G. Siwe, E. Fajemisin, Masala Mugeri, K. Naran, Stefan Barth
Atopic dermatitis (AD) represents the most common inflammatory skin disease with a highly intricated immune fingerprint. Until recently, AD management mostly relied on topical corticosteroids, calcineurin inhibitors, and systemic immunosuppressants, with a range of safety and tolerability concerns including toxicity, drug interactions, and contraindications. With the onset of biologics, safer and more targeted therapeutics have become available, displaying various degrees of success in treating AD, but not yet able to meet all the needs of AD patients. Some of the challenges encountered included variability of responses among patients, long-term safety, and limited access due to prohibitive costs. As the pathophysiology of AD has been increasingly understood within the last years, new approaches are explored, leading to an unprecedented diversification of therapeutic options to address these hurdles. This review highlights current immunotherapeutic strategies developed towards AD, whether already in the clinical pipeline or still in preclinical exploration.
{"title":"Revisiting immunotherapeutic strategies for the management of atopic dermatitis","authors":"G. Siwe, E. Fajemisin, Masala Mugeri, K. Naran, Stefan Barth","doi":"10.37349/eaa.2024.00052","DOIUrl":"https://doi.org/10.37349/eaa.2024.00052","url":null,"abstract":"Atopic dermatitis (AD) represents the most common inflammatory skin disease with a highly intricated immune fingerprint. Until recently, AD management mostly relied on topical corticosteroids, calcineurin inhibitors, and systemic immunosuppressants, with a range of safety and tolerability concerns including toxicity, drug interactions, and contraindications. With the onset of biologics, safer and more targeted therapeutics have become available, displaying various degrees of success in treating AD, but not yet able to meet all the needs of AD patients. Some of the challenges encountered included variability of responses among patients, long-term safety, and limited access due to prohibitive costs. As the pathophysiology of AD has been increasingly understood within the last years, new approaches are explored, leading to an unprecedented diversification of therapeutic options to address these hurdles. This review highlights current immunotherapeutic strategies developed towards AD, whether already in the clinical pipeline or still in preclinical exploration.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Indolfi, Lorena Fortuna Izzo, Margherita Luciano, M. Mercogliano, Angela Klain, G. Dinardo, F. Decimo, M. M. del Giudice
Aim: This study investigated changes in pediatric respiratory health resulting from the easing of COVID-19-related social restrictions, following a noted decrease in respiratory infections during the lockdown. The COVID-19 restrictions have inadvertently influenced the epidemiology of other viruses and contributed to changes in patterns of recurrent respiratory infections (RRIs) in children. Methods: This cross-sectional study analyzed the records of children who underwent at “Respiratory Diseases of Pediatric Interest Unit” at the University Hospital “Luigi Vanvitelli” in Naples, Italy, between October 2022 and June 2023. The study aimed to assess associations with RRIs, the occurrence of febrile episodes, and antibiotic usage. Results: Out of 262 patients (38.2% females, median age 6 years), 81.7% experienced at least one respiratory infection over six months, and 23.7% suffered from RRIs [RRIs in the last six months (RRIS)]. Notably, being underweight was significantly associated with RRIs in the last six months (P-value 0.043), resulting in a 47% increased incidence of respiratory infections (P-value 0.012). No significant associations were observed with sex or age. With increasing age, there was a decreasing incidence rate of 3% for the number of RRIs (P-value 0.019), 4% for febrile episodes (P-value 0.031), and 7% for the number of antibiotic courses (P-value < 0.001). Conclusions: The study emphasizes age and weight’s role in children’s post-COVID-19 RRI prevalence. It signifies the need for proactive preparedness, targeting younger underweight populations and tailored interventions for recurrent cases.
{"title":"Impact of reduced COVID-19 restrictions on pediatric recurrent respiratory infections in Southern Italy: a cross-sectional analysis","authors":"C. Indolfi, Lorena Fortuna Izzo, Margherita Luciano, M. Mercogliano, Angela Klain, G. Dinardo, F. Decimo, M. M. del Giudice","doi":"10.37349/eaa.2024.00049","DOIUrl":"https://doi.org/10.37349/eaa.2024.00049","url":null,"abstract":"Aim: This study investigated changes in pediatric respiratory health resulting from the easing of COVID-19-related social restrictions, following a noted decrease in respiratory infections during the lockdown. The COVID-19 restrictions have inadvertently influenced the epidemiology of other viruses and contributed to changes in patterns of recurrent respiratory infections (RRIs) in children.\u0000Methods: This cross-sectional study analyzed the records of children who underwent at “Respiratory Diseases of Pediatric Interest Unit” at the University Hospital “Luigi Vanvitelli” in Naples, Italy, between October 2022 and June 2023. The study aimed to assess associations with RRIs, the occurrence of febrile episodes, and antibiotic usage.\u0000Results: Out of 262 patients (38.2% females, median age 6 years), 81.7% experienced at least one respiratory infection over six months, and 23.7% suffered from RRIs [RRIs in the last six months (RRIS)]. Notably, being underweight was significantly associated with RRIs in the last six months (P-value 0.043), resulting in a 47% increased incidence of respiratory infections (P-value 0.012). No significant associations were observed with sex or age. With increasing age, there was a decreasing incidence rate of 3% for the number of RRIs (P-value 0.019), 4% for febrile episodes (P-value 0.031), and 7% for the number of antibiotic courses (P-value < 0.001).\u0000Conclusions: The study emphasizes age and weight’s role in children’s post-COVID-19 RRI prevalence. It signifies the need for proactive preparedness, targeting younger underweight populations and tailored interventions for recurrent cases.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"14 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent decades, atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), allergic rhinitis (AR), and food allergy (FA) have been estimated rapidly increasing in prevalence. These diseases are characterized by the presence of specific immunoglobulin E (sIgE) and often relate to each other and develop in sequence (the so-called “atopic march”). AD may be the first early manifestation in infants followed by FA often within the first year of life. Moreover, AD is a risk factor for developing sensitization to airborne allergens later in life that can cause clinical manifestations of AA and AR. According to the dual-allergen exposure hypothesis, allergic sensitization to food allergens is promoted through cutaneous exposure, rather than the oral route. Moreover, there is evidence that exposure to food allergens, in particular peanuts, in the airway would also lead to food sensitization. The most frequent route of sensitization for inhalant allergens is still debated. Of note, a recent case report supports the development of sensitization to cat dander through a cat bite. Our review aims to provide an overview of current knowledge and unmet needs in the pathophysiology of respiratory and FAs.
近几十年来，特应性皮肤炎（AD）、过敏性哮喘（AA）、过敏性鼻炎（AR）和食物过敏（FA）等特应性疾病的发病率迅速上升。这些疾病的特点是存在特异性免疫球蛋白 E（sIgE），而且往往相互关联，依次发展（即所谓的 "特应性进行曲"）。AD可能是婴儿的第一个早期表现，随后是FA，通常在出生后第一年内出现。此外，AD 是日后对空气传播过敏原过敏的风险因素，可导致 AA 和 AR 的临床表现。根据双重过敏原接触假说，对食物过敏原的过敏是通过皮肤接触而非口服途径引起的。此外，有证据表明，通过气道接触食物过敏原（尤其是花生）也会导致食物过敏。对于吸入性过敏原最常见的致敏途径仍存在争议。值得注意的是，最近的一份病例报告支持通过猫咬而对猫皮屑过敏。我们的综述旨在概述呼吸道和 FA 病理生理学方面的现有知识和尚未满足的需求。
{"title":"The search for still unknown pathomechanisms of allergy","authors":"G. Leo, C. Incorvaia, Stefania Arasi","doi":"10.37349/eaa.2024.00048","DOIUrl":"https://doi.org/10.37349/eaa.2024.00048","url":null,"abstract":"In recent decades, atopic diseases, such as atopic dermatitis (AD), allergic asthma (AA), allergic rhinitis (AR), and food allergy (FA) have been estimated rapidly increasing in prevalence. These diseases are characterized by the presence of specific immunoglobulin E (sIgE) and often relate to each other and develop in sequence (the so-called “atopic march”). AD may be the first early manifestation in infants followed by FA often within the first year of life. Moreover, AD is a risk factor for developing sensitization to airborne allergens later in life that can cause clinical manifestations of AA and AR. According to the dual-allergen exposure hypothesis, allergic sensitization to food allergens is promoted through cutaneous exposure, rather than the oral route. Moreover, there is evidence that exposure to food allergens, in particular peanuts, in the airway would also lead to food sensitization. The most frequent route of sensitization for inhalant allergens is still debated. Of note, a recent case report supports the development of sensitization to cat dander through a cat bite. Our review aims to provide an overview of current knowledge and unmet needs in the pathophysiology of respiratory and FAs.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141815754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Bergmann, Teresa Hartung, S. Kugler, Katarina Stevanovic, T. Zuberbier
Aim: Evaluation of real-world data regarding the use of omalizumab on lung function, asthma control, exacerbations, and oral corticosteroid (OCS). Methods: The single-centre, retrospective study included data from adult patients with severe allergic asthma treated with omalizumab for at least five years to ten years to evaluate its long-term efficacy. The primary outcome parameters were lung function (FEV1), the asthma control test (ACT) score, the number of exacerbations, and OCS use. Results: Data from 74 adults (mean age 51 years, 61% females, median IgE 276 kU/L), with severe allergic asthma, due to perennial allergens, who were treated for at least 5 years with omalizumab in one centre could be evaluated up to 10 years. The mean improvement in FEV1 from baseline was 13.4% in the first year and constantly remained high throughout the duration of the treatment. The ACT improved from baseline (12.4 points) to 16.4 in the first year and reached 18.8 after 5 years, followed by values nearly reaching 20 (19.2 in year 8). The rate of exacerbations decreased from 3.3 events in the last 12 months before omalizumab initiation to 0.4 in the first year and remained low (e.g., 0.2 after 5 years). The mean OCS use was 20.9 mg/day in 44/74 patients before the first injection of omalizumab and decreased to 5 mg/day in the same patients within the first year. Following 6 years of omalizumab treatment, OCSs were used by 22 patients, and by 12 patients after 8 years. Conclusions: The consistent improvement in lung function, asthma control, reduction in exacerbations, and OCS use throughout a minimum of five up to ten years confirms that omalizumab remains effective for many years. There were no signs of tolerance or tachyphylaxis against the biologic.
{"title":"Long-term evaluation of omalizumab therapy in patients with severe allergic asthma","authors":"K. Bergmann, Teresa Hartung, S. Kugler, Katarina Stevanovic, T. Zuberbier","doi":"10.37349/eaa.2024.00047","DOIUrl":"https://doi.org/10.37349/eaa.2024.00047","url":null,"abstract":"Aim: Evaluation of real-world data regarding the use of omalizumab on lung function, asthma control, exacerbations, and oral corticosteroid (OCS).\u0000Methods: The single-centre, retrospective study included data from adult patients with severe allergic asthma treated with omalizumab for at least five years to ten years to evaluate its long-term efficacy. The primary outcome parameters were lung function (FEV1), the asthma control test (ACT) score, the number of exacerbations, and OCS use.\u0000Results: Data from 74 adults (mean age 51 years, 61% females, median IgE 276 kU/L), with severe allergic asthma, due to perennial allergens, who were treated for at least 5 years with omalizumab in one centre could be evaluated up to 10 years. The mean improvement in FEV1 from baseline was 13.4% in the first year and constantly remained high throughout the duration of the treatment. The ACT improved from baseline (12.4 points) to 16.4 in the first year and reached 18.8 after 5 years, followed by values nearly reaching 20 (19.2 in year 8). The rate of exacerbations decreased from 3.3 events in the last 12 months before omalizumab initiation to 0.4 in the first year and remained low (e.g., 0.2 after 5 years). The mean OCS use was 20.9 mg/day in 44/74 patients before the first injection of omalizumab and decreased to 5 mg/day in the same patients within the first year. Following 6 years of omalizumab treatment, OCSs were used by 22 patients, and by 12 patients after 8 years.\u0000Conclusions: The consistent improvement in lung function, asthma control, reduction in exacerbations, and OCS use throughout a minimum of five up to ten years confirms that omalizumab remains effective for many years. There were no signs of tolerance or tachyphylaxis against the biologic.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":" 492","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Monk, Cameron P Worden, E. Benaim, Cristine N. Klatt-Cromwell, B. Thorp, Charles S. Ebert, Brent A. Senior, A. Kimple
Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.
{"title":"The impact of occupational exposures on chronic rhinosinusitis: a scoping review","authors":"A. Monk, Cameron P Worden, E. Benaim, Cristine N. Klatt-Cromwell, B. Thorp, Charles S. Ebert, Brent A. Senior, A. Kimple","doi":"10.37349/eaa.2024.00046","DOIUrl":"https://doi.org/10.37349/eaa.2024.00046","url":null,"abstract":"Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"117 31","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Torres-Duque, Isabella Perna-Reyes, A. Alí-Munive
There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.
在中低收入国家（LMICs），最佳循证哮喘治疗方法应该有所不同，这一点没有任何可信的论据。几十年前，人们认识到哮喘是一种气道炎症性疾病，将吸入性皮质类固醇（ICS）作为治疗这种疾病的基石，而支气管扩张剂，尤其是短效β-受体激动剂（SABA），则作为缓解症状的药物，根据需要使用。然而，定期使用 ICS 的依从性非常低，尤其是在低收入国家，这有利于 SABA 的过度使用，而 SABA 的过度使用与病情恶化和死亡率过高有关。最近，全球哮喘倡议（GINA）战略建议，每次根据需要（为缓解症状）使用支气管扩张剂时，都必须使用 ICS，无论是根据需要还是在常规剂量 ICS 的基础上使用，并将其命名为：抗炎缓解剂（AIR）疗法。这种疗法能显著减少哮喘病的恶化，对那些病人没有适当的医疗随访保障、非处方药的使用率较高的低收入和中等收入国家非常有吸引力。然而，在低收入和中等收入国家实施空气呼吸疗法将面临许多已被公认的哮喘诊断和治疗障碍，尤其是在不同的医疗系统中获得治疗的机会有限、患者和社区的教育水平较低、初级医疗保健中哮喘方面的医务人员培训不足、药物费用难以承受以及缺乏政治承诺等。本综述分析了低收入与中等收入国家面临的其中一些挑战和应对策略。
{"title":"How to implement the anti-inflammatory reliever treatment proposed by the Global Initiative for Asthma in low- and middle-income countries","authors":"C. Torres-Duque, Isabella Perna-Reyes, A. Alí-Munive","doi":"10.37349/eaa.2024.00042","DOIUrl":"https://doi.org/10.37349/eaa.2024.00042","url":null,"abstract":"There are no plausible arguments to consider that the best evidence-based asthma treatment should be different in low- and middle-income countries (LMICs). A few decades ago, the recognition of asthma as an inflammatory disease of the airways positioned the inhaled corticosteroids (ICS) as the cornerstone of the treatment of this disease, maintaining bronchodilators, especially the short-acting beta-agonists (SABA), as symptom-reliever medications for use as needed. However, adherence to regular use of ICS is very low, especially in LMICs, favoring the overuse of SABA, which has been related to an excess of exacerbations and mortality. Recently, the Global Initiative for Asthma (GINA) strategy has recommended the mandatory use of ICS every time a bronchodilator is used as needed (for symptoms relief), whether only as needed or with a background of regular dose of ICS, and has named it: anti-inflammatory reliever (AIR) therapy. This form of therapy, which has been related to a significant reduction of asthma exacerbations, is very attractive for LMICs where patients do not have guaranteed a proper medical follow-up and the access to on-the-counter medications is high. However, the implementation of AIR therapy in LMICs will face many of the already recognized barriers for the diagnosis and treatment of asthma in these countries, especially related to limited access to care in very different health systems, low education level of patients and communities, insufficient health personnel training in asthma in primary care, the unfordable cost of medications, and the lack of political commitment. This review analyzes some of these challenges and strategies for facing them in LMICs.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"79 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141350242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent data has resulted in an interest in the metabolic shift in cellular metabolism to aerobic glycolysis, increased reactive oxygen species (ROS), and mitochondrial dysfunction associated with asthma. There has been a push to better understand the immune and metabolic changes in allergy to improve understanding of disease pathology and treatment. Aerobic glycolysis seen in epithelial cells in asthma promotes chronic inflammation and the production of inflammatory cytokines. Asthma epithelial cells share a number of features proposed in the stages of cancer initiation including aerobic glycolysis and increased apoptosis with proliferation, all within a chronic inflammatory microenvironment. Metabolic reprogramming in malignant cells has been widely investigated since the glycolytic characteristics were first described last century. It is still debated whether these metabolic changes are the cause or consequence of carcinogenesis and oncogenic cell-selective pressures. Although historic results have been conflicting, recent data has found an increased lung cancer risk in asthma patients, independent of risk factors. A review of emerging research on the metabolic changes seen in asthma helps us to propose a pathway between the initiation of aerobic glycolysis and the selective pressures of the epithelial microenvironment and resulting malignant transformation risk.
{"title":"Metabolic adaption of epithelial cells in asthma: a window to the initiation of carcinogenesis?","authors":"Thomas Dymond","doi":"10.37349/eaa.2024.00043","DOIUrl":"https://doi.org/10.37349/eaa.2024.00043","url":null,"abstract":"Recent data has resulted in an interest in the metabolic shift in cellular metabolism to aerobic glycolysis, increased reactive oxygen species (ROS), and mitochondrial dysfunction associated with asthma. There has been a push to better understand the immune and metabolic changes in allergy to improve understanding of disease pathology and treatment. Aerobic glycolysis seen in epithelial cells in asthma promotes chronic inflammation and the production of inflammatory cytokines. Asthma epithelial cells share a number of features proposed in the stages of cancer initiation including aerobic glycolysis and increased apoptosis with proliferation, all within a chronic inflammatory microenvironment. Metabolic reprogramming in malignant cells has been widely investigated since the glycolytic characteristics were first described last century. It is still debated whether these metabolic changes are the cause or consequence of carcinogenesis and oncogenic cell-selective pressures. Although historic results have been conflicting, recent data has found an increased lung cancer risk in asthma patients, independent of risk factors. A review of emerging research on the metabolic changes seen in asthma helps us to propose a pathway between the initiation of aerobic glycolysis and the selective pressures of the epithelial microenvironment and resulting malignant transformation risk.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"33 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141354235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgia Papaiakovou, Apostolos Papageorgiou, Agamemnon Bakakos, Athanasios C. Sinaniotis, N. Rovina
Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic conditions, characterized by an excessive accumulation of eosinophils in various areas of the mucosal of the gastrointestinal (GI) tract. EGIDs encompass a spectrum of diseases, including eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC), each affecting different segments of the GI tract. The pathogenesis of EGIDs is multifaceted and involves an intricate interplay between genetic predisposition, environmental triggers, and dysregulated immune responses. Although the exact etiology behind EGIDs is not fully understood, it is clear that they are immune-mediated, with eosinophils having a central role in inflammation and tissue damage of GI mucosal. Clinical manifestations depend on the organ that is affected by the disease and on the depth of the eosinophil infiltration of the bowel wall. They range from mild discomfort to severe dysphagia, abdominal pain, malnutrition, and growth failure, particularly in pediatric cases. Regarding EGID management, it is a challenging issue to achieve clinical and histologic remission using pharmacotherapy and dietary elimination. Corticosteroids and proton pump inhibitors can be selected as an effective first-line treatment for certain patients and six-food elimination diet (6-FED) has been proven effective in inducing remission. Furthermore, biologic therapies have emerged as essential tools in controlling eosinophilic-driven inflammation. This review focuses on the complex pathogenesis and treatment of these inflammatory diseases, especially EoE.
{"title":"Eosinophilic gastrointestinal diseases: current perspectives on pathogenesis and management","authors":"Georgia Papaiakovou, Apostolos Papageorgiou, Agamemnon Bakakos, Athanasios C. Sinaniotis, N. Rovina","doi":"10.37349/eaa.2024.00041","DOIUrl":"https://doi.org/10.37349/eaa.2024.00041","url":null,"abstract":"Eosinophilic gastrointestinal diseases (EGIDs) are a group of chronic conditions, characterized by an excessive accumulation of eosinophils in various areas of the mucosal of the gastrointestinal (GI) tract. EGIDs encompass a spectrum of diseases, including eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC), each affecting different segments of the GI tract. The pathogenesis of EGIDs is multifaceted and involves an intricate interplay between genetic predisposition, environmental triggers, and dysregulated immune responses. Although the exact etiology behind EGIDs is not fully understood, it is clear that they are immune-mediated, with eosinophils having a central role in inflammation and tissue damage of GI mucosal. Clinical manifestations depend on the organ that is affected by the disease and on the depth of the eosinophil infiltration of the bowel wall. They range from mild discomfort to severe dysphagia, abdominal pain, malnutrition, and growth failure, particularly in pediatric cases. Regarding EGID management, it is a challenging issue to achieve clinical and histologic remission using pharmacotherapy and dietary elimination. Corticosteroids and proton pump inhibitors can be selected as an effective first-line treatment for certain patients and six-food elimination diet (6-FED) has been proven effective in inducing remission. Furthermore, biologic therapies have emerged as essential tools in controlling eosinophilic-driven inflammation. This review focuses on the complex pathogenesis and treatment of these inflammatory diseases, especially EoE.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":" 69","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141374753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study aims at assessing dupilumab’s response in severe chronic rhinosinusitis with nasal polyps (CRSwNP) and its impact on concurrent mild to moderate asthma. Methods: The study involved severe, uncontrolled CRSwNP patients starting dupilumab treatment (300 mg/2 weeks) at the Allergy unit in University General Hospital “Attikon” in Athens, Greece, from May 2020 to July 2022. Assessments were conducted at baseline (week 0) and weeks 2, 4, 16, 24, and 52, covering 22-item Sino-Nasal Outcome Test (SNOT22), blood eosinophil counts, fractional exhaled nitric oxide (FeNO) concentration, Lund-Mackay CT scores (weeks 0, 16, and 52), Asthma Control Test (ACT) scores (weeks 0, 16, and 52), and forced expiratory volume in one second (FEV1) measurements (weeks 0, 16, and 52). Systemic corticosteroid usage, nasal surgeries, and anosmia improvements were also monitored throughout the study. Results: Six patients (50% male, mean age 53.1 years) with severe CRSwNP had severe uncontrolled baseline symptoms: complete anosmia, impaired quality of life (mean SNOT22: 71.6 ± 16.2), and Lund-Mackay CT score of 19.3 ± 2. Within the past year, 83.3% received over three courses of systemic corticosteroids for CRSwNP, and 50% had more than three polypectomies. After two weeks of dupilumab treatment, notable improvements were seen: reduced SNOT22 scores (week 2: 32.5, week 4: 18.1, week 16: 14, week 24: 13.8, week 52: 9.3), improved olfaction (weeks 4–16), reduced polyp size based on Lund-Mackay CT score (week 16: 13.3, week 52: 12.8), and enhanced lung function (FEV1 baseline: 3.15 L, week 16: 3.22 L, week 52: 3.22 L). Control was achieved by week 16 (ACT: 25/25). FeNO levels decreased [week 2: (18.2 ± 8.7) ppb, week 4: (16.5 ± 7.4) ppb, week 16: (16.9 ± 7.8) ppb, week 24: (13.7 ± 8.3) ppb, week 52: (13.4 ± 5.6) ppb]. No patients required nasal surgery. Conclusions: Dupilumab effectively targets interleukin 4 (IL4) and IL13, controlling type 2 inflammation spectrum, thus providing significant disease control for CRSwNP patients. Moreover, it improves asthma, even in mild to moderate cases, showcasing its broader therapeutic benefits.
{"title":"Dupilumab treatment for severe chronic rhinosinusitis with nasal polyps: efficacy and impact on co-existing mild to moderate asthma","authors":"Niki Papapostolou, M. Makris","doi":"10.37349/eaa.2024.00039","DOIUrl":"https://doi.org/10.37349/eaa.2024.00039","url":null,"abstract":"Aim: This study aims at assessing dupilumab’s response in severe chronic rhinosinusitis with nasal polyps (CRSwNP) and its impact on concurrent mild to moderate asthma. Methods: The study involved severe, uncontrolled CRSwNP patients starting dupilumab treatment (300 mg/2 weeks) at the Allergy unit in University General Hospital “Attikon” in Athens, Greece, from May 2020 to July 2022. Assessments were conducted at baseline (week 0) and weeks 2, 4, 16, 24, and 52, covering 22-item Sino-Nasal Outcome Test (SNOT22), blood eosinophil counts, fractional exhaled nitric oxide (FeNO) concentration, Lund-Mackay CT scores (weeks 0, 16, and 52), Asthma Control Test (ACT) scores (weeks 0, 16, and 52), and forced expiratory volume in one second (FEV1) measurements (weeks 0, 16, and 52). Systemic corticosteroid usage, nasal surgeries, and anosmia improvements were also monitored throughout the study. Results: Six patients (50% male, mean age 53.1 years) with severe CRSwNP had severe uncontrolled baseline symptoms: complete anosmia, impaired quality of life (mean SNOT22: 71.6 ± 16.2), and Lund-Mackay CT score of 19.3 ± 2. Within the past year, 83.3% received over three courses of systemic corticosteroids for CRSwNP, and 50% had more than three polypectomies. After two weeks of dupilumab treatment, notable improvements were seen: reduced SNOT22 scores (week 2: 32.5, week 4: 18.1, week 16: 14, week 24: 13.8, week 52: 9.3), improved olfaction (weeks 4–16), reduced polyp size based on Lund-Mackay CT score (week 16: 13.3, week 52: 12.8), and enhanced lung function (FEV1 baseline: 3.15 L, week 16: 3.22 L, week 52: 3.22 L). Control was achieved by week 16 (ACT: 25/25). FeNO levels decreased [week 2: (18.2 ± 8.7) ppb, week 4: (16.5 ± 7.4) ppb, week 16: (16.9 ± 7.8) ppb, week 24: (13.7 ± 8.3) ppb, week 52: (13.4 ± 5.6) ppb]. No patients required nasal surgery. Conclusions: Dupilumab effectively targets interleukin 4 (IL4) and IL13, controlling type 2 inflammation spectrum, thus providing significant disease control for CRSwNP patients. Moreover, it improves asthma, even in mild to moderate cases, showcasing its broader therapeutic benefits.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"114 S1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141377785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: Chronic migraine (CM) is a condition characterized by attacks of severe headaches leading to an increase in time off work, decrease in work productivity and in physical functioning. The aim of this study was to investigate the role of sinus anatomic variants (SAV) on the evolution of migraine from episodic to chronic form. Methods: Two hundred and seven migraineurs [110 with episodic migraine (EM) and 97 with CM] with no evidence of nasal septal deviation with a contact point on the lateral nasal wall were evaluated for endoscopic, radiologic and anatomic variant (AV) abnormalities using Lund-Kennedy endoscopy (LKES) and Lund-Mackay radiology scores (LMRS). Headache day frequency, duration, severity and lost time at work were compared with regard to the presence of any AV and concha bullosa (CB) as well. Results: There was a very significant difference between EM and CM patients with regard to overall SAV and endoscopy scores. However, no significant difference was seen between the groups with regard to radiology scores and headache pain severity. The presence of one AV increased headache day frequency, severity and days off work in all patients. CB was found to worsen headache severity and lost time at work in all patients. Conclusions: Patients with CM have more SAV and worse endoscopy scores than patients with EM. The presence of any of the AVs increases headache day frequency, pain severity and days off work in migraineurs.
目的：慢性偏头痛（CM）是一种以发作性剧烈头痛为特征的疾病，会导致请假时间增加、工作效率降低和身体机能下降。本研究旨在探讨窦解剖变异（SAV）对偏头痛从发作型向慢性型演变的作用。研究方法采用伦德-肯尼迪内窥镜检查法（LKES）和伦德-马凯放射学评分法（LMRS）对无鼻中隔偏曲证据且鼻侧壁有接触点的 27 名偏头痛患者（110 名发作性偏头痛患者和 97 名慢性偏头痛患者）进行内窥镜、放射学和解剖变异（AV）异常评估。比较了头痛日频率、持续时间、严重程度和误工时间，以及是否存在任何房室和结节（CB）。结果显示EM和CM患者在SAV和内窥镜检查的总体评分方面存在非常明显的差异。但是，在放射学评分和头痛疼痛严重程度方面，两组之间没有明显差异。在所有患者中，一个 AV 的存在会增加头痛日频率、严重程度和请假天数。研究发现，CB 会加重所有患者的头痛严重程度和误工时间。结论：与 EM 患者相比，CM 患者的 SAV 更多，内镜检查评分更差。任何一种视网膜病变的存在都会增加偏头痛患者的头痛日频率、疼痛严重程度和请假天数。
{"title":"Relation of sinonasal anatomic variants with the frequency, pain severity and time off work in patients with migraine","authors":"A. Verim, S. Külekçi, Tuğba Çelik","doi":"10.37349/eaa.2024.00040","DOIUrl":"https://doi.org/10.37349/eaa.2024.00040","url":null,"abstract":"Aim: Chronic migraine (CM) is a condition characterized by attacks of severe headaches leading to an increase in time off work, decrease in work productivity and in physical functioning. The aim of this study was to investigate the role of sinus anatomic variants (SAV) on the evolution of migraine from episodic to chronic form. Methods: Two hundred and seven migraineurs [110 with episodic migraine (EM) and 97 with CM] with no evidence of nasal septal deviation with a contact point on the lateral nasal wall were evaluated for endoscopic, radiologic and anatomic variant (AV) abnormalities using Lund-Kennedy endoscopy (LKES) and Lund-Mackay radiology scores (LMRS). Headache day frequency, duration, severity and lost time at work were compared with regard to the presence of any AV and concha bullosa (CB) as well. Results: There was a very significant difference between EM and CM patients with regard to overall SAV and endoscopy scores. However, no significant difference was seen between the groups with regard to radiology scores and headache pain severity. The presence of one AV increased headache day frequency, severity and days off work in all patients. CB was found to worsen headache severity and lost time at work in all patients. Conclusions: Patients with CM have more SAV and worse endoscopy scores than patients with EM. The presence of any of the AVs increases headache day frequency, pain severity and days off work in migraineurs.","PeriodicalId":438747,"journal":{"name":"Exploration of Asthma & Allergy","volume":"340 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141380889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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