Asthma is a heterogeneous disease characterized by chronic airway inflammation. Group 2 innate lymphoid cells (ILC2) play an important role in the pathogenesis of asthma. ILC2s lack antigen-specific receptors and respond to epithelial-derived cytokines, leading to the induction of airway eosinophilic inflammation in an antigen-independent manner. Additionally, ILC2s might be involved in the mechanism of steroid resistance. Numerous studies in both mice and humans have shown that ILC2s induce airway inflammation through inflammatory signals, including cytokines and other mediators derived from immune or non-immune cells. ILC2s and T helper type 2 (Th2) cells collaborate through direct and indirect interactions to organize type 2 immune responses. Interestingly, the frequencies or numbers of ILC2 are increased in the blood and bronchoalveolar lavage fluid of asthma patients, and the numbers of ILC2s in the blood and sputum of severe asthmatics are significantly larger than those of mild asthmatics. These findings may contribute to the regulation of the immune response in asthma. This review article highlights our current understanding of the functional role of ILC2s in asthma.

Eosinophilic asthma is the most prevalent and well-defined phenotype of asthma. Despite a majority of patients responding to corticosteroid therapy and T2 biologics, there remains a subset that have recurrent asthma exacerbations, highlighting a need for additional therapies to fully ameliorate airway eosinophilia. Group 2 innate lymphoid cells (ILC2) are considered key players in the pathogenesis of eosinophilic asthma through the production of copious amounts of type 2 cytokines, namely IL-5 and IL-13. ILC2 numbers are increased in the airways of asthmatics and with the greatest numbers of activated ILC2 detected in sputa from severe prednisone-dependent asthma with uncontrolled eosinophilia. Although epithelial-derived cytokines are important mediators of ILC2 activation, emerging evidence suggests that additional pathways stimulate ILC2 function. The tumor necrosis factor super family (TNFSF) and its receptors (TNFRSF) promote ILC2 activity. In this review, we discuss evidence supporting a relationship between ILC2 and TNFSF/TNFRSF axis in eosinophilic asthma and the role of this relationship in severe asthma with airway autoimmune responses.

Mepolizumab, a humanized anti‐IL‐5 monoclonal antibody used for severe asthma, results in a reduced rate of asthma exacerbation, improved lung function, reduced oral corticosteroid use, and improved quality of life. A 62‐year‐old man using high‐dose inhaled corticosteroid visited our hospital because of poorly‐controlled asthma. He had eosinophilia in peripheral blood and sputum, and high levels of fraction of exhaled nitric oxide. Therefore, he was treated with mepolizumab for severe asthma. Mepolizumab treatment resulted in significantly improved pulmonary function and reduced frequencies of asthma exacerbations. Because of his good asthma control, mepolizumab treatment was discontinued after 3 years. Since discontinuing mepolizumab, his asthma control has remained without exacerbation. Previous studies suggest that mepolizumab should be continued to sustain clinical benefits. However, cases of long‐term controlled asthma have not been reported after mepolizumab withdrawal, and our case may be instructive.

A 75‐year‐old woman presented at our hospital with bilateral visual impairment. Ophthalmological examination revealed multiple choroidal tumours. Chest computed tomography revealed a tumour shadow in the right lower lobe and multiple lymph node metastases in the mediastinum and pulmonary hilum. Following a detailed examination, the patient was diagnosed with primary lung adenocarcinoma (cT1cN3M1c Stage IVB) with choroid metastases. The tumour proportion score of programmed death ligand 1 (PD‐L1) was 1% and EGFR exon 20 insertion mutations were also detected. The patient was administered combination chemotherapy with nivolumab and ipilimumab. Primary lung and metastatic tumours, including the choroid, were reduced, and visual disturbances improved completely. Herein, we describe a rare case in which a combination of chemotherapy with nivolumab and ipilimumab significantly reduced vision loss due to choroidal metastasis.

Aim: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Patients with EGPA are treated with systemic glucocorticoids and immunosuppressive drugs to induce and maintain remission. However, most patients relapse after tapering glucocorticoids, and there are refractory cases with inadequate response to glucocorticoids. Mepolizumab, a humanized anti-IL-5 antibody, is approved for relapsing or refractory EGPA. Furthermore, recent studies have reported the efficacy of benralizumab, a humanized anti-IL-5 receptor α antibody, in EGPA. Here, we investigate the efficacy of biologics on consecutive cases of EGPA. Methods: We retrospectively collected patients with EGPA treated with mepolizumab in addition to glucocorticoids at the Department of Pulmonary Medicine in Kagoshima University Hospital and Imakiire General Hospital. In this study, we compared the effects of biologics on inflammatory parameters between pre- and post-treatment of biologics in patients with EGPA. Results: Ten patients were included in the study. All patients were treated with mepolizumab, and one was switched to benralizumab later. Treatment with biologics markedly reduced EGPA relapse from 70% (pre-treatment) to 20% (post-treatment), Birmingham Vasculitis Activity Score from 8.4 to 4.0, peripheral blood eosinophil counts from 470.3 /µL to 40.5 /µL, and glucocorticoid doses from 7.3 mg/dL to 1.6 mg/dL. In contrast, lung function and fractional exhaled nitric oxide levels were not affected by treatment with biologics. Furthermore, the duration of biologics was positively correlated with symptom improvement. Conclusions: Treatment with mepolizumab for EGPA was effective in glucocorticoid sparing, symptom reduction, and relapse prevention. Mepolizumab is expected to reduce the risk of glucocorticoid-related adverse events. Therefore, continued administration as well as early intervention with mepolizumab for EGPA might be important to conserve future medical resources and control the disease.

A 65-year-old man with dyspnea and hemoptysis presented with a right upper lobe mass associated with enlarged mediastinal lymph nodes and bilateral pulmonary nodules on chest computed tomography (CT), suspected lung cancer. Bronchial and CT-guided biopsies revealed poorly differentiated carcinoma. His condition deteriorated rapidly before a definitive diagnosis could be made. Autopsy revealed primary mediastinal choriocarcinoma. Primary mediastinal choriocarcinomas are rare, difficult to diagnose early and have a poor prognosis. In patients with a tumor expanding across the lung and mediastinum and exhibiting pathologic findings of a pooly differentiated carcinoma, we should consider choriocarcinoma, evaluating the serum β-human chorionic gonadotropin levels.