Suneela Zaigham, Nils Oskar Jõgi, Robert Movérare, Anders Sjölander, Niclas Rydell, Magnus Molin, Christer Janson, Andrei Malinovschi
<p>Eosinophilic inflammation in asthma is related to disease severity, lung function decline, disease control and response to corticosteroids during exacerbations [<span>1-3</span>]. Eosinophil activation leads to the release of cytokines, lipid mediators, chemotactic polypeptides and cytotoxic proteins that promote a pro-inflammatory host response and neutralises pathogens [<span>4</span>]. One of the cytotoxic granule proteins released during degranulation of activated eosinophils is the eosinophil-derived neurotoxin (EDN). Serum EDN is emerging as a novel marker of eosinophilic inflammation in patients with asthma [<span>4</span>]. In order to implement serum EDN as a marker in clinical practice, determinants and reference ranges for EDN need to be clearly established. Recently, EDN reference values were defined in early childhood [<span>5</span>]; however, further large studies defining values in older adults are needed. We aimed to study determinants of EDN using the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population study of middle-aged adults and propose reference values for EDN, including the lower (LLN) and upper limit of normal (ULN), in a healthy sub-population.</p><p>The Swedish CArdioPulmonary bioImage Study is a national, multicentred, population-based study of randomly selected men and women aged 50–64 years. Nationally, 30,154 men and women participated and from the Uppsala cohort 5036 subjects [<span>6</span>]. Serum EDN was an add-on measurement in the Uppsala cohort of SCAPIS (<i>n</i> = 4916) and was measured using an ImmunoCAP EDN research assay as described elsewhere [<span>7</span>]. EDN values were log-transformed for analysis. Univariate analyses were carried out to assess determinants of EDN, including age, sex, lifestyle, clinical conditions (assessed via questionnaire) and laboratory data. Independent sample <i>t</i>-tests were used to obtain mean values of EDN by each potential determining factor. The <i>p</i>-values were adjusted for false discovery rate (FDR) using the Benjamini–Hochberg method. Multiple linear regression models were used to assess the effect of determining factors on EDN. To define normal values of EDN, we selected a healthy population based on subjects free from EDN-modifying conditions. In this healthy sub-cohort, we used the 5<sup>th</sup> (LLN), 50<sup>th</sup> (median), 75<sup>th</sup>, 90<sup>th</sup> and 95<sup>th</sup> (ULN) percentiles to determine reference levels for serum EDN.</p><p>Male sex, body mass index (BMI) > 25, current smoking, presence of atopy, ever asthma, allergic rhinitis, angina pectoris, heart failure, hypertension, diabetes and impaired kidney function were all associated with higher mean EDN levels. Both pre-bronchodilatory FEV<sub>1</sub> < LLN and a post-bronchodilatory FEV<sub>1</sub>/FVC ratio < 0.70 were associated with higher mean EDN levels. After adjusting the <i>p</i>-values for FDR, these determining factors remained significantly
{"title":"Eosinophil-Derived Neurotoxin Determinants and Reference Values in a Swedish Middle-Aged General Population","authors":"Suneela Zaigham, Nils Oskar Jõgi, Robert Movérare, Anders Sjölander, Niclas Rydell, Magnus Molin, Christer Janson, Andrei Malinovschi","doi":"10.1111/cea.14579","DOIUrl":"10.1111/cea.14579","url":null,"abstract":"<p>Eosinophilic inflammation in asthma is related to disease severity, lung function decline, disease control and response to corticosteroids during exacerbations [<span>1-3</span>]. Eosinophil activation leads to the release of cytokines, lipid mediators, chemotactic polypeptides and cytotoxic proteins that promote a pro-inflammatory host response and neutralises pathogens [<span>4</span>]. One of the cytotoxic granule proteins released during degranulation of activated eosinophils is the eosinophil-derived neurotoxin (EDN). Serum EDN is emerging as a novel marker of eosinophilic inflammation in patients with asthma [<span>4</span>]. In order to implement serum EDN as a marker in clinical practice, determinants and reference ranges for EDN need to be clearly established. Recently, EDN reference values were defined in early childhood [<span>5</span>]; however, further large studies defining values in older adults are needed. We aimed to study determinants of EDN using the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population study of middle-aged adults and propose reference values for EDN, including the lower (LLN) and upper limit of normal (ULN), in a healthy sub-population.</p><p>The Swedish CArdioPulmonary bioImage Study is a national, multicentred, population-based study of randomly selected men and women aged 50–64 years. Nationally, 30,154 men and women participated and from the Uppsala cohort 5036 subjects [<span>6</span>]. Serum EDN was an add-on measurement in the Uppsala cohort of SCAPIS (<i>n</i> = 4916) and was measured using an ImmunoCAP EDN research assay as described elsewhere [<span>7</span>]. EDN values were log-transformed for analysis. Univariate analyses were carried out to assess determinants of EDN, including age, sex, lifestyle, clinical conditions (assessed via questionnaire) and laboratory data. Independent sample <i>t</i>-tests were used to obtain mean values of EDN by each potential determining factor. The <i>p</i>-values were adjusted for false discovery rate (FDR) using the Benjamini–Hochberg method. Multiple linear regression models were used to assess the effect of determining factors on EDN. To define normal values of EDN, we selected a healthy population based on subjects free from EDN-modifying conditions. In this healthy sub-cohort, we used the 5<sup>th</sup> (LLN), 50<sup>th</sup> (median), 75<sup>th</sup>, 90<sup>th</sup> and 95<sup>th</sup> (ULN) percentiles to determine reference levels for serum EDN.</p><p>Male sex, body mass index (BMI) > 25, current smoking, presence of atopy, ever asthma, allergic rhinitis, angina pectoris, heart failure, hypertension, diabetes and impaired kidney function were all associated with higher mean EDN levels. Both pre-bronchodilatory FEV<sub>1</sub> < LLN and a post-bronchodilatory FEV<sub>1</sub>/FVC ratio < 0.70 were associated with higher mean EDN levels. After adjusting the <i>p</i>-values for FDR, these determining factors remained significantly ","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 1","pages":"91-93"},"PeriodicalIF":6.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459404","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}
Lichen Li, Dean J. Naisbitt, Yonghu Sun, Furen Zhang
Biological agents are widely used across medicine, including for immune-mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased. Herein, we discuss the pathomechanism of adverse reactions to biological agents used to treat skin conditions and apply these to Pichler's classification system. This classification differentiates five distinct types, namely overstimulation (type α), hypersensitivity or immunogenicity (β), immunodeviation (γ), cross-reactivity (δ) and nonimmunologic adverse reactions (ε). This classification covers most types of adverse reactions associated with use of biological agents and could be used to better understand the reaction pathogenesis and manage the clinical features of biological adverse effects.
{"title":"Pathomechanism of Adverse Reactions to Biological Treatment of Inflammatory Skin Conditions","authors":"Lichen Li, Dean J. Naisbitt, Yonghu Sun, Furen Zhang","doi":"10.1111/cea.14583","DOIUrl":"10.1111/cea.14583","url":null,"abstract":"<div>\u0000 \u0000 <p>Biological agents are widely used across medicine, including for immune-mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased. Herein, we discuss the pathomechanism of adverse reactions to biological agents used to treat skin conditions and apply these to Pichler's classification system. This classification differentiates five distinct types, namely overstimulation (type α), hypersensitivity or immunogenicity (β), immunodeviation (γ), cross-reactivity (δ) and nonimmunologic adverse reactions (ε). This classification covers most types of adverse reactions associated with use of biological agents and could be used to better understand the reaction pathogenesis and manage the clinical features of biological adverse effects.</p>\u0000 </div>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"54 12","pages":"973-983"},"PeriodicalIF":6.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abigail Lang, Samantha Gadd, Lauren Gunderman, Elizabeth Lippner, Ashley Devonshire, Matthew J. Schipma, Sergejs Berdnikovs, Rajesh Kumar
<p>Peanut allergy affects up to 2%–4% of children in the United States [<span>1</span>]. Despite advances in peanut allergy prevention through early introduction [<span>2</span>], there is limited understanding of molecular processes that drive development of peanut allergy. Similarly, differences between infants who tolerate peanut but demonstrate allergic sensitization and those with clinical reactivity to peanut are poorly understood. In a pilot study by our group, infants at high risk for peanut allergy demonstrated differential gene expression by clinical phenotype, but the magnitude of differences was not clinically significant given the variance of expression [<span>3</span>]. Further exploration of gene networks from differentially expressed gene (DEG) signatures may provide better targets for future studies. The primary objective of this study was to analyse the transcriptomic signature of a cohort of infants at risk for peanut allergy utilising whole blood RNA sequencing. We hypothesized that infants with peanut allergy would have differential expression of genes involved in immune pathways when compared to infants tolerant of peanut, with or without sensitization to peanut.</p><p>Infants aged 4–11 months (<i>n</i> = 70) with peanut allergy risk factors (egg allergy, moderate to severe atopic dermatitis, or both) were recruited from Ann and Robert H. Lurie Children's Hospital of Chicago between 2018 and 2021. Subjects were classified as either peanut non-allergic (PNA), peanut sensitised (PS), or peanut allergic (PA). PA subjects had a convincing clinical history of reaction to peanut and peanut skin prick (SPT) wheal ≥ 3 mm or peanut SPT wheal ≥ 8 mm without history of consumption. Subjects regularly consuming peanut without history of an adverse reaction to peanut or who had never consumed peanut and had peanut SPT wheal size of 0–2 mm were classified as PNA. Infants who had ingested peanut without clinical reaction or passed a peanut oral food challenge (OFC) and had a peanut SPT wheal size of 3–7 mm or positive peanut specific IgE (sIgE) were classified as PS.</p><p>RNA-seq was performed on whole blood. Deconvolution of gene expression by immune cell type showed no clinically significant differences between peanut allergy groups. Comparison of gene expression profiles by peanut allergy status was carried out using <i>DESeq2</i> [<span>4</span>]. DEGs were split into upregulated and downregulated groups and were analysed separately in pathway analyses performed using Metascape [<span>5</span>]. Significant differences in single gene expression between groups were reported if there was ≥ ± absolute log<sub>2</sub> fold change of 0.3 and FDR-corrected <i>p</i> ≤ 0.05.</p><p>Half of the population was PNA (<i>n =</i> 35, 50%), 12 subjects (17%) were PS, and 23 subjects were PA (33%). Most subjects in each sub-group were male and had eczema. When adjusted for multiple comparisons, there were no statistically significant DEGs between PA a
{"title":"Whole Blood Transcriptomics Identifies Differences in Innate Immune Pathway Expression in Infants at Risk for Peanut Allergy","authors":"Abigail Lang, Samantha Gadd, Lauren Gunderman, Elizabeth Lippner, Ashley Devonshire, Matthew J. Schipma, Sergejs Berdnikovs, Rajesh Kumar","doi":"10.1111/cea.14587","DOIUrl":"10.1111/cea.14587","url":null,"abstract":"<p>Peanut allergy affects up to 2%–4% of children in the United States [<span>1</span>]. Despite advances in peanut allergy prevention through early introduction [<span>2</span>], there is limited understanding of molecular processes that drive development of peanut allergy. Similarly, differences between infants who tolerate peanut but demonstrate allergic sensitization and those with clinical reactivity to peanut are poorly understood. In a pilot study by our group, infants at high risk for peanut allergy demonstrated differential gene expression by clinical phenotype, but the magnitude of differences was not clinically significant given the variance of expression [<span>3</span>]. Further exploration of gene networks from differentially expressed gene (DEG) signatures may provide better targets for future studies. The primary objective of this study was to analyse the transcriptomic signature of a cohort of infants at risk for peanut allergy utilising whole blood RNA sequencing. We hypothesized that infants with peanut allergy would have differential expression of genes involved in immune pathways when compared to infants tolerant of peanut, with or without sensitization to peanut.</p><p>Infants aged 4–11 months (<i>n</i> = 70) with peanut allergy risk factors (egg allergy, moderate to severe atopic dermatitis, or both) were recruited from Ann and Robert H. Lurie Children's Hospital of Chicago between 2018 and 2021. Subjects were classified as either peanut non-allergic (PNA), peanut sensitised (PS), or peanut allergic (PA). PA subjects had a convincing clinical history of reaction to peanut and peanut skin prick (SPT) wheal ≥ 3 mm or peanut SPT wheal ≥ 8 mm without history of consumption. Subjects regularly consuming peanut without history of an adverse reaction to peanut or who had never consumed peanut and had peanut SPT wheal size of 0–2 mm were classified as PNA. Infants who had ingested peanut without clinical reaction or passed a peanut oral food challenge (OFC) and had a peanut SPT wheal size of 3–7 mm or positive peanut specific IgE (sIgE) were classified as PS.</p><p>RNA-seq was performed on whole blood. Deconvolution of gene expression by immune cell type showed no clinically significant differences between peanut allergy groups. Comparison of gene expression profiles by peanut allergy status was carried out using <i>DESeq2</i> [<span>4</span>]. DEGs were split into upregulated and downregulated groups and were analysed separately in pathway analyses performed using Metascape [<span>5</span>]. Significant differences in single gene expression between groups were reported if there was ≥ ± absolute log<sub>2</sub> fold change of 0.3 and FDR-corrected <i>p</i> ≤ 0.05.</p><p>Half of the population was PNA (<i>n =</i> 35, 50%), 12 subjects (17%) were PS, and 23 subjects were PA (33%). Most subjects in each sub-group were male and had eczema. When adjusted for multiple comparisons, there were no statistically significant DEGs between PA a","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 1","pages":"100-103"},"PeriodicalIF":6.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459420","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}
Robert J. Boyle, Victoria L. Sibson, Christoffer van Tulleken
<p>Last month, the World Health Organisation (WHO) published new resources to support Healthcare Professional Associations (HCPA) wishing to avoid conflicts of interest in relation to nutrition companies marketing foods for infants and young children. The new WHO resources include a model policy, suggestions for alternative funding sources and case studies of good practice [<span>1</span>]. The case studies include the Indian Academy of Paediatrics and examples from Africa, which are especially important given the harms associated with formula marketing in these regions [<span>2</span>]. The new resources underscore a long-standing WHO recommendation, made more explicit since 2016—that HCPA (and health workers) should not accept funding from companies that market foods for infants and young children, for either the general running of the HCPA or for supporting HCPA educational or scientific meetings such as an annual congress [<span>3</span>]. The scope of ‘foods’ that relevant companies might market is quite broad, including formula, ‘growing up’ drinks, specialised low-allergy formula, non-liquid foods and even bottles and teats sold for formula feeding. The scope of ‘infants and young children’ is from birth through to age 36 months, the period of time covered by the International Code of Marketing of Breastmilk Substitutes.</p><p>This WHO recommendation has met with significant resistance from HCPAs, including some allergy HCPAs [<span>4</span>]. Two key reasons cited for continuing to accept nutrition industry funding are access to scientific information about nutrition products, and difficulty funding educational and scientific activities without nutrition industry support [<span>5</span>]. Access to scientific information about nutrition products does not require a financial relationship, since companies already provide product information in the public domain and on request, without any exchange of funding. Finding alternative resources for educational and scientific activities is more challenging. So these new WHO resources aim to support HCPAs to address this challenge.</p><p>This month, the British Society for Allergy and Clinical Immunology (BSACI) hosted its first annual conference without sponsorship from any company that markets foods for infants and young children. It is 5 years since the society's announcement that it will no longer accept funding from commercial formula milk companies for its conference and educational activities. Culture change takes time, and reducing income sources is not something which organisations find easy. This is recognised by the WHO, hence the inclusion of case studies to help HCPAs understand that they are not alone in finding this difficult, and a journey is often required to transition away from nutrition industry funding. There are a number of other allergy societies which take a similar approach to BSACI of avoiding formula industry sponsorship. However, these are dwarfed by the major allergy HC
{"title":"Nutrition Industry Sponsorship of Healthcare Professional Associations","authors":"Robert J. Boyle, Victoria L. Sibson, Christoffer van Tulleken","doi":"10.1111/cea.14581","DOIUrl":"https://doi.org/10.1111/cea.14581","url":null,"abstract":"<p>Last month, the World Health Organisation (WHO) published new resources to support Healthcare Professional Associations (HCPA) wishing to avoid conflicts of interest in relation to nutrition companies marketing foods for infants and young children. The new WHO resources include a model policy, suggestions for alternative funding sources and case studies of good practice [<span>1</span>]. The case studies include the Indian Academy of Paediatrics and examples from Africa, which are especially important given the harms associated with formula marketing in these regions [<span>2</span>]. The new resources underscore a long-standing WHO recommendation, made more explicit since 2016—that HCPA (and health workers) should not accept funding from companies that market foods for infants and young children, for either the general running of the HCPA or for supporting HCPA educational or scientific meetings such as an annual congress [<span>3</span>]. The scope of ‘foods’ that relevant companies might market is quite broad, including formula, ‘growing up’ drinks, specialised low-allergy formula, non-liquid foods and even bottles and teats sold for formula feeding. The scope of ‘infants and young children’ is from birth through to age 36 months, the period of time covered by the International Code of Marketing of Breastmilk Substitutes.</p><p>This WHO recommendation has met with significant resistance from HCPAs, including some allergy HCPAs [<span>4</span>]. Two key reasons cited for continuing to accept nutrition industry funding are access to scientific information about nutrition products, and difficulty funding educational and scientific activities without nutrition industry support [<span>5</span>]. Access to scientific information about nutrition products does not require a financial relationship, since companies already provide product information in the public domain and on request, without any exchange of funding. Finding alternative resources for educational and scientific activities is more challenging. So these new WHO resources aim to support HCPAs to address this challenge.</p><p>This month, the British Society for Allergy and Clinical Immunology (BSACI) hosted its first annual conference without sponsorship from any company that markets foods for infants and young children. It is 5 years since the society's announcement that it will no longer accept funding from commercial formula milk companies for its conference and educational activities. Culture change takes time, and reducing income sources is not something which organisations find easy. This is recognised by the WHO, hence the inclusion of case studies to help HCPAs understand that they are not alone in finding this difficult, and a journey is often required to transition away from nutrition industry funding. There are a number of other allergy societies which take a similar approach to BSACI of avoiding formula industry sponsorship. However, these are dwarfed by the major allergy HC","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"54 10","pages":"720-722"},"PeriodicalIF":6.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449087","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>Reflux is commonly cited as the cause of common issues in babies, such as vomiting and crying. Though it is often self-limiting, in many cases, anti-reflux medications and feed thickeners are prescribed to infants and young children. Their use is controversial, and it is not clear whether they are effective. Data shown are trends in community prescribing for total quantity of thickener (Gaviscon infant and Instant Carobel) sachets/live births in England in the previous year (Figure 1); total items of infant anti-reflux medications prescribed/live birth in England in the previous year (Figure 2) [<span>1</span>].</p><p>This Cochrane Corner aims to assess the evidence for pharmacological agents in treating GORD in infants and children.</p><p>GOR is common [<span>2</span>], and GORD incidence in children is estimated at 0.84 per 1000 person years [<span>3</span>]. Several pharmacological treatments are available to treat reflux, including PPIs and H2 receptor antagonists, and they are being prescribed more frequently in recent years [<span>4</span>]. This Cochrane review aimed to establish which were beneficial in children split into subgroups of infants and older children. In addition to the cost of prescribing these medications, it is important to consider the potential side effects, which include infection risk, electrolyte abnormalities and fractures [<span>5</span>]. Similarly, whilst prokinetics such as domperidone, cisapride and erythromycin are effective in managing reflux, they have been associated with the very rare but serious risks of drug-induced long-QT syndrome, Torsades de Pointes and sudden cardiac death, due to a combination of non-modifiable (age, family history of arrhythmias, genetic conditions and co-morbidities) and modifiable risk factors (electrolyte imbalances, concurrent use of other medications). Thus, use of these prokinetics is cautioned against, though cardiac complications of domperidone have not been noted in children [<span>6</span>].</p><p>This Cochrane Review analysed 36 randomised control trials involving 2251 infants and children, out of which 22 trials were excluded due to insufficient data for extraction. The sample sizes of the studies included were small (range = 10–268), and due to methodological differences between the studies, a meta-analysis could not be performed. The trials often used subjective questionnaires, and blinding the trials was a challenge. Although blinding is less of an issue for trials using objective data such as 24-h pH impedance studies and endoscopic findings, the subjective outcome assessments used in these trials are vulnerable to detection bias in the absence of blinding. Such questionnaires do have the benefit of aiding clinicians with decision-making as they are patient-centred.</p><p>Though one trial [<span>7</span>] performed endoscopic studies at baseline, they did not repeat them after the intervention; therefore, no comparisons could be made. In another case, pH indices w
{"title":"Cochrane Corner: Pharmacological Treatment of Gastro-Oesophageal Reflux in Children","authors":"Aahil Damani, Nabeela Bhaloo","doi":"10.1111/cea.14577","DOIUrl":"10.1111/cea.14577","url":null,"abstract":"<p>Reflux is commonly cited as the cause of common issues in babies, such as vomiting and crying. Though it is often self-limiting, in many cases, anti-reflux medications and feed thickeners are prescribed to infants and young children. Their use is controversial, and it is not clear whether they are effective. Data shown are trends in community prescribing for total quantity of thickener (Gaviscon infant and Instant Carobel) sachets/live births in England in the previous year (Figure 1); total items of infant anti-reflux medications prescribed/live birth in England in the previous year (Figure 2) [<span>1</span>].</p><p>This Cochrane Corner aims to assess the evidence for pharmacological agents in treating GORD in infants and children.</p><p>GOR is common [<span>2</span>], and GORD incidence in children is estimated at 0.84 per 1000 person years [<span>3</span>]. Several pharmacological treatments are available to treat reflux, including PPIs and H2 receptor antagonists, and they are being prescribed more frequently in recent years [<span>4</span>]. This Cochrane review aimed to establish which were beneficial in children split into subgroups of infants and older children. In addition to the cost of prescribing these medications, it is important to consider the potential side effects, which include infection risk, electrolyte abnormalities and fractures [<span>5</span>]. Similarly, whilst prokinetics such as domperidone, cisapride and erythromycin are effective in managing reflux, they have been associated with the very rare but serious risks of drug-induced long-QT syndrome, Torsades de Pointes and sudden cardiac death, due to a combination of non-modifiable (age, family history of arrhythmias, genetic conditions and co-morbidities) and modifiable risk factors (electrolyte imbalances, concurrent use of other medications). Thus, use of these prokinetics is cautioned against, though cardiac complications of domperidone have not been noted in children [<span>6</span>].</p><p>This Cochrane Review analysed 36 randomised control trials involving 2251 infants and children, out of which 22 trials were excluded due to insufficient data for extraction. The sample sizes of the studies included were small (range = 10–268), and due to methodological differences between the studies, a meta-analysis could not be performed. The trials often used subjective questionnaires, and blinding the trials was a challenge. Although blinding is less of an issue for trials using objective data such as 24-h pH impedance studies and endoscopic findings, the subjective outcome assessments used in these trials are vulnerable to detection bias in the absence of blinding. Such questionnaires do have the benefit of aiding clinicians with decision-making as they are patient-centred.</p><p>Though one trial [<span>7</span>] performed endoscopic studies at baseline, they did not repeat them after the intervention; therefore, no comparisons could be made. In another case, pH indices w","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"54 12","pages":"956-959"},"PeriodicalIF":6.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388512","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}
Danilo Di Bona, Massimo Bilancia, Claudia Crimi, Michelina Daddato, Alida Benfante, Maria Filomena Caiaffa, Cecilia Calabrese, Raffaele Campisi, Santi Nolasco, Giovanna Elisiana Carpagnano, Maria D'Amato, Corrado Pelaia, Girolamo Pelaia, Angelantonio Maglio, Nicola Scichilone, Giulia Scioscia, Giuseppe Spadaro, Massimo Triggiani, Isabella Carrieri, Giuseppe Valenti, Alessandro Vatrella, Luigi Macchia, Nunzio Crimi
This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.
{"title":"Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab","authors":"Danilo Di Bona, Massimo Bilancia, Claudia Crimi, Michelina Daddato, Alida Benfante, Maria Filomena Caiaffa, Cecilia Calabrese, Raffaele Campisi, Santi Nolasco, Giovanna Elisiana Carpagnano, Maria D'Amato, Corrado Pelaia, Girolamo Pelaia, Angelantonio Maglio, Nicola Scichilone, Giulia Scioscia, Giuseppe Spadaro, Massimo Triggiani, Isabella Carrieri, Giuseppe Valenti, Alessandro Vatrella, Luigi Macchia, Nunzio Crimi","doi":"10.1111/cea.14584","DOIUrl":"10.1111/cea.14584","url":null,"abstract":"<p>This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 2","pages":"202-204"},"PeriodicalIF":6.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dimitry Buyansky, Roy Khalaf, Sofianne Gabrielli, Julia Upton, Eyal Grunebaum, Edmond S. Chan, Ingrid Baerg, Liane Beaudette, Danbing Ke, Bruce Mazer, Christine McCusker, Duncan Lejtenyi, Moshe Ben-Shoshan
<p>Following anaphylaxis, previous guidelines mandate the transfer of the affected individual to the emergency department (ED) for further assessment. The Canadian Paediatric Society (CPS) suggests a minimum period of observation in the ED of 4–6 h following onset of allergic symptoms to evaluate the need for additional interventions and manage potential biphasic reactions. Translating Emergency Knowledge for Kids (TREKK) has similar recommendations depending on the severity of the reaction and patient-specific risk factors, ranging from a 2-h observation to an overnight stay if deemed necessary [<span>1, 2</span>]. More recent US guidelines call against routine transfer to ED of all anaphylaxis cases following epinephrine use, advising case-by-case evaluation based on patient factors and relation circumstances [<span>3, 4</span>]. This paper aims to examine the differences in anaphylaxis management and associated characteristics among two groups: those who presented to the ED after an anaphylactic episode and those who did not in a cohort of children who have challenge-confirmed diagnoses of milk allergy and are currently undergoing oral immunotherapy to cow's milk (OIT).</p><p>In this retrospective cohort study, we analysed data from the year 2014 to 2023 inclusively. Participants selected were paediatric patients undergoing milk OIT at three children's hospitals across Canada: the Montreal Children's Hospital (Montreal), the British Columbia Children's Hospital (Vancouver) and the Hospital for Sick Children (Toronto). Only adverse reactions meeting the definition of anaphylaxis according to the National Institute of Allergy and Infectious Disease classification were included in the analysis [<span>5</span>]. The Muraro et al. [<span>6</span>] grading system was used to categorise the severity of anaphylactic reactions. Participants were grouped into two categories based on their response post-reaction: those who visited the ED and those who managed the reaction entirely at home. Descriptive statistics were used to present demographic, clinical management characteristics and levels of biomarkers. All statistical data were analysed using R 4.2.3 binary for macOs 10.3 (R Foundation for Statistical Computing, Vienna, Austria). Categorical data were presented as percentages, and continuous data as a median (interquartile range [IQR]). Fisher's test was used to compare categorical variables and Mann–Whitney test was used to compare continuous variables. This study was approved by participating centres ethics committees.</p><p>The study included 27 paediatric patients undergoing cow's milk OIT. The median age of patients at the start of OIT was 12.0 years (9.5–14.0) and 51.9% were males. Out of the 27 patients included in the study, 92.6% had asthma. A total of 60 anaphylactic reactions were reported from 2014 to 2023. Notably, 63.3% resulted in a visit to the ED. The updosing phase was identified as a particularly vulnerable period, with most anaphy
{"title":"Anaphylaxis Management in Paediatric Patients Undergoing Milk Oral Immunotherapy","authors":"Dimitry Buyansky, Roy Khalaf, Sofianne Gabrielli, Julia Upton, Eyal Grunebaum, Edmond S. Chan, Ingrid Baerg, Liane Beaudette, Danbing Ke, Bruce Mazer, Christine McCusker, Duncan Lejtenyi, Moshe Ben-Shoshan","doi":"10.1111/cea.14582","DOIUrl":"10.1111/cea.14582","url":null,"abstract":"<p>Following anaphylaxis, previous guidelines mandate the transfer of the affected individual to the emergency department (ED) for further assessment. The Canadian Paediatric Society (CPS) suggests a minimum period of observation in the ED of 4–6 h following onset of allergic symptoms to evaluate the need for additional interventions and manage potential biphasic reactions. Translating Emergency Knowledge for Kids (TREKK) has similar recommendations depending on the severity of the reaction and patient-specific risk factors, ranging from a 2-h observation to an overnight stay if deemed necessary [<span>1, 2</span>]. More recent US guidelines call against routine transfer to ED of all anaphylaxis cases following epinephrine use, advising case-by-case evaluation based on patient factors and relation circumstances [<span>3, 4</span>]. This paper aims to examine the differences in anaphylaxis management and associated characteristics among two groups: those who presented to the ED after an anaphylactic episode and those who did not in a cohort of children who have challenge-confirmed diagnoses of milk allergy and are currently undergoing oral immunotherapy to cow's milk (OIT).</p><p>In this retrospective cohort study, we analysed data from the year 2014 to 2023 inclusively. Participants selected were paediatric patients undergoing milk OIT at three children's hospitals across Canada: the Montreal Children's Hospital (Montreal), the British Columbia Children's Hospital (Vancouver) and the Hospital for Sick Children (Toronto). Only adverse reactions meeting the definition of anaphylaxis according to the National Institute of Allergy and Infectious Disease classification were included in the analysis [<span>5</span>]. The Muraro et al. [<span>6</span>] grading system was used to categorise the severity of anaphylactic reactions. Participants were grouped into two categories based on their response post-reaction: those who visited the ED and those who managed the reaction entirely at home. Descriptive statistics were used to present demographic, clinical management characteristics and levels of biomarkers. All statistical data were analysed using R 4.2.3 binary for macOs 10.3 (R Foundation for Statistical Computing, Vienna, Austria). Categorical data were presented as percentages, and continuous data as a median (interquartile range [IQR]). Fisher's test was used to compare categorical variables and Mann–Whitney test was used to compare continuous variables. This study was approved by participating centres ethics committees.</p><p>The study included 27 paediatric patients undergoing cow's milk OIT. The median age of patients at the start of OIT was 12.0 years (9.5–14.0) and 51.9% were males. Out of the 27 patients included in the study, 92.6% had asthma. A total of 60 anaphylactic reactions were reported from 2014 to 2023. Notably, 63.3% resulted in a visit to the ED. The updosing phase was identified as a particularly vulnerable period, with most anaphy","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 1","pages":"94-96"},"PeriodicalIF":6.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388510","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}
Marcus Sim, Vibha Sharma, Karen Li, Mary Hazel Gowland, Tomaz Garcez, Cassandra Shilladay, Richard Pumphrey, Nandinee Patel, Paul J. Turner, Robert J. Boyle
Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human in vivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1–2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100–500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.
{"title":"Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis","authors":"Marcus Sim, Vibha Sharma, Karen Li, Mary Hazel Gowland, Tomaz Garcez, Cassandra Shilladay, Richard Pumphrey, Nandinee Patel, Paul J. Turner, Robert J. Boyle","doi":"10.1111/cea.14565","DOIUrl":"10.1111/cea.14565","url":null,"abstract":"<p>Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human in vivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1–2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100–500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.</p>","PeriodicalId":10207,"journal":{"name":"Clinical and Experimental Allergy","volume":"55 1","pages":"19-35"},"PeriodicalIF":6.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388509","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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