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Abstract Sarcoidosis is a multisystemic granulomatous disease that is frequently localized in the lungs and lymph nodes. We herein report a case of pulmonary sarcoidosis secondary to shin'iseihaito administration. During remission with 5 mg prednisolone/day of maintenance treatment, chest computed tomography revealed a mass in the left lower lobe with re‐enlarged bilateral hilar/mediastinal lymph nodes. Transbronchial lung biopsy of the mass and endobronchial ultrasound‐guided transbronchial needle aspiration of mediastinal lymph nodes revealed adenocarcinoma and noncaseating granulomas, respectively. Based on these findings, the patient was diagnosed with sarcoidosis recurrence associated with lung cancer without cancer metastasis. We present the case of sarcoidosis recurrence associated with lung cancer after drug‐induced pulmonary sarcoidosis with lung injury. To our knowledge, this is the first report of sarcoidosis triggered by drug administration and lung cancer. Histological diagnosis of mediastinal lymphadenopathy with lung cancer is essential for differentiating metastasis from sarcoidosis.

Abstract Severe asthma affects approximately 5%–10% of patients with asthma. Herein, we describe a case of non‐type 2 asthma that progressively worsened over the years. An 80‐year‐old woman was diagnosed with asthma 11 years back. She experienced repeated exacerbations requiring treatment with systemic corticosteroid despite therapy with medications including high‐dose inhaled corticosteroids/long‐acting beta‐agonists plus long‐acting muscarinic antagonist. The patient presented with non‐eosinophilic asthma. Therefore, the patient was initially treated with bronchial thermoplasty, which was effective for 1 year only. Treatment with bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab was ineffective. The fourth treatment, which included tezepelumab, was initiated. The patient's symptoms and quality of life improved significantly. This is the first case of a patient who did not respond to sequential bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab but who presented with good clinical response to tezepelumab. Therefore, tezepelumab may be useful for patients with non‐type 2 asthma.

Abstract Chronic eosinophilic pneumonia (CEP) is an eosinophilic lung disease. Treatment for CEP includes corticosteroids; however, CEP often recurs. A 53‐year‐old woman was referred to our hospital because of poorly controlled asthma. She was treated with combination of moderate‐dose inhaled corticosteroid (ICS), a long‐acting β2‐agonist (LABA), and betamethasone/dexchlorpheniramine. She was switched to single‐inhaler triple therapy, after which her asthma control improved; thus, betamethasone/dexchlorpheniramine was discontinued. Ten weeks later, she was diagnosed with CEP due to marked eosinophilia and pulmonary eosinophilic infiltrates. Oral corticosteroid treatment was initiated, symptoms improved, and peripheral blood eosinophilia decreased with improved infiltrative shadows. Remission induction therapy was initiated with benralizumab combined with corticosteroid therapy. Eosinophilia and inflammatory responses decreased. After 7 months, corticosteroid was discontinued, and she was treated with benralizumab alone. She remained in remission for 4 months. This case suggests that benralizumab may be useful as a remission induction therapy in patients with CEP.

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by abnormally high eosinophils and frequent peripheral neuropathy. Mepolizumab is an approved therapy for EGPA, but its efficacy against peripheral neuropathy remains unknown. Case presentation A 41-year-old woman was admitted in the hospital with dyspnea and neuropathy. Ground glass opacity and infiltrative shadow in the bilateral lungs were evident on chest computed tomography images. Eosinophils were increased in serum, in bronchoalveolar lavage fluid (BALF), and in transbronchial lung biopsy, and bacteria were not detected in BALF. EGPA resulting in severe eosinophilic asthma, sinusitis, pulmonary infiltrates, and peripheral neuropathy was diagnosed. Prednisolone (50 mg/day) caused remission of eosinophilic pneumonia and sinusitis, but not peripheral neuropathy. During prednisolone tapering (7 mg/day, 10 months after treatment), eosinophils were increased, and peripheral neuropathy relapsed. The humanized anti-IL-5 antibody mepolizumab (300 mg) was initially administered, followed by prednisolone. Mepolizumab caused sustained peripheral neuropathy remission and effective prednisolone tapering. Conclusions Introduction of mepolizumab combined with prednisolone may improve peripheral neuropathy.

Abstract Neurosarcoidosis is a rare complication of sarcoidosis and unusually presents as optic neuritis. We present the case of a 51‐year‐old man who complained of right vision loss. Brain magnetic resonance imaging showed asymmetrical enlargement of the right optic nerve. Chest computed tomography detected mediastinal and hilar lymphadenopathy. There were cutaneous nodules on the back. Biopsy of the mediastinal lymph node by endobronchial ultrasound‐guided transbronchial needle aspiration and the skin showed noncaseating granulomas consistent with sarcoidosis. Serum angiotensin‐converting enzyme level was elevated (34.2 IU/L) (normal: 8.3–21.4 IU/L). Based on these findings, he was diagnosed as neurosarcoidosis with optic neuritis. He was started on 1000‐mg/day methylprednisolone intravenously for 3 days, followed by oral 50‐mg/day prednisolone, which was gradually tapered for 8 weeks. Thereafter, the skin nodules and lymphadenopathy decreased and the right vision partially improved. Based on this rare case, sarcoidosis should be considered as a differential diagnosis in cases of optic neuritis.

Abstract Primary pulmonary diffuse large B‐cell lymphoma is a rare entity. We describe a case of pulmonary lymphoma with multiple nodules mimicking metastases in a treated patient with rheumatoid arthritis. A 73‐year‐old man was diagnosed with rheumatoid arthritis at the age of 30. He was treated with leflunomide. He was followed up for a nontuberculous mycobacterial infection. He underwent percutaneous coronary intervention for acute myocardial infarction at the age of 70. In April 2022, routine follow‐up revealed new‐onset multiple nodules on chest computed tomography (CT). A position emission tomography/CT scan with 18F‐fluorodeoxyglucose showed a low‐high maximum standardized uptake value by multiple nodules. Pathologic examination of a video‐assisted thoracic surgical biopsy revealed pulmonary diffuse large B‐cell lymphoma. Systemic chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisolone reduced and eliminated multiple nodules. Pulmonary lymphoma should be considered as a differential diagnosis in the case of multiple nodules on a chest CT.

Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by a hypersensitivity reaction to antigens of the Aspergillus species. Recently, allergic bronchopulmonary mycosis (ABPM) caused by fungi other than Aspergillus species but with the same symptoms has been described. ABPM commonly affects patients with allergic diseases including bronchial asthma. ABPM is characterized by radiographic appearance, with the most common findings being proximal bronchiectasis and signs of mucoid impaction. However, the differentiation of ABPM is often necessary to enable accurate diagnosis of lung cancer. A 73-year-old man visited the outpatient clinic with symptoms of exertional dyspnea. He was diagnosed with ABPM due to suspicious bronchiectasis and mucoid impaction observed in computed tomography (CT) of his chest. After 3 months, he visited our hospital with continued exertional dyspnea and suspicion of a possible tumor in his lung. Marked eosinophilia and high-attenuation mucus impaction were not taken into consideration as diagnosis was conducted as per clinical diagnostic criteria for ABPA/ABPM. We hereby report a case of lung cancer in a patient initially evaluated for suspected ABPM of the right lung. The diagnosis of lung cancer was established using bronchoscopy. If any definitive diagnosis is not achieved by following the clinical diagnostic criteria for ABPM, physicians should achieve a histological diagnosis by performing a prompt bronchoscopy.

Although immune checkpoint inhibitors (ICIs) can be used for lung cancer treatment, the activated immune response may cause immune-related adverse effects (irAEs). We present here a case of cytomegalovirus (CMV) enterocolitis during steroid therapy for an irAE. A 70-year-old man diagnosed with small-cell lung carcinoma (limited disease) received radiotherapy plus two chemotherapy cycles of cisplatin and etoposide. The tumor exhibited complete response but recurred after 3 years. After treatment with two cycles of carboplatin, etoposide, and atezolizumab, an inhibitors of programmed cell death receptor-1, he was switched to atezolizumab every 3 weeks for maintenance therapy. Diarrhea occurred after nine atezolizumab doses. With a strong suspicion of ICI-induced colitis, we administered methylprednisolone 500 mg for 3 days, followed by oral prednisolone 40 mg/day. Total colonoscopy during the treatment revealed mucosal inflammation of the total colon, suggesting immune-related colitis. Biopsies from the ulceration revealed crypt abscess with highly infiltrative plasma cells and lymphocytes. Furthermore, immunohistochemical staining showed positivity for CMV. With no improvement in watery diarrhea, the prednisolone dose was increased to 80 mg/day on the 11th day, and ganciclovir was additionally administered twice daily on the 26th day. On the 28th day, the patient had abdominal pain, and abdominal computed tomography revealed free air, resulting in the diagnosis of colon perforation. He underwent subtotal colectomy followed by ileostomy as emergency surgery. A colon specimen revealed colitis with CMV infection. We describe colon perforation in a patient with CMV enterocolitis complicated by refractory immune-related colitis.

Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung sarcomatoid carcinoma that has a poor prognosis, and no standard therapy has been established. Here, we report the case of a 74-year-old man with PCC who showed rare duodenal metastasis. He was referred to our hospital with a mass shadow in the right lung. The patient was diagnosed with PPC clinical stage II B on the basis of immunohistochemical staining from bronchoscopy, and the tumor proportion score of programmed death-ligand 1 was 80%. He did not want any treatment. A year and a half later, progressive anemia was detected. The primary tumor was stable; however, abdominal computed tomography and esophagogastroduodenoscopy revealed a duodenal tumor with stenosis. He was diagnosed with duodenal metastasis from PPC, and he underwent gastrojejunal bypass surgery to prevent bowel obstruction. After surgery, he received pembrolizumab for chemotherapy. However, owing to the progression of peritoneum dissemination, he died 2 months later due to the onset of melena.

Abstract A 28‐year‐old man with ankylosing spondylitis (AS) who was treated with a tumour necrosis factor‐alpha (TNF‐α) inhibitor, adalimumab, presented with newly detected multiple bilateral pulmonary nodules on chest computed tomography (CT). We suspected bacterial infection, including those caused by acid‐fast bacilli, or adalimumab‐related condition, such as sarcoidosis. After adalimumab cessation, no resolution of the pulmonary shadows was observed. Moreover, pulmonary cavitation appeared on chest CT at 7 weeks, prompting surgical lung biopsy. Acid‐fast bacteria culture of the lung tissue showed negative results. Pathological examination suggested that confluent granulomas associated with sarcoidosis might have obstructed the blood vessels, causing necrosis and lung cavitation. Consequently, prednisolone was initiated, and these shadows were reduced. After administering anti‐interleukin (IL)‐17A antibody for treatment of AS and prednisolone withdrawal, these shadows were not exacerbated. TNF‐α inhibitor‐induced sarcoidosis could cause cavitary lesions due to vascular invasion of granulomas.

Abstract Nintedanib is a multi‐target receptor tyrosine kinase inhibitor that reduces the decline in forced vital capacity (FVC) and prevents acute exacerbations in idiopathic pulmonary fibrosis (IPF), which is a risk factor for lung cancer. However, it remains unclear whether nintedanib is an effective treatment for lung cancer in patients with IPF. Here, we describe an 82‐year‐old man with non‐small cell lung carcinoma complicated by IPF who was treated with nintedanib. High‐resolution computed tomography (HRCT) showed a subpleural basal‐predominant reticular shadow and traction bronchiectasis with a honeycomb pattern. His FVC decreased over time, and his 6‐min walk test showed oxygen desaturation. Furthermore, an enlarged nodular lesion was detected after 6 months of referral. Biopsy confirmed non‐small cell carcinoma. Because of the risk of acute exacerbation of IPF by chemotherapy, supportive care was selected. Nintedanib was started as treatment for the IPF. Nine months later, HRCT revealed partial remission without exacerbation of IPF. This case indicates the possibility of nintedanib monotherapy in suppressing lung cancer complicated by IPF. Patients with lung cancer complicated by IPF in whom treatment is effective remain unknown. Additional research is needed to identify effective therapy for lung cancer with IPF.

Abstract Urachal carcinoma is a rare malignancy of all bladder carcinomas. Metastatic lung tumours showing multiple nodules are rare without a local recurrence. We describe a case of multiple metastatic lung cancer from urachal carcinoma that required differentiation from primary lung cancer.

An 81-year-old woman presented to our hospital due to an abnormal shadow on a chest X-ray and a 4-week-old persistent cough. Laboratory examination revealed increased serum eosinophils and immunoglobulin E. The Asthma Control Test (ACT) score and forced expiratory volume in 1 sec indicated airway obstruction. Chest computed tomography (CT) revealed mucoid impaction in the dilated left-lingular lobar bronchus. She was diagnosed with bronchial asthma and treated with a high-dose inhaled corticosteroid/long-acting β2 agonist. Two months later, her mucoid impaction in the CT image worsened; moreover, bronchoscopy revealed the white mucus plug with Charcot–Leyden crystals and filamentous fungi. The patient was diagnosed with Allergic bronchopulmonary aspergillosis (ABPA) and treatment with 30 mg/day prednisolone was started. Both the blood eosinophil count and the chest image improved almost substantially, and the steroid was discontinued after a year. Sixteen months after cessation of prednisolone treatment, peripheral eosinophilia and mucoid impaction in the left B3b recurred. For the treatment of bronchial asthma and recurrent ABPA, administration of mepolizumab was initiated. Subsequently, although her peripheral eosinophils count decreased, chest CT showed expansion of the mucoid impaction and IgE increased despite mepolizumab treatment. Alternative subcutaneous injection therapy with dupilumab improved chest image, serum IgE level, and her ACT score.After changing from mepolizumab to dupilumab, her ABPA, asthma, and pulmonary function improved remarkably. This case illustrates the potential utility of dupilumab for ABPA without re-administration of oral prednisolone. Additional research is needed to identify an effective therapy for ABPA with asthma.

Abstract A 66‐year‐old woman was hospitalized for recurrent pneumonia twice in 1 year. After treatment for pneumonia, chronic coughing, sputum and low‐grade fever continued, so she was referred and admitted to our hospital for investigation. Chest computed tomography revealed a lung infiltrative shadow and diffuse centrilobular micronodules. Histological findings from transbronchial lung biopsy showed chronic inflammation and giant cells in the bronchiole. These findings were compatible with diffuse aspiration bronchiolitis (DAB), which is characterized by chronic inflammation of the bronchioles caused by recurrent aspiration of foreign bodies. Oesophagogastroduodenoscopy revealed stenosis of the oesophageal entrance, which was thought to be caused by radiation therapy for hypopharyngeal cancer 20 years before. Antibiotic treatment ameliorated the centrilobular nodule shadow. After discharge, there was no recurrence. This is the first case report of DAB resulting from oesophageal stenosis associated with hypopharyngeal cancer and will serve as an educational case.

Abstract Dupilumab, a human monoclonal antibody against interleukin‐4 (IL‐4) and IL‐13, has been approved for treating severe asthma and eosinophilic chronic rhinosinusitis (ECRS). Patients with ECRS are often candidates for endoscopic sinus surgery (ESS). However, a considerable number of patients have recurrent ECRS. ECRS is an important factor influencing asthma control. Here, we present two cases of severe asthma and recurrent ECRS after ESS. Although they had been treated with inhaled corticosteroids and a long‐acting β2‐agonist, they experienced frequent asthma exacerbations. Laboratory examinations revealed increased serum eosinophils and immunoglobulin E (IgE). Furthermore, the Asthma Control Test (ACT) score and forced expiratory volume in 1 sec (FEV1) were indicative of airway obstruction. After treatment with dupilumab, asthma, rhinosinusitis symptoms, and pulmonary function improved remarkably. Dupilumab therapy improved quality of life in these patients with severe asthma and ECRS.

Abstract A two‐dimensional macroelement is proposed for reinforced concrete interior beam‐column joints based on an innovative theory of joint shear hinging failure. The new joint model maintains the original aspect of the mechanical model of the joint shear hinging failure theory, in which concrete struts are used to model the concrete core, which differs from other multispring models discussed in the literature and developed from the theory. The applicable scope of the new joint element encompasses interior joints where the beams and columns have the same depth and width. Moreover, within the scope of this study, only the monotonic responses were computed to capture the backbone of the joint hysteresis responses. Verification of the test data indicated the reliability of the new joint models for predicting the backbone of the load‐deflection relationship and the yielding of reinforcements under cyclic loadings.

We describe a case of Trousseau's syndrome in a patient with lung carcinoma. A 69-year-old man presented with pleural effusion. Further evaluation revealed EGFR mutation-positive non-small cell carcinoma in the upper lobe with extensive lymph node, bone, and brain metastases. Administration of osimertinib, an EGFR tyrosine kinase inhibitor, resulted in partial tumor response, but caused osimertinib-induced pneumonitis 10 weeks later. Prednisolone restrained lung injury progression and was gradually tapered. However, he presented with impaired consciousness and right hemiplegia. Magnetic resonance imaging revealed a left middle cerebral artery M1 segment occlusion. D-dimer level was elevated to 19.5 μg/mL. In the absence of atherosclerotic or cardiogenic thrombi, these findings led to the diagnosis of Trousseau syndrome. Endovascular therapy, but not tissue plasminogen activator, improved his condition with no recurrences. These treatment strategies are crucial to restore function in patients with potentially disabling cerebral infarction due to Trousseau syndrome.

Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E. CS-E augments cell contraction and CHST15 siRNA inhibits collagen production. We found that bleomycin treatment increased CHST15 expression in interstitial fibroblasts at day 14. CHST15 siRNA was injected intranasally on days 1, 4, 8, and 11, and CHST15 mRNA was significantly suppressed by day 14. CHST15 siRNA reduced lung CSPG and the grade of fibrosis. CHST15 siRNA repressed the activation of fibroblasts, as evidenced by suppressed expression of α smooth muscle actin (αSMA), connective tissue growth factor (CTGF), lysyl oxidase like 2 (LOXL2), and CC-chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1). Inflammatory infiltrates in the bronchoalveolar lavage fluid (BALF) and interstitium were diminished by CHST15 siRNA. These results indicate a pivotal role for CHST15 in fibroblast-mediated lung fibrosis and suggest a possible new therapeutic role for CHST15 siRNA in pulmonary fibrosis. Keywords: bleomycin, chondroitin sulfate proteoglycans, pulmonary fibrosis, macrophages, fibroblasts, chondroitin sulfate, idiopathic pulmonary fibrosis

Background: Chondroitin sulfate proteoglycans are an important mediators in inflammation and leukocyte trafficking. However, their roles in pulmonary emphysema have not been explored. In a murine model of elastase-induced pulmonary emphysema, we found increased carbohydrate sulfotransferase 3 (CHST3), a specific enzyme that synthesizes chondroitin 6-sulfate proteoglycan (C6SPG). To elucidate the role of C6SPG, we investigated the effect of small interfering RNA (siRNA) targeting CHST3 that inhibits C6SPG-synthesis on the pathogenesis of pulmonary emphysema.Methods: Mice were intraperitoneally injected with CHST3 siRNA or negative control siRNA on day0 and 7 after intratracheal instillation of elastase. Histology, respiratory function, glycosaminoglycans (GAGs) content, bronchoalveolar lavage (BAL), elastin staining and gene expressions of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 mRNA were evaluated on day7 and/or day21.Results: CHST3 mRNA increased at day 7 and decreased thereafter in lung. CHST3 siRNA successfully inhibited the expression of CHST3 mRNA throughout the study and this was associated with significant reduction of GAGs and C6SPG. Airway destruction and respiratory function were improved by the treatment with CHST3 siRNA. CHST3 siRNA reduced the number of macrophages both in BAL and lung parenchyma and also suppressed the increased expressions of TNF-α and MMP-9 mRNA. Futhermore, CHST3 siRNA improved the reduction of the elastin in the alveolar walls.Conclusions: CHST3 siRNA diminishes accumulation of excessive macrophages and the mediators, leading to accelerate the functional recovery from airway damage by repair of the elastin network associated with pulmonary emphysema. [ABSTRACT FROM AUTHOR]