| PART Ⅰ:Clinical and Prognostic Relevance of Ectopic Lymphoid Structure in Nonspecific Interstitial PneumoniaObjective:Clinical and prognostic relevance of ectopic lymphoid structure(ELS)in pulmonary disease remains unclear.This part explored the relationship between ELS structure and clinical manifestations,treatment response and prognosis of patients with nonspecific interstitial pneumonia(NSIP).Method:Baseline and follow-up data of patients who were diagnosed as NSIP by clinicradiologic-pathologic diagnosis in Peking Union Medical College Hospital from April 2003 to December 2012 were retrospectively collected.The number and average size of ELS and related structures were quantitatively assessed.According to change rate of forced vital capacity(FVC)after 1 year of treatment,patients were divided into improved,stable and worsened group.Survival group and death group were divided based on their 5-year status.Differences in pathological indexes among groups were compared.Results:A total of 60 patients with NSIP were enrolled in this study.Their mean age was 49±11 years and 19(31.67%)of which were men.The proportions of ELS positivity was 58.33%.After 1 year of standard therapy,15(58.33%)patients improved and 4(7.55%)patients worsened in FVC,and the other 34(64.15%)patients remained stable.14(23.33%)patients died within 5 years.There was no significant difference in ELS features between autoimmune disease-related NSIP and idiopathic NSIP.The improvement rate of FVC and DLCO in ELS-positive group was significantly lower than that in ELS-negative group.Numbers and average size of ELS related structures were significantly increased in FVC worsened group and were negatively correlated with the change rate of FVC.No significant difference was seen in ELS number and size between survival group and death group.Conclusion:ELS is an important pathological manifestations of lung injury in NSIP patients and may predict less improvement in lung function after steroid treatment with or without immunosuppressant.Its pathophysiological mechanisms warrant further studies.PART Ⅱ:Formation Regularities and Biomarkers of EctopicLymphoid Structure in Monocrotaline-induced Lung Injury Model Objective:Monocrotaline(MCT)can induce chronic inflammation in lung tissue.This part aimed to observe ectopic lymphoid structures(ELS)in the MCT lung injury model and to search for relevant serum and bronchoalveolar lavage fluid(BALF)markers.Method:Lung injury model was established in SD rats by intraperitoneal injection of MCT.Serum,BALF and lung tissues were collected regularly from 3 to 17 weeks after modeling.LUMINEX xMAP was used to detect inflammatory factors in serum and BALF.Number and average size of ELS were quantitatively evaluated in H&E-stained lung tissues.The relationship between ELS and inflammatory factors was analyzed.Results:In MCT group,ELS formed on the basal side of bronchial epithelium and in the perivascular space as early as 3 weeks after modeling and increased with time.Compared with the control group,certain inflammatory factors significantly increased in serum and BALF.Serum levels of IL-1β,IL-6 and TNF-α reached their peaks 7 weeks after modeling,which was earlier than in BALF.Serum levels of IL-4 and IFN-γ reached their peaks 13 weeks after modeling,which was later than in BALF.Formation of ELS during week 5-9 accorded with elevating levels of IL-1β,IL-6,TNF-α,and IL-17,and their maintenance and progression during week 11-15 corresponded with the increase in IL-4 and IFN-γ.Conclusion:The formation of ELS is associated with MCT-induced chronic inflammation in lung tissue.Reaction phase of inflammatory factors in peripheral blood was out of sync with that in BALF,which may be involved in the formation of ELS. |
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