Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation.

AIMS: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. METHODS AND RESULTS: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). CONCLUSIONS: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. METHODS: A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. RESULTS: In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01-1.07; IL-8, HR = 1.04, 95% CI 1.01-1.08; MIP-1α, HR = 1.19, 95% CI 1.00-1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02-1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01-1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. CONCLUSIONS: CTACK is a novel prognostic biomarker of IPF. Trial registration None (because of no healthcare intervention).

Phenotyping of IgG4-related diseases based on affected organ pattern: A multicenter cohort study using cluster analysis.

OBJECTIVES: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, multiorgan disease of unknown etiology. We aimed to classify IgG4-RD by a combination pattern of affected organs and identify the clinical features, including the comorbidities of each subgroup. METHODS: Patients diagnosed with IgG4-RD between April 1996 and June 2018 were enrolled from three institutes. Hierarchical cluster analysis was performed using six frequently affected organs (lacrimal gland and/or orbit, salivary gland, lung, pancreas, kidney, and retroperitone and/or aorta). Clinical features, such as comorbidities and outcomes, were compared between clusters. RESULTS: In total, 108 patients enrolled in this cohort could be stratified into five distinct subgroups: group 1, lung dominant group; group 2, retroperitoneal fibrosis and/or aortitis dominant group; group 3, salivary glands limited group; group 4, Mikulicz's disease dominant group; and group 5, autoimmune pancreatitis with systemic involvement group. There were significant between-group differences in sex (male dominant in group 1, 2, and 5), history of asthma and allergies on the respiratory tract (most frequent in group 5), and malignancy (most frequent in group 5). CONCLUSION: IgG4-RD can be classified into subgroups according to the pattern of affected organs. Group 5 may have frequent complications with allergies and malignancies.

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in a patient with anti-melanoma differentiation-associated gene 5-positive dermatomyositis: A case report and systematic literature review.

A 58-year-old man with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5-DM) developed Epstein-Barr virus (EBV)-associated malignant lymphoma as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) during the combined immunosuppressive therapy of high-dose prednisolone, tacrolimus, and intravenous cyclophosphamide for MDA5-DM. Serum EBV DNA was detected, and EBV-encoded small RNA was positive in the tissue sample of LPD, indicating that EBV reactivation contributed to the pathogenesis of LPD in our case. The patient underwent chemotherapy, including rituximab, promptly after discontinuation of tacrolimus and cyclophosphamide, resulting in complete remission of the malignant lymphoma, and MDA5-DM has not recurred with 3.5 mg/d of prednisolone monotherapy. We reviewed 19 cases of OIIA-LPD in patients with idiopathic inflammatory myopathies and herein report the first case of MDA5-DM complicated with OIIA-LPD. Among the 19 patients, 7 showed regression of LPD only following withdrawal of immunosuppressants, 9 took chemotherapy for LPD, and 5 died. It should be noted that patients with MDA5-DM-associated rapidly progressive interstitial lung disease could develop OIIA-LPD because they receive aggressive immunosuppressive therapy.

Novel Artificial Intelligence-based Technology for Chest Computed Tomography Analysis of Idiopathic Pulmonary Fibrosis.

Rationale: There is a growing need to accurately estimate the prognosis of idiopathic pulmonary fibrosis (IPF) in clinical practice, given the development of effective drugs for treating IPF. Objectives: To develop artificial intelligence-based image analysis software to detect parenchymal and airway abnormalities on computed tomographic (CT) imaging of the chest and to explore their prognostic importance in patients with IPF. Methods: A novel artificial intelligence-based quantitative CT image analysis software (AIQCT) was developed by applying 304 high-resolution CT (HRCT) scans from patients with diffuse lung diseases as the training set. AIQCT automatically categorized and quantified 10 types of parenchymal patterns as well as airways, expressing the volumes as percentages of the total lung volume. To validate the software, the area percentages of each lesion quantified by AIQCT were compared with those of the visual scores using 30 plain high-resolution CT images with lung diseases. In addition, three-dimensional analysis for similarity with ground truth was performed using HRCT images from 10 patients with IPF. AIQCT was then applied to 120 patients with IPF who underwent HRCT scanning of the chest at our institute. Associations between the measured volumes and survival were analyzed. Results: The correlations between AIQCT and the visual scores were moderate to strong (correlation coefficient 0.44-0.95) depending on the parenchymal pattern. The Dice indices for similarity between AIQCT data and ground truth were 0.67, 0.76, and 0.64 for reticulation, honeycombing, and bronchi, respectively. During a median follow-up period of 2,184 days, 66 patients died, and 1 underwent lung transplantation. In multivariable Cox regression analysis, bronchial volumes (adjusted hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.16-1.53) and normal lung volumes (adjusted HR, 0.97; 95% CI, 0.94-0.99) were independently associated with survival after adjusting for the gender-age-lung physiology stage of IPF. Conclusions: Our newly developed artificial intelligence-based image analysis software successfully quantified parenchymal lesions and airway volumes. Bronchial and normal lung volumes on HRCT imaging of the chest may provide additional prognostic information on the gender-age-lung physiology stage of IPF.