Diisocyanates, occupational asthma and IgE antibody: implications for hazard characterization

Pârvu

Medicine and Pharmacy Reports

et al. 2016

Background and aimThe aim of the study was to evaluate vitamin E effect upon oxidative stress associated with toluene −2, 4-diisocyanate (TDI)-induced asthma in rats.MethodsThe five study groups were: control, vehicle, TDI, vehicle+E, TDI+E. TDI animals were sensitized by nasal administration of TDI 10% (5μl/nostril) between days 1–7 and 15–21. Between days 22–28 groups TDI+E and vehicle+E rats received vitamin E (50 mg/kg, i. v.), and control, vehicle and TDI groups received saline solution. On day 29 the rats were challenged by intranasal application of 5% TDI (5 μl/nostril). On day 30 blood, BALF and lung biopsy were harvested. Oxidative stress tests were malondialdehyde (MDA), protein carbonyls (PC), total thiols (tSH), 1,1-diphenyl-2-picryl hydrazyl (DPPH) and reduced glutathione (GSH).ResultsTDI sensitization increased oxidative stress systemically, but also locally in the respiratory airways and lung tissue. There was an increase of MDA and PC formation associated with a deficiency of the antioxidant defense reflected by DPPH decreases. There were no differences between systemic and local lung concentrations of oxidized molecules.After vitamin E treatment oxidative stress was reduced mostly due to serum, BALF and lung tissue GSH and DPPH increase.ConclusionThe study showed that in rat TDI-induced asthma there was oxidative stress caused by increased ROS production and antioxidants deficiency, and vitamin E reduced ROS production and improved antioxidant defense.

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin E Effect in a Rat Model of Toluene Diisocyanate-Induced Asthma

Pârvu

Medicine and Pharmacy Reports

et al. 2016

“…Perhaps the greatest uncertainty is the role of IgE antibody in sensitisation of the respiratory tract to chemicals. Although the majority, if not all, chemical respiratory allergens have been associated with the production in sensitised subjects of IgE antibody, it is the case that in many instances -and in particular with the diisocyanates -patients with chemical respiratory allergy and occupational asthma lack detectable IgE antibody Isola et al, 2008;Kimber et al, 2014a). For reasons that are outside the scope of this paper, it may be the case that the correlation between IgE antibody production and chemical respiratory allergy is underestimated.…”

Section: Mechanisms Through Which Sensitisation Of the Respiratory Trmentioning

confidence: 64%

“…For reasons that are outside the scope of this paper, it may be the case that the correlation between IgE antibody production and chemical respiratory allergy is underestimated. It could even be the case that IgE antibody plays a mandatory and universal role in sensitisation of the respiratory tract to chemicals, but this is unproven Jones et al, 2003;Kimber et al, 2014a). Nevertheless, it must be acknowledged that there may exist IgE antibody-independent mechanisms through which sensitisation of the respiratory tract to chemicals may be acquired.…”

Section: Mechanisms Through Which Sensitisation Of the Respiratory Trmentioning

confidence: 93%

Thresholds in chemical respiratory sensitisation

et al. 2015

Self Cite

There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment.

Int Forum Allergy Rhinol

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Wise

Damask

Roland

et al. 2023

113

Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.