Promoting smoking cessation in China: a foot-in-the-door approach to tobacco control advocacy.

INTRODUCTION: The Chinese government's implementation of the MPOWER policies and compliance with the WHO Framework Convention on Tobacco Control requirements has been slow. We used the 'foot-in-the-door' approach to promote tobacco control advocacy through capacity building of healthcare leaders, and establishment of smoking cessation clinics in Guangzhou and Beijing (two of the largest cities in China). METHODS: This collaborative pilot project involved the University of Hong Kong and three major hospitals in Guangzhou and Beijing. A steering committee conducted the smoking cessation training workshops starting from April 2006, and set up three smoking cessation model clinics during August 2006 to October 2008. We followed up the trained health care professionals (HCPs) in 2014 and 2015 to assess their impacts on tobacco control beyond smoking cessation. RESULTS: We emphasized the importance of the general tobacco control atmosphere during smoking cessation training of 139 HCPs to motivate them to engage in tobacco control advocacy. In addition to enhancing their knowledge and skills in cessation, the HCPs were then involved in the establishment of three in-hospital smoking cessation clinics and served as smoking cessation counselors since June 2008. Moreover, they ventured outside the clinics and the community to publicize smoking cessation. Their effort has contributed to smoke-free legislation, better surveillance on smoking and media advocacy on tobacco control in China. CONCLUSIONS: The training and establishment of smoking cessation clinics could serve as a means to motivate and empower HCPs who could contribute to broaden tobacco control policy in China.

Role of Diabetes Mellitus on Treatment Effects in Drug-susceptible Initial Pulmonary Tuberculosis Patients in China.

We assessed the role of diabetes mellitus (DM) on treatment effects in drug-susceptible initial pulmonary tuberculosis (PTB) patients. A prospective study was conducted in eight provinces of China from October 2008 to December 2010. We enrolled 1,313 confirmed drug-susceptible initial PTB patients, and all subjects received the treatment regimen (2H3R3E3Z3/4H3R3) as recommended by the national guidelines. Of the 1,313 PTB patients, 157 (11.9%) had DM; these patients had more sputum smear-positive rates at the end of the second month [adjusted odds ratios (aOR) 2.829, 95% confidence intervals (CI) 1.783-4.490], and higher treatment failure (aOR 2.120, 95% CI 1.565-3.477) and death rates (aOR 1.536, 95% CI 1.011-2.628). DM was a contributing factor for culture-positive rates at the end of the second month and treatment failure and death of PTB patients, thus playing an unfavorable role in treatment effects of PTB.

Progress in resistance mechanisms and diagnosis of non-first line anti-TB drugs.

Tuberculosis (TB) is one of the three major infectious diseases in China and all over the world. In 2014, for the first time, TB killed more people than HIV did. Non-first line anti-TB drugs are used as main drugs in the treatment of MDR-TB. However, MDR-TB can gradually develop as extensively drug-resistant TB (XDR-TB) because of poor diagnosis, the unreasonable treatment, poor medical conditions and so on. The death rate of XDR-TB is close to lung cancer. Research on the mechanism of drug resistance of Mycobacterium tuberculosis has turned to non first-line anti-TB drugs: second and third line drugs and some new anti-TB drugs in development. In this review, we summarized the drug resistance mechanisms of the common non-first line anti-TB drugs. Most of drug resistant TB patients can't get timely diagnosis and correct treatment. So at the end of this article, we also summarized the common methods to diagnose drug-resistant TB.

Risk of Treatment Failure in Patients with Drug-susceptible Pulmonary Tuberculosis in China.

The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis (PTB) was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled. Demographic characteristics, bacteriological test results, and patient outcome, i.e., cure or treatment failure were recorded and compared using the chi-square or Fisher's exact tests. Multivariate logistic regression was used to identify factors associated with risk of treatment failure. Of the 1447 patients who were enrolled, 1349 patients (93.2%) were successfully treated and 98 (6.8%) failed treatment. Failure was significantly associated with age 365 years [odds ratio (OR)=2.522, 95% confidence interval (CI): (1.097-5.801)], retreatment [OR=2.365, 95% CI: (1.276-4.381)], missed medicine [OR=1.836, 95% CI: (1.020-3.306)], treatment not observed [OR=1.879 95% CI: (1.105-3.195)], and positive culture result after the first [OR=1.971, 95% CI: (1.080-3.597)] and second month [OR=4.659, 95% CI: (2.590-8.382)]. The risk factors associated with treatment failure were age 365 years, retreatment, missed medication, treatment not observed, and positive culture at the end of month 1 or month 2. These risk factors should be monitored during treatment and interventions carried out to reduce or prevent treatment failure and optimize treatment success.

An open-label, randomized and multi-center clinical trial to evaluate the efficacy of Silibinin in preventing drug-induced liver injury.

UNLABELLED: To assess the clinical efficacy and safety of Silibinin in preventing drug-induced liver injury (DILI) in the general population (high-risk patients with non-drug induced liver injury). METHOD: A prospective, multi-center, randomized, open-label and controlled trial was conducted with 568 patients undergoing primary treatment of pulmonary tuberculosis. The study included 277 patients in experimental group and 291 patients in control group. The patients in the two group were treated with conventional 2HREZ (S)/4HR for tuberculosis (TB), and additional Silibinin capsules (oral administration of 70 mg/time, 3 times/day for 8 weeks in experimental group. Outcomes of liver function, interruption of anti-TB treatment and therapeutic results, as well as adverse reactions were observed and analyzed. RESULTS: At 2, 4 and 8 weeks of treatment, the incidences of liver injury in experimental group were 3.97%, 1.44% and 2.17%, respectively; the incidences in control group were 4.12%, 4.12% and 2.41%, respectively. Statistical analysis showed that there was no difference in the incidence between the two groups at each treatment period (P>0.05). At 8 weeks, the numbers of patients diagnosed of DILI were 18 (7.22%) and 27 (9.28%) in experimental and control groups, respectively (P>0.05). 34.30% and 27.49% of the patients in experimental and control groups had transient abnormal liver function or symptoms, respectively; similar percentages (3.25% and 6.19%) of the patients in two groups have liver function injury and symptoms, and were suspended for anti-TB treatment (P>0.05). The incidence of anorexia and nausea symptoms was lower in experimental group than in control group, and the differences were significant at 4 and 8 weeks (P<0.05). 8 weeks after the treatment, 98.30% of the sputum smear culture were negative in experimental group, which was significantly higher (P<0.01) than that in control group (92.98%). CONCLUSION: Preventive hepatoprotective therapy in the general population may reduce drug discontinuation rate, improve patient's compliance and outcomes of anti-TB treatment.

[The treatment outcomes of 21 cases of rapidly growing mycobacteria related pulmonary disease].

OBJECTIVE: To explore the efficacy of the chemotherapeutic regimen with clarithromycin (CTM) and amikacin (AMK) as the main drugs in the therapy of rapidly growing mycobacteria (RGM) related pulmonary disease. METHODS: The clinical efficacy of 21 patients with RGM related pulmonary disease was retrospectively analyzed from January 2008 to October 2011 in Guangzhou Chest Hospital. The individual chemotherapeutic regimen was mainly based on azithromycin (ATM) 0.5 g/d or CTM 0.5 - 1.0 g/d, AMK 0.4 - 0.6 g/d according to the medication history and antimicrobial susceptibility tests. After 6 months of treatment, symptomatic improvement, changes of imaging findings, sputum cultures and adverse effects were observed. RESULTS: In the 21 cases of RGM related pulmonary disease, drug resistance to amikacin (9 cases) and clarithromycin (5 cases) were relatively low as compared to other antituberculous drugs. Lesions involving more than 3 lung fields were seen in 17 cases, cough and phlegm in 21, bloody sputum in 18, chest pain and shortness of breath in 15, and fever in 15 cases. After 2-week treatment, fever disappeared and shortness of breath improved in all the cases. Cough and phlegm improved in 12 and bloody sputum improved in 16 cases. After 6-month treatment, lesion absorption occurred in 12 cases, lung cavity became smaller in 9 cases and sputum culture became negative in 8 cases. Of the 16 cases sensitive to CTM, 11 was smear-negative, and of the 12 cases sensitive to AMK, 11 was smear-negative. Common adverse effects included gastrointestinal symptoms, liver damage and blood abnormalities. CONCLUSIONS: Patients with RGM related pulmonary disease had low rates of drug resistance to CTM and AMK. However, individual chemotherapy regimen based on CTM and AMK showed unsatisfactory clinical efficacy. More sensitive drugs combined with potent chemotherapy regimen are needed for the treatment of this disease.

[Comparison of P-nitrobenzoic acid and hydroxylamine hydrochloride for the primary screening of mycobacterial species].

OBJECTIVES: To examine the screening methods for mycobacteria recommended by the China Anti-tuberculosis Association, in order to increase laboratory diagnostic accuracy for mycobacterial screening. METHODS: Using P-nitrobenzoic acid (PNB 0.5 g/L) as the control group, and hydroxylamine hydrochloride (HA, in 125, 150 and 175 mg/L concentrations) as the study group, laboratory preserved strains of H37Rv M.tuberculosis, and standard and clinically isolated strains of M.nontuberculosis (NTM) from Guangzhou Chest Hospital were tested for both PNB and HA sensitivity. Differences between groups were analyzed by χ(2) test. RESULTS: Among the 2529 MTB strains, the resistance rate to PNB was 3.0% (76/2529), to HA was 12.2% (308/2529), 4.8% (121/2529), and 0.9% (23/2529), respectively, corresponding to the aforementioned 3 different concentrations of HA. Among the 1766 NTM strains, the sensitive rate to PNB was 8.3% (147/1766), to HA was 0.1% (2/1766), 0.5% (9/1766), and 0.9% (16/1766), respectively, corresponding to the aforementioned 3 different concentrations of HA. There was significant difference (χ(2) = 5.44-83.50, P < 0.05). CONCLUSION: HA at 175 mg/L concentration was the optimal condition for laboratory tuberculosis preliminary screening.

Monitoring of peptide-specific and gamma interferon-productive T cells in patients with active and convalescent tuberculosis using an enzyme-linked immunosorbent spot assay.

To establish a high-efficiency gamma interferon-specific enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT assay) for detection of tuberculosis (TB), peptides (E6, E7, and C14) and peptide mixtures (E6 plus E7 and E6 plus E7 plus C14) were used to monitor peripheral blood (PBL) samples from patients with pulmonary TB (PTB), as well as control samples. The positive detection rates of the five IFN-γ ELISPOT assays were 78.38%, 74.86%, 55.83%, 90.43%, and 91.51%, respectively, and there were similar detection rates between the two combined peptide mixture IFN-γ ELISPOT assays and the tuberculin skin test (TST) (90.62% versus 95.59%). No significant difference was found between the detection rates of the two combined peptide mixture IFN-γ ELISPOT assays and the T-SPOT.TB assay for 86 patients with PTB (P > 0.05), but the median number of spot-forming cells/10(6) cells (SFP value) for positive results was higher by the former than by the latter assay (P < 0.05). In contrast, the 29.93% positive detection rate and median SFP value of 482 by the two combined peptide mixture IFN-γ ELISPOT assays were significantly higher than the corresponding values of 14.29% and 152 by T-SPOT.TB assay for the same 147 community donors (P < 0.05). For nine PTB patients tracked, the SFP value of 7 for the two peptide mixture IFN-γ ELISPOT assays began to decrease from the second month after regular treatment. A relatively low, almost normal, SFP level was reached and maintained after the third or fourth month. Two in-house IFN-γ ELISPOT assays and the T-SPOT.TB assay could reduce the false-positive and false-negative detection rates of TST and sputum acid-fast staining. Therefore, these two combined peptide mixture IFN-γ ELISPOT assays have a potential advantage, beyond their greater specificity and sensitivity, for use in screening and detection of active TB infection (TBI) and latent TB infection (LTBI) in China.

[The clinical significance of changes in CD4+ T cell counts by peripheral blood from patients with pulmonary tuberculosis after antitubercular treatment].

AIM: To explore the clinical significance of changes in CD4+ T cell counts by peripheral blood from patients with pulmonary tuberculosis after antitubercular treatment. METHODS: CD4+ T cell counts in the peripheral blood of 62 pulmonary TB patients were counted by flow cytometry from groups auording to the radiologic extent of disease, and compared with those obtained from 30 controls. RESULTS: (1) The baseline levels of CD4+ T cell counts (439.21+/-210.56)/mm3 in pulmonary tuberculosis group before antituberculosis therapy were significantly lower than those (748.47+/-261.85)/mm3 in the control group (P<0.01). (2) The baseline levels of CD4+ T cell counts (399.83+/-194.17)/mm3 before antituberculosis therapy in diffuse group were significantly lower than those (521.90+/-224.40)/mm3 in limited group (P<0.05). (3) After two months of antituberculosis therapy, the levels of CD4+ T cell counts in the improved group increased from (480.75+/-228.49)/mm3 to (616.75+/-280.57)/mm3, and the values were not significantly different from those in controls (P>0.05). Whereas, the levels of CD4+ T cell counts in the stable group increased from (412.97+/-197.00)/mm3 to (447.55+/-204.60)/mm3, which were still significantly lower than those in the control group (P<0.01). CONCLUSION: These results suggested that peripheral CD4+ lymphopenia was demonstrated in patients with pulmonary tuberculosis, and such lymphopenia was reversible partly with antitubercular treatment. The numbers of peripheral CD4+ T cell counts were related to the severity of the disease, the more severe of the disease was, the less numbers of the CD4+ T cell counts were.

[Effects of glucocorticoids on tuberculous pleural effusion: experiment with rats].

OBJECTIVE: To explore the effects of systemic glucocorticoid treatment on tuberculous pleural effusion. METHODS: Ninety Wistar rats were intrapleurally injected with 0.03 mg of standard human Mycobacterium tuberculosis to establish models of tuberculous pleural effusions and then were randomly divided into 2 equal groups both without anti-tuberculosis treatment: glucocorticoids group (GG) undergoing intramuscular injection of 0.3 mg triamcinolone acetonide in the right thigh 24 h after intrapleural injection, and control group (CG) received nothing as control. 8, 24, 32, and 48 hours, and 3, 5, 7, 10, and 15 days after intramuscular injection 5 rats from each group were killed. The thorax was opened, the amount of pleural effusion (PE) was recorded, and the pleural cavity, histopathology of pleura and lung parenchyma were examined. The white blood cell (WBC) count and differential leukocyte count, and levels of total protein (TP), glucose (GLU), and lactic dehydrogenase (LDH) in the PE were determined. Bioassays were used to detect the PE levels of soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta1 (TGF-beta1), and interferon gamma (IFN-gamma). RESULTS: The PE volumes of GG 8 - 48 h after the intramuscular injection were significantly lower than those of CG (P < 0.05, P < 0.01), and PE completely disappeared on day 3. The WBC in PE 24 - 48 h after and the percentages of neutrophils 8 - 48 h after the intramuscular injection of GG were all significant lower than those of CG (all P < 0.01). The TP levels 32 and 48 h after the intramuscular injection of GG were both significantly higher than those of CG (both P < 0.01). The LDH level of GG within 24 h after the intramuscular injection was significantly lower than that of CG (P < 0.01). Both the sICAM-1 and TGF-beta1 levels of GG were higher 8 h after the intramuscular injection, but lower 48 h after the intramuscular injection than those of CG (both P < 0.01). The IFN-gamma levels 8 - 48 h after the intramuscular injection of GG were all higher than those of CC (all P < 0.01). The IFN-gamma/TGF-beta1 ratios at different time points of GG were all higher than those of CG, and there were significant differences in those 8 - 48 h after the intramuscular injection between these 2 groups (all P < 0.01). Pathologically, the mean thickness of pleura in GG was significantly less than that in CG. Congestion and edema in subpleural and pulmonary interstitium were less in GG than in CG. CONCLUSION: Early use of glucocorticoids helps reduce the inflammatory response in pleural cavity in tuberculous pleurisy accelerate the absorption of pleural effusion and decrease the thickness of pleura.

Treatment of severe acute respiratory syndrome with glucosteroids: the Guangzhou experience.

STUDY OBJECTIVE: To investigate the efficacy and safety profiles of corticosteroid therapy in severe acute respiratory syndrome (SARS) patients. DESIGN: Four hundred one of 1,278 SARS cases treated in Guangzhou China between December 2002 and June 2003 fulfilled the diagnostic criteria issued by the World Health Organization for confirmed identification of SARS. Among them, the diagnosis of critical SARS was defined by criteria of SARS guidelines incorporated with a low oxygenation index (OI) [< 300 mm Hg]. Data of these patients retrieved from a database were retrospectively analyzed by logistic regression and Cox regression for the effect of corticosteroid therapy on death, hospitalization days, and complication presentation. RESULTS: Among the 401 SARS patients studied, 147 of 249 noncritical patients (59.0%) received corticosteroids (mean daily dose, 105.3 +/- 86.1 mg) [+/- SD], and all survived the disease; 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 +/- 102.3 mg, and 25 died. Analysis of these 401 confirmed cases did not show any benefits of corticosteroid on the death rate and hospitalization days. However, when focused on 152 critical SARS cases, factors correlated with these end points indicated by univariate analysis included use of corticosteroid, age, rigor at onset, secondary respiratory infections, pulmonary rales, grading of OI, and use of invasive ventilation. After adjustment for possible confounders, treatment with corticosteroid was shown contributing to lower overall mortality, instant mortality, and shorter hospitalization stay (p < 0.05). Incidence of complications was significantly associated with the need for invasive ventilation but not with use of corticosteroids. CONCLUSION: This Guangzhou retrospective study revealed that proper use of corticosteroid in confirmed critical SARS resulted in lowered mortality and shorter hospitalization stay, and was not associated with significant secondary lower respiratory infection and other complications.

[A retrospective study of one case of X-linked agammaglobulinemia].

OBJECTIVE: To investigate the clinical manifestations, diagnostic methods and treatment of X-linked agammaglobulinemia (XLA). METHODS: Flow cytometric analysis of the peripheral monocytes using the anti-BTK antibody was used to characterize the expression of BTK in a 21 year old male patient and his mother. The patient suffered from frequent pneumonia, and was found to be complicated with lymphocytopenia in the B cell populations, hypogammaglobulinemia (IgG 1.38 g/L, IgA 0.25 g/L, IgM 0.17 g/L) and angiotelectasis (which had not been reported in XLA patients). Sequencing of the BTK cDNA obtained from the peripheral monocytes of the patient and his mother was performed to confirm the genetic defect. RESULTS: The BTK expressions in peripheral monocytes of the patient and his mother were 96.9% and 97.8% respectively. Sequencing of the BTK gene revealed a missense mutation of R525Q in exon 16, and his mother was confirmed to be an XLA carrier. The patient was treated with immunoglobulin replacement therapy (2 g/kg). One month later, the serum IgG level of the patient was elevated to 5.79 g/L, and the clinical symptoms (included angiotelectasis), lung function and the CT scan results significantly improved. CONCLUSION: Genetic diagnosis was made for one Chinese XLA adult patient complicated with angiotelectasis. This case suggests that some XLA cases may present angiotelectasis. High dose intravenous immunoglobulin given at 2 g/kg may be of efficacy in severe XLA cases. More attention should be paid to the disease in China.

[A study on the model of tuberculous pleurisy and intrapleural inflammatory and immunological responses in rats].

OBJECTIVE: To develop a rat model of tuberculous pleurisy and to explore the mechanism of intrapleural inflammatory and immunological responses. METHODS: Fifty Wistar rats were injected intrapleurally with 0.03 mg of standard human mycobacterium tuberculous bacilli H37Rv each. The rats were killed in group on days 1, 2, 3, 5, 7, 10, 15, 20, 30 and 60 after the day of intrapleural injection. The thorax was opened and the amount of pleural effusion was recorded, and histopathology of pleural tissues and lung tissues were observed. The white blood cell (WBC) count and differentials, levels of total protein (TP), glucose (GLU) and lactic dehydrogenase (LDH) of pleural effusions were determined. Pleural fluid was analyzed for the levels of soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta1 (TGF-beta1) and interferon gamma (IFN-gamma) by using appropriate bioassays. Ten rats were intrapleurally received 2 ml of normal saline and another 10 rats received 2 ml of undiluted PPD solution each as control. RESULTS: Bilateral pleural effusions appeared within 15 days in all rats intrapleurally received tuberculous bacilli. The peak amount of pleural fluid was on day 5 (6.7 +/- 0.5 ml). The neutrophils were the predominant cells for the first 24 hours, and then were followed by lymphocytes. In the pleural fluid, total protein concentration was between 51-55 g/L. The levels of glucose and LDH were 5.2 mmol/L and 18.1 micromol.s(-1).L(-1) on day 1 and changed to 2.8 mmol/L and 28.9 micromol.s(-1).L(-1) on day 15 respectively. The biochemistry parameters were in accordance with characteristics of tuberculous pleurisy. The sICAM-1 level increased early (21.9 ng/ml on day 1) and peaked on day 3 (38.0 ng/ml), then decreased over time (4.4 ng/ml on day 15). The level of IFN-gamma was 41.2 pg/ml on day 1 and increased and maintained at high levels over time. TGF-beta1 levels increased and peaked on day 7 (47.2 ng/ml), and then on day 15 decreased to a level lower than that of day 1. The ratio of IFN-gamma/TGF-beta1 increased from 1.32 on day 1 to 5.69 on day 15. Correlation analysis showed that sICAM-1 and IFN-gamma were closely related with WBC count and its differentials, as well as with LDH levels. Histopathological study revealed early pleural inflammation and late caseation. CONCLUSIONS: Wistar rats can be used as an experimental model for tuberculous pleurisy. Tuberculous inflammatory and immunological responses in acute tuberculous pleurisy is enhanced rather than suppressed.

[The long-term effect and associated factors of double embolization of bronchial artery in patients with lung tuberculosis and hemoptysis].

OBJECTIVE: To investigate the long-term effect and the key factors associated with relapse of double embolization of bronchial artery in patients with lung tuberculosis and hemoptysis. METHODS: Fifty patients with lung tuberculosis and hemoptysis receiving the radiography and double embolization of bronchial artery (BAG + BAE) had been followed up for two years. The causes for hemoptysis relapse was determined, followed by specific treatment, and the effect was evaluated. Among them, 37 were males, 13 females, with the age of 8-75 years (mean age 47.6 years). RESULTS: The 2 year follow-up showed that the cure rate and the effective rate were 62% (31/50) and 94% (47/50) respectively. In a short term after embolization, hemoptysis relapsed in 9 cases, the major causes being active tuberculosis and secondary bronchiectasis complicated with infection. Other responsible factors included missed-embolization of bronchial artery and remaining blood supply from systemic circulation. In mid and long term follow-up, hemoptysis relapsed in 10 cases, the major causes being secondary pulmonary mycotic infection and recurrence of tuberculosis. CONCLUSIONS: The long term result of double embolization of bronchial artery in patients with lung tuberculosis and hemoptysis was significant. It could prevent the danger from massive hemoptysis, and therefore allows the medical therapy for tuberculosis. Embolization of bronchial artery is effective for hemostasis, while etiologic therapy aimed at removing the infection leading to chronic inflammation is the cure for tuberculosis and hemoptysis.