实习面包师和糖果师呼气一氧化氮分数(FeNO)和肺活量测定指标的纵向研究。

IF 5.2 2区 医学 Q1 ALLERGY
Gina-Maria Klaut, Ludwig Frei-Stuber, Stefan Karrasch, Susanne Kutzora, Jonas Huss, Doris Gerstner, Dennis Nowak, Caroline Quartucci
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Optimal FeNO cut-off values for the diagnosis of asthma in adults range from 15 ppb to 64 ppb (sensitivity 29%–79%, specificity 55%–95%) [<span>4</span>].</p><p>Our aim was to examine associations between the exposure to baking ingredients, FeNO, and spirometry, taking into account nonoccupational influences.</p><p>We performed a longitudinal study (observation period from September 2021 to July 2022) carried out at a Vocational School of Bakery and Confectionery in Germany. During each visit (intervals of preferably 3–5 weeks), subjects' health status and workplace conditions were assessed by questionnaires and spirometry (using Global Lung Initiative reference values (2012)) [<span>5</span>], and FeNO measurements were performed. The main aspects of the questionnaires are listed in Table 1. Details on the study design have been described earlier (Klaut, G.-M. et al. (2024)) [<span>6</span>].</p><p>For the consideration of both occupational and non-occupational influences on FeNO as well as the <i>z</i>-scores of forced expiratory vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio, Generalized Linear Mixed Models (GLMM) analyses for longitudinal analysis were implemented. All study participants were included in the GLMM analyses. The calculation models took the duration of exposure, profession (bakery/confectionery), respiratory infection, allergy, tobacco consumption, vapor extraction systems, low-dust flour and transfer of flour with low dust development into account. The outcome FeNO was logarithmically transformed to approximate a normal distribution and the delogarithmized values of the coefficients of the predictors of FeNO were reported as e<sup>β</sup>. A significance level of <i>α</i> = 0.05 was chosen in all analyses. SAS 9.4 (SAS Institute Inc., Cary, NC) was used to fit GLMM.</p><p>Descriptive statistics are presented in Table 1.</p><p>Very rarely, relevant exposures to flour dust were reported during the first examination before the start of apprenticeship (baker apprentices: <i>n</i> = 2; confectionery apprentices: <i>n</i> = 1). No additional non-occupational exposure to flour dust was reported.</p><p>The number of participants decreased during the course of the study. Regarding the trainee bakers, in the beginning, 50 took part in the measurement of FeNO and 33 performed spirometry; after 24–26 weeks, there were only four participating in the determination of FeNO and three carrying out spirometry. The situation among the confectionery apprentices was similar. Overall, no clinically relevant changes were found.</p><p>GLMM analysis revealed a significant increase of FeNO with more days of exposure to flour dust. Due to the utilisation of a logarithmic transformation, the e<sup>β</sup>-value of 1.0005 indicates an approximate daily increase in FeNO of 0.05%, which corresponds to an annual increase of approximately 19.3%. In the analysis of the influence of respiratory infections, allergy, and tobacco consumption on FeNO, only diagnosed allergy showed a significant association. The use of low-dust flour resulted in a significantly lower FeNO.</p><p>All <i>z</i>-scores of spirometric parameters significantly decreased with longer exposure adjusted for respiratory infection, allergy, smoking, and safety measures. Higher <i>z</i>-scores of FEV1 and FVC, respectively, were associated with installed vapor extraction systems. 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However, the examined bakers usually had significantly longer exposure times (Olivieri et al.: Mean age 40.2 years, only bakers, observation period 11 years; Crivellaro et al.: Mean age 39.9 years, only bakers, mean exposure time 14.1 years).</p><p>Our observation of lower FeNO in settings with low-dust flour use indicates the preventive effectiveness of this established measure [<span>9</span>].</p><p>Our results showed a decline of the <i>z</i>-scores of FVC, FEV1, and FEV1/FVC ratio in association with increasing time since first exposure to flour dust.</p><p>An examination by Crivellaro et al. reported a lower FEV1/FVC ratio with longer exposure time (overall <i>p</i> = 0.02) [<span>8</span>]. 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引用次数: 0

摘要

过敏性疾病(如支气管哮喘和鼻炎)仍然是与接触面粉过敏原有关的常见职业病。过敏症状多发生在面包房学徒期。影响分数呼气一氧化氮(FeNO)结果的多种因素已被描述[3,4]。诊断成人哮喘的最佳FeNO临界值范围为15ppb至64ppb(敏感性29%-79%,特异性55%-95%)。我们的目的是在考虑非职业影响的情况下,研究暴露于烘焙原料、FeNO和肺活量测定之间的关系。我们在德国一家烘焙和糖果职业学校进行了一项纵向研究(观察期为2021年9月至2022年7月)。在每次访问期间(间隔最好为3-5周),通过问卷调查和肺活量测定(使用全球肺倡议参考值(2012))[5]评估受试者的健康状况和工作场所条件,并进行FeNO测量。问卷调查的主要方面列于表1。研究设计的细节已经在前面描述过(Klaut, g.m。等人(2024)。考虑职业和非职业对FeNO的影响,以及用力呼气肺活量(FVC)、1s用力呼气容积(FEV1)和FEV1/FVC比值的z分数,采用广义线性混合模型(GLMM)进行纵向分析。所有研究参与者均纳入GLMM分析。计算模型考虑了暴露时间、职业(烘焙/糖果)、呼吸道感染、过敏、烟草消费、蒸汽提取系统、低粉尘面粉和低粉尘发展的面粉转移。结果FeNO被对数变换为近似正态分布,FeNO预测因子系数的去对数化值被报告为eβ。所有分析均采用显著性水平α = 0.05。采用SAS 9.4 (SAS Institute Inc., Cary, NC)进行GLMM拟合。描述性统计如表1所示。在学徒开始之前的第一次检查中,很少有相关的面粉粉尘暴露报告(面包师学徒:n = 2;糖果学徒:n = 1)。没有其他非职业接触面粉粉尘的报告。在研究过程中,参与者的数量减少了。在实习面包师方面,开始时,50人参加了FeNO的测量,33人进行了肺活量测定;24-26周后,仅4只参与FeNO测定,3只进行肺活量测定。糖果学徒的情况也类似。总体而言,未发现临床相关的变化。GLMM分析显示,随着暴露于面粉粉尘的天数增加,FeNO显著增加。由于利用了对数变换,eβ-值为1.0005表明FeNO的日增长约为0.05%,相当于年增长约19.3%。在呼吸道感染、过敏和烟草消费对FeNO的影响分析中,只有诊断为过敏的人显示出显著的关联。使用低粉尘面粉可显著降低FeNO。经呼吸道感染、过敏、吸烟和安全措施调整后,暴露时间越长,肺量测定参数的所有z分数均显著降低。FEV1和FVC的z分数越高,分别与安装蒸汽提取系统有关。此外,FVC的z分数的下降与低粉尘面粉的使用有显著的关系。总体而言,本研究表明,随着粉尘暴露时间的增加,FVC、FEV1和FEV1/FVC比值的z分数显著升高,FEV1/FVC比值显著降低。这表明需要改善学徒期间的职业安全条件和职业健康检查。因此,建议在最初(基线)和定期(至少一年后的第一次随访)进行肺活量测定和FeNO测定。此外,在我们的分析中,蒸汽萃取系统与FVC和FEV1的较高z分数的关联表明该措施具有预防效益。先前的研究发现,FeNO水平与在面包店工作的时间之间没有关系[7,8]。然而,被调查的面包师的暴露时间通常明显更长(Olivieri等人:平均年龄40.2岁,仅面包师,观察期11年;Crivellaro等人:平均年龄39.9岁,仅面包师,平均暴露时间14.1年)。我们在使用低粉尘面粉的环境中观察到较低的FeNO,表明这一既定措施的预防效果[9]。结果表明,FVC、FEV1和FEV1/FVC比值的z分数随首次接触粉尘时间的增加而下降。Crivellaro等人的检验。 曝光时间越长,FEV1/FVC比值越低(总体p = 0.02)。虽然由于研究设计和研究人群的差异,直接可比性有限,但FEV1/FVC比率的下降与我们的结果一致。然而,令人惊讶的是,低粉尘面粉的使用与较低的FVC z-分数有关,并且,从趋势来看,也与较低的FEV1 z-分数有关(p = 0.0667)。一种可能的解释是同时使用了本计算中未包括的其他职业安全措施(例如,佩戴呼吸口罩)。根据我们的研究结果,我们建议定期进行职业健康检查,包括肺活量测定和FeNO测量,以便在学徒期间早期发现职业过敏性疾病。建议采取优化的职业安全措施(例如,安装蒸汽抽取系统)。所有作者都对所呈现的工作做出了重大贡献。Gina-Maria Klaut:通过问卷调查、FeNO和肺活量测定收集数据。Ludwig Frei-Stuber:登记研究,分析描述性统计数据,撰写手稿。Stefan Karrasch:在整个研究过程中提供专业建议。Susanne Kutzora:在整个研究过程中提供专业建议。Jonas Huss:广义线性混合模型的计算及其解释的专业建议。Doris Gerstner:关于广义线性混合模型的专业建议。Dennis Nowak:在整个研究过程中提供专业建议,并对手稿进行修改。Caroline Quartucci:在整个研究过程中提供专业建议,获得伦理投票,科学领导,以及手稿的修改。研究注册:该研究在波恩和科隆联邦药物和医疗器械研究所的德国临床研究登记处(代码:DRKS00036088)以及慕尼黑Ludwig-Maximilians-Universität诊所的中央研究登记处(代码:103114)进行了注册。该研究于2021年5月4日得到德国慕尼黑Ludwig-Maximilians-Universität医学院伦理委员会(批准代码:21-0289)的批准,并按照1964年《赫尔辛基宣言》的伦理标准进行。所有参与研究的参与者都提供了书面知情同意书。如果受试者年龄小于18岁,在他们成为参与者之前,还需要他们的法定监护人的书面同意。作者声明无利益冲突。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Longitudinal Study of Fractional Exhaled Nitric Oxide (FeNO) and Spirometric Indices in Trainee Bakers and Confectioners

Longitudinal Study of Fractional Exhaled Nitric Oxide (FeNO) and Spirometric Indices in Trainee Bakers and Confectioners

Allergic diseases (e.g., bronchial asthma and rhinitis) remain common occupational diseases involving exposure to flour allergens [1]. Allergic symptoms mostly occur during the apprenticeship for bakery [2].

Multiple factors influencing fractional exhaled nitric oxide (FeNO) results have been described [3, 4]. Optimal FeNO cut-off values for the diagnosis of asthma in adults range from 15 ppb to 64 ppb (sensitivity 29%–79%, specificity 55%–95%) [4].

Our aim was to examine associations between the exposure to baking ingredients, FeNO, and spirometry, taking into account nonoccupational influences.

We performed a longitudinal study (observation period from September 2021 to July 2022) carried out at a Vocational School of Bakery and Confectionery in Germany. During each visit (intervals of preferably 3–5 weeks), subjects' health status and workplace conditions were assessed by questionnaires and spirometry (using Global Lung Initiative reference values (2012)) [5], and FeNO measurements were performed. The main aspects of the questionnaires are listed in Table 1. Details on the study design have been described earlier (Klaut, G.-M. et al. (2024)) [6].

For the consideration of both occupational and non-occupational influences on FeNO as well as the z-scores of forced expiratory vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio, Generalized Linear Mixed Models (GLMM) analyses for longitudinal analysis were implemented. All study participants were included in the GLMM analyses. The calculation models took the duration of exposure, profession (bakery/confectionery), respiratory infection, allergy, tobacco consumption, vapor extraction systems, low-dust flour and transfer of flour with low dust development into account. The outcome FeNO was logarithmically transformed to approximate a normal distribution and the delogarithmized values of the coefficients of the predictors of FeNO were reported as eβ. A significance level of α = 0.05 was chosen in all analyses. SAS 9.4 (SAS Institute Inc., Cary, NC) was used to fit GLMM.

Descriptive statistics are presented in Table 1.

Very rarely, relevant exposures to flour dust were reported during the first examination before the start of apprenticeship (baker apprentices: n = 2; confectionery apprentices: n = 1). No additional non-occupational exposure to flour dust was reported.

The number of participants decreased during the course of the study. Regarding the trainee bakers, in the beginning, 50 took part in the measurement of FeNO and 33 performed spirometry; after 24–26 weeks, there were only four participating in the determination of FeNO and three carrying out spirometry. The situation among the confectionery apprentices was similar. Overall, no clinically relevant changes were found.

GLMM analysis revealed a significant increase of FeNO with more days of exposure to flour dust. Due to the utilisation of a logarithmic transformation, the eβ-value of 1.0005 indicates an approximate daily increase in FeNO of 0.05%, which corresponds to an annual increase of approximately 19.3%. In the analysis of the influence of respiratory infections, allergy, and tobacco consumption on FeNO, only diagnosed allergy showed a significant association. The use of low-dust flour resulted in a significantly lower FeNO.

All z-scores of spirometric parameters significantly decreased with longer exposure adjusted for respiratory infection, allergy, smoking, and safety measures. Higher z-scores of FEV1 and FVC, respectively, were associated with installed vapor extraction systems. Moreover, there was a significant relation between a decline of the z-scores of FVC and the use of low-dust flour.

Overall, the present study showed a significant increase of FeNO and a significant decrease of the z-scores of FVC, FEV1, and FEV1/FVC ratio with increasing duration of exposure to flour dust. This indicates the need of implementing improved occupational safety conditions and occupational health checks during apprenticeship. It is therefore recommended to carry out spirometry and FeNO determination initially (baseline) and regularly (first follow-up after at least one year). Furthermore, the association of vapor extraction systems with higher z-scores of both FVC and FEV1 in our analysis indicates a preventive benefit of this measure.

Previous studies found no relationship between FeNO levels and the time working in a bakery [7, 8]. However, the examined bakers usually had significantly longer exposure times (Olivieri et al.: Mean age 40.2 years, only bakers, observation period 11 years; Crivellaro et al.: Mean age 39.9 years, only bakers, mean exposure time 14.1 years).

Our observation of lower FeNO in settings with low-dust flour use indicates the preventive effectiveness of this established measure [9].

Our results showed a decline of the z-scores of FVC, FEV1, and FEV1/FVC ratio in association with increasing time since first exposure to flour dust.

An examination by Crivellaro et al. reported a lower FEV1/FVC ratio with longer exposure time (overall p = 0.02) [8]. While direct comparability is limited due to differences in study design and study population, the decrease of FEV1/FVC ratio was in line with our results.

Surprisingly, however, the use of low-dust flour was associated with lower FVC z-scores and, by trend, also with lower FEV1 z-scores (p = 0.0667). A possible explanation could be the simultaneous use of other occupational safety measures not being represented in this calculation (e.g., wearing of respiratory masks).

Based on our results, we recommend regular occupational health check-ups including spirometry and FeNO measurements for early detection of occupational allergic diseases during apprenticeship. Optimised occupational safety measures (e.g., installation of vapor extraction systems) are recommended.

All authors have significantly contributed to the work as presented. Gina-Maria Klaut: Collection of data by using questionnaires, FeNO, and spirometry measurements. Ludwig Frei-Stuber: Registration of the study, analysis of descriptive statistics, and writing of the manuscript. Stefan Karrasch: Professional advice throughout the entire study. Susanne Kutzora: Professional advice throughout the entire study. Jonas Huss: Calculation of Generalised Linear Mixed Models and professional advice concerning their interpretation. Doris Gerstner: Professional advice regarding Generalised Linear Mixed Models. Dennis Nowak: Professional advice throughout the entire study and correction of the manuscript. Caroline Quartucci: Professional advice throughout the entire study, obtaining the ethics vote, scientific leadership, and correction of the manuscript.

Registration of the study: The study was registered at the German Register of Clinical Studies of the Federal Institute for Drugs and Medical Devices, Bonn and Cologne (code: DRKS00036088) as well as at the Central Study Register of the Ludwig-Maximilians-Universität Clinic, Munich (code: 103114).

The study was approved by the Ethics Committee at the Medical Faculty of Ludwig-Maximilians-Universität (approval code: 21–0289), Munich, Germany on May 4th, 2021, and was performed in accordance with the ethical standards of the 1964 Helsinki Declaration.

All participants included in the study provided written informed consent. If the subjects were younger than 18 years, the written consent of their legal guardian was additionally required before they could become participants.

The authors declare no conflicts of interest.

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来源期刊
CiteScore
10.40
自引率
9.80%
发文量
189
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Allergy strikes an excellent balance between clinical and scientific articles and carries regular reviews and editorials written by leading authorities in their field. In response to the increasing number of quality submissions, since 1996 the journals size has increased by over 30%. Clinical & Experimental Allergy is essential reading for allergy practitioners and research scientists with an interest in allergic diseases and mechanisms. Truly international in appeal, Clinical & Experimental Allergy publishes clinical and experimental observations in disease in all fields of medicine in which allergic hypersensitivity plays a part.
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