[Effect of corticosteroids upon the prognosis of idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the therapeutic effect of corticosteroids upon idiopathic pulmonary fibrosis (IPF) and the impact of corticosteroids upon survival time. METHODS: Clinical data of 94 corticosteroid treatment and 32 non-corticosteroid treatment IPF patients during 2000 - 2004 were retrospectively analyzed and their survival rates compared between two groups. The corticosteroid treatment patients were divided into 3 groups: improved, steady and worsened group according to the pulmonary function data. Therapeutic effects and survival rates were compared between these 3 groups. RESULTS: In the treatment group, 6 (6.4%) patients could not be located, 22 (23.4%) patients survived, and 66 (70.2%) patients died. In the non-corticosteroid treatment group, 1 (3.1%) patients could not be located, 2 (6.3%) patients survived and 29 (90.6%) patients died. No statistically significant difference existed between the two groups (P > 0.05). Sixty-two corticosteroid treatment patients were followed up for 3-6 months. Among them, 19 (30.7%) patients improved, 11 (17.7%) patients remained steady and 32 (51.6%) patients worsened in pulmonary function. In 19 improved patients, 7 (36.8%) survived and 12 (63.2%) died. In 11 steady patients, 3 (27.2%) survived and 8 (72.7%) died. In 32 worsened patients, 3 (9.4%) could not be located, 1(3.1%) survived and 28 (87.5%) died. The survival rate of the improved and steady groups was higher than that of the worsened group (P < 0.01). CONCLUSIONS: There is some therapeutic effect of corticosteroids in the early alveolitis stage of IPF. The prognosis of the patients with improved and steady pulmonary function parameters during the first 3 - 6 months is better than that of worsened patients.

[A retrospective cohort study of prognostic factors for death in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the prognostic implications of clinical, radiographic, and physiological variables in idiopathic pulmonary fibrosis (IPF). METHODS: The clinical, pulmonary physiological, bronchoalveolar lavage fluid (BALF) cell differentials and lung high-resolution computed tomography (HRCT) at diagnosis in 126 patients with IPF were retrospectively analyzed. Univariate and multivariate Cox proportional-hazards regression analysis was used to evaluate various parameters associated with hazard ratio (HR). The survival rates of all groups were compared using the Kaplan-Meier method. RESULTS: In 29.6 months of average follow-up time, the survival rate of the IPF patients was 46.8% (59/126), and the median survival time was 30 months after diagnosis. Glucocorticoids and/or cytotoxic drugs for patients with IPF did not change the prognosis. The survival rates between groups by gender and smoking status showed no statistically significant difference (Ward: 0.11, 1.65, P>0.05). The patients were divided into 2 groups by the median (the cutoff point value) of significant variables in univariate Cox proportional-hazards regression analysis, and the survival rates showed statistically significant difference by dyspnea scale, FVC%, TLC%, DLCO%, neutrophil percentage and eosinophil percentage in BALF, and the reticular and honeycomb lung score (Logrank: 13.52-57.52, P<0.05). The results of multivariate Cox proportional-hazards regression analysis showed that TLC%, DLCO%, HRCT reticular score and honeycomb lung score were factors that affected the prognosis of patients with IPF (Wald=5.76-21.48, P<0.05). CONCLUSIONS: TLC%, DLCO%, cell differentials of BALF and the degree of pulmonary fibrosis were the main factors affecting the prognosis of patients with IPF. TLC% and DLCO% showed a negative correlation with the prognosis of patients with IPF. Glucocorticoids and/or cytotoxic drug therapy had no effect on the prognosis of patients with IPF.

[Cell profiles of bronchoalveolar lavage fluid as prognostic indicators of idiopathic pulmonary fibrosis].

OBJECTIVE: To determine whether clinical and physiologic variables and bronchoalveolar lavage fluid (BALF) cell profiles affect the survival of patients with idiopathic pulmonary fibrosis (IPF). METHODS: There were 43 patients with clinically diagnosed IPF in the study. The Kaplan-Meier method and the Log-rank test were used to estimate the survival in the two groups and Cox proportional hazard regression was used to evaluate the Hazard Ratio in the IPF patients. RESULTS: The IPF patients presented with restrictive ventilatory disorders [FVC%: (61 +/- 18)%, TLC%: (54 +/- 13)%] and gas exchange impairment [D(L)CO%: (48 +/- 14)%]. The mean follow-up time was 30.7 months, and the median survival of IPF patients was 28.5 months after diagnosis. FVC ( Wald = 6.71, P < 0.01), TLC ( Wald = 12.37, P < 0.01) , D(L)CO ( Wald = 22.78, P < 0.01), neutrophil ( Wald = 16.26, P < 0.01) and eosinophil ( Wald = 7.73, P < 0.01) percentages were prognostic variables in the univariate Cox proportional hazard regression, and only D(L)CO (HR = 0.93, Wald = 15.77, P < 0.01) and the neutrophil percentage (HR = 1.07, Wald = 6.83, P < 0.01) were prognostic variables for IPF patients in the multivariate Cox proportional hazard regression. CONCLUSIONS: The IPF patients were predominantly old males and presented with restrictive ventilatory disorders and gas exchange impairment. Glucocorticoids and/or cytotoxic drugs could not improve the prognosis for the IPF patients. DLCO and BALF neutrophil percentage were prognostic variables, and DLCO was negatively correlated with the prognosis while the neutrophil percentage was positively correlated with the prognosis in the IPF patients.

[Changes of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the bronchoalveolar lavage fluid and the serum of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To detect the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the significance of the changes in the pathogenesis of IPF. METHODS: Enzyme-linked immunoadsorbent assay (ELISA) was used to detect MMP-9 and TIMP-1 in the BALF and serum of 30 patients with IPF. RESULTS: The levels of MMP-9 in the BALF and serum of the patients showed no significant difference as compared with those of the control group. The levels of TIMP-1 in the BALF [(522 +/- 81) ng/L] and serum [(166 +/- 29) ng/L] of the patients were higher than those [(201 +/- 31), (87 +/- 16) ng/L] of the control group (P < 0.01). The ratios of MMP-9/TIMP-1 in the BALF (0.53 +/- 0.18) and serum (1.5 +/- 0.3) of patients with IPF were lower than those (1.06 +/- 0.38, 2.6 +/- 0.5) of the control group (P < 0.01, < 0.05). TIMP-1 in the BALF of the patients showed a strong positive correlation with chest CT fibrosis and pulmonary function test scores (P < 0.01), while MMP-9/TIMP-1 in the BALF had negative correlation with them (P < 0.01). CONCLUSION: Pulmonary fibrosis may be associated with increased TIMP-1 and decreased MMP-9/TIMP-1, which is able to inhibit the degradation of extracellular matrix.

[Cell apoptosis and the change of Fas/FasL gene in experimental pulmonary fibrosis].

OBJECTIVE: To investigate the changes and significance of cell apoptosis and Fas/FasL gene in pulmonary fibrosis. METHODS: Forty mice were divided into two groups randomly, each group contained twenty mice. TUNEL, immunohistochemistry and in situ hybridization were used to detect the change of cell apoptosis, Fas/FasL mRNA and protein in mice with pulmonary fibrosis caused by bleomycin. RESULTS: The apoptosis index of lung cells in the pulmonary fibrosis group (55.3 +/- 12.2) was higher than that of control group (4.7 +/- 1.0, t = 13.06, < 0.01). The expression of Fas/FasL mRNA (175.8 +/- 21.6, 5.2 +/- 1.6) and protein (956 +/- 96, 285 +/- 76) in the pulmonary fibrosis group was higher than that of control group (mRNA: 26.6 +/- 1.9, 0.5 +/- 0.4, t = 21.7, 8.79, all < 0.01; protein: 491 +/- 96, 100 +/- 18, t = 5.03, 12.81, < 0.01). CONCLUSION: The apoptosis index of lung cells, Fas/FasL genes and protein were up-regulated in lung tissue of pulmonary fibrosis, which may play an important role in the development of disease.

[Effect of Shenluotong on secretion of ECM and expression of TGF-beta1 in rats mesangial cells of rats].

OBJECTIVE: To investigate the effect of Shenluotong on the expression of transforming growth factor-beta1 (TGF-beta1) and extracellular matrix (ECM) in Ang II-induced MCs. METHOD: Fibronectin (FN) and collagen type IV (Col IV) of extracellular matrix were detected by enzyme-linked immunosorbent assay; the expression of TGF-beta1 mRNA were measured by semi-quantitative reverse transcription-polymerase chain reaction. RESULT: A positive correlation between TGF-beta1 and ECM were found in the present study. FN, Col IV and TGF-beta1 mRNA were inhibited by Shenluotong significantly. CONCLUSION: Shenluotong can decrease the accumulation of ECM and inhibit the expression of TGF-beta1, suggesting further that shenluotong can be used to prevent and treat various glomerular diseases and delay glomerular sclerosis.

[Respiratory control in obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate the role of ventilatory control in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Thirty-five patients with OSAHS were compared with 15 obese controls in pulmonary function, hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR) and polysomnography (PSG). RESULTS: (1) There were no differences in HVR and HCVR between patients with OSAHS and the control (t = 1.28, 0.57; P > 0.05). In OSAHS patients, HVR was correlated with nadir nocturnal oxygen saturation (MmS(P)O(2)) (r = -0.54, P < 0.01) and HCVR (r = 0.57, P < 0.01). (2) Patients with mild and moderate OSAHS had higher HVR than those with severe OSAHS (t = 2.74, P < 0.01). When 5 < or = apnea and hypopnea index (AHI) < 40, HVR was negatively correlated to forced expiratory volume in one second (FEV(1))/peak expiratory flow (PEF) (r = -0.42, P < 0.05) and AHI (r = -0.68, P < 0.01). For those whose AHI > or = 40, HVR was negatively correlated with MmSpO(2) (r = -0.58, P < 0.05) and positively correlated with HCVR (r = 0.59, P < 0.05). CONCLUSION: In OSAHS patients, HCVR did not show significant change, but HVR showed two phasic change-increase first and then decrease-following the elevation of AHI, which was also related to MmSpO(2) and HCVR.

[Change of prostaglandin E2 and interleukin-12, interleukin-13 in the bronchoalveolar lavage fluid and the serum of the patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To detect the levels of prostaglandin E2 (PGE2) and interleukin-12 (IL-12), IL-13 in the bronchoalveolar lavage fluid (BALF) and the serum of patients with idiopathic pulmonary fibrosis (IPF) and to investigate the significance of their change in the pathogenesis of IPF. METHODS: Radioimmunoassay (RIA) and enzyme-linked immunoadsorbent assay (ELISA) were used to detect the levels of PGE2 and IL-12, IL-13 in the BALF and the serum of patients with IPF. RESULTS: In the BALF of patients with IPF, the levels of PGE2 (591 +/- 88) ng/L and IL-13 (38 +/- 5) ng/L were higher than that of the control group (P < 0.01), and the level of IL-12 (1.34 +/- 0.25) ng/L was lower than that of control group. In the patients with IPF, the change of IL-13 in the serum was consistent with the change in the BALF. But the levels of PGE2 (235 +/- 13) ng/L and IL-12 (2.35 +/- 0.14) ng/L in the serum showed no significant difference between the patients with IPF and the control group. CONCLUSIONS: In the patients with IPF the increase of PGE2 may be correlated with the increase of IL-13 and the decrease of IL-12. It suggests that disequilibrium of Th1/Th2 plays an important role in the development of IPF. The increase of PGE2 in IPF is a local event rather than a systemic effect.

[Ventilatory control in familial obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the genetic abnormality of ventilatory control may play a role in the familial aggregation of obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Ten severe patients with OSAHS, 16 first relatives of them and 14 obese subjects were studied and the hypoxic ventilatory response (HVR), the hypercapnic ventilatory response (HCVR) and the results of PSG were analyzed. HVR and HCVR of OSAHS patients were re-examined in the first, second and third month of continuous positive airway pressure(CPAP) treatment. RESULTS: (1) For the relatives of the OSAHS patients, the apnea-hypopnea index (AHI) was (28.4 +/- 39.1)/h, the incidences of snoring and daytime sleepiness were 100% and 90%, They were higher than those of the control (P < 0.05, P < 0.01, P < 0.01). OSAHS had familial aggregation. (2) The HVR and HCVR were (-19 +/- 24) cm H2O and (0.31 +/- 0.35) cm H2O/mm Hg for the relatives.Neither HVR nor HCVR showed difference between the relatives and the control (P > 0.05). Only two of the relatives with severe OSAHS had lower HVR, while the others, whether accompanied with OSAHS or not, had similar HVR and HCVR to the control. (3) HVR and HCVR returned to normal after CPAP therapy in patients of OSAHS. CONCLUSION: OSAHS had familial aggregation, but it was not related to genetic abnormality of ventilatory control.

[Evaluation of interleukin-13 in the serum and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To study the significance of interleukin-13 (IL-13) in peripheral blood and bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF). METHODS: The level of IL-13 was determined with ELISA in the serum and BALF of 17 patients with IPF and 8 subjects with non-interstitial lung diseases (non-smokers). RESULTS: The level of IL-13 in the BALF of the patients with IPF was significantly higher than that in non-interstitial lung disease group [(301 +/- 86) ng/L vs. (103 +/- 24) ng/L (P < 0.01)] and was higher than that in serum [(178 +/- 36) ng/L vs. (55 +/- 15) ng/L, P < 0.01]. The level of IL-13 in the BALF of the patients with IPF was positively correlated with the percentage of neutrophils (r = 0.786, P < 0.01). The analysis of Spearman correlation showed that the level of IL-13 in the BALF was correlated with lung function, PaO(2), and D(LCO) (Spearman correlation coefficient r = -0.898, -0.878, -0.874, -0.890, respectively, P < 0.01). CONCLUSION: IL-13 may play an important role in the pathogenesis of IPF and be a potential marker of IPF activity.