Carmen Venegas Garrido, Manali Mukherjee, Sarah Svenningsen, Parameswaran Nair
{"title":"Eosinophil-mucus interplay in severe asthma: Implications for treatment with biologicals","authors":"Carmen Venegas Garrido, Manali Mukherjee, Sarah Svenningsen, Parameswaran Nair","doi":"10.1016/j.alit.2024.03.001","DOIUrl":"10.1016/j.alit.2024.03.001","url":null,"abstract":"<div><p>Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The predominant mucins in human mucus, MUC5AC and MUC5B, are secreted by specialized cells within the airway epithelium both in normal conditions and in response to various stimuli. Their relative proportions are correlated with specific inflammatory responses and disease mechanisms. The dysregulation of mucin expression is implicated in numerous respiratory diseases, including asthma, COPD, and cystic fibrosis, where the pathogenic role of mucus has been extensively described yet often overlooked. In airway diseases, excessive mucus production or impaired mucus clearance leads to mucus plugging, with secondary airway occlusion that contribute to airflow obstruction, asthma severity and poor control. Eosinophils and Charcot Leyden crystals in sputum contribute to the mucus burden and tenacity. Mucin may also contribute to eosinophil survival. Other mechanisms, including eosinophil-independent IL-13 release, mast-cell activation and non-type-2 (T2) cytokines, are also likely to participate in mucus pathobiology. An accurate assessment of mucus and its clinical and functional consequences require a thorough approach that includes evaluation of cellular predominance in sputum, airway cytokines and other inflammatory markers, mucus characteristics and composition and structural and functional impact measured by advanced lung imaging. This review, illustrated with clinical scenarios, provides an overview of current methods to assess mucus and its relevance to the choice of biologics to treat patients with severe asthma.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 351-361"},"PeriodicalIF":6.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000182/pdfft?md5=d635d13d9bd94db1f60e301b0de24772&pid=1-s2.0-S1323893024000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of dupilumab for airway hypersecretion and airway wall thickening in patients with moderate-to-severe asthma: A prospective, observational study","authors":"Tomoko Tajiri , Motohiko Suzuki , Hirono Nishiyama , Yoshiyuki Ozawa , Ryota Kurokawa , Norihisa Takeda , Keima Ito , Kensuke Fukumitsu , Yoshihiro Kanemitsu , Yuta Mori , Satoshi Fukuda , Takehiro Uemura , Hirotsugu Ohkubo , Masaya Takemura , Ken Maeno , Yutaka Ito , Tetsuya Oguri , Kenji Izuhara , Akio Niimi","doi":"10.1016/j.alit.2024.02.002","DOIUrl":"10.1016/j.alit.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><p>Dupilumab has clinical effects in patients with moderate-to-severe asthma. When considering interleukin (IL)-4 and IL-13 signaling, effects of dupilumab on airway mucus hypersecretion and airway remodeling are expected, but they have been reported in only a few short-term studies. Its efficacy for airway hyperresponsiveness (AHR) remains unknown. We comprehensively assessed the efficacy of dupilumab, especially for subjective and objective measures of airway mucus hypersecretion and airway dimensions in moderate-to-severe asthmatic patients.</p></div><div><h3>Methods</h3><p>In 28 adult patients with moderate-to-severe uncontrolled asthma, the comprehensive efficacy of 48-week dupilumab treatment, including the Cough and Sputum Assessment Questionnaire (CASA-Q), radiological mucus scores and airway dimensions on computed tomography (CT), was assessed prospectively. Treatment responsiveness to dupilumab was analyzed.</p></div><div><h3>Results</h3><p>With 48-week dupilumab treatment, all four cough and sputum domain scores of CASA-Q improved significantly. Radiological mucus scores and airway wall thickening on CT were significantly decreased. The decreases in mucus scores were significantly associated with improvements in Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire (AQLQ) overall scores, airway obstruction, and airway type 2 inflammation. When defined by > 0.5 improvement in AQLQ overall scores, 18 patients (64%) were identified as responders.</p></div><div><h3>Conclusions</h3><p>Dupilumab reversed subjective and objective measures of airway mucus hypersecretion and some aspects of airway remodeling in patients with moderate-to-severe uncontrolled asthma.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 406-415"},"PeriodicalIF":6.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000169/pdfft?md5=998de0273c82bd12812db9d9bb47bbfa&pid=1-s2.0-S1323893024000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma","authors":"Yusuke Hayashi , Naoya Tanabe , Hisako Matsumoto , Kaoruko Shimizu , Ryo Sakamoto , Tsuyoshi Oguma , Hironobu Sunadome , Atsuyasu Sato , Susumu Sato , Toyohiro Hirai","doi":"10.1016/j.alit.2024.01.013","DOIUrl":"10.1016/j.alit.2024.01.013","url":null,"abstract":"<div><h3>Background</h3><p>Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma.</p></div><div><h3>Methods</h3><p>The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored.</p></div><div><h3>Results</h3><p>Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20–35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence.</p></div><div><h3>Conclusions</h3><p>Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 397-405"},"PeriodicalIF":6.8,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000157/pdfft?md5=6336b96d162de606b9647933894c8103&pid=1-s2.0-S1323893024000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis","authors":"Minori Sasakura , Hitoshi Urakami , Kota Tachibana , Kenta Ikeda , Ken-ichi Hasui , Yoshihiro Matsuda , Ko Sunagawa , Daisuke Ennishi , Shuta Tomida , Shin Morizane","doi":"10.1016/j.alit.2023.12.006","DOIUrl":"10.1016/j.alit.2023.12.006","url":null,"abstract":"<div><h3>Background</h3><p>Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders.</p></div><div><h3>Methods</h3><p>Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the <em>in vivo</em> study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the <em>in vitro</em> study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines.</p></div><div><h3>Results</h3><p>AP-1/c-Jun was phosphorylated at skin lesions in AD patients. <em>In vivo</em>, topical T-5224 application inhibited ear swelling (P < 0.001), restored <em>filaggrin</em> (<em>Flg</em>) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed <em>Il17a</em> and <em>l17f</em> expression, whereas baricitinib did not. Baricitinib suppressed <em>Il4, Il19, Il33</em> and <em>Ifnb</em> expression, whereas T-5224 did not. <em>Il1a, Il1b, Il23a, Ifna, S100a8,</em> and <em>S100a9</em> expression was cooperatively downregulated following the combined use of T-5224 and baricitinib. <em>In vitro,</em> T-5224 restored the expression of <em>FLG</em> and <em>loricrin (LOR)</em> (P < 0.05) and suppressed <em>IL33</em> expression (P < 0.05) without affecting cell viability and cytotoxicity.</p></div><div><h3>Conclusions</h3><p>Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 2","pages":"Pages 323-331"},"PeriodicalIF":6.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023001417/pdfft?md5=0807f48bc05fab1f1d3ae6c04dce9c29&pid=1-s2.0-S1323893023001417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of diesel exhaust particle-induced cellular senescence in the development of asthma in young and old mice","authors":"Hyun Seung Lee , Heung-Woo Park","doi":"10.1016/j.alit.2024.01.010","DOIUrl":"10.1016/j.alit.2024.01.010","url":null,"abstract":"<div><h3>Background</h3><p>Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced cellular senescence on the development of asthma according to age have not been thoroughly studied.</p></div><div><h3>Methods</h3><p>We first confirmed that DEP induced cellular senescence in mouse lungs, and then that DEP-induced cellular senescence followed by intranasal instillation of a low-dose house dust mite (HDM) allergen resulted in murine asthma. Second, we examined age-dependent differential effects using 6-week-old (young) and 18-month-old mice (old), and tested whether the mammalian target of the rapamycin (mTOR) pathway plays an important role in this process. Finally, we performed <em>in vitro</em> experiments using human bronchial epithelial cells (HBEC) originating from young and elderly adults to identify the underlying mechanisms.</p></div><div><h3>Results</h3><p>DEP induced cellular senescence in the airway epithelial cells of young and old mice characterized by increased senescence-associated beta-galactosidase, S100A8/9, and high mobility group box 1 (HMGB1) expressions. DEP-induced cellular senescence with subsequent exposure to a low-dose HDM allergen resulted in asthma in young and old mice. Rapamycin (mTOR pathway inhibitor) administration before DEP instillation significantly attenuated these asthmatic features. In addition, after treatment with a low-dose HDM allergen, S100A9 and HMGB1 over-expressed HBEC originating from young and elderly adults greatly activated co-cultured monocyte-derived dendritic cells (DCs).</p></div><div><h3>Conclusions</h3><p>This study showed that DEP-induced senescence made both young and old mice susceptible to allergic sensitization and resultant asthma development by enhancing DC activation. Public health efforts to reduce DEP exposure are warranted.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 453-463"},"PeriodicalIF":6.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S132389302400011X/pdfft?md5=1821534fa8c0400eab73c1ee49f4223d&pid=1-s2.0-S132389302400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors contributing to the diagnosis and onset prediction of perennial allergic rhinitis in high-risk children: A sub-analysis of the CHIBA study","authors":"Syuji Yonekura , Yoshitaka Okamoto , Fumiya Yamaide , Taiji Nakano , Kiyomi Hirano , Urara Funakoshi , Sawako Hamasaki , Tomohisa Iinuma , Toyoyuki Hanazawa , Naoki Shimojo","doi":"10.1016/j.alit.2024.01.012","DOIUrl":"10.1016/j.alit.2024.01.012","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to clarify the diagnostic and predictive factors for perennial allergic rhinitis (PAR) onset in children by analyzing the results of the Chiba High-risk Birth Cohort for Allergy study, which examined newborns with a family history of allergies.</p></div><div><h3>Methods</h3><p>Overall, 306 pregnant women were recruited. Their newborns were examined by otolaryngologists and pediatric allergists at 1, 2, and 5 years of age. Participants with clinical and laboratory data available at all consultation points were considered eligible.</p></div><div><h3>Results</h3><p>Among 187 eligible participants, the prevalence rates of PAR were 2.1%, 4.3%, and 24.1% at 1, 2, and 5 years of age, respectively. AR-specific nasal local findings and eosinophils in nasal smear were observed in a substantial number of patients with PAR at 1 and 2 years of age. Factors present up to 2 years of age that were associated with PAR onset at 5 years of age, in descending order, were as follows: sensitization to house dust mites (HDM), nasal eosinophilia, and sensitization to cat dander. In 44 cases with HDM sensitization, nasal eosinophilia up to 2 years of age achieved a sensitivity of 76.0% and a specificity of 73.7% for predicting PAR onset at 5 years.</p></div><div><h3>Conclusions</h3><p>Rhinitis findings and nasal eosinophilia are useful auxiliary diagnostic items for pediatric PAR. Sensitization to HDM and nasal eosinophilia were the most influential factors associated with future PAR onset. A combination of these factors may facilitate the prediction of PAR onset.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 436-444"},"PeriodicalIF":6.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000133/pdfft?md5=ca5cf1eb1c18e38ab69595b022695806&pid=1-s2.0-S1323893024000133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of the relationship between comorbid obstructive sleep apnea and clinical outcomes in patients with asthma in Japan","authors":"Hitomi Ikegami-Tanaka, Naoya Yasokawa, Koji Kurose, Shonosuke Tajima, Masaaki Abe, Shigeki Katoh, Yoshihiro Kobashi, Toru Oga","doi":"10.1016/j.alit.2024.01.009","DOIUrl":"10.1016/j.alit.2024.01.009","url":null,"abstract":"<div><h3>Background</h3><p>Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders, which often coexist and interact with each other. Obesity is an important risk factor shared by them. The rate of obesity is lower in Japan versus Western countries. Hence, the co-existence of asthma and OSA has not been investigated in Japan.</p></div><div><h3>Methods</h3><p>Ninety-seven outpatients with asthma were recruited. Patients wore a portable monitor for sleep study. Background data, pulmonary function, blood tests, and patient-reported outcomes including gastroesophageal reflux disease, sleepiness, sleep quality, asthma control, cough and respiratory symptoms, and health status, were assessed.</p></div><div><h3>Results</h3><p>Of the patients, 19 (19.6 %), 40 (41.2 %), 24 (24.7 %), and 14 (14.4 %) were classified into non-, mild, moderate, and severe OSA groups. Non-OSA patients were younger than those in other groups (p < 0.05). The BMI of patients with moderate and severe OSA, was higher than that of non-OSA patients (p < 0.05). Pulmonary function, FeNO, serum IgE, and the number of peripheral eosinophils were not significantly different between groups. Nonetheless, compared with the other groups, treatment step was the highest, and the Asthma Control Test, Leicester Cough Questionnaire, COPD Assessment Test, and Asthma Health Questionnaire-33 yielded worst scores in the severe OSA group, and predicted the severe OSA after adjustment by BMI.</p></div><div><h3>Conclusions</h3><p>Moderate and severe OSA are highly prevalent among patients with asthma in Japan. Pulmonary function did not differ between groups. However, patients with asthma and severe OSA were linked to more asthma treatment, worse asthma control, more symptoms and cough, and worse health status.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 390-396"},"PeriodicalIF":6.8,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000108/pdfft?md5=7b59586cb4bbcbcbc84e83ee54e67e81&pid=1-s2.0-S1323893024000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Anvari , Melanie A. Ruffner , Anna Nowak-Wegrzyn
{"title":"Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES)","authors":"Sara Anvari , Melanie A. Ruffner , Anna Nowak-Wegrzyn","doi":"10.1016/j.alit.2024.01.006","DOIUrl":"10.1016/j.alit.2024.01.006","url":null,"abstract":"<div><p>Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 2","pages":"Pages 188-195"},"PeriodicalIF":6.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000078/pdfft?md5=a30dff50061d598041fff07f721bbb90&pid=1-s2.0-S1323893024000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}