[The clinical characteristics of intra-acinar pulmonary artery inflammation and its effect on clinical parameters in smokers with normal lung function and patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). METHODS: Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD, n = 10). The lung tissue far away from tumor were resected to compare the pathological changes of intra-acinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups. The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV(1)%Pred), six-minute-walk distance (6MWD) and BODE index. RESULTS: (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C (P < 0.05 or P < 0.01). (2) In group B and group C, the percentage of the intra-acinar pulmonary arteries that contained leukocytes, T lymphocytes, CD(8)(+)T lymphocytes and the number of these positive cells infiltrating the intra-acinar pulmonary arteries were increased, especially an increased number of CD(8)(+)T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P < 0.05 or P < 0.01). In group B and group C, the degree of these positive cells infiltrating NMA, PMA and MA presented a decreasing sequence (P < 0.05 or P < 0.01). Among the intima, media and adventitia of MA, the infiltration of these positive cells was the highest in the adventitia. Among group A, group B and group C, infiltration degree of CD(4)(+)T lymphocyte, B lymphocyte, macrophage and neutrophil demonstrated no significant difference, also among NMA, PMA and MA (P > 0.05). (3) The number of leukocytes, T lymphocytes, CD(8)(+)T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r = 0.563, 0.627, 0.589, P < 0.01, respectively) and smoking index (r = 0.551, 0.665, 0.600, P < 0.01, respectively), moreover the degree of these cells infiltrating MA demonstrated negative correlation with FEV(1)%Pred (r = -0.763, -0.703, -0.767, P < 0.01, respectively). Also infiltrating degree of T lymphocytes and CD(8)(+)T lymphocytes was positively correlated with BODE (r = 0.390, 0.476, P < 0.05, respectively). Furthermore the infiltrating degree of CD(8)(+)T lymphocytes had negative correlation with 6MWD (r = -0.356, P < 0.05). CONCLUSIONS: (1) Pulmonary arterial inflammation appears in smokers with normal lung function and smokers with COPD patients. It involves in all types of intra-acinar pulmonary arteries especially NMA and infiltrates whole layer of MA with a characteristic of CD(8)(+)T lymphocytes infiltrating in the adventitia of intra-acinar pulmonary arteries. (2) Pulmonary inflammation is closely correlated to cigarette smoking and clinical parameters such as BODE index, FEV(1)% pred and 6MWD. It is one of the key factors affecting the progression of COPD.

[Interleukin-17 expression and significance in normal lung function smokers and chronic obstructive pulmonary disease patients].

OBJECTIVE: To study the effect of interleukin 17 (IL-17) with mechanism of pulmonary inflammatory in smokers with normal lung function and chronic obstructive pulmonary disease (COPD) patients. METHODS: The peripheral lung cancer patients in need of a surgical therapy were divided into normal lung function and non-smoking group (NS group, n = 10), normal lung function and smoking group (S group, n = 13) and smoking with stable COPD group (COPD group, n = 10). The fresh normal lung tissue was harvested from the surgical specimens with a margin of 5 cm away from resection foci. Then the lung tissue levels of IL-17 were detected with enzyme-linked immunosorbent assay. The average alveolar area, the total small airway pathology score and the pulmonary muscular artery (MA) wall thickness were measured by HE and Victoria blue-Van Gieson's stains. The IL-17+ cells and CD4+, CD8+ lymphocytes in alveolar walls, small airways and lung MA were analyzed by immunohistochemistry. The investigators also explored the relationships between IL-17 level, pathological morphology of pulmonary parenchyma, small airway, pulmonary artery reconstruction and pulmonary functions. RESULTS: The IL-17 levels in lung tissue of NS, S and COPD groups were 6.1 (3.7 - 12.4), 9.7 (3.5 - 69.7) and 22.7 (7.0 - 114.4) pg/mg respectively. The S and COPD groups were significantly higher than the NS group (P < 0.05, P < 0.01). The S group was significantly higher than the NS group (P < 0.05). The average alveolar area were (50 708 +/- 14 125), (106 517 +/- 13 851) and (152 344 +/- 43 783) microm(2), the total small airway pathology score (49 +/- 10), (101 +/- 34) and (163 +/- 36), and the MA wall thickness (119 +/- 11), (139 +/- 25) and (172 +/- 28) microm respectively. The S and COPD groups were significantly higher than the NS group (P < 0.05, P < 0.01). And the COPD group was significantly higher than the S group (P < 0.05, P < 0.01). IL-17 was predominantly expressed in lung infiltration of inflammatory cells. IL-17 of alveolar walls, small airway wall and MA wall in the S and COPD groups were significantly higher than the NS group. And the COPD group was significantly higher than NS group (P < 0.05). IL-17+ cells were positively correlated with the average alveolar area in pulmonary parenchyma (r = 0.561, P < 0.01), the pulmonary artery wall thickness in MA (r = 0.682, P < 0.01) and the pathological score in small airways (r = 0.425, P < 0.05). IL-17+ cells of pulmonary parenchyma, small airways and MA were positively correlated with CD4+ and CD8+ lymphocytes in lung (P < 0.05, P < 0.01). The levels of IL-17 in lung homogenate tissue showed a negative correlation with the FEV(1) percentage of predicted value (r = -0.471, P < 0.01). CONCLUSIONS: IL-17 is up-regulated in lung tissues of normal lung function smokers and COPD patients. And it has a close correlation with CD4+ and CD8+ lymphocytes in lung, lung parenchyma destruction, pulmonary inflammation, pulmonary artery reconstruction and airflow limitation. All of these suggest that IL-17 plays an important pro-inflammatory role in COPD.

[The changes and significance of interleukin-16 and CXC chemokine receptor 3 expression in pulmonary artery of smokers with chronic obstructive pulmonary disease].

OBJECTIVE: To study the pathological characteristics of interleukin-16 (IL-16) and CXC chemokine receptor 3(CXCR3) in pulmonary artery of smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). METHODS: We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: group NS (nonsmokers with normal lung function, n = 10); group S (smokers with normal lung function, n = 13); group COPD (smokers with stable COPD, n = 10). The clinical datas including blood gas analysis, pulmonary function, BMI, smoking index, BODE index, six-minute-walk distance (6MWD), Medical Research Council dyspnea scale (MRC), St. George Respiratory Questionnaire (SGRQ) were recorded in all subjects before the operation. We applied technique of hematoxylin-eosin staining to observe pathomorphological changes of the pulmonary arteries. The concentration of IL-16 in lung tissues were measured by ELISA. Muscularized arteries were examined with immunohistochemical methods to identify T-lymphocytes (CD(3)), CD(4) T-lymphocytes, CD(8) T-lymphocytes, IL-16, CXCR3. The correlation of IL-16 and CXCR3 in muscularized arteries in smokers with stable COPD were analysed. RESULTS: (1) The group COPD showed the highest concentration of IL-16 in lung tissue (P < 0.01). The concentration of IL-16 in group S was higher than group NS (P < 0.05). (2) Both in group S and group COPD, the percentage of the muscularized arteries that contained CXCR3 and IL-16 were increased as compared with group NS (P < 0.01). Moreover there were statistical significance have been observed between group COPD and group S (P < 0.01). (3) The intensity of IL-16 infiltrating the muscularized arteries in group COPD showed a positive correlation with CD(3)(+)T-lymphocytes, CD(8)(+)T-lymphocytes, CXCR3 (r = 0.639, 0.803, 0.696; P < 0.05 or P < 0.01), smoking index, BODE index (r = 0.737, 0.704; P < 0.05). There was inverse relationship between the content of IL-16 in the muscularized arteries in group COPD and forced expiratory volume in one second% predicted (FEV(1)% Pred) and 6MWD (r = -0.803, -0.787; P < 0.01). We also found the intensity of CXCR3 infiltrating the muscularized arteries in group COPD showed a positive correlation with CD(3)(+) T-lymphocytes, CD(8)(+)T-lymphocytes (r = 0.650, 0.767; P < 0.05), smoking index, BODE index (r = 0.650, 0.767; P < 0.05). There was inverse relationship between the content of CXCR3 in the muscularized arteries in group COPD and FEV(1)% Pred and 6MWD (r = -0.778, -0.774; P < 0.01). CONCLUSIONS: (1) Both in group S and group COPD, IL-16 and CXCR3 were mainly expressed in lymphocytes which were correlated with CD(8)(+)T-lymphocytes infiltrating the muscularized arteries. There were some suggestion that IL-16 probably recruited CD(8)(+)T-lymphocytes into muscularized arteries by enhancing the expression of CXCR3. (2) The intensity of IL-16 and CXCR3 were correlated with the index of clinical and pulmonary function that suggested pulmonary arterial inflammation might be one of the key factors associated with the progression of COPD, and inhibiting the pulmonary artery inflammation played an important role in prevention and cure of COPD.