Increased Activity Of HDAC2 In Lung Tissue Leads To Corticosteroid Sensitivity In Patients With Organizing Pneumonia

BackgroundOrganizing pneumonia(OP) is histopathologically defined as alveolar spaces buds of granulation tissue. Usually most of the OP is rapidly responsive to Corticosteroids(GCs). However, there is no study on the mechanism of Corticosteroid on OP.ObjectiveTo retrospectively analyze the clinical?radiological and pathological features of OP. The purpose of this study was to demonstrate the mechanism of Corticosteroid sensitivity by comparing Histone deacetylase 2 (HDAC2) and Glucocorticoid reccptor (GR) protein expression in OP with those in Idiopathic pulmonary fibrosis(IPF)?normal lung tissue?Pulmonary inflammatory pseudotumor and pulmonary infected tissue.MethodsThe clinical manifestations, laboratory tests, radiological images,pathological examinations and therapy for OP were analyzed retrospectively from January 2014 to March 2016 in the respiratory department of the first affiliated hospital of guangxi medical university and the people's hospital of Liuzhou. Histone deacetylase 2 (HDAC2)?Glucocorticoid reccptor (GR) and Nuclear factor-KB (NF-?B) protein expression were evaluated by Immunohistochemistry(IHC).This included 9 corresponding biopsy specimens of OP,8 biopsy samples of IPF?7 biopsy samples of Pulmonary inflammatory pseudotumor?6 biopsy samples of pulmonary infectious disease (confirmed by pathology) and 7 normal lung tissue samples from thoracic operations as control.Results(1)General informations: ?There were 9 patients including 4 females and 5 males with the mean age of 60.7±4.9 years.?Out of the 9 patients, 6(66.7%)were diagnosed with COPs and the rest of them were diagnosed with SOPs(33.3%),caused by Sjogren's syndrome.?Two of them were smokers.None of them had dust inhalation. (2)Clinical manifestations: The most common manifestations were nonspecific and the majority of the patients were presented with cough(nonproductive cough 33%, sputum production67%), dyspnea(44%),chest pain(33%), and chest tightness(22%). Some of them also had systemic symptoms like fever(88%), weight loss(33%), fatigue(22%) and anorexia(11%).(3)Examinations:? The WBC (10.2—21.21 ×10^9/L) and CRP(14.98—192mg/L) level of all patients were increased. ESR (41—140mm/H)elevation was found in 8 patients. CRP (1.58—85.4mg/L) level of all patients were decreased after treatment with GC and the difference was statistically significant(P=0.028). The ESR level of all patients were decreased after treatment with GC, but no statistical difference was observed. The results of the 6 patients with COP were the same as that of the 9 patients with OP. ?8 patients had Pulmonary Function Testing (PFT) before being treated. 6 patients with OP presented with a restrictive pattern on Pulmonary Function Testing (PFT) and 8 patients with diffusion dysfunction was observed. The pulmonary ventilation and diffusion functions were improved after treatment with GC, but no statistical difference was observed. ?The most common finding on the computed tomographic scan was consolidation with an air bronchogram in 8 patients that was bilateral in 66.7% and unilateral in 22.2% of patients. Migratory lesions were observed in 3 patients. 7 patients improved in computed tomographic scan after treatment with GC. ?Lung biopsy demonstrated that lung alveoli were filled with buds of granulation tissue consisting of fibroblasts. There was an Infiltration of the alveolar interstitium by inflammatory cells. ( 3 )Immunohistochemical examination: ?The level of HDAC2 was significantly higher in OP tissues than in IPF(P=0.003)?normal lung tissues(P=0.001)?Pulmonary inflammatory pseudotumor(P=0.001) and Pulmonary infected tissues(P=0.002). The level of HDAC2 was significantly higher in IPF tissues than in Pulmonary inflammatory pseudotumor(P=0.001). There was no difference in the level of HDAC2 in between IPF and normal lung tissues and in between IPF and Pulmonary infected tissues. The level of HDAC2 was significantly lower in Pulmonary inflammatory pseudotumor tissues than in normal lung tissues (P=0.002). ?The level of GR was significantly higher in OP tissues than in IPF(P=0.001) and Pulmonary inflammatory pseudotumor(P=0.007). There was no difference in the level of GR in between OP and normal lung tissues and in between OP and Pulmonary infected tissues.The level of GR was significantly lower in IPF than in normal lung tissues(P=0.001) and Pulmonary infected tissues(P=0.005). The level of GR was no different between IPF and Pulmonary inflammatory pseudotumor. The level of GR was significantly lower in Pulmonary inflammatory pseudotumor than in normal lung tissues(P=0.006) and Pulmonary infected tissues(P=0.046).?The level of NF-?B was significantly lower in OP tissues compared to IPF, and was significantly higher than in Pulmonary inflammatory pseudotumor. There was no difference in the level of NF-?B in between OP and normal lung tissues and in between OP and Pulmonary infected tissues. The level of NF-?B was significantly higher in IPF than in normal lung tissues(P=0.005) and Pulmonary inflammatory pseudotumor(P=0.002). The level of NF-?B was no different between IPF and Pulmonary infected tissues. The level of NF-?B was significantly lower in Pulmonary inflammatory pseudotumor than in normal lung tissues(P=0.018) and Pulmonary infected tissues(P=0.007). The level of NF-?B was significantly higher in Pulmonary infected tissues than in normal lung tissues(P=0.015).? HDAC2 is positively related to NF-?B in OP tissues(rs=0.767 , P=0.016).? HDAC2 is positively related to GR in IPF tissues(rs=0.738, P=0.037).Conclusions1?The clinical manifestation of OP is non-specific. OP is sensitive to corticosteroid therapy.2?The high-expression of HDAC2 may be related to corticosteroid sensitivity in OP. And the low-expression of GR may be related to corticosteroid resistance in IPF.3?The level of HDAC2 and GR in interstitial pneumonia, may be an important way to evaluate if the patients with interstitial pneumonia are sensitive to corticosteroid therapy.