Anna Szylling, Boleslaw Samoliński, Filip Raciborski, Konrad Furmańczyk, Mariola Chrzanowska, Oksana Wojas, Edyta Krzych-Fałta, Emilia Gawińska-Drużba, Krzysztof Samoliński, Jean Bousquet, Piotr Samel-Kowalik
Background
Monitoring adherence in chronic diseases remains a significant challenge. Allergic rhinitis (AR), one of the most common chronic conditions, serves as an excellent model for studying determinants of app use in monitoring adherence and health assessment during treatment. The Mask-air® app supports clinical decision-making by involving patients in symptom observation and promoting adherence to therapy. This study aimed to identify the defining characteristics of Mask-air® users, describe their disease phenotype and satisfaction with the app, and explore reasons for discontinuation.
Materials and Methods
Adult patients 20–44 years old suffering from AR (n = 198) receiving care at an allergy outpatient clinic were invited to participate in a trial using the Mask-air® app. Investigators collected data on symptoms, administered treatments, and clinical evaluation results through questionnaires. At a follow-up visit (n = 163), these were compared, and patients were questioned about their satisfaction with the app. Patients presented their app records, and those who declined or stopped using the app were asked to provide reasons in a questionnaire.
Results
No distinguishing characteristics of Mask-air® users (n = 131) were identified compared with those who declined the app (n = 67). App readiness was analyzed according to age, socioeconomic status, disease severity, comorbidities, and therapeutic modality. Respondents were categorized into: those who did not install the app (17.7%), those who installed but did not use it (16.2%), and those who installed and evaluated it (66.2%), with 15.6% failing to produce symptom monitoring records. Overall, satisfaction ratings were high though patients were critical of the app's therapeutic aspect.
Conclusions
The study found no specific features distinguishing Mask-air® users, suggesting that it can be recommended to all patients regardless of gender, socioeconomic or educational status, or disease phenotype. However, with a dropout rate of nearly 50%, it is essential for clinicians to emphasize the app's benefits to improve adherence and engagement.
{"title":"Factors that influence user adherence of the Mask-air® application","authors":"Anna Szylling, Boleslaw Samoliński, Filip Raciborski, Konrad Furmańczyk, Mariola Chrzanowska, Oksana Wojas, Edyta Krzych-Fałta, Emilia Gawińska-Drużba, Krzysztof Samoliński, Jean Bousquet, Piotr Samel-Kowalik","doi":"10.1002/clt2.70054","DOIUrl":"https://doi.org/10.1002/clt2.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Monitoring adherence in chronic diseases remains a significant challenge. Allergic rhinitis (AR), one of the most common chronic conditions, serves as an excellent model for studying determinants of app use in monitoring adherence and health assessment during treatment. The Mask-air® app supports clinical decision-making by involving patients in symptom observation and promoting adherence to therapy. This study aimed to identify the defining characteristics of Mask-air® users, describe their disease phenotype and satisfaction with the app, and explore reasons for discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Adult patients 20–44 years old suffering from AR (<i>n</i> = 198) receiving care at an allergy outpatient clinic were invited to participate in a trial using the Mask-air® app. Investigators collected data on symptoms, administered treatments, and clinical evaluation results through questionnaires. At a follow-up visit (<i>n</i> = 163), these were compared, and patients were questioned about their satisfaction with the app. Patients presented their app records, and those who declined or stopped using the app were asked to provide reasons in a questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No distinguishing characteristics of Mask-air® users (<i>n</i> = 131) were identified compared with those who declined the app (<i>n</i> = 67). App readiness was analyzed according to age, socioeconomic status, disease severity, comorbidities, and therapeutic modality. Respondents were categorized into: those who did not install the app (17.7%), those who installed but did not use it (16.2%), and those who installed and evaluated it (66.2%), with 15.6% failing to produce symptom monitoring records. Overall, satisfaction ratings were high though patients were critical of the app's therapeutic aspect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study found no specific features distinguishing Mask-air® users, suggesting that it can be recommended to all patients regardless of gender, socioeconomic or educational status, or disease phenotype. However, with a dropout rate of nearly 50%, it is essential for clinicians to emphasize the app's benefits to improve adherence and engagement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831066","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":"Correction to “Eosinophils and COVID-19: Insights into immune complexity and vaccine safety”","authors":"","doi":"10.1002/clt2.70056","DOIUrl":"https://doi.org/10.1002/clt2.70056","url":null,"abstract":"<p>Sahli W, Vitte J, Desnues B. Eosinophils and COVID-19: insights into immune complexity and vaccine safety. <i>Clin Transl Allergy</i>. 2025;e70050.</p><p>In Figure 1, the icons of monocyte and T cell and some labels were missing. This should have appeared as the following Figure 1.</p><p></p><p>We apologize for this error.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831194","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}
Joaquim Mullol, Maria D'Amato, Eugenio de Corso, Joseph K. Han, Jody Tversky
Background
Type 2 (T2) inflammation, characterized by blood and airway eosinophilia, underlies severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). In line with the Global Airways theory, SEA and CRSwNP frequently co-occur, creating a multimorbid phenotype. Separately, SEA and CRSwNP are burdensome: when concomitant, they compound each other, creating a more difficult-to-treat disease with increased complications.
Body
Current management approaches rarely control disease and are associated with substantial side-effects. Several recently developed anti-IL-5 monoclonal antibodies have shown efficacy in treating co-morbid SEA with CRSwNP by targeting T2 inflammation with systemic therapies. Of these, only benralizumab directly targets the IL-5 receptor-α, leading to rapid, sustained, near-complete eosinophil depletion. Analyses in patients with co-morbid SEA with CRSwNP are limited, although data from the ANDHI, XALOC-1, and RANS studies suggest benralizumab can effectively target inflammation underlying co-morbid disease.
Conclusion
Despite progress toward more effective therapies, treatment approaches remain siloed, with SEA and CRSwNP often managed separately. There is a need for the development of multidisciplinary approaches for treating patients with comorbid SEA with CRSwNP.
{"title":"Benralizumab and the integrated management of co-morbid severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps","authors":"Joaquim Mullol, Maria D'Amato, Eugenio de Corso, Joseph K. Han, Jody Tversky","doi":"10.1002/clt2.70051","DOIUrl":"https://doi.org/10.1002/clt2.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 (T2) inflammation, characterized by blood and airway eosinophilia, underlies severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP). In line with the Global Airways theory, SEA and CRSwNP frequently co-occur, creating a multimorbid phenotype. Separately, SEA and CRSwNP are burdensome: when concomitant, they compound each other, creating a more difficult-to-treat disease with increased complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>Current management approaches rarely control disease and are associated with substantial side-effects. Several recently developed anti-IL-5 monoclonal antibodies have shown efficacy in treating co-morbid SEA with CRSwNP by targeting T2 inflammation with systemic therapies. Of these, only benralizumab directly targets the IL-5 receptor-α, leading to rapid, sustained, near-complete eosinophil depletion. Analyses in patients with co-morbid SEA with CRSwNP are limited, although data from the ANDHI, XALOC-1, and RANS studies suggest benralizumab can effectively target inflammation underlying co-morbid disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite progress toward more effective therapies, treatment approaches remain siloed, with SEA and CRSwNP often managed separately. There is a need for the development of multidisciplinary approaches for treating patients with comorbid SEA with CRSwNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801275","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}
A. Z. P. Brandão, L. M. L. B. F. Lasmar, L. M. A. S. Pertence, M. I. R. Vieira, G. B. Lasmar, V. O. Ganem, E. V. Mancuzo, M. V. N. P. de Queiroz
Background
Although exacerbations are common in severe asthma, there have been few longitudinal studies evaluating their effect on lung function parameters. This study aimed to evaluate the impact of exacerbations on lung function in children and adolescents with severe asthma in Brazil.
Methods
This was a prospective study in which lung function parameters—forced vital capacity (forced vital capacity [FVC]), forced expiratory volume in 1 s (forced expiratory volume in 1 s [FEV1]), the FEV1/FVC ratio, and the forced expiratory flow between 25% and 75% of FVC (FEF25–75%), each expressed as a percentage of the predicted value—were measured at 3-month intervals for three years in 64 patients (6–18 years of age) with severe asthma. Multivariate regression models of longitudinal data were employed to assess the associations between exacerbations and other predictors show with lung function parameters.
Results
The mean duration of prior use of an inhaled corticosteroid together with a long-acting bronchodilator or other controller was 6.7 (SD 3.2) years. During the study period, 31 patients (48.5%) had exacerbations. We analyzed 479 pulmonary function tests and found no significant association between exacerbation and any of the lung function parameters: FEV1 (p = 0.90); FEF25–75% (p = 0.73); FEV1/FVC (p = 0.29); and FVC (p = 0.51). Passive smoking and being female were associated with mean FEV1 values that were 9.89% and 7.32% lower, respectively.
Conclusions
In children and adolescents with severe asthma who are using preventive treatment, exacerbations do not seem to be associated with impaired lung function.
{"title":"What is the influence of exacerbations on pulmonary function in pediatric and adolescent patients with severe asthma despite controller therapies?","authors":"A. Z. P. Brandão, L. M. L. B. F. Lasmar, L. M. A. S. Pertence, M. I. R. Vieira, G. B. Lasmar, V. O. Ganem, E. V. Mancuzo, M. V. N. P. de Queiroz","doi":"10.1002/clt2.70046","DOIUrl":"https://doi.org/10.1002/clt2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although exacerbations are common in severe asthma, there have been few longitudinal studies evaluating their effect on lung function parameters. This study aimed to evaluate the impact of exacerbations on lung function in children and adolescents with severe asthma in Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a prospective study in which lung function parameters—forced vital capacity (forced vital capacity [FVC]), forced expiratory volume in 1 s (forced expiratory volume in 1 s [FEV1]), the FEV<sub>1</sub>/FVC ratio, and the forced expiratory flow between 25% and 75% of FVC (FEF<sub>25–75%</sub>), each expressed as a percentage of the predicted value—were measured at 3-month intervals for three years in 64 patients (6–18 years of age) with severe asthma. Multivariate regression models of longitudinal data were employed to assess the associations between exacerbations and other predictors show with lung function parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean duration of prior use of an inhaled corticosteroid together with a long-acting bronchodilator or other controller was 6.7 (SD 3.2) years. During the study period, 31 patients (48.5%) had exacerbations. We analyzed 479 pulmonary function tests and found no significant association between exacerbation and any of the lung function parameters: FEV<sub>1</sub> (<i>p</i> = 0.90); FEF<sub>25–75%</sub> (<i>p</i> = 0.73); FEV<sub>1</sub>/FVC (<i>p</i> = 0.29); and FVC (<i>p</i> = 0.51). Passive smoking and being female were associated with mean FEV<sub>1</sub> values that were 9.89% and 7.32% lower, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In children and adolescents with severe asthma who are using preventive treatment, exacerbations do not seem to be associated with impaired lung function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778349","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}
Markus Lilja, Anni Koskinen, Sari Hammarèn-Malmi, Anu Laulajainen-Hongisto, Jura Numminen, Jyri Myller, Seija Vento, Elina Penttila, Maija Hytönen, Paula Virkkula, Peter W. Hellings, Sven F. Seys, John Lee, Heini Huhtala, Johanna Sahlman, Sanna Toppila-Salmi
Objectives
The aim was to evaluate the predictive potential of Sinonasal Radiological (SR) and the Lund-Mackay (LM) score of sinus computed tomography (CT) scans on postoperative relapses of chronic rhinosinusitis (CRS).
Materials and Methods
CRS patients (n = 483, 12–80 years) underwent routine sinus CT scans. The SR score was defined by obstructed frontal recess (0 = no, 1 = yes) and visualization of middle and inferior turbinate (0 = anatomy can be easily visualized, 1 = anatomy cannot be easily visualized) on each side (a total of 0–6 points). Associations were analyzed by nonparametric, survival and Cox's proportional hazard models.
Results
Revision endoscopic sinus surgery (ESS) was performed in 133 (28.0%) patients on average (min–max) of 3.2 (0–12) years after performing the sinus CT scans. Of the 408 patients who underwent the baseline ESS, high preoperative SR or LM scores significantly predicted revision ESS (p < 0.001) and peroral corticosteroid courses purchased during the follow-up (p = 0.009 and p < 0.001, respectively for SR- and LM-scores). In multivariable analysis, both SR score and asthma and/or NSAID exacerbated respiratory disease (N-ERD) were significantly associated with revision ESS risk (p = 0.035, p = 0.007, respectively).
Conclusion
LM and SR and a history of asthma or N-ERD predict CRS relapses, which may help in decision-making.
{"title":"Radiological score, asthma and NSAID-exacerbated respiratory disease predict relapsing chronic rhinosinusitis","authors":"Markus Lilja, Anni Koskinen, Sari Hammarèn-Malmi, Anu Laulajainen-Hongisto, Jura Numminen, Jyri Myller, Seija Vento, Elina Penttila, Maija Hytönen, Paula Virkkula, Peter W. Hellings, Sven F. Seys, John Lee, Heini Huhtala, Johanna Sahlman, Sanna Toppila-Salmi","doi":"10.1002/clt2.70043","DOIUrl":"https://doi.org/10.1002/clt2.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim was to evaluate the predictive potential of Sinonasal Radiological (SR) and the Lund-Mackay (LM) score of sinus computed tomography (CT) scans on postoperative relapses of chronic rhinosinusitis (CRS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>CRS patients (<i>n</i> = 483, 12–80 years) underwent routine sinus CT scans. The SR score was defined by obstructed frontal recess (0 = no, 1 = yes) and visualization of middle and inferior turbinate (0 = anatomy can be easily visualized, 1 = anatomy cannot be easily visualized) on each side (a total of 0–6 points). Associations were analyzed by nonparametric, survival and Cox's proportional hazard models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Revision endoscopic sinus surgery (ESS) was performed in 133 (28.0%) patients on average (min–max) of 3.2 (0–12) years after performing the sinus CT scans. Of the 408 patients who underwent the baseline ESS, high preoperative SR or LM scores significantly predicted revision ESS (<i>p</i> < 0.001) and peroral corticosteroid courses purchased during the follow-up (<i>p</i> = 0.009 and <i>p</i> < 0.001, respectively for SR- and LM-scores). In multivariable analysis, both SR score and asthma and/or NSAID exacerbated respiratory disease (N-ERD) were significantly associated with revision ESS risk (<i>p</i> = 0.035, <i>p</i> = 0.007, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LM and SR and a history of asthma or N-ERD predict CRS relapses, which may help in decision-making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762202","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}
Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial-mesenchymal transition (EMT). However, the mechanisms underlying hypoxia-induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.
Methods
Transcriptome and proteome analyses of hypoxia-treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia-inducible factor-1α (HIF-1α), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.
Results
Hypoxia activated the glycolysis-related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis-related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF-1α and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia-induced EMT in HNECs.
Conclusions
This study is the first to reveal that hypoxia-induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.
{"title":"Targeting PDK1: A novel approach to combat hypoxia-induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps","authors":"Sicen Pan, Mengyan Zhuang, Xiangdong Wang, Qinqin Zhang, Ting He, Ying Li, Jian Jiao, Luo Zhang","doi":"10.1002/clt2.70048","DOIUrl":"https://doi.org/10.1002/clt2.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypoxia is a prevalent pathological process in chronic rhinosinusitis with nasal polyps (CRSwNP), leading to a cascade of pathological events, including epithelial-mesenchymal transition (EMT). However, the mechanisms underlying hypoxia-induced EMT remain unclear. This study aims to elucidate the mechanisms driving EMT under hypoxic conditions in CRSwNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transcriptome and proteome analyses of hypoxia-treated human nasal epithelial cells (HNECs) were performed to identify key molecules and pathways. The expression of hypoxia-inducible factor-1α (HIF-1α), pyruvate dehydrogenase kinase (PDK1), lactate dehydrogenase A (LDHA), and EMT markers was assessed in nasal tissues from CRSwNP patients. In vitro, cultured HNECs were exposed to hypoxia and lactate, or overexpressed PDK1, to evaluate changes in EMT markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia activated the glycolysis-related pathway in HNECs, with PDK1 and LDHA identified as significantly upregulated glycolysis-related enzymes. The expression of PDK1 and LDHA was closely correlated with HIF-1α and EMT markers in nasal tissues. Hypoxia induced an increase in PDK1 and LDHA expression, lactate production, and EMT occurrence in HNECs. PDK1 overexpression or lactate stimulation also triggered EMT, while PDK1 inhibition attenuated hypoxia-induced EMT in HNECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to reveal that hypoxia-induced activation of PDK1 plays a critical role in regulating EMT by promoting lactate production, thereby providing a potential therapeutic target for CRSwNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762203","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}
Giovanni Paoletti, Giovanni Costanzo, Morena Merigo, Francesca Puggioni, Sebastian Ferri, Maria Rita Messina, Fulvio Cordella, Giuseppe Ranieri, Arianna Arienzo, Victor Savevski, Giorgio Walter Canonica, Ayana de Brito Martins, Enrico Heffler
Background
Mobile health applications are increasingly valued for their role in asthma management and the opportunity for large dataset collection. Our study aimed to investigate the feasibility of applying signal-processing and machine-learning technologies to detect alterations in the lower airway caliber and develop a machine-learning algorithm to identify changes in vocal biomarkers and detect bronchoconstriction in patients with airway hyperreactivity.
Methods
This is an explorative observational prospective longitudinal study focused on vocal biomarkers and their association with bronchial constriction and respiratory function. Non-smoker adults with clinical suspicion of asthma were consecutively enrolled from May 2023 to September 2023. At each step of a Methacholine Challenge Test (MCT) performed on these patients, the respiratory sounds were recorded via a smartphone through an app specifically developed. Several biomarkers were extracted and their relationship with the change in Forced Expiratory Volume in the first second (FEV1) was measured.
Results
Forty-two subjects were enrolled. The highest correlation with FEV1 came from exhalation vocal events. No single feature exhibited robust behavior across different subjects, while each subject showed “personal” highly correlated features. All values were strongly statistically significant irrespectively of the result of MCT.
Conclusion
The app’s algorithm is sensitive in correlating specific vocal biomarkers to FEV1 variations during MCT. This feature may assist physicians in diagnosing asthma and its exacerbation and in assessing therapy response and adherence. The socio-economic implications might be significant, and the simplicity of use makes it an ideal tool for research.
{"title":"Vocal biomarkers correlate with FEV1 variations during methacholine challenge","authors":"Giovanni Paoletti, Giovanni Costanzo, Morena Merigo, Francesca Puggioni, Sebastian Ferri, Maria Rita Messina, Fulvio Cordella, Giuseppe Ranieri, Arianna Arienzo, Victor Savevski, Giorgio Walter Canonica, Ayana de Brito Martins, Enrico Heffler","doi":"10.1002/clt2.70055","DOIUrl":"https://doi.org/10.1002/clt2.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mobile health applications are increasingly valued for their role in asthma management and the opportunity for large dataset collection. Our study aimed to investigate the feasibility of applying signal-processing and machine-learning technologies to detect alterations in the lower airway caliber and develop a machine-learning algorithm to identify changes in vocal biomarkers and detect bronchoconstriction in patients with airway hyperreactivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is an explorative observational prospective longitudinal study focused on vocal biomarkers and their association with bronchial constriction and respiratory function. Non-smoker adults with clinical suspicion of asthma were consecutively enrolled from May 2023 to September 2023. At each step of a Methacholine Challenge Test (MCT) performed on these patients, the respiratory sounds were recorded via a smartphone through an app specifically developed. Several biomarkers were extracted and their relationship with the change in Forced Expiratory Volume in the first second (FEV1) was measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-two subjects were enrolled. The highest correlation with FEV1 came from exhalation vocal events. No single feature exhibited robust behavior across different subjects, while each subject showed “personal” highly correlated features. All values were strongly statistically significant irrespectively of the result of MCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The app’s algorithm is sensitive in correlating specific vocal biomarkers to FEV1 variations during MCT. This feature may assist physicians in diagnosing asthma and its exacerbation and in assessing therapy response and adherence. The socio-economic implications might be significant, and the simplicity of use makes it an ideal tool for research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726753","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}
<p>To the Editor,</p><p>We have been following recent clinical trials focusing on new therapies to treat Chronic Spontaneous Urticaria (CSU). While current treatments can manage the debilitating symptoms, a significant number of patients do not achieve symptom control with available medications, including anti-IgE treatment.<span><sup>1, 2</sup></span> New potential solutions to address this include Bruton's tyrosine kinase (BTK) inhibitors, targeting downstream signaling of the Immunoglobulin E high-affinity receptor,<span><sup>3, 4</sup></span> and anti-cytokine biologics, targeting T2/alarmin-driven responses.<span><sup>5</sup></span> However, available literature provides limited comparisons between newer CSU treatments.</p><p>We critically appraised the efficacy and safety of six randomized controlled clinical trials (RCTs), three focusing on BTK inhibitors and three on cytokine blockers, to provide insights into the more promising therapeutic options for CSU. Using the Arksey and O'Malley's framework, we systematically reviewed relevant trials. Our search across Embase and Ovid identified 473 studies from April 2019 to May 2024. A secondary search on ClinicalTrials.gov yielded 123 trials, 15 focusing on BTK inhibitors and cytokine blockers. Based on the CONSORT checklist for methodological quality,<span><sup>6</sup></span> we selected trials scoring a minimum of 10 positive or partially met items out of 25. Six RCTs and two pharmaceutical releases (for trial NCT05107115, whose results were not published at the time of the search) were chosen (Figure 1A, Table 1).</p><p>Common inclusion criteria included CSU duration of at least 6 months and non-response to second-generation H1-antihistamines, while exclusion criteria included recent infections, other dermatological conditions, immunocompromised status, and major health conditions.</p><p>Selected studies were compared across three areas: (A) study characteristics and demographic information (e.g., number of participants, age, gender distribution, ethnic diversity, and dropout rates); (B) CSU outcome measures (e.g., Urticaria Activity Score over 7 days, UAS7); and (C) frequency of serious adverse events.</p><p>Data were normalized for the placebo effect, while statistical differences were as reported by the original authors. Studies NCT03137069 and NCT04180488 involved two cohorts with similar dosage protocols, respectively fenebrutinib 200 mg BID and dupilumab 300 mg SC Q2W. Combined <i>p</i> values were calculated using Fisher's combined probability test, and the survival function of the chi-squared distribution was computed using the <span>chi2.sf</span> function of the <span>scipy</span> Python library.<span><sup>7</sup></span> In studies with multiple dosages, we selected the most effective regimen, resulting in the most significant decrease of UAS7 scores from baseline to endpoint normalized to placebo (Normalized ΔUAS7 = [(UAS7<sub>End of study</sub> – UAS7<sub>Baseline</sub>)]<sub>Tre
{"title":"Comparing novel treatments in chronic spontaneous urticaria: A critical appraisal of Bruton's tyrosine kinase inhibitors versus anti-cytokine biologics in clinical trials","authors":"Anastasia Diamanti, Chiara Tontini, Silvia Bulfone-Paus","doi":"10.1002/clt2.70053","DOIUrl":"https://doi.org/10.1002/clt2.70053","url":null,"abstract":"<p>To the Editor,</p><p>We have been following recent clinical trials focusing on new therapies to treat Chronic Spontaneous Urticaria (CSU). While current treatments can manage the debilitating symptoms, a significant number of patients do not achieve symptom control with available medications, including anti-IgE treatment.<span><sup>1, 2</sup></span> New potential solutions to address this include Bruton's tyrosine kinase (BTK) inhibitors, targeting downstream signaling of the Immunoglobulin E high-affinity receptor,<span><sup>3, 4</sup></span> and anti-cytokine biologics, targeting T2/alarmin-driven responses.<span><sup>5</sup></span> However, available literature provides limited comparisons between newer CSU treatments.</p><p>We critically appraised the efficacy and safety of six randomized controlled clinical trials (RCTs), three focusing on BTK inhibitors and three on cytokine blockers, to provide insights into the more promising therapeutic options for CSU. Using the Arksey and O'Malley's framework, we systematically reviewed relevant trials. Our search across Embase and Ovid identified 473 studies from April 2019 to May 2024. A secondary search on ClinicalTrials.gov yielded 123 trials, 15 focusing on BTK inhibitors and cytokine blockers. Based on the CONSORT checklist for methodological quality,<span><sup>6</sup></span> we selected trials scoring a minimum of 10 positive or partially met items out of 25. Six RCTs and two pharmaceutical releases (for trial NCT05107115, whose results were not published at the time of the search) were chosen (Figure 1A, Table 1).</p><p>Common inclusion criteria included CSU duration of at least 6 months and non-response to second-generation H1-antihistamines, while exclusion criteria included recent infections, other dermatological conditions, immunocompromised status, and major health conditions.</p><p>Selected studies were compared across three areas: (A) study characteristics and demographic information (e.g., number of participants, age, gender distribution, ethnic diversity, and dropout rates); (B) CSU outcome measures (e.g., Urticaria Activity Score over 7 days, UAS7); and (C) frequency of serious adverse events.</p><p>Data were normalized for the placebo effect, while statistical differences were as reported by the original authors. Studies NCT03137069 and NCT04180488 involved two cohorts with similar dosage protocols, respectively fenebrutinib 200 mg BID and dupilumab 300 mg SC Q2W. Combined <i>p</i> values were calculated using Fisher's combined probability test, and the survival function of the chi-squared distribution was computed using the <span>chi2.sf</span> function of the <span>scipy</span> Python library.<span><sup>7</sup></span> In studies with multiple dosages, we selected the most effective regimen, resulting in the most significant decrease of UAS7 scores from baseline to endpoint normalized to placebo (Normalized ΔUAS7 = [(UAS7<sub>End of study</sub> – UAS7<sub>Baseline</sub>)]<sub>Tre","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717335","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}
Alternative non-pharmacological strategies such as breathing exercises can be used in combination with pharmacological treatments.
Objective
The aim of this randomized, controlled, single-blind study was to investigate the effectiveness of breathing exercises in asthma patients on respiratory function, symptom control and quality of life.
Methods
We enrolled pediatric asthma patients who were eligible and motivated for the study and randomly assigned them to either the exercise group (EG) or the control group (CG). The CG received a postural exercise program, while the EG received a breathing exercise program. At baseline and after 12 weeks, respiratory function (FEV1-FVC-FEV1/FVC-PEF), symptom control (using asthma control test, asthma control questionnaire, global initiative for asthma symptom control assessment), quality of life (using pediatric asthma quality of life questionnaire), breath-holding test (BHT) and sit-to-stand test (30sSTS) were assessed and compared.
Results
One hundred twelve patients were randomized, and 99 (n = 51 EG, n = 48 CG) completed the 12-week study. Baseline data were also similar in both groups. After 12 weeks, FEV1, Peak expiratory flow (by spirometry and peak flow meter) and BHT were significantly better in EG than in CG (p = 0.01 and p = 0.007 and p = 0.005, respectively). Asthma Control Test and GINA symptom control tool values were also significantly better in both groups.
Discussion
Our participants were children with mild to moderate asthma. We conclude that our results show that breathing exercises can be an effective intervention for children with partially controlled asthma with FEV1,PEF, and BHTs.
{"title":"Breath of relief: Transforming pediatric asthma care with telemedicine-guided exercises","authors":"Betul Gemici Karaaslan, Hikmet Ucgun, Meltem Kaya, Gokce Nuran Cengiz, Sueda Ozturk, Ozge Barut, Zeynep Korkut, Sezin Aydemir, Zeynep Meric, Birol Topcu, Hilal Denizoglu Kulli, Haluk Cokuğras, Ayca Kiykim","doi":"10.1002/clt2.70049","DOIUrl":"https://doi.org/10.1002/clt2.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alternative non-pharmacological strategies such as breathing exercises can be used in combination with pharmacological treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this randomized, controlled, single-blind study was to investigate the effectiveness of breathing exercises in asthma patients on respiratory function, symptom control and quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled pediatric asthma patients who were eligible and motivated for the study and randomly assigned them to either the exercise group (EG) or the control group (CG). The CG received a postural exercise program, while the EG received a breathing exercise program. At baseline and after 12 weeks, respiratory function (FEV1-FVC-FEV1/FVC-PEF), symptom control (using asthma control test, asthma control questionnaire, global initiative for asthma symptom control assessment), quality of life (using pediatric asthma quality of life questionnaire), breath-holding test (BHT) and sit-to-stand test (30sSTS) were assessed and compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred twelve patients were randomized, and 99 (<i>n</i> = 51 EG, <i>n</i> = 48 CG) completed the 12-week study. Baseline data were also similar in both groups. After 12 weeks, FEV1, Peak expiratory flow (by spirometry and peak flow meter) and BHT were significantly better in EG than in CG (<i>p</i> = 0.01 and <i>p</i> = 0.007 and <i>p</i> = 0.005, respectively). Asthma Control Test and GINA symptom control tool values were also significantly better in both groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our participants were children with mild to moderate asthma. We conclude that our results show that breathing exercises can be an effective intervention for children with partially controlled asthma with FEV1,PEF, and BHTs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689921","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}
COVID-19 exhibits a variety of symptoms and may lead to multi-organ failure and death. This clinical complexity is exacerbated by significant immune dysregulation affecting nearly all cells of the innate and adaptive immune system. Granulocytes, including eosinophils, are affected by SARS-CoV-2.
Objectives
Eosinophil responses remain poorly understood despite early recognition of eosinopenia as a hallmark feature of COVID-19 severity.
Results
The heterogeneous nature of eosinophil responses categorizes them as dual-function cells with contradictory effects. Eosinophil activation can suppress virus-induced inflammation by releasing type 2 cytokines like IL-13 and granular proteins with antiviral action such as eosinophil-derived neurotoxins and eosinophil cationic protein, and also by acting as antigen-presenting cells. In contrast, eosinophil accumulation in the lungs can induce tissue damage triggered by cytokines or hormones like IFN-γ and leptin. Additionally, they can affect adaptive immune functions by interacting with T cells through direct formation of membrane complexes or soluble mediator action. Individuals with allergic disorders who have elevated levels of eosinophils in tissues and blood, such as asthma, do not appear to be at an increased risk of developing severe COVID-19 following SARS-CoV-2 infection. However, the SARS-CoV-2 vaccine appears to be associated with complications and eosinophilic infiltrate-induced immunopathogenicity, which can be mitigated by corticosteroid, anti-histamines and anti-IL-5 therapy and avoided by modifying adjuvants or excipients.
Conclusion
This review highlights the importance of eosinophils in COVID-19 and contributes to a better understanding of their role during natural infection and vaccination.
{"title":"Eosinophils and COVID-19: Insights into immune complexity and vaccine safety","authors":"Wided Sahli, Joana Vitte, Benoit Desnues","doi":"10.1002/clt2.70050","DOIUrl":"https://doi.org/10.1002/clt2.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>COVID-19 exhibits a variety of symptoms and may lead to multi-organ failure and death. This clinical complexity is exacerbated by significant immune dysregulation affecting nearly all cells of the innate and adaptive immune system. Granulocytes, including eosinophils, are affected by SARS-CoV-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Eosinophil responses remain poorly understood despite early recognition of eosinopenia as a hallmark feature of COVID-19 severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The heterogeneous nature of eosinophil responses categorizes them as dual-function cells with contradictory effects. Eosinophil activation can suppress virus-induced inflammation by releasing type 2 cytokines like IL-13 and granular proteins with antiviral action such as eosinophil-derived neurotoxins and eosinophil cationic protein, and also by acting as antigen-presenting cells. In contrast, eosinophil accumulation in the lungs can induce tissue damage triggered by cytokines or hormones like IFN-γ and leptin. Additionally, they can affect adaptive immune functions by interacting with T cells through direct formation of membrane complexes or soluble mediator action. Individuals with allergic disorders who have elevated levels of eosinophils in tissues and blood, such as asthma, do not appear to be at an increased risk of developing severe COVID-19 following SARS-CoV-2 infection. However, the SARS-CoV-2 vaccine appears to be associated with complications and eosinophilic infiltrate-induced immunopathogenicity, which can be mitigated by corticosteroid, anti-histamines and anti-IL-5 therapy and avoided by modifying adjuvants or excipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review highlights the importance of eosinophils in COVID-19 and contributes to a better understanding of their role during natural infection and vaccination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"15 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689385","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}
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