Lung disease caused by inhaling “non toxic” agents

Benoit NEMERY 대한직업환경의학회 2016 대한직업환경의학회 학술대회 논문집 Vol.2016 No.11

Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models

Benoit Nemery,Jeroen A. J. Vanoirbeek,Hung-Chang Tsui 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.

Occupational Exposure to Metals in Shooting Ranges: A Biomonitoring Study

Vandebroek, Eline,Haufroid, Vincent,Smolders, Erik,Hons, Luc,Nemery, Benoit Occupational Safety and Health Research Institute 2019 Safety and health at work Vol.10 No.1

Background: Lead (Pb) exposure in shooting ranges has been reduced by various measures such as jacketed ammunition and lead-free primers. Nevertheless, this may lead to exposure to other metals, potentially resulting in adverse health effects. Methods: In a cross-sectional study, 35 subjects from seven different shooting ranges were studied: four shooting instructors, 10 police officers, 15 Special Forces, and six maintenance staff members. Metals and metalloids were determined in blood and urine by inductively coupled plasma-mass spectrometry. Results: The concentrations of most elements did not differ significantly between groups or compared to reference values, except for Sb and Pt in urine and Pb in blood. Mean values for Sb were considerably higher in urine from the Special Forces ($0.34{\mu}g/L$), the maintenance staff ($0.13{\mu}g/L$), and shooting instructors ($0.32{\mu}g/L$) compared to the police officers before shooting ($0.06{\mu}g/L$) and a Belgian reference value ($0.04{\mu}g/L$). For Pt, the Special Forces showed higher mean urinary concentrations ($0.078{\mu}g/L$) compared to a Belgian reference value (<$0.061{\mu}g/L$). Mean values for blood lead were markedly higher in the Special Forces ($3.9{\mu}g/dL$), maintenance staff ($5.7{\mu}g/dL$), and instructors ($11.7{\mu}g/dL$) compared to police officers ($1.4{\mu}g/dL$). One instructor exceeded the biological exposure index for blood Pb ($38.8{\mu}g/dL$). Conclusion: Since both Pb and Sb were found to be higher in shooting range employees, especially among frequent shooters, it is advisable to provide appropriate protective equipment, education, and medical follow-up for shooting range personnel in addition to careful choice of ammunition.

Occupational Exposure to Metals in Shooting Ranges: A Biomonitoring Study

Eline Vandebroek,Vincent Haufroid,Erik Smolders,Luc Hons,Benoit Nemery 한국산업안전보건공단 산업안전보건연구원 2019 Safety and health at work Vol.10 No.1

Background: Lead (Pb) exposure in shooting ranges has been reduced by various measures such as jacketed ammunition and lead-free primers. Nevertheless, this may lead to exposure to other metals, potentially resulting in adverse health effects. Methods: In a cross-sectional study, 35 subjects from seven different shooting ranges were studied: four shooting instructors, 10 police officers, 15 Special Forces, and six maintenance staff members. Metals and metalloids were determined in blood and urine by inductively coupled plasmaemass spectrometry. Results: The concentrations of most elements did not differ significantly between groups or compared to reference values, except for Sb and Pt in urine and Pb in blood. Mean values for Sb were considerably higher in urine from the Special Forces (0.34 mg/L), the maintenance staff (0.13 mg/L), and shooting instructors (0.32 mg/L) compared to the police officers before shooting (0.06 mg/L) and a Belgian reference value (0.04 mg/L). For Pt, the Special Forces showed higher mean urinary concentrations (0.078 mg/L) compared to a Belgian reference value (<0.061 mg/L). Mean values for blood lead were markedly higher in the Special Forces (3.9 mg/dL), maintenance staff (5.7 mg/dL), and instructors (11.7 mg/dL) compared to police officers (1.4 mg/dL). One instructor exceeded the biological exposure index for blood Pb (38.8 mg/ dL). Conclusion: Since both Pb and Sb were found to be higher in shooting range employees, especially among frequent shooters, it is advisable to provide appropriate protective equipment, education, and medical follow-up for shooting range personnel in addition to careful choice of ammunition.

Involvement of Innate Lymphoid Cells and Dendritic Cells in a Mouse Model of Chemical-induced Asthma

Pollaris Lore,Decaesteker Tatjana,Van den Broucke Sofie,Jonckheere Anne-Charlotte,Cremer Jonathan,Verbeken Erik,Maes Tania,Devos Fien C,Vande Velde Greetje,Nemery Benoit,Hoet Peter H. M.,Vanoirbeek Je 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.2

Purpose: Exposure to low concentrations of toluene diisocyanate (TDI) leads to immune-mediated chemical-induced asthma. The role of the adaptive immune system has already been thoroughly investigated; nevertheless, the involvement of innate immune cells in the pathophysiology of chemical-induced asthma is still unresolved. The aim of the study is to investigate the role of innate lymphoid cells (ILCs) and dendritic cells (DCs) in a mouse model for chemical-induced asthma. Methods: On days 1 and 8, BALB/c mice were dermally treated (20 μL/ear) with 0.5% TDI or the vehicle acetone olive oil (AOO; 2:3). On days 15, 17, 19, 22 and 24, the mice received an oropharyngeal challenge with 0.01% TDI or AOO (1:4). One day after the last challenge, airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and immune-related parameters, including the cytokine pattern in bronchoalveolar lavage fluid, lymphocyte subpopulations of the lymph nodes and their ex vivo cytokine production profile, blood immunoglobulins and DC and ILC subpopulations in the lungs. Results: Both DC and ILC2 were recruited to the lungs after multiple airway exposures to TDI, regardless of the prior dermal sensitization. However, prior dermal sensitization with TDI alone results in AHR and predominant eosinophilic airway inflammation, accompanied by a typical type 2 helper T (Th2) cytokine profile. Conclusions: TDI-induced asthma is mediated by a predominant type 2 immune response, with the involvement of adaptive Th2 cells. However, from our study we suggest that the innate ILC2 cells are important additional players in the development of TDI-induced asthma.