Julia Hiller , Thomas Göen , Hans Drexler , Carola Berking , Nicola Wagner
{"title":"长期接受皮下免疫疗法的患者铝排泄量升高--一项横断面病例对照研究","authors":"Julia Hiller , Thomas Göen , Hans Drexler , Carola Berking , Nicola Wagner","doi":"10.1016/j.ijheh.2024.114337","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones.</p></div><div><h3>Objectives</h3><p>Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans.</p></div><div><h3>Methods</h3><p>This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed.</p></div><div><h3>Results</h3><p>Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Al<sub>urine</sub> = 8.258 + 0.133*Al<sub>cum</sub>; p = 0.001).</p></div><div><h3>Discussion</h3><p>These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. Considering the medical benefits of Al-adjuvants and SCIT a differentiated risk-benefit analysis is needed. For certain scenarios of potential toxicological concern in clinical practice biomonitoring might be advisable.</p></div>","PeriodicalId":13994,"journal":{"name":"International journal of hygiene and environmental health","volume":"258 ","pages":"Article 114337"},"PeriodicalIF":4.5000,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S143846392400018X/pdfft?md5=55cfc4471042238f0e417584adc7a59c&pid=1-s2.0-S143846392400018X-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Elevated aluminum excretion in patients by long-term subcutaneous immunotherapy – A cross-sectional case-control study\",\"authors\":\"Julia Hiller , Thomas Göen , Hans Drexler , Carola Berking , Nicola Wagner\",\"doi\":\"10.1016/j.ijheh.2024.114337\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones.</p></div><div><h3>Objectives</h3><p>Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans.</p></div><div><h3>Methods</h3><p>This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed.</p></div><div><h3>Results</h3><p>Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Al<sub>urine</sub> = 8.258 + 0.133*Al<sub>cum</sub>; p = 0.001).</p></div><div><h3>Discussion</h3><p>These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. 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Elevated aluminum excretion in patients by long-term subcutaneous immunotherapy – A cross-sectional case-control study
Background
Aluminum (Al) adjuvants have been used in vaccines and subcutaneous immunotherapy (SCIT) for decades. Despite indisputable neurotoxic properties of Al, there is no clear evidence of a causal relationship between their use and any neurotoxic side effects. However, recent rat studies have shown an accumulation of Al from adjuvants in tissues, especially in bones.
Objectives
Since the human toxicokinetics of Al-adjuvants are poorly understood, this study aimed to evaluate whether up-dosed or long-term SCIT with Al-coupled extracts leads to increased Al load in humans.
Methods
This observational cross-sectional case-control study explored Al excretion in hymenoptera venom allergy patients recruited in 2020 before initiation (n = 10) and during ongoing (n = 12) SCIT with Al-based preparations. Urine samples were collected before and 24 h after the SCIT injections and analyzed for aluminum content by using atomic absorption spectrometry. The cumulative administered Al dose was extracted from patient records. Patients receiving long-term immunotherapy were treated between 2.8 and 13.6 years (mean 7.1). Other potential sources of Al exposure were surveyed.
Results
Patients who had received Al-coupled immunotherapy for several years showed significantly (p < 0.001) higher Al excretion than the controls at initiation of immunotherapy (mean 18.2 μg/gC vs. 7.9 μg/gC) and predominantly (73%) were above the 95th percentile of the general populations' exposure (>15 μg/gC), however, without reaching levels of toxicological concern (>50 μg/gC). Taking both groups together excreted Al levels correlated with the cumulative administered Al dose from SCIT (linear regression: Alurine = 8.258 + 0.133*Alcum; p = 0.001).
Discussion
These results suggest a relevant iatrogenic contribution of long-term SCIT to human internal Al burden and potential accumulation. Considering the medical benefits of Al-adjuvants and SCIT a differentiated risk-benefit analysis is needed. For certain scenarios of potential toxicological concern in clinical practice biomonitoring might be advisable.
期刊介绍：
The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.
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