Latex allergy. A position paper of the British Society of Allergy and Clinical Immunology.
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Anesthesia↗
Biomedical subjects
P Cullinan
Publications and source records attributed to P Cullinan.
Is there a role for microorganisms in the pathogenesis of sarcoidosis?
Sarcoidosis is a granulomatous disease that has the immunopathological features of being antigen-driven. It is a complex disease that appears to arise from the interaction of one or more triggers with an immunologically predisposed host. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations could reflect differences in ethnic predisposition or differences in local environmental exposures. This review focuses specifically on these areas that have been the subjects of intensive investigation recently. Specific focus is provided on the issue of an infective trigger and highlights popular candidates. It is concluded that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.
Bacterial Infections↗
Occupational asthma from fungicides fluazinam and chlorothalonil.
We report two cases of occupational asthma caused by sensitisation to powdered fungicides fluazinam and chlorothalonil, from the same fungicide formulation plant. Both developed work related lower respiratory symptoms after a latent interval of asymptomatic exposure. The diagnosis in each case was confirmed with a serial peak flow record in the workplace followed by specific inhalation tests. These fungicides are known to cause dermatitis; this report indicates that these compounds can induce specific immunological reactions in the airways as well as skin.
Aminopyridines↗
Exposure-response relations among laboratory animal workers exposed to rats.
AIM: To explore exposure-response relations in a cohort of laboratory animal workers. METHODS: Exposure-response modelling was carried out in a cohort of 342 laboratory animal workers. Three exposure indices, divided into different exposure categories, were used in the analyses: intensity of exposure to rat urinary aeroallergen (RUA, the main allergen workers were exposed to), weekly duration of exposure to rats, and the product of the intensity and weekly duration of exposure. Outcomes studied were work related chest, eyes and nose, and skin symptoms that had started after employment at the sites, specific sensitisation, and a combination of symptoms and sensitisation. Cox proportional hazard modelling was used to explore exposure-response relations. Smoking, atopic status, age, and gender were taken into account. RESULTS: We observed the clearest exposure-response relations for the intensity of exposure to RUA and the various endpoints. No clear exposure-response relations were observed for the weekly duration of exposure or the product of the intensity and weekly duration of exposure. The strongest and clearest exposure-response relations for symptoms were observed among rat sensitised workers, while the non-sensitised workers only showed small increased risks of developing symptoms without clear exposure-response relations. Sensitised workers were almost four times more likely to go on to develop chest symptoms compared to non-sensitised workers.
Adult↗
Estimating the incidence of occupational asthma and rhinitis from laboratory animal allergens in the UK, 1999-2000.
We report a survey of the number of persons handling laboratory animals in the UK in 1999-2000. This estimate has allowed us to calculate annual incidence rates of allergic asthma and rhinitis attributable to laboratory animals, insects, and birds using numerators derived from cases reported to a national surveillance scheme (SWORD). The number of exposed employees has almost halved since the early 1980s. From these data, the estimated annual incidence rate of occupational asthma among persons working with small mammals is 1.56/1000 employees. Although reported cases are rare, estimated incidence rates of asthma attributable to birds (23.9/1000/year) and insects (2.35/1000/year) are high.
Allergens↗
Can early infection explain the sibling effect in adult atopy?
Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection. The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK. The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors. In particular, a higher number of brothers appeared to offer protection. The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life "hygiene". The sibling effect was unexplained by evidence of infection with either hepatitis A or Helicobacter pylori, or by counts of infections or antibiotic prescriptions in early life. There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy. Dog ownership and home moving in early life also displayed potentially protective associations. Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection. The findings support the suggestion that the "sibling effect" in atopy may not simply reflect protection by early infection.
Adult↗
The prevention of occupational asthma.
There is sufficient understanding of the causation of occupational asthma for preventive action to be appropriate. To date, attempts appear to have been largely unsuccessful and this appears to be largely due to nonscientific/technical obstacles. These include the fragmented nature of the disease, its low public and industrial profile, and its comparative rarity in single workplaces. Nonetheless the disease has high individual and societal costs. Prevention strategies should be concentrated on workplace-exposure controls, accompanied by intense educational and managerial improvements. Methods of secondary prevention appear to be successful but require considerable refinement. Screening (out) of potential new employees is inefficient and likely to remain so; and in any case is beset by difficult ethical and legal issues. There are only a handful of published studies reporting evaluations of preventive programmes. None is entirely rigorous but each suggests that primary and secondary prevention are both feasible and highly effective. The evaluation of preventive strategies is difficult, not only because of the low incidence of the disease in individual workplaces but also because of the failure of many epidemiologists to engage in this work. Considerably more cooperation between scientists in the field, regulatory authorities and industry is required.
Air Pollutants, Occupational↗
Has the world forgotten Bhopal?
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Accidents, Occupational↗
Gold as an oral corticosteroid sparing agent in stable asthma.
BACKGROUND: Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Gold compounds are immunosuppressive agents and have benefits in the treatment of a number of inflammatory disorders. They have therefore been identified as an potentially useful agents in the treatment of chronic severe asthma both in terms of possible efficacy and as steroid sparing agents. OBJECTIVES: The objective of this review was to assess the effects of adding gold to oral steroids in the treatment of chronic steroid dependent asthmatics. SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA: Randomised trials looking at the addition of gold compared to placebo in adult steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review and a total of 376 patients were recruited into these studies. Data from 311 patients could be analysed. There was a small but significant treatment effect for gold in terms of steroid dose reduction (Peto Odds Ratio 0.51, 95% confidence intervals 0.31,0.83). No meta-analysis could be done for measures of lung function although overall there were few changes suggesting a positive benefit for gold. There were trends suggestive of adverse effects but no significant changes for gold treated patients with respect to proteinuria (Peto Odds Ratio 1.4, 95% confidence intervals 0.6, 3.3) dermatitis/eczema Peto Odds Ratio 2.1, 95% confidence intervals 0.9, 4.7). REVIEWER'S CONCLUSIONS: The changes seen in these trials are small and probably of limited clinical significance. Given the side effects of gold and necessity for monitoring the use of gold as a steroid sparing agent in asthma cannot be recommended.
Adrenal Cortex Hormones↗
Troleandomycin as an oral corticosteroid steroid sparing agent in stable asthma.
BACKGROUND: Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. troleandomycin is a compound that is established as an effective antibiotic but may also have non antibacterial actions that may be useful in the treatment of asthma. OBJECTIVES: The objective of this review was to assess the effects of adding troleandomycin to oral steroids in the treatment of chronic steroid dependent asthmatics. SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA: Randomised trials looking at the addition of troleandomycin compared to placebo in adult steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review and a total of 112 patients were recruited into these studies. Data from 90 patients were analysed. There was no treatment effect for troleandomycin in terms of steroid dose reduction (SMD -0.29, 95% CI -0.75, 0.17). For measures of lung function a meta-analysis of data derived from two of the included studies showed no benefits for added troleandomycin (SMD 0.06 95% CI -0.8, 0.9). REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of troleandomycin in the treatment of steroid dependent asthma.
Administration, Oral↗
Cyclosporin as an oral corticosteroid sparing agent in stable asthma.
BACKGROUND: Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Cyclosporin is an immunosuppressive agent and has benefits in the treatment of a number of inflammatory disorders. It has therefore been identified as an potentially useful agent in the treatment of chronic severe asthma both in terms of possible efficacy and as a steroid sparing agent. OBJECTIVES: The objective of this review was to assess the effects of adding cyclosporin to oral steroids in the treatment of chronic steroid dependent asthmatics. SEARCH STRATEGY: The Cochrane Airways Group trials register and reference lists of identified articles were searched. SELECTION CRITERIA: Randomised trials looking at the addition of cyclosporin compared to placebo in adult steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. MAIN RESULTS: Three trials fulfilled the criteria for inclusion in the review and a total of 106 patients were recruited into these studies. Data from 98 patients could be analysed. There was a small but significant treatment effect for cyclosporin in terms of steroid dose reduction (SMD -0.5, 95% CI -1.0, -0.04). No meta-analyses could be performed for measures of lung function although one study showed small, but significant improvements in lung spirometry. REVIEWER'S CONCLUSIONS: The changes with cyclosporin are small and of questionable clinical significance. Given the side effects of cyclosporin, the evidence available does not recommend routine use of this drug in the treatment of oral corticosteroid dependent asthma.
Administration, Oral↗
Allergen and dust exposure as determinants of work-related symptoms and sensitization in a cohort of flour-exposed workers; a case-control analysis.
OBJECTIVES: To estimate the incidence of specific IgE sensitization and allergic respiratory symptoms among UK bakery and flour mill workers; and to examine the roles of flour aeroallergen and total dust exposures in determining these outcomes. METHODS: A cohort of 300 new employees, without previous occupational exposure to flour, were followed prospectively for a median (range) of 40 (1-91) months. Cases-defined as those developing work-related symptoms or a positive skin prick test to flour or alpha-amylase during follow up--were compared with controls, matched for duration of employment. Exposures to flour aeroallergen and total inhalable dust were estimated using a questionnaire and personal sampling techniques. RESULTS: Incidence rates for work-related eye/nose and chest symptoms were 11.8 and 4.1 cases per 100 person years (py), respectively. Fewer employees developed positive skin prick tests to flour (2.2 cases per 100 py) or alpha-amylase (2.5 cases per 100 py). Positive skin tests to occupational allergens were more common among those with new work-related symptoms. There were clear relationships between the risks of developing work-related symptoms or a positive skin prick test and three categories of estimated exposure to total dust or flour aeroallergen. Atopic employees were more likely to develop a positive skin prick test-but not work-related symptoms. These findings were unaffected by age, sex or cigarette smoking. CONCLUSIONS: In this population, many work-related symptoms which develop after first employment in modern UK bakeries or flour mills were not accompanied by evidence of IgE sensitization to flour or alpha-amylase. Although average dust exposures were within current occupational standards, the risks of development of upper and lower respiratory symptoms and of specific sensitization were clearly related to total dust and/or flour aeroallergen exposure. The incidence of work-related chest symptoms in the presence of a positive skin test to flour or alpha-amylase in this setting was approximately 1 case per 100 py.
Adult↗
ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse.
The large mucin CD43 is actively excluded from T cell/APC interaction sites, concentrating in a membrane domain distal to the site of TCR engagement. The cytoplasmic region of CD43 was necessary and sufficient for this antipodal movement. ERM cytoskeletal adaptor proteins colocalized with CD43 in this domain. An ERM dominant-negative mutant blocked the distal accumulation of CD43 and another known ERM binding protein, Rho-GDI. Inhibition of ERM function decreased the production of IL-2 and IFNgamma, without affecting PKC(theta) focusing or CD69 upregulation. These results indicate that ERM proteins organize a complex distal to the T cell/APC interaction site and provide evidence that full T cell activation may involve removal of inhibitory proteins from the immunological synapse.
Animals↗
Environmental associations with eczema in early life.
BACKGROUND: Although atopic eczema (AE) is a common disease, little is known about its causes. OBJECTIVES: To investigate the role of dietary and environmental factors associated with the development of AE by the age of 2 years. METHODS: A cohort of children was recruited before birth from a consecutive series of newly pregnant mothers presenting for antenatal care at three general practices in Ashford, Kent, U.K. Data up to the age of 2 years were available for 624 (97%) of the original cohort. AE was defined using components of the U.K. diagnostic criteria for AE, maternal report of doctor-diagnosed eczema and maternally reported eczema. Exposures of interest were family history of allergic disease, dietary and breastfeeding patterns, family size and exposure to indoor domestic allergens. RESULTS: The cumulative prevalence of AE using the U.K. diagnostic criteria was 14% (95% confidence interval, CI 11-17%). The prevalence of maternally reported doctor-diagnosed eczema was much higher (31%, 95% CI 27-35%) and almost half (45%) the mothers reported that their child had ever had eczema (95% CI 41-49%). The relationship between parental atopy, parental history of allergic disease and the child's eczema was consistently stronger for the mothers than the fathers. There was a marked increase in the prevalence of eczema with increasing maternal education and in less crowded homes, associations that remained significant after controlling for other factors. CONCLUSIONS: The associations with environmental factors are consistent with the hypothesis that more crowded houses, increased family size and birth order, which may possibly increase early exposure to infections, may offer protection from subsequent development of eczema.
Adult↗
Maternal atopy and parity.
BACKGROUND: Family size and high birth order were related to the prevalence of hayfever and positive skin prick test. However, this association may be explained by maternal atopy. We examined the relationship between maternal atopy and the number of offspring in three European cohorts of pregnant women. METHODS: The mothers and their children (n = 1487) were recruited for the Asthma Multi-centre Infants Cohort Study (AMICS). The three concurrent cohorts (Ashford, Kent (UK); Menorca island (Spain) and Barcelona city (Spain) followed the same research protocol. Maternal and paternal atopy was identified by skin prick tests at different times at the three centres. RESULTS: Maternal atopy was inversely related to the number of offspring, an association which occurred in each of the three cohorts and remained when atopy was defined separately for individual allergens (a positive response to testing with either Der p 1 or grass pollen) and which was not confounded by maternal age, smoking nor social class (the adjusted odds ratios were 0.71, 0.79 and 0.26 for increasing number of offspring, P = 0.002). Neither maternal asthma (P = 0.43) nor paternal atopy (P = 0.58) were associated with the number of offspring. Maternal atopy was not related to reproductive outcomes. CONCLUSIONS: The association between maternal atopy and parity challenges the role of family size on child atopy, which should be studied in other populations.
Adult↗
Crete: does farming explain urban and rural differences in atopy?
BACKGROUND: Urban-rural differences in the prevalence of atopy and associated allergic diseases have been reported in several non-European countries. Within Europe, where such variations are less striking, a farm childhood has been postulated to be protective. OBJECTIVE: We aimed to compare the prevalence of atopy in urban and rural children living in Crete and to examine the role of early exposure to a farming environment in explaining any measured differences. METHODS: A cross-sectional survey of children attending secondary schools in Iraklion, the capital city, and five villages 100 km to the south. Atopy was determined by the responses to skin prick tests with seven common aeroallergens. RESULTS: Nine-hundred and ninety-seven children participated in the survey. 19.6% of those living in Iraklion, but only 9.6% of those from the villages, had a positive response to one or more skin prick tests. Among urban children there were significant gradients in the prevalence of atopy across several categories of animal contact and consumption of farm (unpasteurized) milk products--before the age of 5 years. These differences, however, were not apparent among the rural children.
Adolescent↗
Idiopathic interstitial pneumonias: the role of environmental triggers.
Idiopathic--or cryptogenic--fibrosing alveolitis is defined by a cluster of clinical, radiological, functional, and pathological features as well as by the exclusion of a recognized "cause.'' The processes by which clinicians assign causes to nonspecific diseases are complex and often subjective. Furthermore, the disease is comparatively rare and is generally diagnosed only after the use of specialized techniques. As a result, the study of its etiological factors is difficult and has been largely unrewarding. The distribution of the disease, so far as it is understood, favors the elderly and, to a lesser extent, males. In some countries mortality has been rising, although it is not clear whether this can be attributed to a diagnostic shift. Studies of occupational classifications among patients dying with the disease offer no striking etiological leads. Four potential etiologies have been formally studied: occupational dust exposures, cigarette smoking, prescription drug use, and viral infections. Three studies have indicated a role for wood and metal dust exposures; methodological issues, however, leave room for remaining doubt and these studies require verification in other populations. There is little epidemiological evidence that cigarette smoking contributes to the disease, or that therapeutic drug use plays an important part. The role of viral infections, particularly those related to Epstein-Barr virus (EBV), is intriguing but remains largely unsubstantiated.
Journal Article↗
Sensitisation to natural rubber latex: an epidemiological study of workers exposed during tapping and glove manufacture in Thailand.
OBJECTIVES: To estimate the prevalence of sensitisation to natural rubber latex in latex tappers and latex glove factory workers, and to relate this to airborne exposure to latex. METHODS: Five hundred workers employed in three latex glove factories, 314 tappers, and 144 college students (control group) were studied. The workers in the glove factories were classified into three exposure groups; high, moderate, and low. Personal exposures to natural rubber latex aeroallergens were measured by immunoassay. Symptom questionnaires and skin prick tests with latex allergens (Stallergènes 1:200 w/v) and other common environmental allergens were performed. The criterion for positivity was a wheal reaction at least 3 mm in diameter greater than that to a diluent control. RESULTS: The geometric mean (GM) concentration of latex in air was 15.4 microg/m(3) for those employed in glove stripping, glove inspections, and packing of powdered gloves. The moderate exposure glove manufacturing group and the tappers had GM concentrations of 2.3 and 2.4 microg/m(3) respectively, compared with United Kingdom users of latex powdered gloves,who had GM concentrations of 0.5 microg/m(3). The prevalence of sensitisation to latex in the tappers and latex glove factory workers was 1.3% and 1.7% respectively. No positive cases were found among the college students. Workers who showed a positive skin prick test to latex were more likely to be atopic. Work related respiratory and dermatological symptoms were found in about 20% of each population studied, but were not related to the presence of positive latex prick tests. CONCLUSIONS: This study suggests that in the Thai latex industries, latex sensitisation is rare despite high concentrations of airborne exposure and is less prevalent than in the healthcare sector in Europe where skin exposure is greater.
Adult↗