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- Klasson, Maria, 1977-
(författare)
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Cobalt in the hard metal production industry : exposure via inhalation and skin and the inflammatory response in human keratinocytes
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cobalt is a strong sensitizer and can cause contact allergy upon both direct contact or from airborne exposure on the skin. In the skin, keratinocytes are the first cells to come in contact with the metal and will react and respond to the danger by triggering an alarm system resulting in an inflammatory response in the skin. Keratinocytes have been shown to produce IL-1β, which is one of the most potent inflammatory agents in our body and is associated with a variety of diseases.The aims of this thesis was to investigate cobalt air concentrations for different particle fractions for possible use as proxies for other article measures and to examine if cobalt skin and inhalable air exposure contributes to uptake. Also, to investigate the effect of cobalt on cultured human keratinocyte cell viability, pro-inflammatory cytokine/chemokine release and NLRP3 inflammasome activation using cells cultured at low or high calcium (the latter yielding a more differentiated cell type).Air exposure to cobalt was found in all departments and for all work tasks in the hard metal production facility and exposures were in general below the Swedish OEL for inhalable cobalt. The highest exposure levels were found in the powder production department and for laboratory and furnace work. Good correlations for the mass based measures enable us to use the findings for future references. When personal inhalable air levels of cobalt, cobalt skin levels skin and biological monitoring of cobalt in blood were analysed, the skin exposure was determined to be import as a route of uptake. Skin exposure to cobalt in the hard metal industry, could further affect the total uptake in the same order of magnitude as air exposure. In vitro investigations of cobalt using the human keratinocyte cell line HaCaT, showed that CoCl2 triggered an alarm system in cells where the proinflammatory cytokines/chemokines IL-6, CXCL8 and CCL2, known to be involved in skin inflammation, were secreted in a time- and dosedependent manner. Comparing HaCaT cells of high- and low differentiation stages indicated that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis. CoCl2 exposure also resulted in secretion of the proinflammatory cytokines IL-1β and IL-18, and caspase-1, which indicates activation of the NLRP3 inflammasome in the cells. CoCl2 regulates the inflammasome both as primer and as an activator. Our mRNA results indicates a negative feedback mechanism in the inflamamsome due to the exposure. The inflammatory response in general is more dose than time dependent, which be important for understanding the mechanisms of allergic sensitization.
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| 2. |
- Jamil, Wasim N., 1985-
(författare)
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Aspects on the hand eczema and the current health care system : the possibility of health related quality of life measure as a tool for follow-up patients
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Contact eczema is the most common occupational skin disease, and it predominantly affects the hands. Hand eczema is a chronic and fluctuating disease with a multidimensional impact on the patient and society, resulting in an increased consumption of health care, long term sick leave, in voluntary change of occupation, and a risk of early retirement and impaired healthrelated quality of life.A meta-analysis was conducted to determine the magnitude of the association between occupations and the risk of hand eczema. An increased risk of hand eczema was quantified among hairdressers, as well as nurses, metal workers and office workers (paper I).Currently, patients with chronic hand eczema are referred to a dermatology clinic for further treatment and investigation. Patch testing is a well established procedure for confirming or excluding the role of causative allergen that comes in contact with the hands. After patch testing, a majority of patients are referred back to primary health care without follow-up. In a questionnaire study, 1-10 years after patch testing, we found that many patients forgot their patch test results, and still reported concerns with aspects of their work (papers II-III). In addition, there was no association between patch test results and reporting a better health-related quality of life (paper III). For hand eczema and/or atopic dermatitis patients, we evaluated the change of health-related quality of life (HRQoL) at every three months, and the need for health care. An impairment in health-related quality of life, corresponding to a significant clinical value, can predict the worsening of eczema and the need of health care to re-evaluate its treatment (paper IV).Our study suggests the importance of the adoption of long-term management for hand eczema patients, and regularly using HRQoL measure,as the dermatology life quality index, to discover which patients require further adjustment of treatment.
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| 3. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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