vasculitis (Group B), and the ANCA negative patients (Group C), the results of syndromes, signs, radiological manifestations, pulmonary function tests, bronchoscope examinations, bronchoalveolar lavage fluid (BALF) cytology and other laboratory examinations were compared. RESULTS: In the 122 DILD patients with ANCA results, 36 patients' ANCA (29.51%) were positive. The numbers of patients in Groups A, B, and C were 7, 29, and 86. Total lung capacity (TLC) decreased less and pleural pathological changes were more seen in Groups A and B than in Group C. Oliguria, haematuria, proteinuria, anaemia, and renal inadequacy in Group A, which were similar in Group C, appeared less than in Group B. Results of bronchoscope examination, BALF cytology, anti-nuclear antibody (ANA), and etc. were not significantly different among the three groups. CONCLUSION: In DILD patients, pulmonary interstitial changes of those with positive ANCA accompany with more pleural pathological changes and TLC decreased less than those with negative ANCA. In patients with positive ANCA, non-primary vasculitis had some similar clinical manifestations as primary systematic vasculitis, however, anaemia and renal damages were less seen in the non-primary vasculitis patients.

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.