Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen.

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.

Genetic Polymorphisms in Antioxidant Enzymes Modulate the Susceptibility of Idiosyncratic Antituberculous Drug-Induced Liver Injury and Treatment Outcomes in Patients with Tuberculosis.

BACKGROUND: The pathogenic mechanism of antituberculous drug-induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK). METHODS: Thirty tag single nucleotide polymorphisms (tag-SNPs) from the all candidate genes were genotyped in a 2-stage cohort study including an initial discovery stage with 461 ATDILI patients and 466 controls and a replication stage with 216 ATDILI patients and 432 controls. The frequencies and distributions of genotypes and haplotypes were compared between the case and control groups. Three different genetic models including dominant, recessive, and additive models were used to determine the associations with susceptibility to ATDILI. RESULTS: The SNPs rs9906835, rs944725, and rs3794764 of the NOS2 gene were significantly associated with an increased risk of ATDILI. The MAFK rs3735656 SNP was significantly associated with a decreased risk for ATDILI. The AAA haplotype of the NOS2 gene was associated with susceptibility to ATDILI. The treatment outcomes of patients with tuberculosis were further affected by genetic variants of the NOS2 and MAFK genes. CONCLUSIONS: Genetic polymorphisms of NOS2 and MAFK are associated with ATDILI susceptibility in Chinese patients with tuberculosis. The variants in NOS2 and MAFK affect treatment outcomes of tuberculosis patients. Further studies are needed to better understand the molecular mechanisms of ATDILI susceptibility via regulation of the expression of ATDILI-susceptibility genes and proteins.

Genetic Polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and Susceptibility to Anti-Tuberculosis Drug-Induced Hepatotoxicity: A Chinese Population-Based Prospective Case-Control Study.

BACKGROUND: Drug transporters and drug-metabolizing enzymes have been linked to drug-induced hepatotoxicity. Solute carrier organic anion transporter family member 1B1 (SLCO1B1), cytochrome P450 2E1 (CYP2E1), and UDP glucuronosyltransferase 1A1 (UGT1A1) were selected as candidate genes to explore their association with susceptibility to anti-tuberculosis drug-induced hepatotoxicity (ATDH). METHODS: Thirty-four tag single nucleotide polymorphisms (tagSNPs) in SLCO1B1, CYP2E1, and UGT1A1 with 10-kb expansion up- and down-stream were genotyped in 461 patients with ATDH and 466 patients without ATDH in a prospective 1:1 matched case-control study. The frequencies and distributions of genotypes and haplotypes were compared between the groups using three genetic models (dominant, recessive, and additive) to identify associations with susceptibility to ATDH. RESULTS: Patients with the rs4149034 G/A, rs1564370 G/C, and rs2900478 T/A genotypes of SLCO1B1 had a significantly lower risk of ATDH, while those carrying the rs2417957 T/T and rs4149063 T/T genotypes had an increased risk. The rs4148323 A/A genotype of UGT1A1 was found to significantly reduce the risk of ATDH. Haplotype analysis showed the TGTG, TTTC, and GTTC haplotypes of SLCO1B1 were associated with an increased ATDH risk, whereas the GACC haplotype was related to a reduced risk. The ATG haplotype of UGT1A1 reduced the risk of ATDH. Moreover, treatment outcomes in tuberculosis patients were further affected by genetic variants of SLCO1B1. CONCLUSIONS: Genetic polymorphisms of SLCO1B1 and UGT1A1 were found to be associated with susceptibility to ATDH. Molecular identification of susceptibility genes provides a theoretical foundation for predicting the likelihood of ATDH and predicting treatment outcomes in tuberculosis patients.

Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis.

OBJECTIVES: Prostaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1-EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis. METHODS: DNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population. RESULTS: The rs937337 polymorphism is associated with increased risk to tuberculosis (p=0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22-2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p=0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41-0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease. CONCLUSIONS: We identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease.

Prevalence, risk factors, management, and treatment outcomes of first-line antituberculous drug-induced liver injury: a prospective cohort study.

PURPOSE: Antituberculosis drug-induced liver injury (ATDILI) is one of the most deleterious side effects associated with chemotherapy against tuberculosis (TB). In this study, our objective was to determine the incidence, risk factors, and management of ATDILI and analyze its impact on the treatment outcome in patients receiving standard anti-TB chemotherapy. METHODS: A prospective cohort study of ATDILI prevalence was conducted in 938 enrolled patients of the 1426 TB cases in Shanghai from March 2011 to September 2012. Patients were followed up until February 2014. Univariate and multivariate logistic regression analyses were used to determine the risk factors of ATDILI. Successful therapeutic outcome, rates of drug resistance conversion, sputum smear/culture conversion, and lung cavity closure were analyzed. RESULTS: Hepatitis B surface antigen/hepatitis B e antigen-positive hepatitis B carriers, complicated with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism were independent risk factors for ATDILI. Of the 121 cases with ATDILI (incidence rate of 12.9%), 84 (69.4%) used modified anti-TB therapy after recovery of liver function. Compared with the non-ATDILI group, patients with ATDILI exhibited remarkably decreased lung cavity closure rate (84.6% vs. 93.0%, P < 0.001) along with significantly reduced sputum smear/culture conversion rate (85.4% vs. 94.0%, P < 0.001). CONCLUSIONS: Our findings indicated that 12.9% patients developed ATDILI during standard anti-TB therapy, resulting in poor therapeutic outcome. Hepatitis B carriers with systemic lupus erythematosus, albumin ≤ 25 g/L, and chronic alcoholism manifested increased risks for ATDILI. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to antituberculosis drugs.

Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug reactions (ADRs). To assess the potential of drug-induced lymphocyte stimulation test (DLST) in screening ADRs in patients treated with anti-TB drugs, we performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without ADRs) treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The ADRs were diagnosed by drug provocation test based on clinical and laboratory examinations. The sensitivities of DLST in the diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and 23.1%, respectively, with the corresponding specificities being 93.4%, 94.0%, 97.5%, and 98.8%. DLST has high specificity and limited sensitivity in the diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation and drug use history, DLST could have a predictive validity of ADRs, especially when a positive result is obtained.

Toll-like receptor polymorphisms and tuberculosis susceptibility: A comprehensive meta-analysis.

The polymorphisms of toll-like receptor (TLR) have been hypothesized to affect the tuberculosis susceptibility. However, the direct evidence remains controversial. Here we performed a comprehensive meta-analysis to summarize the associations between TLR polymorphisms and tuberculosis susceptibility. We systematically searched the PubMed, Embase, Cochrane library, and Chinese National Knowledge Infrastructure up to April 25, 2014. Case-control studies investigating TLR polymorphisms and tuberculosis susceptibility were included in the meta-analysis. Pooled odds ratios and corresponding 95% confidence intervals were calculated for cases and controls. Stata 11.0 and Review Manager 5.1 were adopted to conduct statistical analysis. We included 29 studies, involving 17 804 individuals. The results revealed an obvious increase of tuberculosis risk in TLR2 2258AA, and decreased risk in TLR6 745TT and TLR8 rs3761624 GA genotypes. Meanwhile, different genetic models were performed. TLR8 rs3764879C, TLR8 rs3761624A and TLR8 rs3764880A alleles were associated with high susceptibility, while TLR6 745T and TLR8 rs3788935C alleles were protective. Other polymorphisms, including TLR9 1486C/T, did not show significant associations with tuberculosis infection. Finally, subgroup analysis in TLR8 rs3764880 according to gender found a slight elevated effect of A allele in males. The meta-analysis suggests significant associations between several TLR polymorphisms and tuberculosis, including TLR2 2258G/A, TLR6 745C/T, TLR8 rs3761624, TLR8 rs3764879, TLR8 rs3761624 and TLR8 rs3764880. This study serves as the framework for additional studies to determine further the role of TLRs in tuberculosis infection.

Liver X receptor gene polymorphisms in tuberculosis: effect on susceptibility.

OBJECTIVES: The Liver X receptors (LXRs), Liver X receptor A (LXRA) and Liver X receptor B (LXRB), regulate lipid metabolism and antimicrobial response. LXRs have a crucial role in the control of Mycobacterium tuberculosis (M.tb). Lacking LXRs mice is more susceptibility to infection M.tb, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRs and risk of tuberculosis. METHODS: We sequenced the LXRs genes to detect SNPs and to examine genotypic frequencies in 600 patients and 620 healthy controls to investigate for associations with tuberculosis (TB) in the Chinese Han population. DNA re-sequencing revealed eight common variants in the LXRs genes. RESULTS: The G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p<0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in LXRA and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in LXRB were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p<0.001, p = 0.004, p = 0.008, p = 0.003, respectively). All SNP genotypes were significantly associated with TB. An estimation of the frequencies of haplotypes revealed two potential risk haplotypes,GGCG in LXRB (p = 0.004,) and TTCG in LXRA (p<0.001, p = 0.004). Moreover, three protective haplotypes, TTAT and CCAT in LXRA and CATC in LXRB, were significantly "protective" (p = 0.008, p<0.001, p = 0.031) for TB. Furthermore, we determined that the LXRs SNPs were nominally associated with the clinical pattern of disease. CONCLUSIONS: Our study data supported that LXRs play a fundamental role in the genetic susceptibility to TB and to different clinical patterns of disease. Thus, further investigation is required in larger populations and in additional areas.

Transmission of extensively drug-resistant and multidrug resistant Mycobacterium tuberculosis in families identified by genotyping.

BACKGROUND: Diagnosis and appropriate treatment of multidrug-resistant tuberculosis (MDR-TB) remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. METHODS: We used 12-locus mycobacterial interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects' medical records. RESULTS: All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR (DTM-PCR) identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit (MIRU) pattern (232225172531) and the same MIRU pattern (3677235). Strains from family-2 had the same MIRU pattern (2212261553323) and the same MIRU pattern (3685134). Strains from family-3 did not have the same MIRU pattern and they differed at only one locus (223326173533, 223325173533), and did not have the same VNTR pattern with two locus differed (3667233, 3677234). CONCLUSIONS: Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a family. Household tuberculosis transmission could be prevented with adequate treatment of source patients.

[Comparative study of direct digital radiography and film-screen radiography in diagnosis of asbestosis].

OBJECTIVE: To evaluate the feasibility of direct digital radiography (DDR) in the diagnosis of asbestosis, and to analyze the difference and similarity between DDR and film-screen radiography (FSR) in terms of the radiographic features of asbestosis. METHODS: A total of 60 cases of asbestosis underwent FSR and DDR of the chest in the same day. The FSR and DDR findings were compared with respect to shapes and profusion of small opacities, pleural abnormality, and diagnostic stages. RESULTS: The patients showed "s", "t", and "p" small opacities on chest images, with irregular "s" and "t" ones predominating (FSR: 95.0%; DDR: 91.7%). The small opacities were widely distributed in six lung zones, especially in middle and lower zones. The shapes and distribution of small opacities did not differ significantly between FSR and DDR findings (P > 0.05). For all the 60 cases, the two radiographies demonstrated a concordance rate of 64.2% (231/360) for the profusion of small opacities in lung zones (κ = 0.62, 95%CI: 0.54 ∼ 0.69), and for the 43 cases (258 lung zones) who displayed identical small opacity shapes on the two radiographies, the concordance rate was 81.0% (209/258) (κ = 0.79, 95%CI: 0.72 ∼ 0.87). FSR revealed 10 cases (16.7%) of pleural thickening, compared to 12 cases (20.0%) on DDR (P > 0.05). FSR revealed 53 cases (88.3%) of stage I asbestosis and 7 cases (11.7%) of stage II asbestosis, compared to 51 cases (85.0%) and 9 cases (15.0%) on DDR (P > 0.05). There was no significant difference in diagnostic stages between the two radiographies (P > 0.05), demonstrating a concordance rate of 93.3% (56/60) (κ = 0.71, 95%CI: 0.45 ∼ 0.98). CONCLUSION: DDR is similar to FSR in determining the shapes, distribution, and profusion of small opacities, pleural abnormality, and diagnostic stages.

[Study of optimization of whole lung lavage applied to pneumoconiosis].

OBJECTIVE: To observe and evaluate the performances of intermittent positive pressure ventilation, beta-2 adrenergic receptor agonist, and pressure lavage in promoting residual fluid absorption and improving blood oxygen saturation during massive whole lung lavage (WLL). METHODS: A total of 155 patients were randomly divided into pressure ventilation (PV) group (n = 28), adrenaline (Ad) group (n = 31), PV plus Ad group (n = 29), pressure infusion bag (PIB) group (n = 30), and control group (n = 32). The patients underwent staged MWLL of bilateral lungs. The blood oxygen saturation (SpO2) of arterial blood of finger, chest X-ray findings, clinical symptoms, and lung functions were observed before and after MWLL. RESULTS: There were no significant differences in change in clinical symptoms among the five groups after MWLL (P > 0.05). The Ad group showed 6.3% increase in forced vital capacity (FVC) and 10.9% increase in forced expiratory flow at 25% of vital capacity (FEF(25%)) after MWLL (P < 0.05). The control group showed 5.7% decrease in FVC, 10.9% increase in forced expiratory volume in one second (FEV(1.0)), and 12.0% increase in FEF(25%) after MWLL (P < 0.05). No significant difference was found in other groups (P > 0.05). During and after MWLL, the incidence rates of hypoxemia in PV group, PV plus Ad group, and control group were 0, 0, and 12.5% (8/64), respectively (P < 0.01). There were no significant differences in total amount of lavage fluid and amount of residual fluid in the lung among all groups (P > 0.05). The smallest difference between the optical densities of the two lung fields on chest x-ray at 3 h after WLL was 0.152 ± 0.053 in the PV plus Ad group, compared to 0.194 ± 0.074 in the PV group, 0.197 ± 0.054 in the PIB group, 0.214 ± 0.054 in the Ad group, and 0.241 ± 0.109 in the control group, with significant differences between the saline group and other groups except Ad group (P < 0.05). CONCLUSION: Pressure ventilation, adrenaline, and pressure lavage can promote the transportation and absorption of residual fluid in the lung and decrease the incidence of hypoxemia during WLL.

Variation of Mycobacterium tuberculosis antigen-specific IFN-γ and IL-17 responses in healthy tuberculin skin test (TST)-positive human subjects.

OBJECTIVE: To determine the variation of IFN-γ and IL-17 responses to M. tuberculosis antigens in healthy TST+ humans. METHODS: We isolated peripheral blood mononuclear cells from 21 TST+ healthy adults, stimulated them with phytohemagglutinin (PHA), PPD, Ag85B, ESAT-6, and live M. bovis BCG, and assayed IFN-γ and IL-17 secretion by ELISA in supernatants after 24 or 72 hours of incubation respectively. RESULTS: As in other studies, we found a wide range of IFN-γ responses to M. tuberculosis antigens; the variation significantly exceeded that observed in the same donors to the polyclonal T cell stimulus, phytohemagglutinin (PHA). In addition, we assayed IL-17 secretion in response to the same stimuli, and found less subject-to-subject variation. Analysis of the ratio of IFN-γ to IL-17 secretion on a subject-to-subject basis also revealed a wide range, with the majority of results distributed in a narrow range, and a minority with extreme results all of which were greater than that in the majority of subjects. The data suggest that study of exceptional responses to M. tuberculosis antigens may reveal immunologic correlates with specific outcomes of M. tuberculosis infection. CONCLUSION: Variation of IFNγ and IFN-γ/IL-17 responses to mycobacterial antigens exceeds that of responses to the polyclonal stimulus, PHA, in TST positive healthy humans. This indicates a quantitative spectrum of human immune responses to infection with M. tuberculosis. Since the outcome of human infection with M. tuberculosis varies greatly, systematic study of multiple immune responses to multiple antigens is likely to reveal correlations between selected immune responses and the outcomes of infection.