Subclinical immunologic and physiologic responses in hexamethylene diisocyanate-exposed auto body shop workers

BACKGROUND: Diisocyanates are potent sensitizing agents and currently the most commonly identified cause of occupational asthma in industrialized countries. However, diisocyanate asthma is difficult to diagnose and exposure and host risk factors are unclear. Auto body shops, one of the most common hexamethylene diisocyanate (HDI) exposure settings, are particularly difficult to study due to their small size and episodic exposures. Surveillance studies of such workers are limited. OBJECTIVES: We have initiated a cross-sectional field epidemiologic study, Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), to characterize the effects of diisocyanate exposures on actively employed auto body shop workers. Methods and Results We present here questionnaire, physiologic, immunologic, and exposure data on 75 subjects enrolled in the study. No overt cases of clinically apparent diisocyanate asthma were identified based on spirometry, methacholine challenge, peak flows, and symptoms. HDI-specific lymphocyte proliferation was present in 30% of HDI-exposed workers and HDI-specific IgG in 34% of HDI-exposed workers, but they were not associated. HDI-specific IgE was detected in two workers. HDI-specific lymphocyte proliferation, increased methacholine responsiveness, and symptoms of chest tightness and shortness of breath were more common in the most heavily HDI-exposed workers, the painters. More long-term follow-up of this cohort should clarify the significance of these HDI-specific immunologic responses, physiologic changes, and symptoms. CONCLUSIONS: These findings demonstrate the presence of HDI-specific immune responses in a large proportion of healthy HDI-exposed workers.     

Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant

OBJECTIVE: Workers at a beryllium ceramics plant were tested for beryllium sensitization and disease in 1998 to determine whether the plant-wide prevalence of sensitization and disease had declined since the last screening in 1992; an elevated prevalence was associated with specific processes or with high exposures; exposure-response relationships differed for long-term workers hired before the last plant-wide screening and short-term workers hired since then. METHODS: Current workers were asked to complete a questionnaire and to provide blood for the beryllium lymphocyte proliferation test (BeLPT). Those with an abnormal BeLPT were classified as sensitized, and were offered clinical evaluation for beryllium disease. Task- and time-specific measurements of airborne beryllium were combined with individual work histories to compute mean, cumulative, and peak beryllium exposures for each worker. RESULTS: The 151 participants represented 90% of 167 eligible workers. Fifteen (9.9% of 151) had an abnormal BeLPT and were split between long-term workers (8/77 = 10.4%) and short-term workers (7/74 = 9.5%). Beryllium disease was detected in 9.1% (7/77) of long-term workers but in only 1.4% (1/74) of short-term workers (P = 0.06), for an overall prevalence of 5.3% (8/151). These prevalences were similar to those observed in the earlier survey. The prevalence of sensitization was elevated in 1992 among machinists, and was still elevated in 1998 among long-term workers (7/40 = 18%) but not among short-term workers (2/36 = 6%) with machining experience. The prevalence of sensitization was also elevated in both groups of workers for the processes of lapping, forming, firing, and packaging. The data suggested a positive relationship between peak beryllium exposure and sensitization for long-term workers and between mean, cumulative, and peak exposure and sensitization for short-term workers, although these findings were not statistically significant. Long-term workers with either a high peak exposure or work experience in forming were more likely to have an abnormal BeLPT (8/51 = 16%) than the other long-term workers (0/26, P = 0.05). All seven sensitized short-term workers either had high mean beryllium exposure or had worked longest in forming or machining (7/55 = 13% versus 0/19, P = 0.18). CONCLUSIONS: A plant-wide decline in beryllium exposures between the 1992 and 1998 surveys was not matched by a decline in the prevalence of sensitization and disease. Similar to findings from other studies, beryllium sensitization/disease was associated with specific processes and elevated exposures. The contrast in disease prevalence between long-term and short-term workers suggests that beryllium sensitization can occur after a short period of exposure, but beryllium disease usually requires a longer latency and/or period of exposure. The findings from this study motivated interventions to more aggressively protect and test workers, and new research into skin exposure as a route of sensitization and the contribution of individual susceptibility.     

Humoral and cellular immune responses to split-virion H5N1 influenza vaccine in young and elderly adults

We evaluated the humoral and cellular immunogenicity of adjuvanted and non-adjuvanted H5N1 influenza vaccine in two groups of 300 adults: aged 18–60 and >60 years in a randomized, open-label, uncontrolled phase 2 trial. Participants received two injections (D0, D21) of 7.5 μg hemagglutinin without adjuvant or 30 μg with aluminum hydroxide adjuvant. Antibody responses and cytokine secretion were assessed before and after vaccination. Excluding the 6/300 non-elderly and 47/300 elderly participants with pre-existing antibodies, geometric mean titers (dil⁻¹) on D42 were higher with 30 μg+Ad and were comparable between age groups. Participants with pre-existing antibodies responded strongly to the first vaccination (GMTs in the range 147–228 on D21). Vaccination increased both Th1 and Th2 T-cell responses. The predominantly Th1 profile observed before vaccination was unaffected by vaccination. H5N1 influenza vaccine is no less immunogenic in elderly adults than in younger adults and, due to a higher proportion non-naïve elderly, immunogenicity was higher in this latter group.     

Humoral and cellular immune responses in sheep following administration of different doses of an inactivated phase I vaccine against Coxiella burnetii

An inactivated Coxiella burnetii Phase I (PhI) vaccine (Coxevac®) is licensed in several European countries for goats and cattle to prevent coxiellosis. The vaccine is also applied to sheep, although detailed information about the ovine immune response and vaccine dose is missing. Eighteen gimmers from a C. burnetii unsuspected flock were randomly divided into three groups of six. Group 1 (Cox1) and 2 (Cox2) were vaccinated twice with 1 ml and 2 ml Coxevac®, respectively, three weeks apart (primary vaccination). The same procedure was applied with Cox3 (2 ml sodium chloride, control group). A third injection (booster) was performed after nine months. Potential side effects were determined by measuring the rectal body temperature and skin thickness at the injection site. Blood samples were collected to detect phase-specific IgM and IgG antibodies and interferon-ɣ (IFN-ɣ) release by immunofluorescence assay and ELISAs, respectively. Moreover, a cell infection neutralization assay determined the appearance of neutralizing sera. Body temperatures increased for one day post vaccination, and the skin swelled only slightly. Regardless of the vaccine volume, immunized sheep reacted first with an IgM and IgG PhII response. Ten weeks after the primary vaccination, IgG PhI antibodies predominated. Boosting eight months after primary vaccination resulted in a robust IgG PhI increase and strong IFN-ɣ response. In the vaccinated animals, the neutralizing effect is more widespread after the administration of 1 ml than after the treatment with 2 ml. In summary, differences between 1 and 2 ml Coxevac® are minor, and a vaccine volume of 1 ml seems to be sufficient. A booster after the primary vaccination is apparently necessary to stimulate the cell-mediated immune response in naïve sheep.     

Immunological effects of CaEDTA injection: Observations in two lead workers

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) injection on human immune system in relation to exposure to lead, we administered CaEDTA by intravenous injection for 1 hr three times (three consecutive days) a week to two male lead workers. They had been engaged in recycling lead for 31 and 22 years, aged 61 and 53 years (workers 1 and 2), respectively. Before the treatment of CaEDTA, their blood lead concentrations (PbB) were 81 and 68 μg/dl, respectively. The administration of CaEDTA had been carried out to worker 1 for 10 weeks and to worker 2 for 6 weeks. A significant decrease in PbB between before and after three-times CaEDTA injection was found in both workers. Significant increases in IgG, IgA, IgM, CD8+, and CD57+ cells were found in worker 1. A significant increase in IgD was found in worker 2. During the study period, IgG in worker 1 and CD4+ cells in worker 2 were gradually increasing. There was a significant negative correlation between IgG and PbB in worker 1. It is suggested that the immunological function such as antibody formation in lead workers might be improved by CaEDTA injection. Am. J. Ind. Med. 32:674–680, 1997. © 1997 Wiley-Liss, Inc.     

Reliability and validity of childhood asthma control test in a population of Chinese asthmatic children

Background No quick and easy assessment tool is presently available to measure asthma control and outcome in Chinese children. Methods We translated an established seven-item questionnaire into the Chinese Childhood Asthma Control Test (C-CACT) to measure asthma symptoms and their effect on daily function in 247 children aged 4–11 years enrolled from specialty clinics around Tainan. Subjects were classed as having either intermittent or persistent asthma and were evaluated at two outpatient visits 4–8 weeks apart (baseline and follow-up). Results C-CACT at baseline correlated significantly with physician evaluation scores (PES) except in predicted peak expiratory flow rate. There were significant differences for mean C-CACT score and mean PES between the intermittent group and persistent group. Internal consistency reliability of the survey was 0.741 at baseline and 0.759 at the follow-up visit. Test–retest reliability among 209 patients with the same specialist rating of asthma control at baseline and follow-up was r = 0.546 (P < 0.001). C-CACT scores of patients whose therapy needed to be stepped up was significantly lower than in those with unchanged or stepped-down therapy (F = 39.61, P < 0.001). Conclusions C-CACT provides a reliable, valid, and responsive measure of asthma control in Chinese children. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Early reaction type allergies and diseases of the respiratory passages in employees from persulphate production

The prevalence of positive skin-prick test reactions to ammonium persulphate and potassium persulphate (1% and 5% solutions) was tested in a cross-sectional study on 52 employees of a company producing persulphates after a case of persulphate asthma was observed. A random test of 13 persons without occupational exposure to persulphates served as controls; among them all the skin-prick test reactions were negative. Eight company employees showed a positive skin-prick test reaction to at least one of the persulphate solutions tested. Employees showed lower lung function results with a positive prick test reaction than did employees with a negative result. The positive skin-prick reactions correspond well to the anamnestic data and indicate a possible relationship to obstructive ventilation disorders. The results therefore suggest an IgE-induced, allergic pathomechanism of persulphate asthma triggered by persulphates.     

Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose.UMIN Clinical Trials Registry ID: UMIN000043340.     

Evaluation of cell-mediated immune responses to two BCG vaccination regimes in young children in South Korea

Children in South Korea are vaccinated with either BCG Pasteur vaccine intradermally (ID), or with BCG Tokyo vaccine given by multipuncture device (MP). Data from a recent national survey indicated that in children under 6 years old, 31.1% had received the ID vaccine and 64.5% the MP vaccine. To compare the T cell responses induced by the two vaccines, children aged 3-7 were recruited and tested for tuberculin skin test reactivity and for in vitro IFN-γ responses to mycobacterial antigens. DTH responses were not significantly different in children vaccinated by either the ID or MP vaccines. PPD-induced IFN-γ was measured in supernatants of 6-day diluted whole blood cultures. IFN-γ production to PPD was not significantly different in the two vaccine groups, although there is a trend that the MP group gives a higher proportion of IFN-γ positivity than the ID group. In addition, when IFN-γ responses to the antigens ESAT-6 and CFP-10 were assessed in the 6-7 year old group, there was no significant difference between the two vaccine groups. Thus, there was no evidence that the increasing use of MP vaccination has reduced protection against M. tuberculosis in young children in South Korea, based on immunogenicity as assessed by DTH and IFN-γ responses to PPD, and also equivalent frequency of responses to ESAT-6 and CFP-10.     

Unintentional fatal paraquat poisonings among agricultural workers in Costa Rica: Report of 15 cases

This study analyzes the exposure circumstances of 15 fatal occupational paraquat poisonings. To evaluate the potential danger of dermal absorption and the amount needed to produce a fatal outcome in the event of oral intake, we reviewed the medical records and autopsy protocols and interviewed relatives. Five fatalities were due to ingestion of a mouthful of paraquat concentrate, and five to intake of a smaller amount; three cases were associated with dermal exposure, and in two, there was no evidence of either oral or dermal exposure. Several cases concerned diluted paraquat spray. The clinical and pathomorphological findings, including a “blinded” evaluation of lung slides, were consistent with paraquat poisoning in all cases. Difficulties in establishing the diagnosis and recognizing the exposure were identified, as well as classification of unintentional poisonings as suicides at autopsy. The findings suggest that paraquat may cause fatal poisonings by ingestion of small amounts, by dermal absorption of diluted paraquat, and possibly by inhalation. More conclusive studies are warranted. Am. J. Ind. Med. 32:433–441, 1997. © 1997 Wiley-Liss, Inc.     

Polyisocyanates in occupational environments: a critical review of exposure limits and metrics

BACKGROUND: Determination of polyisocyanates is important because they are a major contributor of exposure to the isocyanate functional group in many workplace environments and are capable of inducing sensitization and asthma. However, with multiple different measurement metrics in use, comparison of isocyanate exposure data between studies and development of occupational exposure limits (OELs) for polyisocyanates is difficult. METHODS: An analysis of existing problems in the measurement and regulation of isocyanates is presented based on the published analytical, toxicological, and regulatory literature, and the authors' own analytical data and experience with isocyanates. RESULTS: This analysis supports a need for standardization of isocyanate measurement metrics and provides a framework for the development of an OEL for polyisocyanates. CONCLUSIONS: The total isocyanate group (microg NCO/m(3)) is recommended as the most feasible and practical metric (unit) by which to express polyisocyanate exposures for research, control, and regulatory purposes. The establishment of a comprehensive isocyanate OEL that simplifies the current agent-by-agent approach and expands coverage to polyisocyanates is also recommended.     

Notified cases of occupational asthma in Norway: exposure and consequences for health and income

BACKGROUND: Estimates of occupational asthma (OA) may vary between countries and within countries. An overview of cases of occupational asthma in Norway has not been presented previously. Norwegian physicians are obliged to report occupational diseases to the Labor Inspection Authority. The registry of these notifications was used to study the cases of OA. METHODS: Data were collected from the notifications for respiratory disease for the period 1995-1999. A postal questionnaire inquiring into work, respiratory symptoms, smoking, and socioeconomic consequences of the disease was sent to 1,239 workers with a physician's diagnosis of obstructive respiratory disease. RESULTS: The response rate to the questionnaire was 81% (1,000 workers of whom 723 had OA). On an average, 223 annual cases of OA were reported in the study period (1995-1999). The highest incidence of notifications was found in the primary aluminum industry and in bakers, car painters, and welders. At the time of notification, more than half of the workers had left their original jobs. At the time of this study 2-6 years later, approximately the same proportion of workers had experienced a reduction in income and had received financial compensation; 60-78% were still on antiasthmatic medication. DISCUSSION: The notification of OA by Norwegian physicians may underestimate the true incidence considerably. A majority of the notified cases seemed to become chronic despite medical treatment. CONCLUSIONS: More emphasis should be put on early recognition of OA and on the reduction or cessation of exposure after the diagnosis of OA.     

87例小儿肺炎型哮喘临床诊疗分析

目的观察小儿肺炎型哮喘的临床特点,提高对该病的认识。方法病例来自于2008年9月至2011年12月我院儿科门诊治疗具有肺炎特点哮喘患儿87例,予以抗哮喘为主要治疗,病情较重静脉点滴地塞米松,病情较轻吸入布地耐德混悬剂等药物作泵吸治疗,临床症状缓解后吸入丙酸倍氯米松气雾剂予以哮喘预防治疗,随访1年观察哮喘复发、反复呼吸道感染情况。其中吸入丙酸倍氯米松治疗56例患儿为观察组,拒绝吸入治疗31例患儿为对照组,采用χ2检验分析观察结果。结果 87例患儿经抗哮喘治疗后病情均被控制,治疗时间(8.39±4.27)d。随访1年后,观察组在哮喘复发、反复呼吸道感染改善方面明显好于对照组,差异有统计学意义(P<0.05)。结论正确判断肺炎型哮喘,及时进行抗哮喘治疗,病情缓解后,吸入药物进行干预治疗,能减少哮喘复发、改善反复呼吸道感染。     

Focus and breadth of cellular immune responses elicited by a heterologous insert prime-boost vaccine regimen in rhesus monkeys

The global sequence diversity of HIV-1 presents a daunting challenge for vaccine development. We investigated whether a heterologous insert prime-boost regimen could expand global coverage by selectively boosting cellular immune responses to conserved epitopes. Rhesus monkeys were primed and boosted with recombinant adenovirus vectors expressing homologous or heterologous HIV-1 Gag sequences that were optimized to focus responses on highly conserved epitopes. We observed comparable responses directed to specific regions of the Gag protein in all experimental groups without evidence of improved coverage or expanded breadth in the heterologous insert group. These data suggest that antigen-independent factors contribute to the immunodominance patterns of vaccine-elicited cellular immune responses.     

肠内营养对长期禁食危重症病人炎性反应和细胞免疫的影响

目的:前瞻性观察长期禁食的危重症病人对恢复肠内营养(EN)初期免疫炎性反应的影响. 方法:将28例禁食14 d以上的危重症病人,分别于实施EN前和EN后第1、第3和第7天检测外周血中内毒素、白细胞(WBC)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-1、IL-6、IL-4、IL-10)、T淋巴细胞亚群(CD3、CD4、CD4/CD8)和抗组织相容性抗原-DR(HLA-DR)水平. 结果:①内毒素、WBC、CRP、TNF-α、IL-6水平在EN实施第1、3天后均较EN前显著提高;IL-1在EN实施第1天显著提高;IL-4和IL-10较EN实施前无明显改变.②CD4和CD4/CD8在EN第7天较EN前显著提高. 结论:长期禁食的危重症病人在恢复EN初期全身炎症反应增强,持续EN可减轻增强的炎性反应,并改善病人的细胞免疫功能.     

Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice

Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host’s immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development.     

Biological miracles and misadventures: Identification of sensitization and asthma in enzyme detergent workers

The discovery that the enzymes used in biological washing powders were asthma-causing sensitizers derived initially from the concern of an industrial physician as to the possibility, of pulmonary damage due to the proteolytic nature of the material. This caused a search for possible cases of enzyme-related illness. Careful history-taking led to a hypothesis concerning sensitization and allergic illness which was supported experimentally by skin prick tests and inhalation challenge tests, and later by radioallergosorbent tests (RAST). It seems that the consequences of handling this potentially allergenic material as a fine powder had not been anticipated; and failure to analyze cases of sickness, to identify asthma, and to consider its workplace source had prevented its recognition elsewhere. Contributing to this failure was the pattern of development and manifestations of allergic illness, which seldom occurred in the workplace and was not confined to enzyme workers or atopics. In some cases the incidence of illness had been suppressed, or investigation prevented. © 1996 Wiley-Liss, Inc.     

Monitoring the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children: Protective anti-HBs levels and cellular immune responses

Vaccination against hepatitis B virus (HBV) is recommended worldwide. The aim of this study was to assess the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children in the context of protective anti-HBs levels and cellular immune responses. Using a random questionnaire survey, 1695 pre-school children were recruited as research subjects during January 2015 to June 2017. Blood samples were obtained to measure HBV serological markers as well as peripheral immunocytes. The children were divided into non-, low- and hyper- responsive groups (NR, LR, and HR) based on the vaccination efficacy. Additionally, the effect of revaccination on the NR group was evaluated at 1 month after completion of the vaccination course. Among a total of 1695 children, 1591 (93.86%) were infants who were followed while undergoing their primary course of hepatitis B vaccination at the 0-1-6 month schedule, and 1249 (79.30%) of them developed antibodies against HBsAg (anti-HBs) titers greater than 10 IU/L. The results of immunocyte studies indicated that the CD8⁺ T cells, CD4⁺CD45RO⁺ T cells, CD8⁺CD45RA⁺ T cells, and T follicular helper (Tfh) cells increased significantly in NR compared with HR. However, lymphocytes, CD4⁺ T cells, and CD4⁺CD45RA⁺ T cells in NR were lower than that in HR. 96 of the non-response cases showed seroprotection after revaccination among 103 cases. Therefore, most of the preschool children who received hepatitis B vaccine in infancy achieved significant seroprotection. Seroconversion rates of individuals revaccinated after initial vaccination failure were significantly higher than those after primary vaccination. Different vaccination efficacy groups showed significant changes in circulating immunocytes, which might be a factor affecting the recombinant HBV vaccine’s immune effectiveness.