Clinical efficacy of tetrandrine in artificial stone-associated silicosis: A retrospective cohort study.

Background: Outbreaks of silicosis have occurred among workers in the artificial stone (AS) industry, and there is currently no effective antifibrosis treatment for silicosis. Design: A retrospective cohort study. Methods: We retrospectively analyzed the clinical data of 89 artificial stone-associated silicosis patients treated in Shanghai Pulmonary Hospital (China). Patients who agreed to be administered tetrandrine entered the observation group and those who disagreed entered the control group. Changes in chest HRCT, pulmonary function, and clinical symptoms of patients in two groups were compared pre- and post-treatment. Results: After treatment for 3-12 months, 56.5%-65.4% of patients in the observation group showed improvements in HRCT imaging, while there was no improvement in the control group (p < 0.05). Disease progression occurred in 0%-17.4% of patients in the observation group after 3-12 months of treatment compared with 44.4%-92.0% of patients in the control group (p < 0.05). After 3 months of treatment, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusing capacity of the lung for carbon monoxide (DLco) in the observation group increased by 136.7 ± 189.2 mL (p < 0.05), 124.2 ± 169.9 mL (p < 0.05), and 1.4 ± 2.3 mL/min/mmHg (p > 0.05), respectively, while those in the control group decreased (145.8 ± 356.5; 107.5 ± 272.1; 1.9 ± 3.8). After 6 months of treatment, FVC, FEV1, and DLco in the observation group increased by 207.8 ± 372.2 mL (p > 0.05), 107.8 ± 295.2 mL (p > 0.05) and 0.7 ± 6.0 mL/min/mmHg (p > 0.05), respectively, while those of the control group decreased (383.3 ± 536.7; 215.6 ± 228.9; 1.4 ± 1.7). The incidences of clinical symptoms such as cough, expectoration, dyspnea, chest tightness, and chest pain in the observation group were decreased-after treatment (all p < 0.05), while the incidences of these symptoms increased in the control group, although the change was not statistically significant (all p > 0.05). Conclusion: Tetrandrine can control and delay the progression of AS-associated silicosis fibrosis, with improved chest HRCT imaging and pulmonary function.

T cell responses in senior patients with community-acquired pneumonia related to disease severity.

Senior individuals older than 65 years of age are at a disproportionally higher risk of developing pneumonia. Impaired capacity to defend against airway infections may be one of the reasons. It is generally believed that weaker regulatory T cell responses may be beneficial to host defense against pathogens. In senior patients with community-acquired bacterial pneumonia, we investigated the frequencies and functions of regulatory T cells. Interestingly, we found that compared to age- and sex-matched healthy controls, senior pneumonia patients presented lower frequencies of Foxp3-expressing and Helios-expressing CD4+ T cells. The quantity of Foxp3 and Helios being expressed, measured by their mRNA transcription levels, was also lower in CD4+ T cells from pneumonia patients. Furthermore, following TCR and TGF-ß stimulation, pneumonia patients presented impaired capacity to upregulate Foxp3 and Helios. Functional analyses revealed that CD4+ T cells from pneumonia patients secreted lower amounts of IL-10 and TGF-ß, two cytokines critical to regulatory T cell-mediated suppression. Also, the expression of granzyme B and perforin, which were cytolytic molecules potentially utilized by regulatory T cells to mediate the elimination of antigen-presenting cells and effector T cells, were reduced in CD4+CD25+ T cells from senior pneumonia patients. In addition, the CD4+CD25+ T cells from senior pneumonia patients presented reduced capacity to suppress effector CD4+ and CD8+ T cell proliferation. Moreover, the value of pneumonia severity index was inversely correlated with several parameters of regulatory T cell function. Together, our results demonstrated that senior pneumonia patients presented a counterintuitive impairment in regulatory T cell responses that was associated with worse prognosis.

Loss of regulatory characteristics in CD4+ CD25+/hi T cells induced by impaired transforming growth factor beta secretion in pneumoconiosis.

Pneumoconiosis is caused by the accumulation of airborne dust in the lung, which stimulates a progressive inflammatory response that ultimately results in lung fibrosis and respiratory failure. It is possible that regulatory cells in the immune system could function to suppress inflammation and possibly slow or reverse disease progression. However, results in this study suggest that in pneumoconiosis patients, the regulatory T cells (Tregs) and B cells are functionally impaired. First, we found that pneumoconiosis patients presented an upregulation of CD4+ CD25+ T cells compared to controls, whereas the CD4+ CD25+ and CD4+ CD25hi T cells were enriched with Th1- and Th17-like cells but not Foxp3-expressing Treg cells and evidenced by significantly higher T-bet, interferon (IFN)-γ, and interleukin (IL)-17 expression but lower Foxp3 and transforming growth factor (TGF)-ß expression. Regarding the CD4+ CD25hi T-cell subset, the frequency of this cell type in pneumoconiosis patients was significantly reduced compared to controls, together with a reduction in Foxp3 and TGF-ß and an enrichment in T-bet, RORγt, IFN-γ, and IL-17. This skewing toward Th1 and Th17 types of inflammation could be driven by monocytes and B cells, since after depleting CD14+ monocytes and CD19+ B cells, the levels of IFN-γ and IL-17 were significantly decreased. Whole peripheral blood mononuclear cells and isolated monocytes and B cells in pneumoconiosis patients also presented reduced capacity of TGF-ß secretion. Furthermore, monocytes and B cells from pneumoconiosis patients presented reduced capacity in inducing Foxp3 upregulation, a function that could be rescued by exogenous TGF-ß. Together, these data indicated a potential pathway for the progression of pneumoconiosis through a loss of Foxp3+ Treg cells associated with impaired TGF-ß secretion.

[Optimization of digital chest radiography image post-processing in diagnosis of pneumoconiosis].

OBJECTIVE: To establish the optimal image post-processing parameters for digital chest radiography as preliminary research for introducing digital radiography (DR) to pneumoconiosis diagnosis in China. METHODS: A total of 204 pneumoconiosis patients and 31 dust-exposed workers were enrolled as the subjects in this research. Film-screen radiography (FSR) and DR images were taken for all subjects. DR films were printed after raw images were processed and parameters were altered using DR workstation (GE Healthcare, U.S.A.). Image gradations, lung textures, and the imaging of thoracic vertebra were evaluated by pneumoconiosis experts, and the optimal post-processing parameters were selected. Optical density was measured for both DR films and FSR films. RESULTS: For the DR machine used in this research, the contrast adjustment (CA) and brightness adjustment (BA) were the main parameters that determine the brightness and gray levels of images. The optimal ranges for CA and BA were 115%∼120% and 160%∼165%, respectively. The quality of DR chest films would be optimized when tissue contrast was adjusted to a maximum of 0.15, edge to a minimum of 1, and both noise reduction and tissue equalization to0.The failure rate of chest DR (0.4%) was significantly lower than that of chest FSR (17%) (P < 0.05). CONCLUSION: After appropriate image post-processing on DR machine purchased from GE Healthcare, the DR chest films can meet all requirements for the quality of chest X-ray films in the Chinese diagnostic criteria for pneumoconiosis.

[Effects of whole lung lavage on pulmonary function and exercise capacity in patients with pneumoconiosis].

OBJECTIVE: To investigate the effects of whole lung lavage (WLL) on the pulmonary function and exercise capacity in patients with pneumoconiosis. METHODS: Forty-one patients with pneumoconiosis who quit dust-exposed work not more than 6 months before underwent WLL. Clinical symptom assessment, pulmonary function test, and cardiopulmonary exercise test were performed before and one week after WLL, and the results were compared. RESULTS: The patients with pneumoconiosis showed no significant changes in clinical symptoms after WLL. At one week after WLL, the patients with pneumoconiosis showed nonsignificant increases in forced vital capacity, forced expiratory volume in one second (FEV1.0), and percent predicted FEV1 (P > 0.05); peak oxygen uptake (peak VO2) increased from 2140.6 ± 353.2 ml/min before WLL to 2374.6 ± 362.4 ml/min after WLL, percent predicted peak VO2 increased from 82.2 ± 13.7% before WLL to 91.0 ± 14.0% after WLL, peak VO2/kg increased from 30.6 ± 3.5 ml/min×kg before WLL to 34.2 ± 3.7 ml/min×kg after WLL, and ventilatory equivalent for carbon dioxide decreased from 30.6 ± 3.1 before WLL to 26.1 ± 2.7 after WLL (P < 0.05). CONCLUSION: WLL can remarkably improve the oxygen uptake and ventilatory efficiency in patients with pneumoconiosis during exercise, so it can improve the exercise capacity of these 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.

[Correlation analysis between cytokines levels in serum and bronchoalveolar lavage fluid, blood T cell subsets and pneumoconiosis severity].

OBJECTIVE: To analyze the correlation between the pneumoconiosis severity and the cytokines levels in serum and bronchoalveolar lavage fluid (BALF) or blood T cell subsets. METHODS: The subjects were divided into five groups: control group (6 cases), group exposed to dusts (6 cases) and 3 pneumoconiosis groups (36 in stage I, 12 in stage II and 10 in stage III). ELISA was used to detect IL-6, sIL-2R and TNF-α levels in serum and BALF. The subsets of blood T cells were classified by flow cytometer. RESULTS: As compared with control group and group exposed to dusts, the levels of serum IL-6 and sIL-2R in patients with II or III stages significantly increased, which were positively correlated with pneumoconiosis stages (r(1) = 0.74, r(2) = 0.81, P < 0.05). The level of serum TNF-α significantly decreased in patients with III stages, as compared with control group and group exposed to dusts. There was a negative correlation between serum TNF-α level and pneumoconiosis severity (r = -0.58, P < 0.05). There was a positive correlation between the levels of IL-6, sIL-2R and TNF-α in BALF and the levels of IL-6, sIL-2R and TNF-α in serum (r(1) = 0.77, r(2) = 0.96 and r(3) = 0.88, P < 0.05). The proportion of CD(4)(+)T cells and the ratio of CD(4)(+)/CD(8)(+) decreased dramatically in patients with II and III stages. But there was no correlation between these values and disease severity. CONCLUSION: The immune function in Th cell was inhibited. The levels of IL-6, sIL-2R and TNF-α in serum and BALF were associated with the severity of pneumoconiosis.

[Application of transbronchial lung biopsy in pneumoconiosis diagnosis].

OBJECTIVE: To evaluate the role of transbronchial lung biopsy (TBLB) pathology in pneumoconiosis diagnosis. METHODS: During Jan 2003 to Jun 2010 in our hospital. 418 patients exposed to dusts were examined with TBLB. The chest radiographs of all subjects showed the pneumoconiosis-like opacities. Because the dust property or accumulated doses didn't match with abnormality on chest radiographs or there were no a series of chest radiographs, it was required for subjects to perform the TBLB for diagnosis. Three hundred seventy nine cases with satisfying samples served as the study subjects. The dust deposition, fibrosis and birefringent particles were found in TBLB pathological examinations. From May 2005, the Prussian blue iron reaction test was conducted on the TBLB samples. A panel made pneumoconiosis diagnosis according to GBZ 70-2002 and GBZ 70-2009 Pneumoconiosis Diagnostic Criteria, consulting subjects' accounts and pathologic results. RESULTS: Among 379 subjects, 376 cases (99.2%) showed the lung interstitial fibrosis, 228 cases (60.2%) demonstrated the dust deposition, 111 cases (29.3%) expressed the birefringent particles by polarized light microscopy. Birefringent particles positive rate was 37.8% (62/164) in 164 patients exposed to either silica or potter dusts or cement dusts or coal-silica dusts or foundry dusts, which was much higher than that (22.7%, 49/215) in patients exposed to other dusts (welding fume or asbestos or aluminum dusts) (P < 0.05). The positive rate of Prussian blue iron reaction in 177 patients exposed to welding fume or burnishing dusts was 53.1% (94/177), which was significantly higher than that (23.2%, 13/56) in patients exposed to other dusts (cement dusts, casting dusts or silica) (P < 0.001). There were no significantly differences in rates of lung fibrosis, dust deposition and birefringent particles between pneumoconiosis and none-pneumoconiosis subjects. The rate of lung fibrosis in pneumoconiosis cases was significantly higher than that in non- pneumoconiosis cases (P < 0.05). CONCLUSION: TBLB could provide the evidence of exposure to dusts and pathological changes, which may be useful to the pneumoconiosis diagnosis.

[Pathologic analysis of transbronchial lung biopsy in workers exposed to dusts].

OBJECTIVE: To explore the role of transbronchial lung biopsy (TBLB) in pathologic diagnosis of pneumoconiosis. METHODS: In our hospital during May 2011 and Sep 2011, the TBLB samples from 35 cases occupationally exposed to dusts were compared with the video-assisted thoracoscopic surgery or lobectomy samples from 27 cases not exposed to dusts for pathological indexes, including fibrotic proliferation, nodule or nodule-like, dust deposition and needle-shaped birefringent particles. RESULTS: In group exposed to dusts, there were 6 cases (17.1%) with the moderate dust deposition and 28 cases (80.0%) with fibrotic proliferation. But in group not exposed to dusts, there were 0 case with the moderate dust deposition and 11 cases (40.0%) with fibrotic proliferation. There were significant differences between two groups (P < 0.05). In group exposed to dusts, there were 6 cases (17.1%) with Nodules-like and needle-shaped birefringent particles, but in group not exposed to dusts, there was 0 case with Nodules-like and needle-shaped birefringent particles. CONCLUSION: TBLB could provide the evidence of pathological changes in lung tissue induced by dusts, and TBLB play an important role in pneumoconiosis diagnosis.