Pub Date : 2026-01-01DOI: 10.1016/j.alit.2025.10.004
Hiromichi Tamaki
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis for which achieving remission is the primary therapeutic goal. Historically, remission in EGPA was defined by the absence of active vasculitis, typically a Birmingham Vasculitis Activity Score (BVAS) of 0. However, this definition is insufficient as it overlooks the significant morbidity associated with long-term glucocorticoid (GC) therapy. Recent evidence highlights that even low-dose GCs carry substantial risks, challenging the traditional acceptance of remission on GC. This review summarizes the evolution of the remission concept in EGPA, highlighting the paradigm shift seen in recent pivotal clinical trials for biologics, which have incorporated stringent GC dose thresholds (e.g., prednisone ≤4 mg/day) into their primary endpoints. This reflects a growing consensus that minimizing GC exposure is a crucial component of a successful treatment outcome. Further, this review explores potential future components for remission criteria, such as organ-specific activity measures and patient-reported outcomes.
{"title":"Current definition of remission in eosinophilic granulomatosis with polyangiitis (EGPA) and future perspectives","authors":"Hiromichi Tamaki","doi":"10.1016/j.alit.2025.10.004","DOIUrl":"10.1016/j.alit.2025.10.004","url":null,"abstract":"<div><div>Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis for which achieving remission is the primary therapeutic goal. Historically, remission in EGPA was defined by the absence of active vasculitis, typically a Birmingham Vasculitis Activity Score (BVAS) of 0. However, this definition is insufficient as it overlooks the significant morbidity associated with long-term glucocorticoid (GC) therapy. Recent evidence highlights that even low-dose GCs carry substantial risks, challenging the traditional acceptance of remission on GC. This review summarizes the evolution of the remission concept in EGPA, highlighting the paradigm shift seen in recent pivotal clinical trials for biologics, which have incorporated stringent GC dose thresholds (e.g., prednisone ≤4 mg/day) into their primary endpoints. This reflects a growing consensus that minimizing GC exposure is a crucial component of a successful treatment outcome. Further, this review explores potential future components for remission criteria, such as organ-specific activity measures and patient-reported outcomes.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 26-31"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heterogeneity of asthma requires a personalized therapeutic approach. However, objective measurements, such as spirometry and fraction of exhaled nitric oxide (FeNO) for implementing treatable traits approach, are limited in low- and middle-income countries and non-specialist settings. To implement precision medicine even with minimal resources, we developed an algorithm using unsupervised machine learning techniques that estimates key treatable traits (airflow limitation, type 2 [T2] inflammation, and frequent exacerbations) based on an asthma patient-reported outcome (PRO).
Methods
We applied hierarchical clustering and Uniform Manifold Approximation and Projection (UMAP) to Asthma Control Questionnaire (ACQ)-5 including five residual symptoms from two asthma cohorts (the discovery cohort with 1697 patients and validation cohort with 157 patients).
Results
We identified five symptom clusters, characterized by key treatable traits: Cluster 1, minimal asthma symptoms; Cluster 2, a little symptom, mild airflow limitation; Cluster 3, predominant shortness of breath and wheezes, airflow limitation; Cluster 4, predominant morning symptoms and nocturnal awakening, T2 inflammation; and Cluster 5, all symptoms severe, airflow limitation, T2 inflammation and frequent exacerbations. The UMAP projections of ACQ-5 (five-dimensional) to two-dimensions allowed to visualize datapoints and clusters, which visually revealed that patients with poorly-controlled asthma were divided into Clusters 3, 4 and 5. These results were externally validated in an independent cohort.
Conclusions
Based on asthma PRO data, the developed algorithm categorized asthma patients into five symptom-based subtypes that provide insights into key treatable traits. Our data-driven digital health approach will extend precision medicine of asthma to medical facilities even in resource-constrained settings.
{"title":"Unsupervised identification of asthma symptom subtypes supports treatable traits approach","authors":"Kazuki Hamada , Takeshi Abe , Keiji Oishi , Yoriyuki Murata , Tsunahiko Hirano , Takahide Hayano , Masahiko Nakatsui , Yoshiyuki Asai , Kazuto Matsunaga","doi":"10.1016/j.alit.2025.06.004","DOIUrl":"10.1016/j.alit.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Heterogeneity of asthma requires a personalized therapeutic approach. However, objective measurements, such as spirometry and fraction of exhaled nitric oxide (FeNO) for implementing treatable traits approach, are limited in low- and middle-income countries and non-specialist settings. To implement precision medicine even with minimal resources, we developed an algorithm using unsupervised machine learning techniques that estimates key treatable traits (airflow limitation, type 2 [T2] inflammation, and frequent exacerbations) based on an asthma patient-reported outcome (PRO).</div></div><div><h3>Methods</h3><div>We applied hierarchical clustering and Uniform Manifold Approximation and Projection (UMAP) to Asthma Control Questionnaire (ACQ)-5 including five residual symptoms from two asthma cohorts (the discovery cohort with 1697 patients and validation cohort with 157 patients).</div></div><div><h3>Results</h3><div>We identified five symptom clusters, characterized by key treatable traits: Cluster 1, minimal asthma symptoms; Cluster 2, a little symptom, mild airflow limitation; Cluster 3, predominant shortness of breath and wheezes, airflow limitation; Cluster 4, predominant morning symptoms and nocturnal awakening, T2 inflammation; and Cluster 5, all symptoms severe, airflow limitation, T2 inflammation and frequent exacerbations. The UMAP projections of ACQ-5 (five-dimensional) to two-dimensions allowed to visualize datapoints and clusters, which visually revealed that patients with poorly-controlled asthma were divided into Clusters 3, 4 and 5. These results were externally validated in an independent cohort.</div></div><div><h3>Conclusions</h3><div>Based on asthma PRO data, the developed algorithm categorized asthma patients into five symptom-based subtypes that provide insights into key treatable traits. Our data-driven digital health approach will extend precision medicine of asthma to medical facilities even in resource-constrained settings.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 92-102"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sublingual immunotherapy (SLIT) involves the induction of allergen-specific regulatory T (Treg) cells in the oral mucosa-draining submandibular lymph nodes (LNs). However, their subsequent maintenance remains unclear, including the involvement of the gut microbiota. We aimed to investigate where and how SLIT-induced Treg cells are maintained to ensure tolerance to allergens.
Methods
We used a mouse model of prophylactic SLIT with ovalbumin as the allergen. SLIT-induced tolerance was assessed by suppressing delayed-type hypersensitivity (DTH) responses. The distribution of SLIT-induced Treg cells was determined based on their ability to suppress the DTH response upon adoptive transfer. The involvement of LNs and gut microbiota was assessed by the surgical removal of LNs and antibiotic depletion of the gut microbiota, respectively.
Results
Suppression of DTH by SLIT was impaired by surgical removal of submandibular LNs prior to SLIT. Functional SLIT-induced Treg cells were detected in submandibular LNs and gut-draining mesenteric LNs, however, not in skin-draining LNs or the spleen. Intriguingly, the surgical removal of mesenteric LNs alone after SLIT was sufficient to abolish the suppressive effect of SLIT. Gut microbiota depletion by antibiotic treatment after SLIT also abolished the suppressive effect of SLIT and impaired the maintenance of functional SLIT-induced Treg cells in mesenteric LNs.
Conclusions
Functional SLIT-induced Treg cells were maintained in mesenteric LNs in a gut microbiota-dependent manner. Thus, this study revealed a previously unrecognized role of the gut microbiota in SLIT and provided a rationale for targeting the gut environment to improve the efficacy and prolong the maintenance of SLIT.
{"title":"Gut microbiota contributes to the maintenance of sublingually induced regulatory T cells and tolerance in mice","authors":"Saka Winias , Kanan Bando , Boonnapa Temtanapat , Masato Nakano , Masahiro Saito , Shunji Sugawara , Mitsuko Komatsu , Akiyoshi Hirayama , Shinji Fukuda , Takaaki Abe , Kentaro Mizuta , Masahiro Iikubo , Yukinori Tanaka","doi":"10.1016/j.alit.2025.06.003","DOIUrl":"10.1016/j.alit.2025.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Sublingual immunotherapy (SLIT) involves the induction of allergen-specific regulatory T (Treg) cells in the oral mucosa-draining submandibular lymph nodes (LNs). However, their subsequent maintenance remains unclear, including the involvement of the gut microbiota. We aimed to investigate where and how SLIT-induced Treg cells are maintained to ensure tolerance to allergens.</div></div><div><h3>Methods</h3><div>We used a mouse model of prophylactic SLIT with ovalbumin as the allergen. SLIT-induced tolerance was assessed by suppressing delayed-type hypersensitivity (DTH) responses. The distribution of SLIT-induced Treg cells was determined based on their ability to suppress the DTH response upon adoptive transfer. The involvement of LNs and gut microbiota was assessed by the surgical removal of LNs and antibiotic depletion of the gut microbiota, respectively.</div></div><div><h3>Results</h3><div>Suppression of DTH by SLIT was impaired by surgical removal of submandibular LNs prior to SLIT. Functional SLIT-induced Treg cells were detected in submandibular LNs and gut-draining mesenteric LNs, however, not in skin-draining LNs or the spleen. Intriguingly, the surgical removal of mesenteric LNs alone after SLIT was sufficient to abolish the suppressive effect of SLIT. Gut microbiota depletion by antibiotic treatment after SLIT also abolished the suppressive effect of SLIT and impaired the maintenance of functional SLIT-induced Treg cells in mesenteric LNs.</div></div><div><h3>Conclusions</h3><div>Functional SLIT-induced Treg cells were maintained in mesenteric LNs in a gut microbiota-dependent manner. Thus, this study revealed a previously unrecognized role of the gut microbiota in SLIT and provided a rationale for targeting the gut environment to improve the efficacy and prolong the maintenance of SLIT.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 71-80"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There have been few epidemiological surveys regarding adult anaphylaxis in Japan. The aim of the study is to investigate the current condition in the diagnosis and management of adult anaphylaxis in Japan.
Methods
An observational, descriptive, cross-sectional study was conducted among physicians who belong to the Japanese Society for Cutaneous Immunology and Allergy and the Japanese Allergology Society, via cloud-based software. A 24-item questionnaire focused on the implementation of diagnostics and management of anaphylaxis, especially in adults.
Results
There were 537 departments that treated anaphylaxis, including 243 pediatrics, 156 dermatology, 124 internal medicine, and 14 allergy departments. Of the group, 362 departments treated adult patients with anaphylaxis, with 149 dermatology being the most common, followed by114 internal medicine, 85 pediatrics and 14 allergy departments. Big prefectures such as Tokyo have the most facilities. However, in terms of population ratio, it became clear that there was not necessarily more coverage in large cities. For anaphylaxis due to foods, specific IgE measurements were the most frequently performed at more than 90 % of all four departments, whereas skin tests and challenge tests were performed less than the IgE measurements at 56.9 % and 35.1 %, respectively. As for the reasons for not performing them, a lack of manpower was mostly cited, followed by lack of preparation for anaphylaxis before testing, unfamiliarity with testing methods, and low or no medical fees.
Conclusions
The survey revealed the uneven geographical distribution of medical departments and the chief barriers for implementation of the examination in adult anaphylaxis.
{"title":"National survey on diagnosis and treatment of adult anaphylaxis in Japan: The learning about anaphylaxis in adolescence and adulthood (LANA) survey Part 1","authors":"Naoko Inomata , Koremasa Hayama , Shunsuke Takahagi , Atsushi Fukunaga , Koji Masuda , Yuma Sunaga , Motohiro Ebisawa , Norito Katoh","doi":"10.1016/j.alit.2025.07.001","DOIUrl":"10.1016/j.alit.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>There have been few epidemiological surveys regarding adult anaphylaxis in Japan. The aim of the study is to investigate the current condition in the diagnosis and management of adult anaphylaxis in Japan.</div></div><div><h3>Methods</h3><div>An observational, descriptive, cross-sectional study was conducted among physicians who belong to the Japanese Society for Cutaneous Immunology and Allergy and the Japanese Allergology Society, via cloud-based software. A 24-item questionnaire focused on the implementation of diagnostics and management of anaphylaxis, especially in adults.</div></div><div><h3>Results</h3><div>There were 537 departments that treated anaphylaxis, including 243 pediatrics, 156 dermatology, 124 internal medicine, and 14 allergy departments. Of the group, 362 departments treated adult patients with anaphylaxis, with 149 dermatology being the most common, followed by114 internal medicine, 85 pediatrics and 14 allergy departments. Big prefectures such as Tokyo have the most facilities. However, in terms of population ratio, it became clear that there was not necessarily more coverage in large cities. For anaphylaxis due to foods, specific IgE measurements were the most frequently performed at more than 90 % of all four departments, whereas skin tests and challenge tests were performed less than the IgE measurements at 56.9 % and 35.1 %, respectively. As for the reasons for not performing them, a lack of manpower was mostly cited, followed by lack of preparation for anaphylaxis before testing, unfamiliarity with testing methods, and low or no medical fees.</div></div><div><h3>Conclusions</h3><div>The survey revealed the uneven geographical distribution of medical departments and the chief barriers for implementation of the examination in adult anaphylaxis.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 103-112"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The risk of asthma exacerbation is intrinsic to female patients. Enhanced type 2 immune responses are considered to be associated with sustained increased susceptibility to asthma exacerbation in female patients; however, the mechanisms mediating this relationship remain unclear.
Methods
Using a Dermatophagoides farinae-induced asthma mouse model, asthma-related features were evaluated. We focused on memory T cells and aimed to determine the cell types responsible for female-predominant long-term asthma exacerbations using a functional S1P1 receptor antagonist and parabiotic mouse model.
Results
Compared to male mice, female mice demonstrated aggravated asthma exacerbation 3 months after allergen re-exposure. Higher levels of Th2 cytokines and IL-33 were observed in the lungs of female mice than in those of male mice. Moreover, enhanced Il33 mRNA synthesis in female mice was attributable to LNGFR + airway epithelial cells. Increased IL-33 production or the female hormonal environment may have led to increased number of ST2+CD4+ memory T cells. Both 17β-estradiol and progesterone were associated with the expansion of these cells; however, only 17β-estradiol maintained elevated numbers of ST2+CD4+ memory T cells over time. The suppressed migration of ST2+CD4+ circulating memory T cells into the lungs attenuated asthmatic inflammation in female mice to levels comparable to those observed in male mice. In contrast, ST2+CD4+ tissue-resident memory T cells are attributable asthmatic inflammation in male mice.
Conclusions
Our findings suggest that the contribution of memory T cells to asthmatic inflammation varies depending on sex, and female predominance is attributable to an increased number of ST2+CD4+ circulating memory T cells.
{"title":"ST2+ effector memory helper T cells are responsible for long-term asthma exacerbation leading to female-predominant airway inflammation","authors":"Tomomitsu Miyasaka , Kaori Kawakami , Hiroyuki Tanaka , Fumi Shishido , Kaoru Toshima , Masayuki Seki , Chiaki Masuda-Suzuki , Tomohiro Arikawa , Masashi Sasaki , Naoko Nagano , Hideaki Morita , Kaori Dobashi-Okuyama , Tasuku Kawano , Tomoko Takahashi , Motoaki Takayanagi , Isao Ohno , Yutaka Nakamura","doi":"10.1016/j.alit.2025.08.001","DOIUrl":"10.1016/j.alit.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>The risk of asthma exacerbation is intrinsic to female patients. Enhanced type 2 immune responses are considered to be associated with sustained increased susceptibility to asthma exacerbation in female patients; however, the mechanisms mediating this relationship remain unclear.</div></div><div><h3>Methods</h3><div>Using a <em>Dermatophagoides farinae</em>-induced asthma mouse model, asthma-related features were evaluated. We focused on memory T cells and aimed to determine the cell types responsible for female-predominant long-term asthma exacerbations using a functional S1P<sub>1</sub> receptor antagonist and parabiotic mouse model.</div></div><div><h3>Results</h3><div>Compared to male mice, female mice demonstrated aggravated asthma exacerbation 3 months after allergen re-exposure. Higher levels of Th2 cytokines and IL-33 were observed in the lungs of female mice than in those of male mice. Moreover, enhanced <em>Il3</em>3 mRNA synthesis in female mice was attributable to LNGFR <sup>+</sup> airway epithelial cells. Increased IL-33 production or the female hormonal environment may have led to increased number of ST2<sup>+</sup>CD4<sup>+</sup> memory T cells. Both 17β-estradiol and progesterone were associated with the expansion of these cells; however, only 17β-estradiol maintained elevated numbers of ST2<sup>+</sup>CD4<sup>+</sup> memory T cells over time. The suppressed migration of ST2<sup>+</sup>CD4<sup>+</sup> circulating memory T cells into the lungs attenuated asthmatic inflammation in female mice to levels comparable to those observed in male mice. In contrast, ST2<sup>+</sup>CD4<sup>+</sup> tissue-resident memory T cells are attributable asthmatic inflammation in male mice.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that the contribution of memory T cells to asthmatic inflammation varies depending on sex, and female predominance is attributable to an increased number of ST2<sup>+</sup>CD4<sup>+</sup> circulating memory T cells.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 121-133"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.alit.2025.08.002
Shan Wang , Ge Peng , Alafate Abudouwanli , Mengyao Yang , Quan Sun , Wanchen Zhao , Arisa Ikeda , Yi Tan , Lin Ma , Hideoki Ogawa , Ko Okumura , François Niyonsaba
The epidermal immune microenvironment is a multifaceted system in which the interplay between the skin microbiome and antimicrobial peptides plays a pivotal role in sustaining skin homeostasis and preventing dysbiosis. Disruption of these interactions can lead to inflammatory skin conditions such as atopic dermatitis. This review aims to explore the complex mechanisms by which antimicrobial peptides and the skin microbiome communicate within the epidermal immune microenvironment, emphasizing causal dynamics and the dual role of antimicrobial peptides. This analysis opens new avenues for targeted interventions, including antimicrobial peptide modulation and microbiome-based therapies, to restore skin health and mitigate inflammatory skin disorders.
{"title":"The interaction between the skin microbiome and antimicrobial peptides within the epidermal immune microenvironment: Bridging insights into atopic dermatitis","authors":"Shan Wang , Ge Peng , Alafate Abudouwanli , Mengyao Yang , Quan Sun , Wanchen Zhao , Arisa Ikeda , Yi Tan , Lin Ma , Hideoki Ogawa , Ko Okumura , François Niyonsaba","doi":"10.1016/j.alit.2025.08.002","DOIUrl":"10.1016/j.alit.2025.08.002","url":null,"abstract":"<div><div>The epidermal immune microenvironment is a multifaceted system in which the interplay between the skin microbiome and antimicrobial peptides plays a pivotal role in sustaining skin homeostasis and preventing dysbiosis. Disruption of these interactions can lead to inflammatory skin conditions such as atopic dermatitis. This review aims to explore the complex mechanisms by which antimicrobial peptides and the skin microbiome communicate within the epidermal immune microenvironment, emphasizing causal dynamics and the dual role of antimicrobial peptides. This analysis opens new avenues for targeted interventions, including antimicrobial peptide modulation and microbiome-based therapies, to restore skin health and mitigate inflammatory skin disorders.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 42-51"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.alit.2025.07.003
Naoya Tanabe , Hisako Matsumoto
Airway mucus plugs are the main pathological and computed tomography (CT) findings that affect clinical outcomes in patients with asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Despite the introduction of biologics targeting type 2 inflammation, mucus plug removal remains challenging and understanding its pathogenesis is critical for improved management. In eosinophilic airways, elevated MUC5AC and eosinophil-derived molecules (galectin-10 and extracellular traps) cause highly viscoelastic plugs detectable as high-density regions on ultra-high-resolution CT. In neutrophilic airways, where phylum Proteobacteria and genus Haemophilus are predominant, excessive neutrophil elastase impairs mucociliary clearance, induces neutrophil extracellular traps (NETs), and promotes mucus overproduction. Since mucus plugs could be reservoirs for bacterial colonization, an altered airway microbiome and airway inflammation may be associated with mucus plugging. Phylum Firmicutes and genus Streptococcus are positively and genus Fusobacterium is negatively associated with mucus plugging in severe eosinophilic inflammation. Anaerobic commensals produce short-chain fatty acids, which suppress eosinophilic inflammation. In moderate eosinophilic inflammation, anaerobic commensals may be replaced by pathogenic bacteria of the phylum Proteobacteria and genus Haemophilus, which triggers severe neutrophilic inflammation and exacerbates mucus plugging. Finally, in eosinophilic inflammation, mucus plugs containing aggregated eosinophils may induce mechanical dilation of the airways. In contrast, the presence of mucus plugs in a neutrophilic milieu may reflect severe inflammation characterized by excessive neutrophil extracellular traps and degenerative tissue remodeling, which is consistent with the pathological features of bronchiectasis. This review provides clues regarding how inflammation and microbiome alterations interact with mucus plugging in chronic airway disease.
{"title":"From mucus plugging to airway dilatation in chronic airway diseases: A perspective on the contribution of the airway microbiome and inflammation","authors":"Naoya Tanabe , Hisako Matsumoto","doi":"10.1016/j.alit.2025.07.003","DOIUrl":"10.1016/j.alit.2025.07.003","url":null,"abstract":"<div><div>Airway mucus plugs are the main pathological and computed tomography (CT) findings that affect clinical outcomes in patients with asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Despite the introduction of biologics targeting type 2 inflammation, mucus plug removal remains challenging and understanding its pathogenesis is critical for improved management. In eosinophilic airways, elevated MUC5AC and eosinophil-derived molecules (galectin-10 and extracellular traps) cause highly viscoelastic plugs detectable as high-density regions on ultra-high-resolution CT. In neutrophilic airways, where phylum Proteobacteria and genus <em>Haemophilus</em> are predominant, excessive neutrophil elastase impairs mucociliary clearance, induces neutrophil extracellular traps (NETs), and promotes mucus overproduction. Since mucus plugs could be reservoirs for bacterial colonization, an altered airway microbiome and airway inflammation may be associated with mucus plugging. Phylum Firmicutes and genus <em>Streptococcus</em> are positively and genus <em>Fusobacterium</em> is negatively associated with mucus plugging in severe eosinophilic inflammation. Anaerobic commensals produce short-chain fatty acids, which suppress eosinophilic inflammation. In moderate eosinophilic inflammation, anaerobic commensals may be replaced by pathogenic bacteria of the phylum Proteobacteria and genus <em>Haemophilus</em>, which triggers severe neutrophilic inflammation and exacerbates mucus plugging. Finally, in eosinophilic inflammation, mucus plugs containing aggregated eosinophils may induce mechanical dilation of the airways. In contrast, the presence of mucus plugs in a neutrophilic milieu may reflect severe inflammation characterized by excessive neutrophil extracellular traps and degenerative tissue remodeling, which is consistent with the pathological features of bronchiectasis. This review provides clues regarding how inflammation and microbiome alterations interact with mucus plugging in chronic airway disease.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 32-41"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite advances in pharmacologic therapy, a subset of patients with bronchial asthma (BA) experience persistent symptoms. Multiple chemical sensitivity (MCS), a non-allergic condition triggered by low-level chemical exposures, may be responsible for asthma-like symptoms. Although epidemiological studies have reported a high co-prevalence of MCS and BA, clinical comparisons among patients with BA between those with and without MCS are limited. We aimed to characterize the clinical and symptomatic profiles of patients with BA and comorbid MCS.
Methods
This cross-sectional study included 100 patients with BA treated at Sagamihara Hospital. MCS-related symptoms were evaluated using the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Clinical data including serum total Immunoglobulin E (IgE) levels, eosinophil counts, pulmonary function, hospitalization frequency, comorbidities, and medications were collected by attending physicians. Fifteen patients who exceeded the QEESI MCS cut-off value (BA-MCS group) were compared with 30 age- and sex-matched controls without MCS (BA-control group).
Results
Compared to BA-controls, the BA-MCS group had strong symptoms in multiple organs other than the respiratory system (p = 0.000), exhibited significantly higher percentage forced expiratory volume (%FEV1) (p = 0.047), lower serum IgE levels (p = 0.028), more frequent hospitalizations (p = 0.002), and higher incidence of atopic dermatitis history (p = 0.001).
Conclusions
The BA-MCS group had a distinct phenotype characterized by preserved lung function, low IgE levels, systemic symptoms, and high disease burden. For these patients, a multidisciplinary approach addressing BA and MCS may be more effective than intensifying asthma pharmacotherapy alone.
{"title":"Clinical findings and subjective symptoms in patients with bronchial asthma and chemical hypersensitivity in Japan","authors":"Sachiko Hojo , Naomi Tsurikisawa , Kentaro Watai , Atsushi Mizukoshi , Yosiyuki Kuroiwa , Kenichi Azuma","doi":"10.1016/j.alit.2025.08.008","DOIUrl":"10.1016/j.alit.2025.08.008","url":null,"abstract":"<div><h3>Background</h3><div>Despite advances in pharmacologic therapy, a subset of patients with bronchial asthma (BA) experience persistent symptoms. Multiple chemical sensitivity (MCS), a non-allergic condition triggered by low-level chemical exposures, may be responsible for asthma-like symptoms. Although epidemiological studies have reported a high co-prevalence of MCS and BA, clinical comparisons among patients with BA between those with and without MCS are limited. We aimed to characterize the clinical and symptomatic profiles of patients with BA and comorbid MCS.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 100 patients with BA treated at Sagamihara Hospital. MCS-related symptoms were evaluated using the Quick Environmental Exposure and Sensitivity Inventory (QEESI). Clinical data including serum total Immunoglobulin E (IgE) levels, eosinophil counts, pulmonary function, hospitalization frequency, comorbidities, and medications were collected by attending physicians. Fifteen patients who exceeded the QEESI MCS cut-off value (BA-MCS group) were compared with 30 age- and sex-matched controls without MCS (BA-control group).</div></div><div><h3>Results</h3><div>Compared to BA-controls, the BA-MCS group had strong symptoms in multiple organs other than the respiratory system (p = 0.000), exhibited significantly higher percentage forced expiratory volume (%FEV<sub>1</sub>) (p = 0.047), lower serum IgE levels (p = 0.028), more frequent hospitalizations (p = 0.002), and higher incidence of atopic dermatitis history (p = 0.001).</div></div><div><h3>Conclusions</h3><div>The BA-MCS group had a distinct phenotype characterized by preserved lung function, low IgE levels, systemic symptoms, and high disease burden. For these patients, a multidisciplinary approach addressing BA and MCS may be more effective than intensifying asthma pharmacotherapy alone.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 134-141"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dupilumab is approved in Japan for the treatment of atopic dermatitis in patients aged 6 months to 18 years. However, long-term data are lacking in this patient population. Here we report the final analysis of a long-term open-label extension (OLE) of a phase 3 study that assessed dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis inadequately controlled with existing therapies.
Methods
Study participants were randomly assigned to dupilumab or placebo with concomitant topical corticosteroids for 16 weeks, then to open-label dupilumab until approval or for 3 years, whichever came first.
Results
Of the 62 participants randomized, 60 entered the OLE and continued to receive dupilumab (n = 28) or initiated dupilumab (n = 32). Improvements in clinical severity scores seen with dupilumab at Week 16 persisted up to Week 116, as confirmed by several efficacy endpoints (proportion of patients who achieved ≥75 % or ≥90 % improvement in Eczema Area and Severity Index [EASI] score, and Investigator's Global Assessment score of 0/1, and percent change in EASI scores from baseline). During the dupilumab exposure period, 93.5 % of patients experienced a treatment-emergent adverse event (TEAE). No adverse events leading to death, or TEAEs leading to study treatment discontinuation were observed during the OLE period. One (3.1 %) treatment-emergent positive anti-drug antibody response was observed during the OLE period in the placebo/dupilumab group.
Conclusions
This analysis supports the long-term efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis.
{"title":"Long-term efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: Results from a phase 3 open-label extension study","authors":"Yoko Kataoka , Motohiro Ebisawa , Akio Tanaka , Mizuho Nagao , Elizabeth Laws , Hisakatsu Nawata , Kazuhiko Arima , Daisuke Watanabe , Xin Lu , Jennifer Maloney , Ariane Dubost-Brama , Ashish Bansal , Kenji Yahata","doi":"10.1016/j.alit.2025.09.002","DOIUrl":"10.1016/j.alit.2025.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Dupilumab is approved in Japan for the treatment of atopic dermatitis in patients aged 6 months to 18 years. However, long-term data are lacking in this patient population. Here we report the final analysis of a long-term open-label extension (OLE) of a phase 3 study that assessed dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis inadequately controlled with existing therapies.</div></div><div><h3>Methods</h3><div>Study participants were randomly assigned to dupilumab or placebo with concomitant topical corticosteroids for 16 weeks, then to open-label dupilumab until approval or for 3 years, whichever came first.</div></div><div><h3>Results</h3><div>Of the 62 participants randomized, 60 entered the OLE and continued to receive dupilumab (n = 28) or initiated dupilumab (n = 32). Improvements in clinical severity scores seen with dupilumab at Week 16 persisted up to Week 116, as confirmed by several efficacy endpoints (proportion of patients who achieved ≥75 % or ≥90 % improvement in Eczema Area and Severity Index [EASI] score, and Investigator's Global Assessment score of 0/1, and percent change in EASI scores from baseline). During the dupilumab exposure period, 93.5 % of patients experienced a treatment-emergent adverse event (TEAE). No adverse events leading to death, or TEAEs leading to study treatment discontinuation were observed during the OLE period. One (3.1 %) treatment-emergent positive anti-drug antibody response was observed during the OLE period in the placebo/dupilumab group.</div></div><div><h3>Conclusions</h3><div>This analysis supports the long-term efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"75 1","pages":"Pages 142-149"},"PeriodicalIF":6.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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