RESUMEN
BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.
Asunto(s)
Alérgenos/inmunología , Desensibilización Inmunológica/métodos , Ambiente Controlado , Exposición por Inhalación , Desensibilización Inmunológica/normas , Desensibilización Inmunológica/tendencias , Política de Salud , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Exposición por Inhalación/efectos adversos , Reproducibilidad de los ResultadosRESUMEN
Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung function and normal bronchial reactivity were randomly exposed for 3 h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m³ (low) and 400 µg/m³ (high) under controlled environmental conditions. The range for PM2.5 load observed for single experiments was 165-303 µg/m³ for the low exposure and 205-662 µg/m³ for the high exposure, whereas particle loads during clean air exposure most often were below the detection limit (< 20 µg/m³). Health effects were evaluated in relation to rated changes in symptoms and environmental perception using a computerized questionnaire and a potentiometer. Subjective symptoms were generally weak, but when combining the effect of each of the symptoms into categorical symptom indices, significant effects were found for "environmental perception" (p = 0.0007), "irritative body perceptions" (p = 0.0127), "psychological/neurological effects" (p = 0.0075) and "weak inflammatory responses" (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating and caused irritated mucosas in humans. The knowledge gained in this study on subjective-rated symptoms may be important for understanding human response to wood-smoke exposure.
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Contaminación del Aire Interior/efectos adversos , Exposición por Inhalación/efectos adversos , Humo/efectos adversos , Adulto , Cámaras de Exposición Atmosférica , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Material Particulado , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/fisiopatología , Encuestas y Cuestionarios , Madera , Adulto JovenRESUMEN
UNLABELLED: Short-term exposure to dust and dust added with beta-(1,3)-d-glucan or aldehydes may cause sensory reactions. In random order, we exposed 36 volunteers in a climate chamber to clean air, office dust, dust with glucan, and dust with aldehydes. Three groups of subjects were exposed, eleven were non-atopic with nasal histamine hyperreactivity, 13 were non-atopic, and 12 were atopic. Subjective ratings of symptoms and general health were registered four times during four 6-h exposure sessions. Six symptom intensity indices were constructed. The nasal hyperreactive group had a high and time-dependent increase of mucous membrane irritations, whereas the atopic group had a low and stable rate of irritations with exposure time, close to the reference group (P = 0.02 for differences between the groups with respect to time under exposure for Weak Inflammatory Responses and P = 0.05 for Irritative Body Perception, significance mainly because of the nasal hyperreactive group). Exposure to dust, with or without glucan or aldehydes, showed increased discomfort measured by the index for Constant Indoor Climate, and dust with glucan had a similar effect for the index for Lower Respiratory Effects. For Psychological and Neurological Effects these were dependent on group affiliation, thus preventing a uniform statement of exposure effects for all three investigated groups. PRACTICAL IMPLICATIONS: Opportunities for identifying persons with high or low sensitivity to low-level exposures are important in preventive medicine and will reduce intra-group variability and thus increase the power of experimental and epidemiological studies searching for correlations between exposures and health effects. The contrast between nasal hyperreactive on one side and atopic and reference subjects on the other side is particularly important. The atopic group indicated a non-homogenous reaction depending on their hyperreactive status, a finding that could be important but needs further confirmation.
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Contaminación del Aire Interior/efectos adversos , Hipersensibilidad Inmediata/fisiopatología , Mucosa Nasal/fisiopatología , Adulto , Aldehídos/efectos adversos , Estudios de Casos y Controles , Polvo , Femenino , Histamina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/efectos de los fármacos , Proteoglicanos , Hipersensibilidad Respiratoria/fisiopatología , Adulto Joven , beta-Glucanos/efectos adversosRESUMEN
UNLABELLED: Thirty-six volunteers (in three susceptibility groups: 11 subjects were non-allergic with nasal histamine hypersensitivity, 13 were non-allergic with normal sensitivity, and 12 were pollen allergic with or without nasal hypersensitivity) were exposed for three and a half hours in a climate chamber. Each subject was exposed to clean air (dust 45 +/- 38 microg/m(3) total suspended particle, TSP), house dust at 357 +/- 180 microg/m(3) TSP, house dust 382 +/- 175 microg/m(3) TSP with added glucan (50 ng/m(3)) and house dust 394 +/- 168 microg/m(3) TSP with added aldehydes corresponding to a gaseous phase of 300 microg/m(3) in the air. The study was explorative by nature. No significant effects of exposures as such were seen on break-up time, conjunctival epithelial damage score and Trolox Equivalent Antioxidant Capacity (TEAC) in tear film and subjective ratings. However, in TEAC a significant different time course was seen during exposures to aldehyde-containing dust indicating a subacute and late response to the exposures. Perceived eye irritation increased significantly during exposures to normal dust. The perception ratings were highly correlated, whereas no correlation was found between the subjective responses and the objective measurements. PRACTICAL IMPLICATIONS: The findings indicate that measurement effects on the eyes are rather insensitive measures of short time effects of office dust exposures.
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Contaminantes Ocupacionales del Aire/efectos adversos , Aldehídos/efectos adversos , Polvo , Oftalmopatías/etiología , Hipersensibilidad/etiología , beta-Glucanos/efectos adversos , Humanos , ProteoglicanosRESUMEN
A case of occupational asthma complicated by pneumothorax is reported. The disease was caused by work at a fish filleting station. The diagnosis was based on measurements of lung function and specific IgE against plaice. Occupational asthma must be considered in workers exposed to organic dust and the serious potential consequences of prolonged exposure be borne in mind.