Chronic Obstructive Pulmonary Disease Patients With High Peripheral Blood Eosinophil Counts Have Better Predicted Improvement in 6MWD After Rehabilitation: A PRELIMINARY STUDY.

PURPOSE: The objective of this investigation was to determine whether chronic obstructive pulmonary disease (COPD) patients with high blood eosinophil (EOS) counts had better improvement in 6-min walk test (6MWT) after pulmonary rehabilitation (PR). METHODS: Fifty COPD patients were randomly assigned to either the rehabilitation group (RG) or the control group (CG). Patients in the RG (8 wk PR + routine medication) and the CG (routine medication) were followed for 32 wk. According to the blood EOS level, the RG was divided into an EOS ≥ 200 cells/µL group and EOS < 200 cells/µL group. The 6MWT distance, Borg Scale, and COPD Assessment Test (CAT) were evaluated before intervention and 8 wk and 32 wk later. RESULTS: After the 8-wk intervention, 37 patients (19 RG/18 CG) completed the study. At 8-wk and 32-wk follow-up from baseline, a statistically significant difference was found between these two groups in the 6MWT, Borg Scale, and CAT. Compared with baseline, the 6MWT in the RG increased 49.1 ± 40.2 m (95% CI, 29.7-68.5, P < .001) at 8 wk and 60.8 ± 42.1 m (95% CI, 40.5-81.6, P < .001) at 32 wk. In addition, the improvement of 6MWT in the EOS ≥ 200 cells/µL RG group was higher than that in the EOS < 200 cells/µL group (40.1 ± 17.6 m, 95% CI, 36.8-43.4; P = .036) at 32-wk follow-up from baseline. CONCLUSION: An 8-wk PR can improve the exercise capacity of COPD patients, and the benefits persistent for 24 wk. The improvement in the 6MWT was more significant in COPD patients with a high blood EOS count.

Successful management of isolated pulmonary Langerhans cell histiocytosis in a 50-year-old man with early diagnosis using transbronchial cryobiopsy: A case report.

RATIONALE: Isolated pulmonary Langerhans cell histiocytosis (PLCH) is rare in adults. The gold standard diagnosis requires surgical lung biopsy. However, few cases have been diagnosed with transbronchial cryobiopsy (TBCB) sampling in the early stages of the disease, particularly in China. PRESENTING CONCERNS: A 50-year-old man was referred for dry cough and exertional dyspnea of more than 1 week. High-resolution computed tomography (HRCT) of the chest revealed symmetric nodules and cyst lesions with upper lobe infiltrate. Further history taking indicated that he had smoked 20 cigarettes per day for more than 30 years. Therefore, PLCH was highly suspected. However, he refused surgical lung biopsy, and TBCB was attempted to complete diagnosis. DIAGNOSIS: Emission computed tomography excluded the possibility of extrapulmonary involvements, and pathological findings supported the diagnosis of isolated PLCH. INTERVENTIONS: Smoking cessation and prednisone treatment were used for patient management. OUTCOMES: The symptoms receded with significant improvement of chest HRCT during 2-months of follow-up. LESSONS: Early diagnosis contributes to the prognosis of isolated PLCH in adults, and TBCB may be an alternative to conventional surgical lung biopsy for pathological diagnosis of PLCH.

Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-ß1/CyclinD1/CDK4 pathway.

This study was aimed to investigate the effect of phospholipid transfer protein (PLTP) on cigarette smoke extract (CSE)-induced alteration of the cell cycle and the possible mechanism. Male Wistar rats and the rat alveolar epithelial cell line (RLE-6TN) were exposed to normal air or different concentrations of CSE. Then PLTP siRNA was transfected into cells and an inhibitor of transforming growth factor-ß1 (TGF-ß1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-ß1, CyclinD1 and CDK4. Resulting morphological changes included diffuse interstitial substance incrassation and elevated alveolar rupturing. Flow cytometry analysis revealed an increase in the number of cells in the G1 phase in a time- and dose-related manner. Both PLTP and TGF-ß1 were up-regulated at protein and mRNA levels, whereas CyclinD1 and CDK4 expression was down-regulated after CSE exposure. Furthermore, PLTP siRNA significantly suppressed CSE-induced TGF-ß1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-ß1 inhibitor was not able to abrogate CSE-induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF-ß1/CyclinD1/CDK4 pathway and may mediate the CSE-induced G1 arrest in RLE-6TN cells. Our work provides some new insight into the relation between PLTP and cell cycle progression.

[A guinea pig model of latent Mycobacterium tuberculosis H37Rv infection].

OBJECTIVE: To establish the guinea pig model of latent Mycobacterium tuberculosis (MTB) H37Rv infection, and to study the multiplication dynamics of MTB in vivo, and the relationship between latent MTB infection and PPD skin test. METHODS: Sixty-two guinea pigs were randomly divided into the model group (n = 42) and the control group (n = 20), and the model group was subdivided into a 4 weeks group (n = 12), an 8 weeks group (n = 21) and a 12 weeks group (n = 9), challenged by 500 CFU H37Rv with restored toxicity. After 2 weeks challenge, the model groups were treated with isoniazid (INH, 10 mg/kg) + pyrazinamidum aldinamide (PZA, 40 mg/kg) for 4 weeks, 8 weeks and 12 weeks respectively. The natural recurrence of tuberculosis was observed in the model 4 weeks group, and the natural and induced recurrence by dexamethasone was observed in the model 8 weeks group and 12 weeks group. PPD skin test, the pathologic changes, and MTB quantity of organs were observed. RESULTS: In the control group, the average MTB quantity of spleen was 3.3 lg CFU after 2 weeks challenge, and the average MTB quantity of spleen and lung in guinea pigs were 4.5 lg CFU and 1.8 lg CFU respectively after 6 weeks challenge, and they reached 5.3 lg CFU and 5.4 lg CFU at 18 weeks respectively. The latent MTB infection of the model 4 weeks group recurred naturally 12 weeks after stopping treatment. The latent MTB infection of the model 8 weeks group recurred naturally and by dexamethasone treatment. The latent MTB infection of the model 12 weeks group did not recur naturally, but dexamethasone induced recurrence. The positive PPD response correlated with recurrence. CONCLUSIONS: A latent MTB infection model was established successfully by H37Rv challenge and treatment with INH and PZA. The latent MTB infection may recur naturally or by induction. The PPD response was related to tuberculosis recurrence.

[The animal experimental study on rifampicin-dependent Mycobacterium tuberculosis].

OBJECTIVE: To investigate the presence of rifampicin-dependent Mycobacterium tuberculosis strains by use of a guinea pig model of tuberculosis of rifampicin-dependent Mycobacterium tuberculosis. METHODS: Guinea pigs were randomly divided into groups of infection by rifampicin-dependent Mycobacterium tuberculosis strains (1130 strain, 1219 strain, b858 strain), rifampicin-resistant Mycobacterium tuberculosis strain (1290 strain) and ATCC 35810 strain and each group was further divided into an experimental group and a control group. The guinea pigs were challenged with 1130 strain, 1219 strain, b858 strain, 1290 strain and ATCC 35810 strain to establish the tuberculosis model. The experimental groups were treated with rifampicin. The parameters including macroscopic visceral pathological change index, visceral weight index (spleen, lungs and liver), the colony-forming units (CFU) quantity of visceral Mycobacterium tuberculosis culture (spleen, lungs) and tissue pathology of guinea pigs were observed. RESULTS: At the 7th week after challenged with 1130 strain, 1219 strain, 1290 strain and b858 strain, all animals were sacrificed. The macroscopic visceral pathological change indices of the experimental group were 68.7 +/- 13.8, 60.0 +/- 13.5, 70.0 +/- 5.8 and 23.8 +/- 18.9, whereas all those parameters of the control group were 76.2 +/- 18.9, 40.0 +/- 16.8, 63.8 +/- 10.3 and 22.5 +/- 15.5 respectively, and there was no significance between the experimental group and the control group (t = 0.64, 1.85, 0.35 and 0.10, all P > 0.05). The spleen weight indices of experimental group were 0.229 +/- 0.048, 0.256 +/- 0.067, 0.324 +/- 0.054 and 0.199 +/- 0.029, whereas all those parameters of control groups were 0.278 +/- 0.025, 0.216 +/- 0.076, 0.368 +/- 0.033 and 0.213 +/- 0.038 respectively, and there was no significance between the experimental group and the control group (t = 1.75, 0.79, 1.41 and 0.57, all P > 0.05). The CFU quantity of spleen Mycobacterium tuberculosis culture of the experimental group were 4.98 +/- 0.30, 4.68 +/- 1.26, 5.07 +/- 0.47 and 3.85 +/- 0.45, whereas all those parameters of control groups were 4.90 +/- 1.03, 4.79 +/- 0.45, 5.08 +/- 0.55 and 4.23 +/- 0.95 respectively, and there was no significance between the experimental group and the control group (t = 0.11, 0.15, 0.03 and 0.73, all P > 0.05); Moreover, the tissue pathology of both groups was similar. CONCLUSIONS: The tuberculosis model of rifampicin-dependent Mycobacterium tuberculosis strains was similar to the model of rifampicin-resistant Mycobacterium tuberculosis in guinea pigs. Rifampicin-dependency was not evident in this guinea pig tuberculosis model.

[Differentiation of infection with Mycobacterium tuberculosis by recombinant Mycobacterium tuberculosis 11000 protein].

OBJECTIVE: To study the differentiation effect of recombinant Mycobacterium tuberculosis 11000 protein on infection of Mycobacterium tuberculosis. METHODS: Guinea pigs were immunized with different strains of mycobacterium, and then all guinea pigs were given intradermal injections with recombinant Mycobacterium tuberculosis 11000 protein and purified protein derivative of tuberculin (PPD) or purified protein derived from M. intracellulare (PPD-B). Skin reactions defined with two transverse diameters were read double-blinded after 24 and (or) 48 hours, and the means of the two transverse diameters were counted as the reaction diameters. RESULTS: All guinea pigs immunized with different strains of Mycobacteria responded to PPD or PPD-B with positive skin reactions. The recombinant Mycobacterium tuberculosis 11000 protein elicited positive skin reactions in guinea pigs infected with live Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum and Mycobacterium kansasii, and the reaction diameters were (14.7 +/- 2.0) mm, (9.3 +/- 3.8) mm, (18.7 +/- 2.4) mm and (14.8 +/- 4.2) mm, respectively. But it failed to elicit positive skin reaction in guinea pigs immunized with killed Mycobacterium tuberculosis, live BCG and other MOTT (mycobacteria other than Mycobacterium tuberculosis). CONCLUSIONS: Recombinant Mycobacterium tuberculosis 11000 protein can differentiate infection with live Mycobacterium tuberculosis from immunization with killed Mycobacterium tuberculosis, live BCG or other MOTT.

[The in vitro killing of intracellular Mycobacterium smegmatis by Mycobacteriophage].

OBJECTIVE: To study the effect of Mycobacteriophage on the lysis of intracellular Mycobacterium smegmatis. METHODS: Peritoneal macrophages from BALB/C mice were incubated with Mycobacterium smegmatis for 4 h, and the extracellular bacteria were removed. Then the infected macrophages were treated for 2 h with normal saline, or different doses of Mycobacteriophages (2.1 x 10(7) PFU, 2.1 x 10(6) PFU, and 2.1 x 10(5) PFU, respectively), all in a volume of 0.1 ml, and then the extracellular phages and Mycobacterium smegmatis were removed by washing. After incubation for 24 h, the number of viable intracellular bacteria was determined. The intracellular changes after infection of host bacteria by bacteriophages in the macrophages were observed by electron microscopy. RESULTS: The logarithm 10 of viable intracellular bacteria unit was 5.74 +/- 0.18 in the saline group, 4.77 +/- 0.08 in the high dose phage group (P < 0.01), 4.97 +/- 0.17 in the moderate dose phage group (P < 0.01), and 5.33 +/- 0.13 in the low dose phage group (P > 0.05). Electron microscopy confirmed the infection of intracellular bacteria by the bacteriophages and the production of filial bacteriophages. CONCLUSIONS: Mycobacteriophages phagocytosed by macrophages are capable of killing the infected mycobacteria. The result suggests that the use of Mycobacteriophages is a potentially novel strategy in the treatment of intracellular bacterial infection.