Integrating asthma hazard characterization methods for consumer products

Despite extensive study, definitive conclusions regarding the relationship between asthma and consumer products remain elusive. Uncertainties reflect the multi-faceted nature of asthma (i.e., contributions of immunologic and non-immunologic mechanisms). Many substances used in consumer products are associated with occupational asthma or asthma-like syndromes. However, risk assessment methods do not adequately predict the potential for consumer product exposures to trigger asthma and related syndromes under lower-level end-user conditions. A decision tree system is required to characterize asthma and respiratory-related hazards associated with consumer products. A system can be built to incorporate the best features of existing guidance, frameworks, and models using a weight-of-evidence (WoE) approach. With this goal in mind, we have evaluated chemical hazard characterization methods for asthma and asthma-like responses. Despite the wealth of information available, current hazard characterization methods do not definitively identify whether a particular ingredient will cause or exacerbate asthma, asthma-like responses, or sensitization of the respiratory tract at lower levels associated with consumer product use. Effective use of hierarchical lines of evidence relies on consideration of the relevance and potency of assays, organization of assays by mode of action, and better assay validation. It is anticipated that the analysis of existing methods will support the development of a refined WoE approach.     

老年人支气管哮喘危险因素和临床特点分析

目的 探讨老年人支气管哮喘的危险因素和临床特点.方法 回顾性分析221例成人支气管哮喘病例临床资料,根据年龄将患者分为青壮年组（15～59岁）和老年组（≥60岁）,对比分析两组各项观察指标异同,以发现危险因素和临床特点.结果 221例支气管哮喘中老年哮喘患者64例（28.96%）,平均年龄73.4岁,其中男39例（60.93%）、女25例（39.06%） 其中吸烟人数明显高于青壮年组（x2=4.753,P〈0.05） 感染和气候变化是老年哮喘的危险因素（x2=6.352、9.376,均P〈0.05） 季节方面老年组以冬春季易发,青壮年组以冬夏季易发 老年组并发症及基础疾病明显高于青壮年组（x2=126.270,P〈0.01）.结论 老年人支气管哮喘患者男多于女,吸烟率高.以感染和气候变化为主要危险因素,冬春季易发,并发症及基础疾病多.     

Assessing the risk of type 1 allergy to enzymes present in laundry and cleaning products: Evidence from the clinical data

Microbial enzymes have been used in laundry detergent products for several decades. These enzymes have also long been known to have the potential to give rise to occupational type 1 allergic responses. A few cases of allergy among consumers using dusty enzyme detergents were reported in the early 1970s. Encapsulation of the enzymes along with other formula changes were made to ensure that consumer exposure levels were sufficiently low that the likelihood of either the induction of IgE antibody (sensitization) or the elicitation of clinical symptoms be highly improbable. Understanding the consumer exposure to enzymes which are used in laundry and cleaning products is a key step to the risk management process. Validation of the risk assessment conclusions and the risk management process only comes with practical experience and evidence from the marketplace. In the present work, clinical data from a range of sources collected over the past 40 years have been analysed. These include data from peer reviewed literature and enzyme specific IgE antibody test results in detergent manufacturers’ employees and from clinical study subjects. In total, enzyme specific IgE antibody data were available on 15,765 individuals. There were 37 individuals with IgE antibody. The majority of these cases were from the 1970s where 23 of 4687 subjects (0.49%) were IgE positive and 15 of the 23 were reported to have symptoms of allergy. The remaining 14 cases were identified post-1977 for a prevalence of 0.126% (14/11,078). No symptoms were reported and no relationship to exposure to laundry and cleaning products was found. There was a significant difference between the pre- and post-1977 cohorts in that the higher rates of sensitization with symptoms were associated with higher exposure to enzyme. The clinical testing revealed that the prevalence of enzyme specific IgE in the population is very rare (0.126% since 1977). This demonstrates that exposure to these strong respiratory allergens via use of laundry and cleaning products does not lead to the development of sensitization and disease. These data confirm that the risk to consumers has been properly assessed and managed and support the concept that thresholds of exposure exist for respiratory allergy. Expansion of enzyme use into new consumer product categories should follow completion of robust risk assessments in order to continue ensuring the safe use of enzymes among consumers.     

About hazard and risk assessment: Regulatory approaches in assessing safety in the European Union chemicals legislation

Hazard classification and labelling is the main and basic requirement for all industrial and consumer chemicals in the European Union, if they are not regulated under more specific legislation such as drugs, food ingredients or cosmetics. The first approach in hazard classification is hazard identification describing the hazardous properties of chemicals. Refinements in the classification criteria include the assessment of toxic potency (hazard characterisation) where feasible and the possibility to set higher or lower specific concentration limits for classification. In the past only a minor portion of the classified chemicals underwent a risk assessment including exposure assessment and risk characterisation. Risk assessment will become more frequent with the implementation of REACH. However, as risk assessment is rather labour-intensive even under REACH risk assessment will be performed in a targeted approach for a selected number of chemical substances while hazard classification and labelling will remain the basic approach for all chemicals.     

Enzymes in cleaning products: An overview of toxicological properties and risk assessment/management

Enzymes used in cleaning products have an excellent safety profile, with little ability to cause adverse responses in humans. For acute toxicity, genotoxicity, sub-acute and repeated dose toxicity, enzymes are unremarkable. Reproductive toxicity and carcinogenicity are also not endpoints of concern. Exceptions are the ability of some proteases to produce irritating effects at high concentrations and more importantly, the intrinsic potential of these bacterial/fungal proteins to act as respiratory sensitizers. It is a reasonable assumption that the majority of enzyme proteins possess this hazard. However, methods for characterising the respiratory sensitisation hazard of enzymes are lacking and the information required for risk assessment and risk management, although sufficient, remains limited. Previously, most data was generated in animal models and in in vitro immunoassays that assess immunological cross-reactivity. Nevertheless, by the establishment of strict limits on airborne exposure (based on a defined minimal effect limit of 60 ng active enzyme protein/m³) and air and health monitoring, occupational safety can be assured. Similarly, by ensuring that airborne exposure is kept similarly low, coupled with knowledge of the fate of these enzymes on skin and fabrics, it has proven possible to establish a long history of safe consumer use of enzyme containing products.     

新药研发中药物临床试验方案的风险管理

本文为新药临床试验风险管理提供参考。在临床试验方案中引入风险管理方法，从风险管理的基本程序：风险识别、风险评估、风险控制等方面展开论证。充分认识和把握临床试验方案中存在的风险因素：临床前研究资料不足的风险、入选与排除标准制订的风险、有效性与安全性评价的风险、统计设计的风险、研究者和受试者依从性的风险等。根据风险性质的不同，可采用风险减轻、风险规避、风险转移、风险接受等控制措施，以有效减少后期临床试验过程中风险发生和降低损失。     

Narrow-and-sharp or broad-and-blunt--regulations of hazardous chemicals in consumer products in the European Union

Chemicals are incorporated into a vast number of consumer products, and it has been recognized that considerable exposures of humans and the environment to chemicals are due to diffuse emissions from everyday products. Different approaches to the management of risks concerning chemicals in products are discussed on the international arena, but no general strategy has yet been adopted. The aim of this study is to investigate how health and environmental risks associated with chemicals in consumer products are currently managed in European Union legislations, mainly by the Toys Directive, the RoHS Directive, and REACH. Significant differences were found between the risk reduction strategies in these legislations, including substance prioritization, type of restrictions and requirements, and information dissemination to consumers. REACH regulates chemicals in products to a limited extent, and via quite complicated processes. Product-specific rules are therefore useful supplements to REACH for regulating chemicals in products. The combined effects of the RoHS and WEEE directives seem to be effective in promoting substitution of substances identified as problematic in electrical and electronic equipment, and it is recommended that the possibility to develop similar systems should be considered also for other product categories.     

清热化痰 平喘宣肺中药组方治疗支气管哮喘患儿的临床研究

目的探究清热化痰、平喘宣肺中药组方治疗支气管哮喘患儿的临床效果。方法选取2019年10月至2021年2月西峡县人民医院收治的支气管哮喘患儿102例,按治疗方案不同分为中医组(51例)、西医组(51例)。西医组采用常规西医方案治疗,中医组在常规西医治疗的基础上给予清热化痰、平喘宣肺中药汤剂治疗。观察2组总有效率、治疗前后单项证候积分、治疗前后肺功能指标[第1秒用力呼气容积(FEV₁)、第1秒用力呼气容积占预计值百分比(FEV₁%)、呼气峰流量(PEF)、呼出气一氧化氮(FeNO)]变化、治疗前后免疫相关指标变化[免疫球蛋白E(IgE)、T淋巴细胞亚群(CD4⁺、CD8⁺、CD4⁺/CD8⁺)]变化。结果中医组总有效率94%(49/51)高于西医组80%(41/51)(P<0.05);治疗后中医组FEV₁、FEV₁%、PEF、FeNO优于西医组(P<0.05);治疗后中医组喘息、哮鸣音、胸闷中医证候积分低...     

Statins and asthma: where we stand,and the next critical steps in research

Asthma remains a formidable public health problem with ever increasing annual costs and prevalence. There are 300 million people with asthma worldwide. Per the Centers for Disease Control and Prevention, there are over 25 million Americans with asthma (both children and adults), i.e. one in 12 people have asthma, and this is increasing annually. Asthma results in approximately half a million hospitalizations and two million emergency department (ED) visits per year. In 2007 alone, 185 children and 3262 adults died from asthma, i.e. nine to ten patients die a day from asthma. This resulted in an annual cost of $56 billion in medical costs, lost work/school days, and early deaths. Therefore, we need novel and innovative therapies for asthma.

In this Editorial, I review results from a study by Tse et al. evaluating the therapeutic potential of statins, within the context of our current state of knowledge. I review observational studies and clinical trials, highlight some potential pitfalls in clinical trial design, and discuss important questions for future research.     

Efficacy,safety, and tolerability of mometasone furoate in adult Japanese patients with mild asthma: open-label clinical trial findings

Abstract

Objective:

To evaluate the clinical efficacy and safety of mometasone furoate administered via a dry powder inhaler (MF-DPI) in Japanese patients with intermittent or mild persistent asthma who were not previously receiving inhaled corticosteroids.     

Reconstruction of historical exposures in the US nickel alloy industry and the implications for carcinogenic hazard and risk assessments

Recently, various regulatory authorities have been reexamining the potential carcinogenic hazards and risks associated with exposures to nickel and certain nickel compounds. In making their assessments, the authorities have focused on occupational cohorts at facilities where nickel-containing sulfidic ores were processed and where increased lung and nasal cancer risks were found in specific groups of workers. Little attention, however, has been paid to the vast number of workers in nickel-using industries, where no excess respiratory cancer risks have been observed. In this paper, the historical exposures of one such group of workers engaged in the production of nickel alloys are reconstructed, and the implications for cancer risk assessments are analyzed. The results indicate that nickel alloy workers were exposed to insoluble oxidic and metallic nickel species at levels comparable to those found in certain nickel processing cohorts; yet they experienced no increase in respiratory cancer risks. This suggests that extrapolating risks from certain primary nickel producers to other nickel industry sectors may not be appropriate.     

Interaction of diet and toxicity — the future role of purified diet in toxicological research

There is a growing awareness of the importance of diet as a determinant of the toxicity of many compounds. This paper briefly reviews some of the ways in which diet affects toxicity, and draws some conclusions regarding the ideal diet for toxicological investigations. Then the two competing types of diet, stock and purified (including those frequently called semi-synthetic or semi-purified), are described and their characteristic strengths and weaknesses are discussed. Stock diets are very variable commodities, may be nutritionally poorly balanced, and also contain many non-nutritive components that influence toxicity. The formulation and preparation of purified diet are discussed. It is concluded that investigations of the mechanisms of toxicity, as well as studies of absorption, distribution and metabolism of toxic compounds, could benefit from the use of well-defined purified diets.     

小气道功能指标在儿童哮喘病情严重程度评估及临床诊断中的应用

目的 探讨小气道功能指标在儿童哮喘病情严重程度评估及临床诊断中的应用价值。方法 选取2013年5月至2016年4月于郑州市第二人民医院56例哮喘急性发作期病儿作为哮喘组,并根据哮喘急性发作严重程度分为轻度(21例)、中度(20例)和重度(15例)三个亚组,同时选取同期、年龄相仿及性别相匹配的30例因其他原因引起喘息咳嗽的慢性炎症病儿和32例入院检查健康儿童分别作为非哮喘组和对照组,收集各组儿童一般资料,采用肺功能测定系统检测各组儿童用力肺活量(FVC)、最大呼气流量(PEF)、第1秒用力呼气容积(FEV1)和FEV1/FVC比值、呼出25%肺活量时呼气流速(FEF25%)、呼出50%肺活量时呼气流速(FEF50%)、呼出75%肺活量时呼气流速(FEF75%)、最大中期呼气流速(MMEF)等指标。结果 与对照组比较,非哮喘组和哮喘组病儿FVC、FEV1、PEF、FEF25%、FEF50%、FEF75%和MMEF等指标均显著降低(P<0.05),且哮喘组病儿上述指标显著低于非哮喘组[(1.42±0.36)L比(1.85±0.47)L、(1.25±0.32)L比(1.42±0.41)L、(2.68±0.64)L比(3.25±0.77)L/s、(2.54±0.65)L/s比(3.74±0.68)L/s、(1.58±0.36)L/s比(2.24±0.71)L/s、(0.61±0.37)L/s比(1.02±0.41)L/s、(1.42±0.49)L/s比(1.89±0.68)L/s)](均P<0.05),而三组病儿FEV1/FVC指标差异无统计学意义(P>0.05)。哮喘急性发作期不同程度病儿用力呼出25%肺活量的呼气流量占预计值百分比(FEF25pred%)、用力呼出50%肺活量的呼气流量占预计值百分比(FEF50pred%)、用力呼出75%肺活量的呼气流量占预计值百分比(FEF75pred%)、最大呼气中期流量占预计值的百分比(MMEFpred%)等指标比较差异有统计学意义(P<0.05),且随着病情程度增加,病儿FEF25pred%、FEF50pred%、FEF75pred%、MMEFpred%等指标呈现明显降低趋势(P<0.05),FEF25%和FEF75%指标在不同严重程度哮喘病儿中异常率比较,差异有统计学意义(P<0.05),FEF50%和MMEF指标比较差异无统计学意义(P>0.05),其中FEF25%主要表现为轻度异常,而FEF75%主要表现为重度异常。结论 小气道功能指标在儿童哮喘病情严重程度评估及临床诊断具有重要意义,随着病情加剧,小气道功能指标明显降低,且异常率显著增加。     

Evaluating heavy metals contamination in soil and vegetables in the region of North India: Levels,transfer and potential human health risk analysis

This study determined the heavy metals (HMs) accumulation in different vegetables in different seasons and attributed a serious health hazard to human adults due to the consumption of such vegetables in Jhansi. The total amounts of zinc (Zn), lead (Pb), nickel (Ni), manganese (Mn), copper (Cu), cobalt (Co), and cadmium (Cd) were analysed in 28 composite samples of soil and vegetables (Fenugreek, spinach, eggplant, and chilli) collected from seven agricultural fields. The transfer factor (TF) of HMs from soil to analysed vegetables was calculated, and significant non-carcinogenic health risks due to exposure to analysed heavy metals via consumption of these vegetables were computed. The statistical analysis involving Principal Component Analysis (PCA) and Pearson's correlation matrix suggested that anthropogenic activities were a major source of HMs in the study areas. The target hazard quotient of Cd, Mn, and Pb for fenugreek (2.156, 2.143, and 2.228, respectively) and spinach (3.697, 3.509, 5.539, respectively) exceeded the unity, indicating the high possibilities of non-carcinogenic health risks if regularly consumed by human beings. This study strongly suggests the continuous monitoring of soil, irrigation water, and vegetables to prohibit excessive accumulation in the food chain.     

呼出气一氧化氮(FeNO)监测在哮喘控制治疗中的评估指导作用

目的 对应用呼出气一氧化氮监测方式对哮喘疾病控制治疗效果进行评估的临床指导价值进行研究.方法 选择本院收治的患有支气管炎和支气管哮喘疾病的患儿各46例,分别将其定义为研究1组和研究2组.再抽取同期接受健康体检的健康人资料46例,定义为对照组.采用本院现有的呼出气一氧化氮分析仪对三组研究对象的呼出气一氧化氮水平进行测定,对比测定结果和观察指标测定结果阳性率.对研究2组患儿实施统一模式的治疗,对该组患儿治疗后3d、出院时的呼出气一氧化氮水平进行测定,并将上述两时段该项指标水平与对照组进行比较.结果 研究2组患儿呼出气一氧化氮水平明显高于研究1组和对照组,组间比较差异有统计学意义(P＜0.05);研究1组患儿呼出气一氧化氮水平明显高于对照组,组间比较差异有统计学意义(P＜0.05).研究2组呼出气一氧化氮水平检测阳性患儿人数明显多于研究1组和对照组,组间比较差异有统计学意义(P＜0.05);研究1组呼出气一氧化氮水平检测阳性患儿人数明显多于对照组,组间比较差异有统计学意义(P＜0.05).研究2组患儿治疗前呼出气一氧化氮水平明显高于治疗后3d、出院当天、对照组,组间比较差异有统计学意义(P＜0.05);研究2组患儿治疗后3d呼出气一氧化氮水平明显高于出院当天、对照组,组间比较差异有统计学意义(P＜0.05);研究2组患儿治疗出院当天呼出气一氧化氮水平明显高于对照组,组间比较差异有统计学意义(P＜0.05).结论 呼出气一氧化氮监测方式在哮喘疾病控制治疗效果评估方面具有较高的指导价值.     

Pharmacists' perceptions of their role in asthma management and barriers to the provision of asthma services

Objectives Few studies have explored pharmacists' perceptions of their potential role in asthma management. This study aimed to investigate community pharmacists' perceptions of their role in the provision of asthma care, to compare the perceptions of metropolitan and regional pharmacists with regards to their role, to identify barriers to the provision of asthma management services and to explore their level of inter‐professional contact. Methods A 29‐item questionnaire was mailed to a convenience sample of community pharmacists. Items included pharmacists' perceptions of their role in asthma management, barriers to pharmacy asthma services and inter‐professional contact. The setting was community pharmacies in metropolitan and rural New South Wales, Australia. Key findings Seventy‐five pharmacists (63% male, 69% in metropolitan pharmacies) returned completed questionnaires (response rate 89%). Pharmacists perceived their role in asthma management along three major dimensions: ‘patient self‐management’, ‘medication use’ and ‘asthma control’. Regional pharmacists described a broader role than metropolitan pharmacists. Most participants perceived time and patient‐related factors to be the main barriers to optimal asthma care with pharmacist's lack of confidence and skills in various aspects of asthma care less important barriers. Almost 70% indicated that they would like more inter‐professional contact regarding the care of patients with asthma. Conclusions Community pharmacists perceived a three‐dimensional role in asthma care with regional pharmacists more likely to embrace a broader role in asthma management compared to metropolitan pharmacists. Pharmacists identified time and patient‐related factors as the major barriers to the provision of asthma services. Future research should explore barriers and facilitators to expansion of the pharmacist's role in asthma management in a holistic way.     

Current approaches of nanomedicines in the market and various stage of clinical translation

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.     

心血管内科临床护理工作的风险分析与对策

目的探讨心血管内科临床护理工作的风险及其对策。方法对心血管内科72例发生风险事件患者的临床资料进行回顾性分析。结果风险因素主要包括护理人员因素、药品设备因素、患者和家属因素以及其他因素。结论针对相应的风险提出对策,帮助心血管内科护理人员提高风险意识,降低护理风险事件的发生率。     

Assessment of user safety, exposure and risk to veterinary medicinal products in the European Union

Safety is an important part of veterinary drug assessment while user safety is a critical part of the overall safety assessment. In the European Union (EU), user safety is addressed through preclinical studies and by relationships with exposure but a key part of the process is the user safety assessment. EU user safety guidelines are available and these make certain recommendations but in places they lack detail and clarity. This paper seeks to examine the relevant factors that lie behind user risk assessments for veterinary medicinal products in general while focusing on EU requirements, the determination of risk management and risk communication strategies and how this relates to user safety assessment and pharmacovigilance responsibilities.