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Purpose To characterize the clinical phenotypes of severe eosinophilic asthma based on early responsiveness to benralizumab in terms of forced expiratory volume in 1 second (FEV1) improvement. Patients and methods Sixty-four participants diagnosed with severe eosinophilic asthma and who had completed 4 months of benralizumab treatment were included in this analysis. Pre-treatment clinical factors were compared between responders and non-responders according to improvements in ACT or FEV1. Correlations between the sums of increased Type 2-related inflammatory parameters and changes of ACT or FEV1 were also evaluated before and after the 4-month treatment. A two-step cluster analysis was performed to identify distinct phenotypes related to benralizumab responsiveness in terms of FEV1. Results At the 4-month timepoint, all parameters, except for FeNO, were significantly improved after benralizumab treatment. FEV1 responders were associated with higher levels of Type 2-related inflammatory parameters. An improvement in FEV1 but not in ACT was clearly associated with increases in the sums of increased type 2-related inflammation parameters (p = 0.0001). The cluster analysis identified 5 distinct phenotypes of severe eosinophilic asthma according to the variable FEV1 responsiveness to benralizumab. The greatest response was found in the distinct phenotype of severe eosinophilic asthma, which was characterized by modest increase in total IgE and FeNO relative to blood eosinophils with least exposure to smoking. Conclusion This study, to the best of our knowledge, is the first cluster analysis to report distinct phenotypes related to clinical benralizumab response in a real-world population with severe eosinophilic asthma. These results may help to predict responsiveness to benralizumab in patients with severe eosinophilic asthma.

Reports of crizotinib‐induced pleural effusion in non‐small cell lung cancer (NSCLC) are limited. A 35‐year‐old Japanese woman was diagnosed with ROS1‐rearranged lung adenocarcinoma (primary left lower lobe, cT4N3M1c). Crizotinib was administered as first‐line therapy, and the primary and mediastinal hilar lymph node metastases rapidly shrank. On the fourth day of treatment, chest X‐ray demonstrated contralateral pleural effusion. On the 41st day of treatment, crizotinib was discontinued because of grade 3 neutropenia. Examination including surgical thoracoscopy did not reveal causative findings, and the continued cessation of drug administration enabled the right pleural effusion to decrease gradually and disappear, suggesting that this event was a side effect of crizotinib. The disease did not progress even though the drug was withdrawn for more than one year. In conclusion, crizotinib was considered to cause pleural effusion as an adverse event in a case of ROS1‐rearranged lung adenocarcinoma with a complete response.

Recently, it has become clear that inhaled indium-tin oxide causes emphysematous as well as interstitial changes in the lung. Here, we present a 59-year-old male ex-smoker, quitting smoking at the age of 55, who had been engaged in indium-tin oxide processing from 27 to 37 years of age, with 22 years having passed since the final exposure to indium. He was found to have a high serum indium concentration and KL-6. Furthermore, bilateral centrilobular emphysema was recognized in HRCT. After transferring jobs to a non-indiumtin oxide section, KL-6 returned to a normal level within 4 years, whereas neither serum indium concentration nor emphysema had decreased to normal despite 22 years having passed since the exposure ended. At the age of 59, a thoracoscopic lung biopsy was performed to assess the contribution of smoking and that of indium to the lung destruction.The pathological findings demonstrated cholesterol granulomas with the accumulation of macrophages and multinucleated giant cells that had phagocytosed particles. Together with the typical findings of indium lung, fibrotic and emphysematous changes were observed. The elemental analysis of the biopsied specimens revealed excessive deposition of indium throughout the airways, interstitial spaces and alveoli. The pathological findings of this case may be the result of two kinds of pulmonary damage, i.e., smoking and indium. This report indicates that occupationally-inhaled indium could remain in the lung for as long as 22 years and continue to insult the lung tissue with inflammation caused by smoking.