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.

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.

A Cluster of Paragonimiasis with Delayed Diagnosis Due to Difficulty Distinguishing Symptoms from Post-COVID-19 Respiratory Symptoms: A Report of Five Cases.

Paragonimiasis caused by trematodes belonging to the genus Paragonimus is often accompanied by chronic respiratory symptoms such as cough, the accumulation of sputum, hemoptysis, and chest pain. Prolonged symptoms, including respiratory symptoms, after coronavirus disease 2019 infection (COVID-19) are collectively called post-COVID-19 conditions. Paragonimiasis and COVID-19 may cause similar respiratory symptoms. We encountered five cases of paragonimiasis in patients in Japan for whom diagnoses were delayed due to the initial characterization of the respiratory symptoms as a post-COVID-19 condition. The patients had consumed homemade drunken freshwater crabs together. One to three weeks after consuming the crabs, four of the five patients were diagnosed with probable COVID-19. The major symptoms reported included cough, dyspnea, and chest pain. The major imaging findings were pleural effusion, pneumothorax, and nodular lesions of the lung. All the patients were diagnosed with paragonimiasis based on a serum antibody test and peripheral blood eosinophilia (560-15,610 cells/µL) and were treated successfully with 75 mg/kg/day praziquantel for 3 days. Before diagnosing a post-COVID-19 condition, it is necessary to consider whether other diseases, including paragonimiasis, may explain the symptoms. Further, chest radiographic or blood tests should be performed in patients with persistent respiratory symptoms after being infected with COVID-19 to avoid overlooking the possibility of infection.

Airway hyperresponsiveness and inflammation in Japanese patients with human immunodeficiency virus 1 infection.

INTRODUCTION: Despite the growing population of long-term survivors with human immunodeficiency virus 1 (HIV) exhibiting asthma-like features worldwide, the pathogenesis underlying airway hyperresponsiveness (AHR) and airway inflammation remains unclear. We aimed to investigate AHR and airway inflammation in an HIV-infected Japanese population. METHODS: Of 94 Japanese participants, 10 HIV-infected participants with asthma were excluded from the study. We compared the characteristics of HIV-infected (n = 34) and non-HIV-infected participants (n = 50). Eosinophilic, neutrophilic, mixed (eosinophilic and neutrophilic), and paucigranulocytic airway inflammatory phenotypes were classified based on induced sputum characteristics. RESULTS: The prevalence of AHR in HIV-infected participants (32.4%) was significantly higher than that in their non-HIV-infected counterparts (10.0%) (P = 0.0213). The multivariate nominal logistic regression analysis revealed HIV as an independent risk factor for AHR. HIV-infected participants were significantly more likely to have a neutrophilic airway inflammatory phenotype than non-HIV-infected participants (P = 0.0358). Furthermore, HIV-infected participants with AHR demonstrated a significant correlation between AHR levels and the percentage of sputum neutrophils (r = -0.65, P = 0.0316). The percentage of sputum neutrophils was negatively associated with the blood CD4 cell count (r = -0.66, P = 0.0266). CONCLUSIONS: We observed the high prevalence of AHR and neutrophilic airway inflammatory phenotype in Japanese participants with stable HIV infection. Our findings provide insight into the mechanisms of AHR and may facilitate the development of novel treatment for individuals with AHR and HIV infection.

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.

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.

A Case in which Eosinophilic Meningoencephalitis Occurred during Oral Corticosteroid Tapering and after Switching from Anti-IL-5 to Anti-IgE Treatment.

A 49-year-old man with severe eosinophilic asthma, sinusitis, and esophagitis was admitted with a sudden severe headache. The patient was diagnosed with eosinophilic meningoencephalitis based on frontotemporal abnormalities on brain magnetic resonance imaging and high eosinophil counts in the cerebrospinal fluid. His allergic-disease control levels were poor, requiring regular oral corticosteroid (OCS) use. He was switched from anti-interleukin (IL)-5 to anti-IgE therapy because of worsening urticaria and asthma symptoms during OCS tapering. We suspect this was a case of complex eosinophilic meningoencephalitis caused by the combination of OCS tapering and anti-IL-5 therapy cessation that acquired anti-IgE antibody sensitization based on positive drug-induced lymphocyte stimulation test results.

Lung miliary micro-nodules in human T-cell leukemia virus type I carriers.

Human T-cell leukemia virus type 1 (HTLV-1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well-known complication, adult T-cell leukemia/lymphoma (ATLL). HTLV-1 associated bronchiolo-alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV-1 carriers. The reported clinico-pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV-1 carriers showing miliary micro-nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro-nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.

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.

A Case of STAT1 Mutations in Chronic Mucocutaneous Candidiasis Diagnosed in an Adult.

A 30-year-old man presented with oral candidiasis and a history of lung abscess. He experienced recurring oral and skin candidiasis in childhood but spent long periods without any infections. Therefore, immunodeficiency was suspected. T and B lymphocyte and natural killer cell counts as well as immunoglobulin levels were normal. Human immunodeficiency virus test results were negative. Therefore, we suspected chronic mucocutaneous candidiasis (CMC). The signal transducer and activator of transcription (STAT) mutation, the leading cause of CMC, was detected by exome sequencing. Most cases of STAT-1 mutations are diagnosed in childhood, but a few are diagnosed in adulthood because Candida infections may not be severe.

Acute exacerbation of idiopathic pulmonary fibrosis after bivalent {tozinameran and famtozinameran} mRNA COVID-19 vaccination.

An 82-year-old man diagnosed with interstitial lung disease through computed tomography (CT) 1 year prior received a bivalent (tozinameran and famtozinameran) mRNA COVID-19 vaccine. He developed respiratory symptoms 1.5 months later, and chest high-resolution CT revealed new ground-glass opacities showing traction bronchiectasis. Transbronchial lung cryobiopsy revealed organizing acute lung injury and fibrosis with architectural destruction. The patient was diagnosed with an acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The bivalent mRNA COVID-19 vaccination was determined as the cause of the AE-IPF based on detailed medical history and examination findings. High-dose corticosteroid therapy improved the patient's symptoms and radiological findings.

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.

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.

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.

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.

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.

Combination of Prednisolone and Calcineurin Inhibitors Prevents Lung Function Decline in Patients with Anti-aminoacyl-tRNA Synthetase Antibody-Positive Polymyositis/Dermatomyositis.

OBJECTIVE: Anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associ ated interstitial lung disease (ARS-ILD) has a good prognosis, with few cases progressing to respiratory failure. This study aimed to determine factors predictive of lung function changes in patients with ARS-ILD. METHODS: We retrospectively studied 49 patients with ARS-ILD treated at Kurume University Hospital Hospital between 2000 and 2018. We followed 30 patients for more than 2 years after prednisolone (PSL) therapy, with or without calcineurin inhibitors (CNIs), evaluating clinical, physiological, computed tomography, pulmonary func tion, and serological data. RESULTS: After treatment for 24 months, no significant differences were noted between clinical parameters and improvement in forced vital capacity (FVC), %FVC, % carbon monoxide diffusing capacity/alveolar volume (%DLCO), and %DLCO/alveolar volume. Conversely, the annual change of %FVC significantly correlated with the Medical Research Council dyspnea scale grade and %FVC at the first visit and treatment. Furthermore, the annual change of %DLCO/VA significantly correlated with the duration from the first visit to treatment initiation. CONCLUSION: Compared with PSL monotherapy, combining PSL and CNI showed greater mitigation of %FVC decline. The time from onset of ARS-ILD to the first visit is critical for preventing a decline in lung function, and as such, patients should be monitored carefully.

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.

Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls. The aim of this study was to review cases fulfilling published imaging and histological criteria, and identify any common clinical features that may suggest an underlying aetiology for a condition that has previously been regarded as idiopathic. Of 12 patients (seven females, median age 57 yrs), the presenting symptoms were shortness of breath (11 out of 12 patients) and dry cough (six out of 12 patients). Seven patients reported recurrent infections during the course of their disease. Five demonstrated nonspecific autoantibody positivity. Two patients had a family history of interstitial lung disease (ILD). High-resolution computed tomography features of lung disease remote from the pleuroparenchymal changes were present in six out of 12 patients (coexistent fibrosis, n=5; bronchiectasis, n=1). Of seven patients with tissue sampled from the lower lobes, four patients showed less intense PPFE changes (one with additional features of hypersensitivity pneumonitis) and three showed usual interstitial pneumonia. PPFE is a distinct clinicopathological entity, with clinical data suggesting a link to recurrent pulmonary infection. Genetic and autoimmune mechanisms may also contribute to the development of these changes. PPFE may also present with more diffuse involvement than previously reported, and coexist with different patterns of ILD.