The ability to monitor lymphocyte responses is critical for developing our understanding of the immune response in humans. In the current clinical setting, relying on the metabolic incorporation of [³H] thymidine into cellular DNA via a lymphocyte proliferation test (LPT) is the only method that is routinely performed to determine cell proliferation. However, techniques that measure DNA synthesis with a radioactive material such as [³H] thymidine are intrinsically more sensitive to the different stages of the cell cycle, which could lead to over-analyses and the subsequent inaccurate interpretation of the information provided. With cell proliferation assays, the output should preferably provide a direct and accurate measurement of the number of actively dividing cells, regardless of the stimuli properties or length of exposure. In fact, an ideal technique should have the capacity to measure lymphocyte responses on both a quantitative level, i.e., cumulative magnitude of lymphoproliferative response, and a qualitative level, i.e., phenotypical and functional characterization of stimulated immune cells. There are many LPT alternatives currently available to measure various aspects of cell proliferation. Of the nine techniques discussed, we noted that the majority of these LPT alternatives measure lymphocyte proliferation using flow cytometry. Across some of these alternatives, the covalent labelling of cells with a high fluorescence intensity and low variance with minimal cell toxicity while maximizing the number of detectable cell divisions or magnitude of proliferation was achieved. Herein, we review the performance of these different LPT alternatives and address their compatibility with the [³H] thymidine LPT so as to identify the “best” alternative to the [³H] thymidine LPT.

Background: Sarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.Objective: To investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosisMethods: We retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.Results: We included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).Conclusions: Our study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

Domestic cleaners have an increased risk of asthma-like and other respiratory symptoms and conditions. Uncertainty exists about which products are most hazardous. We aimed to investigate, among professional domestic cleaners, the associations of ocular/respiratory outcomes with using specific types of products at work and with the ability to choose their own products. Among domestic cleaners employed by "service vouchers" companies in Belgium, we administered an online questionnaire on ocular/respiratory symptoms (frequency and time relation to workdays), frequency of use of 40 types of products, and ability to choose one's own products. Work-relatedness was defined as symptoms improving/disappearing on days off-work. We studied associations between frequency of product-use with work-related outcomes (eye irritation, rhinitis symptoms, sore throat, laryngeal symptoms, asthma symptoms, cough) and with chronic bronchitis, using multivariable logistic and elastic net regression. Adjusted odds ratios (OR) with 95%-confidence intervals were obtained per time a product was used per week. Among 1,586 domestic cleaners (99% women), the number of times sprays were used (median 13/week) was significantly associated with all outcomes (ORs between 1.012 and 1.024 per time sprays were used per week). Bleach/disinfectant-containing liquid products were associated with all outcomes, except for laryngeal symptoms (ORs 1.086 to 1.150); ammonia with work-related upper airway symptoms and chronic bronchitis. Cleaners able to choose their own products had fewer work-related eye symptoms (OR 0.728;0.556-0.954), rhinitis (OR 0.735;0.571-0.946) and cough (OR 0.671;0.520-0.865). Using elastic net regression, work-related rhinitis was most strongly associated with mould removal spray (OR 1.108;1.006-1.248), carpet/seat/curtain spray (OR 1.099;1.001-1.304) and ammonia (OR 1.081;1.002-1.372); work-related asthma with carpet/seat/curtain spray (OR 1.103;1.017-1.322), mould removal spray (OR 1.029;0.995-1.199) and drain cleaner (OR 1.023;0.979-1.302). In a large group of domestic cleaners, we documented that cleaning products have a range of adverse respiratory effects. Empowering cleaners to choose their products may reduce the burden of symptoms.

Tsui HC, et al. Allergy Asthma Immunol Res. 2020 Jul;12(4):579-598. https://doi.org/10.4168/aair.2020.12.4.579