Hiroki Tashiro

Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

Background Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation. Methods BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes. Results The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung. Conclusion IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.

β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells

BackgroundLong-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs.ResultsWe assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation.ConclusionThese results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.

Coexistence of lung cancer and immunoglobulin G4-related lung disease in a nodule: a case report

BackgroundImmunoglobulin G4-related disease is characterized by infiltration of immunoglobulin G4-positive plasmacytes in various organs. The radiological findings of lung involvement of immunoglobulin G4-related disease include hilar and mediastinal lymphadenopathies, thickness of bronchovascular bundles, peribronchovascular consolidation, and lung nodules. Although a pathological approach is needed to diagnose immunoglobulin G4-related disease, it is ordinarily diagnosed by biopsy from one lesion even if there are multiple lesions. We reported a rare case of the coexistence of immunoglobulin G4-related disease and lung cancer in the same lung nodule.Case presentationA 72-year-old Japanese man visited our hospital for evaluation of a nodular shadow in the middle lobe of his right lung that was seen on chest radiograph and computed tomography scan. An abdominal computed tomography scan showed a tumefactive lesion in his anterior sacral spine. Blood examinations revealed high serum immunoglobulin G4 concentration at 346 mg/dl, renal dysfunction, and anemia. He underwent right upper lobectomy and regional lymph node dissection. Pathologic findings of the lung nodule showed lepidic pattern adenocarcinoma with infiltration of immunoglobulin G4-positive plasma cells and obliterative phlebitis.ConclusionsTo date, there have been only few reports on the coexistence of immunoglobulin G4-related disease and lung cancer; here, we report such a rare case. Histologic examination should be considered in cases of suspicious immunoglobulin G4-related disease appearing in a lung nodule.

Chronic and Asymptomatic Diffuse Alveolar Haemorrhage with Microscopic Polyangiitis: A Case Report and Review of the Literature

Diffuse alveolar haemorrhage (DAH) is one of the major causes of death in microscopic polyangiitis (MPA) patients, because of acute respiratory failure with various respiratory symptoms. We, herein, present a case of chronic and asymptomatic DAH in a patient with MPA who was diagnosed by fibreoptic bronchoscopy. The patient showed localized reticular shadows, without any respiratory symptoms, and absence of inflammatory reactions, such as fever and CRP elevation, which is atypical for DAH. Three months after appearance of the lung abnormalities, DAH with MPA was diagnosed by fibreoptic bronchoscopy. She was initially treated with only corticosteroids and has thereafter been maintained with corticosteroids and azathioprine without relapse to date. We reviewed the literature for similar cases and opined that physicians should perform fibreoptic bronchoscopy in MPA patients with chronic lung abnormalities and anaemia to identify DAH, even if the patients show no respiratory symptoms and in the absence of inflammatory reactions.

Successful treatment of pulmonary nocardiosis with fluoroquinolone in bronchial asthma and bronchiectasis: Fluoroquinolone in pulmonary nocardiosis

A 72‐year‐old Japanese woman was admitted at Saga University Hospital for fever, malaise, and productive cough. Six years ago, she had been diagnosed with bronchial asthma and was treated with inhaled corticosteroids. Chest radiograph and computed tomography on admission showed infiltrates in the right middle lobe, a mass lesion in the left lower lobe, and bronchiectasis in both lower lobes. Sputum examination showed Gram‐positive rods with phagocytosis by neutrophils. These bacilli were identified as Nocardia otitidiscaviarum by 16S ribosomal RNA sequencing. Therefore, she was diagnosed with pulmonary nocardiosis and was treated with trimethoprim/sulfamethoxazole (TMP–SMX) and minocycline (MINO). However, she had to discontinue these antibiotics because of severe nausea and anorexia and instead was treated with fluoroquinolone for 6 months. There was resolution of the disease thereafter. Pulmonary nocardiosis with bronchial asthma and bronchiectasis can be successfully treated with fluoroquinolone, an alternative to TMP–SMX or MINO.

Thin-section Computed Tomographic Findings of Multicentric Castleman Disease Changing Over 10 Years

C disease (CD) is one of the uncommon benign lymphoproliferative disorders characterized by hyperplasia of lymphoid follicles that was first described in 1956 by Castleman et al.1 Histologically, CD is classified into 2 types: hyaline-vascular type and plasma cell type. In total, 90% of CD is hyaline-vascular type; 10% is plasma cell type, which is usually associated with systemic manifestation including fever, fatigue, anemia, and polyclonal hypergammaglobulinemia. Cases with systemic lymph node involvement are referred to as multicentric Castleman disease (MCD). Although there are some reports describing the computed tomography (CT) findings of pulmonary MCD, serial changes on CT were not well known. Here, we report thin-section CT findings of MCD changing over 10 years without treatment.

Characteristics and prognosis of microscopic polyangiitis with bronchiectasis

BACKGROUND Major pulmonary manifestations associated with microscopic polyangiitis (MPA) include diffuse alveolar hemorrhage (DAH) and interstitial pneumonia (IP).We previously showed bronchiectasis (BE) was one of the pulmonary complications of MPA. However, clinical features of BE patients with MPA are not fully understood. We investigated the characteristics and prognosis of BE patients with MPA. METHODS Forty-five MPA patients were retrospectively studied. The patients were divided into two groups: patients with BE and those without BE. RESULTS Thirty-one of 45 patients (69%) had pulmonary involvement including IP (23/45, 51%), BE (7/45, 16%), and DAH (5/45, 11%). There were no differences between the patients with BE versus those without with regard to clinical characteristics and initial treatments. However, the prognosis for patients with BE was better than those without BE during the first year after diagnosis, but it was worse between 1 and 5 years, which was statistically significant. Two BE patients died between 1 and 5 years as a result of pneumonia. CONCLUSIONS BE as a complication of MPA might be related to lower mortality in the acute phase and higher mortality in the chronic phase compared to other pulmonary manifestations. More attention to pulmonary infection is needed for patients with BE during the chronic phase.

Pre-existing chronic interstitial pneumonia is a poor prognostic factor of Goodpasture’s syndrome: a case report and review of the literature

BackgroundGoodpasture’s syndrome is a rare disease that is characterized by rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage.Case presentationA 71-year-old Japanese man who had chronic interstitial pneumonia was diagnosed as having Goodpasture’s syndrome. Both anti-glomerular basement membrane antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody were increased. Despite intensive treatments, including mechanical ventilation, he died from respiratory failure. Pathological findings at autopsy showed rapidly progressive glomerulonephritis in his kidneys, diffuse alveolar hemorrhage, hyaline membranes, and fibroblastic foci in his lungs. The cause of death was diagnosed as respiratory failure as a result of diffuse alveolar damage induced by a combination of diffuse alveolar hemorrhage and exacerbation of interstitial pneumonia.ConclusionsWe report a case of Goodpasture’s syndrome complicated with pre-existing chronic interstitial pneumonia and positive myeloperoxidase anti-neutrophil cytoplasmic antibody. We reviewed six similar cases reported in the literature and concluded that Goodpasture’s syndrome with pre-existing interstitial pneumonia and myeloperoxidase anti-neutrophil cytoplasmic antibody is related to a poor prognosis.