ObjectiveTo investigate the role of Krüppel-like factor 4 (KLF4) mediated monocyte/macrophage subtype switch in the pathological progression of pulmonary fibrosis.MethodsThirty-six patients with interstitial pneumonia were recruited from Characteristic Medical Center of the Chinese People's Armed Police Force between May 2015 and January 2017. Peripheral venous blood and bronchoalveolar lavage fluid were collected in the morning. Pulmonary function and arterial blood gas were tested after admission. Flow cytometry was used to test monocyte subtypes of peripheral blood and macrophage subtypes of bronchoalveolar lavage fluid. KLF4 of peripheral blood was detected by enzyme linked immunosorbent assay. Thirty normal subjects were selected as control group of peripheral blood mononuclear cell subtypes and KLF4 (control group A), and 10 patients without pulmonary fibrosis who needed bronchoscopy were selected as control group of macrophage subtypes in alveolar lavage fluid (control group B). The relationship between the expression of KLF4 and the differentiation of monocytes and macrophages were observed. Furthermore, the relationship between the differentiation of monocytes subtypes, macrophages subtypes and lung function were observed.ResultsMonocyte of CD14++CD16– subtype in pulmonary fibrosis group was significantly lower than that in control group A (P<0.05). Monocyte of CD14++CD16+ subtype in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). No significant difference was found between the two groups regarding CD14+CD16++. No correlation was found between three subtypes of monocyte and DLCO of patients and between three subtypes of monocyte and PaO2 of patients. M1 macrophage in pulmonary fibrosis group was significantly lower than that in control group B (P<0.05). M2 macrophage in pulmonary fibrosis group was significantly higher than that in control group B (P<0.05). Negative correlation was found between the ratio of M2 subtypes and DLCO of patients and between the ratio of M2 subtypes and PaO2 of patients (P<0.05). KLF4 protein of blood in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). Positive correlation was found between the ratio of M2 subtypes and KLF4 protein (P<0.05).ConclusionsCD16+ monocyte plays a role in the occurrence and development of pulmonary fibrosis, but no evidence is found there is a direct correlation between monocyte subtypes of peripheral blood and fibrosis degree of lung tissue. M2 macrophage subtype plays an important role in the development of interstitial pneumonia. The number of M2 macrophages is positively correlated with the severity of pulmonary fibrosis. Monocyte/macrophage subtype differentiation by KLF4 may play a role in the pathological progression of pulmonary fibrosis.
ObjectiveTo compare the clinical characteristics,high-resolution computed tomography (HRCT) manifestations,pulmonary function results,serum autoantibodies and treatment modality of connective tissue diseases related interstitial lung diseases (CTD-ILDs) and idiopathic interstitial pneumonias (ⅡPs). MethodsPatients explicitly diagnosed with CTD-ILDs and ⅡPs were retrospectively selected from Nanjing Drum Tower Hospital between January 2004 and December 2012.The clinical features were abstracted,including age,gender,symptoms,signs,serum autoantibody results,HRCT findings,and treatment.Patient characteristics were compared between CTD-ILDs and ⅡPs using a Pearson's χ2 test for categorical variables,and a Student's t test for continuous variables. ResultsA total of 692 patients with complete data were included in this study,with 240 CTD-ILDs cases and 452 ⅡP cases.CTD-ILDs could exist in different types of CTDs,which were mainly shown in Sjogren's syndrome,rheumatoid arthritis,and dermatomyositis/polymyositis.Age,gender,connective tissue diseases related characteristics such as dry eyes,dry mouth,and arthralgia,and several autoantibodies such as ANA,SSA,SSB all showed significantly difference between CTD-ILDs and ⅡPs (P<0.05).However there were no significant differences in cough,dyspnea after exertion,velcro crackles on auscultation,or finger clubbing between two groups (P>0.05). The HRCT manifestations of CTD-ILDs were reticular opacities,patchy consolidation,band-like shadows,and pleural thickening.Pulmonary function tests commonly showed restrictive lung function and decreased diffusing capacity.The histopathologic findings of lung biopsies of CTD-ILDs were mostly chronic inflammatory cell infiltration,as well as hyperplasia of fibrous tissue and septal thickness.The finding of chronic inflammatory cell infiltration showed significant difference between CTD-ILDs and ⅡPs (P<0.05),while the HRCT manifestations,pulmonary function results or other histopathologic findings did not(P>0.05).The current treatment modality was corticosteroids plus immunosuppressants. ConclusionDespite the similarities,CTD-ILDs show distinct clinical,laboratory and imaging features from from ⅡPs in clinical practice.
Objective To investigate the clinical characteristics of interstitial pneumonia patients with positive anti-signal recognition particle antibody (SRP-IP), and compare those with interstitial pneumonia patients with positive anti-Jo-1 antibody (Jo1-IP). Methods Clinical data of SRP-IP patients admitted to Department of Respiratory and Critical Care Medicine of Drum Tower Hospital affiliated to Nanjing University Medical School from May 2017 to May 2021, including clinical manifestations, laboratory examinations, pulmonary function tests and radiographic types, were retrospectively analyzed. The results were compared with those of Jo1-IP patients admitted during the same period. Results The SRP-IP patients were older than Jo1-IP patients (P=0.044). There were no significant differences in clinical manifestations or pulmonary function tests results between the two groups. The proportion of SRP-IP patients combined with positive anti-EJ antibody (P<0.001) or perinuclear anti-neutrophil cytoplasmic antibody (P=0.028) was significantly higher than that of Jo1-IP patients, while the proportion of SRP-IP patients combined positive anti-Ro-52 antibody was significantly lower than that of Jo1-IP patients (P=0.009). The erythrocyte sedimentation rate (ESR) of SRP-IP patients was faster than that of Jo1-IP patients (P=0.026). The serum IgM level (P=0.039) and peripheral NK cell counts (P=0.013) of SRP-IP patients were significantly lower than those of Jo1-IP patients. The most common chest CT findings in SRP-IP patients were organizing pneumonia and the proportion of usual interstitial pneumonia in SRP-IP patients was higher than that of Jo1-IP patients (P=0.032). The levels of creatine kinase (P=0.010), creatine kinase myocardial brand (P=0.025) and alanine aminotransferase (P=0.045) in interstitial pneumonia patients with high titer (++~+++) SRP antibody were higher than those in interstitial pneumonia patients with low titer (+) SRP antibody. SRP-IP and Jo1-IP patients were mainly treated with glucocorticoids combined with or without immunosuppressants, and there was no significant difference in the choice of treatment between the two groups. The proportion of patients with Jo1-IP evaluated as improved was significantly higher than that of patients with SRP-IP (p=0.005), while the proportion of patients with SRP-IP evaluated as stable was significantly higher than that of patients with Jo1-IP (P=0.035). The mortality of SRP-IP patients within 3 months was significantly higher than that of Jo1-IP patients (P=0.028). Conclusion Compared with Jo1-IP patients, SRP-IP patients are older, have faster ESR, are more likely to be combined with other autoantibodies, have lower serum IgM level and peripheral blood NK cell count, have more UIP imaging manifestations, and have a worse short-term prognosis.
Objective To highlight the characteristics of giant cell interstitial pneumonia ( GIP) . Methods The clinical, radiological, and pathological data of two patients with GIP pathologically proven by open lung and TBLB biopsy were presented respectively, and relevant literatures were reviewed. Results Patients with GIP usually had a history of exposure to metal dust. Clinical presentations included cough and dyspnea on exertion, and pulmonary function testing showed a restrictive abnormality. On chest radiography and high-resolution CT scans, it presented as bilateral areas of ground-glass attenuation, areas of consolidation, diffuse small nodules, extensive reticular opacities, and traction bronchiectasis. The main pathological findings included a desquamative interstitial pneumonia ( DIP) -like reaction with intra alveolar macrophages and numerous large multinucleated histiocytes that ingested inflammatory cells were admixed with macrophages. The finding of GIP was almost pathognomonic for hard metal pneumoconiosis. Conclusions GIP is a very rare chronic interstitial pneumonia, and has no characteristic clinical manifestations. Radiographic findings are similar to other idiopathic interstitial pneumonias. Careful collection of the occupational history can help to minimize misdiagnosis.
Objective To analyze the clinical symptoms, imaging, laboratory tests, efficacy and other indicators of patients diagnosed as diffuse parenchymal lung disease ( DPLD) , in order to provide a reference for differential diagnosis of secondary DPLD and idiopathic interstitial pneumonia ( IIP) .Methods Sixtytwo patients diagnosed as DPLD were retrospectively analyzed. Results In 62 patients with DPLD, 19 patients ( 30. 6% ) were diagnosed as secondary DPLD, 42 cases ( 67. 7% ) as IIP, 1 case ( 1. 6% ) as Langerhans cell histiocytosis. The smoking rate of the DPLD patient was 33. 8% , which was higher than general population ( 29. 7% ) . 94. 7% of the secondary DPLD patients had cough, which was higher than the IIP patients ( 71. 4%) . The average age of onset of the secondary DPLD and IIP was ( 45. 9 ±16. 8) years and ( 60. 5 ±7. 7) years respectively, without significant difference ( P gt; 0. 05) . Etiological factors of secondary DPLD were dust, pets, drugs, pesticides, decoration material, etc. The secondary DPLD patients had higher response rate to steroid therapy, but had no statistical difference compared with the IIP patients ( 46. 2% vs. 37. 5% , P gt;0. 05) . Conclusions As a group of diseases of known causes, history taking is very important for DPLD diagnosis and differential diagnosis. Clinical symptoms, imaging, and laboratory tests may provide reference for differential diagnosis of secondary DPLD and IIP.
ObjectiveTo investigate the clinical characteristics of polymyositis (PM)/dermatomyositis (DM) with acute interstitial pneumonia (AIP) as the presenting symptoms, and identify characteristics of such disease. MethodsA retrospective analysis was conducted on the hospitalized patients with PM/DM with AIP as the presenting symptoms, from October 2009 to June 2015 in the Departemnt of Respiratory Medicine, Guangzhou Institute of Respiratory Diseases. ResultsThey were two males and six females with a mean age of 54.8±7.5 years. The common clinical features included fever (8 cases), shortness of breath (8 cases), rapidly progressive exertional dyspnea (8 cases), dry cough (6 cases), decreased muscle strength (8 cases), and typical rash (7 cases). Electromyography showed neurogenic or myogenic leision in these 8 cases. Muscle biopsy revealed myositis in 7 cases. High resolution CT (HRCT) revealed widespread ground glass patterns in all patients. All patients received noninvasive positive pressure mechanical ventilation on the first hospital day. High dose of methylprednisolone or combination with intravenous cyclophosphamide were initiated on 2.3±1.4 hospital day. Six patients survived to hospital discharge and two patient died. ConclusionsThe most common symptoms in patients of PM/DM with AIP are shortness of breath, progressive exertional dyspnea, and dry cough. Typical rash is seen in most of the patients.The diagnosis can be established by combinating the characteristics of HRCT, electromyography and muscle biopsy. Earlier intervention with noninvasive positive pressure mechanical ventilation and immunosuppressive may improve clinical outcome in patients of PM/DM with AIP.
ObjectiveTo compare the expressive differences of plasma Kerbs von den lungen-6 (KL-6) in patients with idiopathic interstitial pneumonia (IIP) and connective tissue disease associated secondary interstitial pneumonia (CTD-SIP), and analyze the clinical significances.MethodsThe clinical data and peripheral blood of 399 inpatients with interstitial pneumonia and 50 healthy controls were collected from January 2011 to December 2014 in Nanjing Drum Tower Hospital. The level of plasma KL-6 was measured by chemiluminescence immunoassay method. The subjects were divided into IIP (n=233) group and CTD-SIP (n=166) group, usual interstitial pneumonia (UIP) pattern and non-UIP pattern, and stable (S) UIP group and acute exacerbation (AE) UIP group. Statistical analyses were performed by using IBM SPSS 19.0 (SPSS, Inc., Chicago IL, USA) to compare the differences of plasma KL-6 in groups.ResultsThere were more male subjects (61.8%) in the IIP group, and the average age of (62.3±12.5) years was significantly older (both P<0.01). Plasma KL-6 levels in the IIP ［(1 822.7±1 505.2) U/ml) and the CTD-SIP group ［(1 846.7±1 625.3) U/ml］ were significantly higher than the healthy control group ［(190.2±88.7) U/ml］ (both P<0.001). However, there was no any difference of KL-6, white blood cell count (WBC), lactate dehydrogenase (LDH), C-reactive protein (CRP) and erythrocyte sedimentation rate between the IIP and the CTD-SIP group. The level of plasma KL-6 was positively correlated to WBC, LDH and CRP in the IIP group (r=0.159, P=0.016; r=0.380, P<0.001; r=0.158, P=0.015, respectively); and it was positively correlated to LDH and CRP in the IIP group (r=0.187, P=0.016 and r=0.068, P=0.032) in the CTD-SIP group. There was no significant difference of plasma KL-6 between the UIP and non-UIP subgroups (P>0.05). The difference of plasma KL-6 between the S-UIP and AE-UIP subgroup was significant (P<0.001 and P=0.023). There was no any significant difference of plasma KL-6 among the subgroups with CTD patients (primary Sjögren’s syndrome, n=90; rheumatoid arthritis, n=20; polymyositis/dermatomyositis, n=26; undifferentiated connective tissue disease, n=10; anti-neutrophil cytoplasmic antibody associated vasculitis, n=15 and systemic sclerosis, n=5) (P=0.785 2).ConclusionsPlasma KL-6 may be a useful biomarker for interstitial pneumonia. It can show the disease activities, but is not able to distinguish IIP from SIP.