Takehiro Uemura

Background/Objectives: The rates and predictors of clinical remission, a novel and practical therapeutic goal in severe asthma, have been inconsistently reported across studies. Data on clinical remission in Japanese patients remain limited. The aim of this study was to assess the rate of four-component clinical remission and its predictors in Japanese adult patients with severe asthma. Methods: This retrospective study enrolled adult patients with severe asthma who had initiated biologic therapy at least 12 months prior to inclusion at Nagoya City University Hospital. The primary endpoint was the achievement rate of four-component clinical remission, defined as (1) no maintenance oral corticosteroids (OCS); (2) no exacerbations for 12 months; (3) Asthma Control Test (ACT) score ≥ 20; and (4) forced expiratory volume in one second (FEV₁) ≥ 80% of predicted. The secondary endpoint was to identify factors, including airway structural indices measured using chest computed tomography (CT), associated with clinical remission at 12 months. Results: Among 87 patients with severe asthma, 26 (30%) achieved four-component clinical remission after 12 months of biologic therapy. In univariate analysis, clinical remission was more frequently achieved in patients with chronic rhinosinusitis, higher FEV₁ (% predicted), higher blood eosinophil counts, higher ACT scores, fewer exacerbations in the previous year, higher Lund–Mackay scores, and smaller airway wall thickness and luminal areas on CT (all p < 0.05). Multivariate analysis revealed that higher blood eosinophil counts and fewer exacerbations in the previous year were independently associated with clinical remission (both p < 0.05). Conclusions: After 12 months of biologic therapy, 30% of patients with severe asthma achieved four-component clinical remission. Higher blood eosinophil counts and fewer prior exacerbations were associated with higher remission rates.

Suzuki T, et al. Allergy Asthma Immunol Res. 2026 May;18(3):362-378. https://doi.org/10.4168/aair.2026.18.3.362

Summary This study investigated the association between ATP-binding cassette (ABC) transporter gene polymorphisms and Epidermal Growth Factor Receptor (EGFR)- Tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC). Our goal was to determine if these genetic variations could serve as valuable biomarkers for predicting treatment efficacy. We examined the associations between ABC transporter mRNA expression and EGFR-TKI sensitivity in 16 NSCLC cell lines. Expression of ABCB1, ABCG2, ABCC10, and ABCC11 was quantified by real-time PCR and correlated with IC₅₀ values of gefitinib and osimertinib. Additionally, associations between transporter gene single nucleotide polymorphisms (SNPs) (ABCB1 C1236T, ABCB1 C3435T, ABCG2 C421A, ABCC10 T2843C, ABCC11 G538A) and EGFR-TKI sensitivity were evaluated. To assess clinical relevance, blood samples from 109 gefitinib/erlotinib- and 54 osimertinib-treated patients were analyzed for these SNPs. While no significant correlation was found between mRNA expression and IC₅₀ values in cell lines, we did find that specific SNPs significantly correlated with drug cytotoxicity in vitro. Clinically, the ABCB1 C1236T T/T genotype was associated with prolonged PFS in patients on first-generation EGFR-TKIs, while the ABCC10 T2843C T/T genotype was linked to longer PFS with third-generation EGFR-TKIs. These findings suggest that ABC transporter SNPs could be valuable biomarkers for personalized medicine in NSCLC. These findings suggest that ABC transporter SNPs may serve as valuable biomarkers for predicting EGFR-TKI efficacy in NSCLC patients with EGFR mutations, which will contribute to personalized medicine.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive cancer with limited treatment options and poor prognosis. Although immunotherapy with ipilimumab (IPI) and nivolumab (NIVO) has the potential to improve outcomes, disease progression, including recurrent pleural effusions, often occurs during or after the initial treatment. OK‑432, an immunotherapeutic agent, is commonly used for pleurodesis to control malignant pleural effusions; however, its role in combination with immune checkpoint inhibitors (ICIs) remains underexplored. The present report describes 2 MPM cases in which patients initially responded to IPI and NIVO, but experienced disease progression. Following intrathoracic administration of OK‑432, the patients were successfully rechallenged with ICI therapy. Both cases exhibited sustained disease control and resolution of pleural effusions. These findings suggested that OK‑432 may modulate immune responses and potentially enhance the efficacy of ICIs. Further studies are warranted to validate the synergistic potential of OK‑432 and ICIs in MPM and other thoracic malignancies.

Background: When considering the effects of dupilumab on severe chronic rhinosinusitis with nasal polyps (CRSwNPs), dupilumab is expected to achieve CRSwNPs remission. The aim of this study was to assess the rate of remission of CRSwNPs with comorbid asthma and its predictors on a 24-month course of dupilumab. Methods: Adult patients with severe CRSwNPs and comorbid asthma who had completed a 24-month course of dupilumab were included in this post hoc analysis. The primary outcome was the rate of CRSwNPs remission at 12 and 24 months of dupilumab. The secondary outcome was to identify factors associated with CRSwNPs remission at 12 and 24 months. Based on the European criteria and a previous definition, remission was defined as the absence of symptoms, improved quality of life, no need for surgery, no exacerbations, recovery of olfactory function, and inactive disease by nasal endoscopy for ≥12 months. A rigorous six-component remission, including olfactory testing, was initially used. Results: Of 16 patients, 4 (25%) and 5 (31%) achieved six-component remission of CRSwNPs at 12 and 24 months, respectively. Patients with shorter disease duration and better olfactory function at baseline achieved six-component remission of CRSwNPs more frequently than those without at 24 months (both p < 0.05). Conclusions: Remission of severe CRSwNPs with comorbid asthma is attainable with a 24-month course of dupilumab.

We report a case of a 69‐year‐old woman with pleural mesothelioma presenting in the posterior mediastinum with a maximum diameter of 25 cm. She had a chronic cough and a pleural effusion was noted on chest X‐ray. The examination of the effusion showed high hyaluronic acid levels, and mesothelioma was suspected. A chest computed tomography scan showed a huge mediastinal mass, which caused rapid progression of respiratory failure and compression of the heart. Sufficient tissue samples could not be obtained before death. The patient died approximately 1 month after the initial visit, and a pathological autopsy was performed. The diagnosis of malignant pleural mesothelioma was made. Malignant pleural mesothelioma with a huge posterior mediastinal mass such as in this case is considerably rare; however, it is a rapidly progressing form of the disease and is reported here as an important differential diagnosis for mediastinal tumours.

Purpose Determining whether patients’ unrealistic expectations of chemotherapy as a cure were associated with their perception of the disclosure of incurability. Methods This prospective study included consecutive patients with pretreated non-small cell lung cancer from four study sites. Patients and their oncologists were asked whether they perceived the disclosure of cancer incurability. Patients were also asked if they thought that chemotherapy was curative. We followed up on whether the deceased patients received specialized palliative care 14 months after their last enrollment. Multiple regression analyses were conducted to examine the association between the expectation of chemotherapy as a cure and patient/oncologist-reported perceptions of the disclosure of incurability. Results We analyzed 200 patients, 77 (38.5%) of whom had unrealistic expectations of a cure. Based on patients’ perceptions, incurability was disclosed to 138 (69.0%) patients, and based on their oncologists’ perceptions, incurability was disclosed to 185 (92.5%) patients (patient/oncologist agreements, κ = 0.19). Patients without a perception of the oncologist’s disclosure of incurability—regardless of their oncologist’s perception—were more likely to have unrealistic expectations of a cure than patients for whom both patient and oncologist perceptions were present. Patients who had unrealistic expectations of chemotherapy as a cure were shown to be significantly less likely to have received specialized palliative care, after adjusting for covariates (adjusted OR, 0.45; 95% CI, 0.23–0.91; p = .027). Conclusion Oncologists’ disclosure of incurability was not fully recognized by patients, and expectations of chemotherapy as a cure were associated with patients’ perception of the disclosure of incurability.

Background: Immune checkpoint inhibitors (ICIs) can cause severe immune‐related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs.Methods: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti‐PD‐1, anti‐PD‐L1, or anti‐CTLA‐4 plus anti‐PD‐1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non‐irAE group). Eosinophils were examined before the two‐course treatment.Results: Patients in the irAE group who received anti‐PD‐1 or anti‐CTLA‐4 plus anti‐PD‐1 therapy had higher eosinophils before the two‐course treatment than those in the non‐irAE group (p < 0.05). The eosinophils in the anti‐PD‐L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non‐irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79–3.67).Conclusion: An increased eosinophil before the two‐course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Background: Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non‐small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow‐on next‐generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing.Methods: Patients with untreated advanced (Stage IIIB–IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single‐plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes.Results: Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre‐defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0–41.1, p < 0.001 [one‐sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5–17 days).Conclusion: Rapid follow‐on comprehensive testing of ctDNA should be considered prior to first‐line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single‐plex tissue testing.

Purpose: Recently, single-inhaler triple therapy (SITT) has demonstrated efficacy in patients with uncontrolled asthma who were symptomatic despite treatment with inhaled corticosteroids/long-acting β 2 agonists. However, the characteristics of patients who benefit from SITT remain unclear in the real-world. The aim of this study was to examine the predictors of responsiveness to SITT in patients with asthma. Patients and Methods: A total of 45 patients with asthma who had regularly visited our respiratory clinic and were started on SITT from March 2019 to March 2021 were retrospectively analyzed. Patients’ demographic characteristics, residual respiratory symptoms, type 2 biomarkers, and lung function before SITT were assessed from the patients’ medical records. Predictors of responsiveness to four-week SITT were evaluated in these patients. The definition of responders was based on the physician-assessed global evaluation of treatment effectiveness. Results: Thirty-four (75%) of 45 patients were identified as responders to SITT. Non-responders showed significantly lower forced vital capacity (FVC) (%predicted) values, and complained of dyspnea more frequently than responders before SITT (p = 0.01 and p = 0.02, respectively). There were no significant differences in demographic characteristics and type 2 biomarkers between responders and non-responders. Clinical predictors of poor response to SITT were residual dyspnea (OR = 0.14, p = 0.02), low FVC (%predicted) values (OR = 1.05, p = 0.01), and FVC (%predicted) < 80% (OR = 0.11, p = 0.02). Multivariate analysis showed that poor response to SITT was associated with residual dyspnea before SITT (OR = 0.14, p = 0.02). On the other hand, patients with residual dyspnea had significantly lower FEF_{25– 75} (%predicted) values than patients without residual dyspnea before SITT (p = 0.04). Conclusion: Residual dyspnea, reflecting small airways dysfunction, may predict poor responsiveness to short-term SITT in patients with asthma.