An Autopsy Case of COVID-19 with New Diffuse Pulmonary Ossification.

We present the case of a 61-year-old man who developed coronavirus disease 2019 (COVID-19) and died during treatment for relapsing polychondritis. The patient was intubated and treated with steroid pulse therapy, remdecivir, antibacterial agents, baricitinib, and tocilizumab. However, his respiratory condition worsened, and he died 108 days after disease onset. An autopsy revealed diffuse alveolar damage in the fibrotic phase in all lung lobes, diffuse pulmonary ossification, and cytomegalovirus-infected cells in the middle lobe of the right lung. We herein discuss the clinical features and pathological findings of COVID-19 in immunosuppressed patients.

A Case of Allergic Bronchopulmonary Aspergillosis With Failure of Benralizumab and Response to Dupilumab.

We report a case of a 68-year-old woman who was being treated for bronchial asthma and developed allergic bronchopulmonary aspergillosis (ABPA) that was unresponsive to benralizumab therapy but went into remission with dupilumab therapy. The patient presented with an exacerbation of dry cough and was diagnosed with ABPA based on new diagnostic criteria. Despite the attempted therapeutic intervention, the patient declined to use systemic corticosteroids due to concerns about potential side effects. Subsequently, itraconazole and benralizumab were administered, with temporary relief before relapse. Given the patient's refusal to continue itraconazole and benralizumab, dupilumab was administered as an alternative therapy, which resulted in significant improvement of both symptoms and imaging. Although the use of biological agents for ABPA lacks clear evidence, our results suggest that dupilumab may provide an effective therapeutic strategy.

Tezepelumab treatment for allergic bronchopulmonary aspergillosis.

An 82-year-old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are required.

The Prognostic Performance of Lung Diffusing Capacity in Preserved Ratio Impaired Spirometry: An Observational Cohort Study.

Purpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm. Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality. Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33-43.89)). Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.

Imaging Changes and Immune-Checkpoint Expression on T Cells in Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis.

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.

Heterogeneous subsets of B-lineage regulatory cells (Breg cells).

B cells represent a key cellular component of humoral immunity. Besides antigen presentation and antibody production, B cells also play a role in immune regulation and induction of tolerance through several mechanisms. Our understanding of B-lineage cells with regulatory ability has been revolutionized by the delineation of heterogeneous subsets of these cells. Specific environmental signals may further determine the polarization and function of B-lineage regulatory cells. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made toward our understanding of the surface phenotype, developmental processes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes the inhibitory function of B cells a rapidly growing field in immunopathology. Here we review highlights of the regulatory activity of B cells and the recent advances in the function and phenotype of these B-cell subsets in healthy and diseased states.

Interstitial pneumonia caused by dabigatran.

We describe the case of a 73-year-old man who experienced dry cough and exertional dyspnea after dabigatran administration. Chest radiographs revealed the development of bilateral consolidative and ground glass opacity, and transbronchial lung biopsy showed organized materials in the alveolar spaces with moderate inflammatory infiltrate and focal fibrosis. Lung opacity gradually disappeared after discontinuing dabigatran. To date, there has been only one report regarding dabigatran-induced lung injury, except for alveolar hemorrhage and eosinophilic pneumonia. Therefore, we should consider that any drug can cause various types of lung injuries.

A case of IgG4-related lung disease complicated by asymptomatic chronic Epstein-Barr virus infection.

INTRODUCTION: IgG4-related disease is characterized by IgG4-positive plasmacyte infiltration into various organs, but its etiology is not unknown. OBJECTIVES: To elucidate the etiology of IgG4-related disease. METHODS: We experienced an interesting case of IgG4-related lung disease complicated by chronic EB virus infection. RESULTS: A 70-year-old male visited our hospital due to failure of pneumonia treatment. Chest computed tomography (CT) showed consolidation in the right middle field and slight mediastinal lymphadenopathy in the subcarinal region. Lung consolidation improved with antibiotics; subcarinal lymphadenopathy progressed after 4 months. Malignant lymphoma was suspected given elevated sIL2-R levels (1862 U/mL). Patchy ground glass opacities appeared in the bilateral lung field just before surgical biopsy. He was diagnosed with IgG4-related lung disease after inspection of a pathological specimen obtained from the right upper lung and right hilar lymph node. EB virus-infected cells were also detected in the lymph node. Blood examination revealed EB virus viremia, but the patient did not present with symptoms or organ involvement. This led to a diagnosis of asymptomatic chronic EB virus infection. CONCLUSION: Recent studies have suggested an association between EB virus infection and IgG4-related diseases in the pathological exploration of surgically resected lymph nodes. Our case is the first case of IgG4-related lung disease in which EB virus infection was both pathologically and clinically proved. The present case is of particular interest in view of this newly reported association, and may serve as a fundamental report for future studies connecting EB virus infection with IgG4-related diseases.