Prognostic Value and Pathological Correlation of Peritumoral Radiomics in Surgically Resected Non-Small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: To determine the additional value of peritumoral radiomics in predicting overall survival (OS) in surgically resected non-small cell lung cancer (NSCLC) and its correlation with pathological findings. METHODS: A total of 526 patients with surgically resected NSCLC were included (191 training, 160 internal validation, and 175 external validation cohorts). CT images were used to segment the gross tumor volume (GTV) and peritumoral volume (PTV) within distances of 3, 6, 9 mm from the tumor boundary (PTV3, PTV6, and PTV9), and radiomic features were extracted. Four prognostic models for OS (GTV, GTV + PTV3, GTV + PTV6, and GTV + PTV9) were constructed using the training cohort. The prognostic ability and feature importance were evaluated using the validation cohorts. Pathological findings were compared between the two patient groups (n = 30 for each) having the top 30 and bottom 30 values of the most important peritumoral feature. RESULTS: The GTV+ PTV3 models exhibited the highest predictive ability, which was higher than that of the GTV model in the internal validation cohort (C-index: 0.666 vs. 0.616, P = 0.027) and external validation cohort (C-index: 0.705 vs. 0.656, P = 0.048). The most important feature was GLDM_Dependence_Entropy, extracted from PTV3. High peritumoral GLDM_Dependence_Entropy was associated with a high proportion of invasive histological types, tumor spread through air spaces, and tumor-infiltrating lymphocytes (all P < 0.05). CONCLUSION: The GTV and PTV3 combination demonstrated a higher prognostic ability, compared to GTV alone. Peritumoral radiomic features may be associated with various pathological prognostic factors.

Examination of Prognostic Factors in Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis.

OBJECTIVE: This study investigated the prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5-DM). METHODS: This study analysed 34 MDA5-DM cases (20 and 14 in the survival and death groups, respectively) encountered at Kurume University between 2008 and 2021. The clinical, physiological, and computed tomography findings, pulmonary function, and serological results were retrospectively evaluated for each MDA5-DM case during the first visit and throughout the next 12 weeks. RESULTS: In the death group, the mean age of patients was higher (47.6 vs. 61.8 years), while the duration from symptom onset to consultation was shorter (110 vs. 34.9 days). During the first visit, the death group demonstrated a significantly higher serum C-reactive protein (CRP) level (0.52 vs. 1.99) and a significantly lower albumin level (3.23 vs. 2.63) than the survival group; this persisted throughout the next 12 weeks. Poor prognosis was associated with CRP and albumin levels above 0.19 mg/dL and below 2.3 g/dL, respectively, 4 weeks after starting treatment. CONCLUSION: Four weeks after beginning treatment, serum CRP and albumin levels of patients with MDA5-DM can be used to evaluate treatment response and predict prognosis.

Obesity may be a risk factor for transbronchial lung cryobiopsy-related adverse events in Japanese patients with interstitial lung disease.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is known to be associated with a high incidence of adverse events. However, few studies have investigated the correlation between obesity and the risk of TBLC-related adverse events, especially in Asians, who are known to have characteristic differences in height and weight as compared to individuals of other ethnicities. METHODS: We retrospectively assessed 102 Japanese patients who underwent TBLC for the diagnosis of interstitial lung disease to evaluate the correlation between patient characteristics and the occurrence of TBLC-related adverse events (hemorrhage, pneumothorax, and acute exacerbation of interstitial lung disease). RESULTS: TBLC-related adverse events occurred in 19 patients (18.6 %), with hemorrhage being the most common adverse event (in 14 patients, 13.7 %). There was no correlation between age, sex, or pulmonary function test results and the occurrence of adverse events. The body mass index (BMI) cut-off predicting the occurrence of all adverse events was 26.6 kg/m2 (sensitivity of 0.389 and specificity of 0.852), and that predicting the occurrence of adverse events of hemorrhage was 26.8 kg/m2 (sensitivity of 0.462 and specificity of 0.907). Among patients with a BMI >26.8 kg/m2, adverse events of hemorrhage occurred in 37.5 % of cases, which was higher than among those with a BMI <26.8 kg/m2. CONCLUSIONS: Obesity is a risk factor for the incidence of TBLC-related adverse events, particularly adverse events of hemorrhage, in Japanese patients. The BMI cut-off values that predicted an increased frequency of TBLC-related adverse events and hemorrhage specifically were 26.6 and 26.8 kg/m2, respectively.

Endobronchial cryptococcosis with bronchial stenosis in a patient with severe asthma treated with inhaled corticosteroids: A case report.

Cryptococcosis typically manifests as pulmonary lesions, with endobronchial lesions occurring rarely. Inhaled corticosteroids (ICS) may be a risk factor for cryptococcosis of the larynx but not of the bronchi. Here, we report a case involving a 73-year-old Japanese man who developed endobronchial cryptococcosis during ICS treatment for asthma. Chest computed tomography showed right mainstem bronchial stenosis and asthma control worsening when he received adequate asthma treatments. Bronchoscopy revealed multiple elevated lesions with white slough from the trachea to the right mainstem bronchus and the right mainstem bronchus lumen entrance narrowing. Bronchial lavage culture revealed Cryptococcus neoformans. Combination treatment with the antifungal agent, mepolizumab, and bronchodilation surgery successfully controlled cryptococcosis and asthma. Attention should be paid to central airway lesions during ICS treatment for uncontrolled asthma.

Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD.

Clinical significance of high monocyte counts for the continuous treatment with nintedanib.

BACKGROUND: Nintedanib is now widely used to treat interstitial lung disease (ILD). Adverse events, which occur in not a few patients, make it difficult to continue nintedanib treatment, but the risk factors for adverse events are not well understood. METHODS: In this retrospective cohort study, we enrolled 111 patients with ILDs treated with nintedanib and investigated the factors involved in starting dosage reduction, withdrawal, or discontinuation within 12 months, even with appropriate symptomatic treatment. We also examined the efficacy of nintedanib in reducing the frequency of acute exacerbations and the prevention of pulmonary function reduction. RESULTS: Patients with high monocyte counts (> 0.454 × 109/L) had a significantly higher frequency of treatment failure, such as dosage reduction, withdrawal, or discontinuation. High monocyte count was as significant a risk factor as body surface area (BSA). Regarding efficacy, there was no difference in the frequency of acute exacerbations or the amount of decline in pulmonary function within 12 months between the normal (300 mg) and reduced (200 mg) starting dosage groups. CONCLUSION: Our study results indicate that patients with higher monocyte counts (> 0.454 × 109/L) should very careful about side effects with regard to nintedanib administration. Like BSA, a higher monocyte count is considered a risk factor for nintedanib treatment failure. There was no difference in FVC decline and frequency of acute exacerbations between the starting doseage of nintedanib, 300 mg and 200 mg. Considering the risk of withdrawal periods and discontinuation, a reduced starting dosage may be acceptable in the patients with higher monocyte counts or small body sizes.

The Characteristic of Transbronchial Lung Cryobiopsy in the Pathological Diagnosis of Hypersensitivity Pneumonitis.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) has widely used for the diagnosis of diffuse lung disease. However, it remains unclear whether TBLC is useful for the diagnosis in hypersensitivity pneumonitis (HP). METHODS: We investigated 18 patients who underwent TBLC and were diagnosed with HP based on pathology or multidisciplinary discussion (MDD). Of the 18 patients, 12 had fibrotic HP (fHP), 2 had non-fibrotic HP (non-fHP) diagnosed with MDD. The remaining 4 patients were diagnosed with fHP by pathology but not by MDD because of clinical features. The radiology and pathology of these cases were compared. RESULTS: All patients with fHP showed radiological findings of inflammation, fibrosis, and airway disease. Conversely, pathology showed fibrosis and inflammation in 11 of 12 cases (92%), but airway disease was significantly less common with 5 cases (42%) (p = 0.014). Non-fHP showed inflammatory cell infiltration mainly in the centrilobule on pathology, which was consistent with radiology. Granulomas were found in 5 patients with HP (36%). In the non-HP group, airway-centered interstitial fibrosis was observed in 3 patients (75%) with pathology. CONCLUSIONS: The pathology with TBLC is difficult to evaluate airway disease of HP. We need to understand this characteristic of TBLC to make a MDD diagnosis of HP.

Effectiveness of one-shot dual-energy subtraction chest radiography with flat-panel detector in distinguishing between calcified and non-calcified nodules.

The purpose of this study was to evaluate the added value of the soft tissue image obtained by the one-shot dual-energy subtraction (DES) method using a flat-panel detector compared with the standard image alone in distinguishing calcified from non-calcified nodules on chest radiographs. We evaluated 155 nodules (48 calcified and 107 non-calcified) in 139 patients. Five radiologists (readers 1 - 5) with 26, 14, 8, 6 and 3 years of experience, respectively, evaluated whether the nodules were calcified using chest radiography. CT was used as the gold standard of calcification and non-calcification. Accuracy and area under the receiver operating characteristic curve (AUC) were compared between analyses with and without soft tissue images. The misdiagnosis ratio (false positive plus false negative ratios) when nodules and bones overlapped was also examined. The accuracy of all radiologists increased after adding soft tissue images (readers 1 - 5: 89.7% vs. 92.3% [P = 0.206], 83.2% vs. 87.7% [P = 0.178], 79.4% vs. 92.3% [P < 0.001], 77.4% vs. 87.1% [P = 0.007], and 63.2% vs. 83.2% [P < 0.001], respectively). AUCs for all the readers improved, except for reader 2 (readers 1 - 5: 0.927 vs. 0.937 [P = 0.495], 0.853 vs. 0.834 [P = 0.624], 0.825 vs. 0.878 [P = 0.151], 0.808 vs. 0.896 [P < 0.001], and 0.694 vs. 0.846 [P < 0.001], respectively). The misdiagnosis ratio for nodules that overlapped with the bone decreased after adding soft tissue images in all readers (11.5% vs. 7.6% [P = 0.096], 17.6% vs. 12.2% [P = 0.144], 21.4% vs. 7.6% [P < 0.001], 22.1% vs. 14.5% [P = 0.050] and 35.9% vs. 16.0% [P < 0.001], respectively), particularly that of readers 3 - 5. In conclusion, the soft tissue images obtained using one-shot DES with a flat-panel detector have added value in distinguishing calcified from non-calcified nodules on chest radiographs, especially for less experienced radiologists.

Proton Beam Therapy as a Curative Treatment for a Young Case of Unresectable Tracheal Adenoid Cystic Carcinoma.

Primary tracheal adenoid cystic carcinoma (TACC) is a rare malignancy without an established treatment. Central airway obstruction due to TACC often decreases the quality of life and has life-threatening consequences. A 19-year-old man with unresectable TACC and central airway obstruction suffered from progressive cough and dyspnea after exercise. Proton beam therapy (PBT) was selected as the preferred treatment over systemic anti-cancer chemotherapy for TACC. PBT led to complete remission of TACC and the almost complete disappearance of the respiratory symptoms without adverse events. PBT is a useful and safe treatment for unresectable primary TACC.

Granulomatous Lymphocytic Interstitial Lung Disease in Multiple Myeloma.

An 82-year-old woman complained of recurring cough and shortness of breath and was diagnosed with progressive multiple myeloma (MM). Chest computed tomography (CT) revealed bilateral ground-glass opacity and interlobular septal thickening predominantly in the lower lung zones. Histopathologic findings obtained by a transbronchial lung cryobiopsy (TBLC) revealed alveolitis and granulomas consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). Aggressive chemotherapy for MM contributed to the improvement in respiratory symptoms and abnormal chest CT findings. In cases of MM with lung abnormalities, the possibility of GLILD must be ruled out, and a TBLC should be considered to attain an accurate diagnosis.

A Rare Case of Diffuse Bilateral Minute Pulmonary Meningothelial-like Nodules Increasing over the Short Term and Resembling Metastatic Lung Cancer.

A 54-year-old woman was referred to our hospital because computed tomography (CT) revealed multiple lung nodules during a health checkup. The nodules were up to 5 mm in diameter and randomly distributed in both lungs, appearing ring-shaped. No clinical symptoms were present. However, the nodes proliferated, and multiple lung metastases could not be ruled out, so a biopsy was performed to establish a diagnosis. She was diagnosed with minute pulmonary meningothelial-like nodules (MPMNs), and her condition had not deteriorated at the latest follow-up. Although rare, MPMNs can proliferate for a short time, but a biopsy to exclude malignant causes is essential.

Sensitivity of transbronchial lung cryobiopsy in the diagnosis of different interstitial lung diseases.

The accuracy of transbronchial lung cryobiopsy (TBLC) in each disease for pathological and multidisciplinary discussion (MDD) diagnosis is not yet established. METHOD: We investigated 431 patients who were classified by MDD diagnosis and were grouped into the disease categories. For each category or disease, we used TBLC samples to calculate the sensitivities of the pathological diagnosis compared with MDD diagnoses. Further, we compared these sensitivities to pathological diagnoses with all clinical/radiological information. RESULT: The sensitivity for diagnosing idiopathic interstitial pneumonia (IIPs) with TBLC was higher than connective tissue disease associated ILD (CTD-ILD). Idiopathic nonspecific interstitial pneumonia (iNSIP), fibrotic hypersensitivity pneumonitis, and some CTD-ILDs were diagnosed with lower sensitivities compared to IPF. The sensitivity of pathological diagnosis with all clinical/radiological information in IPF was higher than in iNSIP, but not significantly different from other diseases. The overall sensitivity of the pathological diagnosis with clinical/radiological information was 69.0%, significantly higher than without clinical/radiological information. CONCLUSION: The sensitivity of pathological diagnosis with TBLC was low for some diseases except IPF. The addition of all clinical/radiological information increased the sensitivity of pathology diagnosis by TBLC, which was no less sensitive than IPF for all diseases except iNSIP.

Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias.

Various autoantibodies are associated with clinical outcomes in patients with idiopathic interstitial pneumonias (IIPs). We retrospectively analyzed the association between autoantibodies and malignancies in IIP patients. Comprehensive analyses of autoantibodies were performed using immunoprecipitation and enzyme-linked immunosorbent assays in 193 consecutive IIP patients. Cancer-related factors were analyzed using logistic regression analysis. In total, 22 of 193 patients (11.4%) with IIP had malignant disease. In univariate analysis, positivity for any autoantibody (odds ratio (OR), 3.1; 95% confidence interval (CI), 1.2-7.7; p = 0.017) and antinuclear antibody titer ≥1:320 (OR, 3.4; CI, 1.2-9.8; p = 0.024) were significantly associated with malignancies. Positive anti-aminoacyl tRNA synthetase (ARS) (OR, 3.7; CI, 0.88-15.5; p = 0.074) and anti-Ro52 antibody (OR, 3.2; CI, 0.93-11.2; p = 0.065) tended to be associated with malignancies. In multivariate analysis, independent risk factors were male sex (OR, 3.7; CI, 1.0-13.5; p = 0.029) and positivity for any autoantibody (OR, 3.9; CI, 1.5-10.1; p = 0.004) in model 1, and male sex (OR, 3.9; CI, 1.0-15.3; p = 0.049), antinuclear antibody titer ≥1:320 (OR, 4.2; CI, 1.4-13.3; p = 0.013), and positivity for anti-ARS antibody (OR, 6.5; CI, 1.2-34.1; p = 0.026) in model 2. Positivity for any autoantibody, antinuclear and anti-ARS antibodies, and male sex were independent risk factors for malignancies in IIP patients. Testing autoantibodies in IIP patients might help the early diagnosis of malignancies.

Role of intratumoral and peritumoral CT radiomics for the prediction of EGFR gene mutation in primary lung cancer.

OBJECTIVES: To determine the added value of combining intratumoral and peritumoral CT radiomics for the prediction of epidermal growth factor receptor (EGFR) gene mutations in primary lung cancer (PLC). METHODS: This study included 478 patients with PLC (348 adenocarcinomas and 130 other histological types) who underwent surgical resection and EGFR gene testing. Two radiologists performed segmentation of tumors and peritumoral regions using precontrast high-resolution CT images, and 398 radiomic features (212 intra- and 186 peritumoral features) were extracted. The peritumoral region was defined as the lung parenchyma within a distance of 3 mm from the tumor border. Model performance was estimated using Random Forest, a machine-learning algorithm. RESULTS: EGFR mutations were found in 162 tumors; 161 adenocarcinomas, and one pleomorphic carcinoma. After exclusion of poorly reproducible and redundant features, 32 radiomic features remained (14 intra- and 18 peritumoral features) and were included in the model building. For predicting EGFR mutations, combining intra- and peritumoral radiomics significantly improved the performance compared to intratumoral radiomics alone (AUC [area under the receiver operating characteristic curve], 0.774 vs 0.730; p < 0.001). Even in adenocarcinomas only, adding peritumoral radiomics significantly increased performance (AUC, 0.687 vs 0.630; p < 0.001). The predictive performance using radiomics and clinical features was significantly higher than that of clinical features alone (AUC, 0.826 vs 0.777; p = 0.005). CONCLUSIONS: Combining intra- and peritumoral radiomics improves the predictive accuracy of EGFR mutations and could be used to aid in decision-making of whether to perform biopsy for gene tests. ADVANCES IN KNOWLEDGE: Adding peritumoral to intratumoral radiomics yields greater accuracy than intratumoral radiomics alone in predicting EGFR mutations and may serve as a non-invasive method of predicting of the gene status in PLC.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated bronchioloalveolar disorder required differentiation from fibrotic chronic hypersensitivity pneumonitis.

We encountered a case of HTLV-1-associated bronchioloalveolar disorder (HABA) that was difficult to distinguish from fibrotic chronic hypersensitivity pneumonitis (CHP). Chest thin-section computed tomography (CT) showed diffuse micronodules and revealed peribronchovascular and perilobular distribution. Further, thickening of the interlobular septa, areas of ground-glass attenuation, traction bronchiectasis/bronchiolectasis, and air trapping were observed. Based on these findings, diseases that cause lymphatic tract abnormalities and fibrotic CHP were considered differential diseases. A surgical lung biopsy was performed, and an HTLV-1 antibody was detected using the Western blot analysis of bronchoalveolar lavage fluid. The final diagnosis of HABA was made through a multidisciplinary discussion.

Clinical Characteristics of Anti-TIF-1γ Antibody-Positive Dermatomyositis Associated with Malignancy.

We retrospectively analyzed the clinical and laboratory data of patients diagnosed with anti-transcriptional intermediary factor 1 (TIF-1γ) antibody-positive polymyositis (PM)/dermatomyositis (DM) to clarify the characteristics of this disease. We identified 14 patients with TIF-1γ antibody-positive DM (TIF-1γ DM), 47 with anti-aminoacyl-tRNA synthetase antibody (ARS)-positive PM/DM, and 24 with anti-melanoma differentiation-associated gene 5 antibody (MDA-5)-positive PM/DM treated at the Kurume University Hospital between 2002 and 2020. Patients with TIF-1γ DM were significantly older than the other two groups. Nine patients with TIF-1γ DM were female, thirteen patients had DM, and one had clinically amyopathic DM. Primary malignant lesions were lung (3), uterus (2), colon (2), breast (2), ovary (1), lymphoma (1), and unknown (2). Cutaneous manifestation and dysphagia were the most common symptoms in TIF-1γ DM. Erythema (9/14), the V-neck sign (8/14), heliotrope (9/14), and nailfold telangiectasia (14/14) were significantly more common in TIF-1γ DM. Furthermore, no patients with TIF-1γ DM had interstitial lung abnormality on high-resolution CT. In patients with TIF-1γ DM, the frequency of dysphagia and unusual erythema, particularly that which spreads from the trunk, and nailfold telangiectasia, were characteristic findings. In most patients with TIF-1γ DM, it is necessary to administer other immunosuppressive drugs along with glucocorticoids.

Cerebrotendinous xanthomatosis with radiological abnormalities of the chest.

A 55-year-old man with mental retardation and calcaneal tendon thickening was referred for a suspected genetic disease. His serum cholestanol was elevated and genetic analysis of his blood cells for CYP27A1 revealed a homozygous missense mutation. We diagnosed him with cerebrotendinous xanthomatosis (CTX). Chest radiography revealed diffuse micronodular and reticular opacities. Histological findings obtained from the transbronchial lung biopsy revealed foamy macrophages and multinucleate giant cells with marked lipid crystal clefts. Although there are few reports of pulmonary lesions in CTX, we concluded from the radiological and histopathological findings that the pulmonary lesions were indeed caused by the CTX. The patient was treated with chenodeoxycholic acid. His neurological findings and calcaneal tendon thickening were unchanged; however, his serum cholestanol and radiological abnormalities of the chest decreased.

A Case of Autoimmune Pulmonary Alveolar Proteinosis with Pulmonary Fibrosis and Asbestosis-Like Features.

A 78-year-old man who had worked in the building industry visited our hospital because of groundglass opacity with smoothly thickened, intralobular interstitial lines and interlobular septal lines on chest high-resolution computed tomography (HRCT). HRCT image also showed a focal area of reticulation and pleural thickening. Lung specimens obtained by surgical lung biopsy showed accumulations of intra-alveolar periodic acid-Schiffpositive materials, usual interstitial pneumonia (UIP)-like subpleural lung fibrosis and asbestos bodies (1 body/cm2 in high-power field, ×400). Serum granulocyte-macrophage colony stimulating factor autoantibody was positive. The patient was diagnosed as having autoimmune pulmonary alveolar proteinosis (PAP) and needed differential diagnosis from secondary PAP caused from pulmonary asbestosis and UIP. Careful observation of the manifestations of pulmonary asbestosis and the progression of fibrosis using HRCT will be necessary in this patient.

Elevation of pulmonary CD163+ and CD204+ macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients.

BACKGROUND: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. METHODS: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-ß1 (TGF-ß1). RESULTS: CD68+, CD163+, and CD204+ cell counts and CD163+/CD68+ and CD204+/CD68+ cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68+ and CD163+ cell counts and CD163+/CD68+ cell ratio compared with IPF samples, whereas CD204+ cell counts and CD204+/CD68+ cells ratio did not differ. High CD163+/CD68+ and CD204+/CD68+ cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro-differentiated human CD163+ and CD204+ macrophages both secreted TGF-ß1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204+ macrophages. CONCLUSIONS: Pulmonary accumulation of CD163+ and CD204+ macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-ß1 secretion may be a potential therapeutic target for IPF.

Low positive titer of anti-melanoma differentiation-associated gene 5 antibody is not associated with a poor long-term outcome of interstitial lung disease in patients with dermatomyositis.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab) is associated with fatal rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). We attempted to clarify whether anti-MDA5-Ab is associated with long-term outcomes in patients with DM-ILD. METHODS: Thirty-six patients with DM-ILD were retrospectively analyzed for their serum anti-MDA5-Ab by using an enzyme-linked immunosorbent assay. We analyzed the association between clinical parameters, including the serum levels of anti-MDA5-Ab and ferritin. RESULTS: Fourteen patients (39%) were positive for anti-MDA5-Ab. The serum levels of anti-MDA5-Ab and ferritin in 7 patients with acute death were higher than those in the surviving patients. An "unclassifiable pattern" on chest computed tomography and the development of RP-ILD were also prognostic markers. The serum levels of anti-MDA5-Ab and ferritin (cut-off levels, 100 IU/mL and 899 ng/mL, respectively) were markers predictive of acute death, showing good sensitivity (86% and 83%) and specificity (97% and 100%). All 7 patients with acute death developed RP-ILD and were positive for anti-MDA5-Ab, including 6 patients with a high titer (≥100 IU/mL), whereas only 2 patients (29%) developed RP-ILD among the 7 survivors with a low titer of anti-MDA5-Ab ( < 100 IU/mL). In contrast, a low positive titer of anti-MDA5-Ab was not associated with changes in pulmonary function for 2 years. CONCLUSIONS: Although a high serum titer of anti-MDA5-Ab (≥100 IU/mL) is associated with acute death via the development of RP-ILD, outcomes in the chronic phase for patients with a low titer of anti-MDA5-Ab ( < 100 IU/mL) were similar to those of patients without anti-MDA5-Ab.