Chronic obstructive pulmonary disease in Welsh slate miners.

BACKGROUND: Exposure to respirable crystalline silica (RCS) causes emphysema, airflow limitation and chronic obstructive pulmonary disease (COPD). Slate miners are exposed to slate dust containing RCS but their COPD risk has not previously been studied. AIMS: To study the cumulative effect of mining on lung function and risk of COPD in a cohort of Welsh slate miners and whether these were independent of smoking and pneumoconiosis. METHODS: The study was based on a secondary analysis of Medical Research Council (MRC) survey data. COPD was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7. We created multivariable models to assess the association between mining and lung function after adjusting for age and smoking status. We used linear regression models for FEV1 and FVC and logistic regression for COPD. RESULTS: In the original MRC study, 1255 men participated (726 slate miners, 529 unexposed non-miners). COPD was significantly more common in miners (n = 213, 33%) than non-miners (n = 120, 26%), P < 0.05. There was no statistically significant difference in risk of COPD between miners and non-miners when analysis was limited to non-smokers or those without radiographic evidence of pneumoconiosis. After adjustment for smoking, slate mining was associated with a reduction in %predicted FEV1 [ß coefficient = -3.97, 95% confidence interval (CI) -6.65, -1.29] and FVC (ß coefficient = -2.32, 95% CI -4.31, -0.33) and increased risk of COPD (odds ratio: 1.38, 95% CI 1.06, 1.81). CONCLUSIONS: Slate mining may reduce lung function and increase the incidence of COPD independently of smoking and pneumoconiosis.

Detergent protease exposure and respiratory disease: case-referent analysis of a retrospective cohort.

OBJECTIVES: To examine the relationship between protease exposure and respiratory disease in a cohort of detergent enzyme manufacturers. METHODS: Case-referent analysis of a cohort of employees working in a European detergent factory between 1989 and 2002. Cases with new lower or upper respiratory disease were ascertained by examination of occupational health records and matched to referents on date of first employment. Personal exposures to airborne detergent protease were estimated, using a job exposure matrix, from >12,000 measurements taken in the factory during the period of study. RESULTS: We found clear, monotonic relationships between estimated protease exposure and both lower and upper respiratory disease. After control for age, sex and smoking, the odds ratio of lower respiratory disease was significantly elevated (1.98, 95% CI 1.04 to 3.79) in those employees working in jobs in the highest quartile of protease exposure (geometric mean 7.9 ng x m(-3)). For employees with upper respiratory disease, the risk was significantly elevated at a lower level of estimated protease exposure (geometric mean 2.3 ng x m(-3)). CONCLUSIONS: These findings provide strong evidence of an association between detergent enzyme exposure and the development of respiratory disease in an occupational setting. Using the routinely collected information on specific sensitisation and the close attention to workplace exposures that are characteristic of this industry, it should be possible to derive meaningful occupational exposure standards for most detergent enzymes.

Atopy and asthma in rural Poland: a paradigm for the emergence of childhood respiratory allergies in Europe.

BACKGROUND: We hypothesized that, in south-west Poland, a 'rural' protective effect on atopy and respiratory allergies would be most pronounced among children but that at all ages would be stronger among those with a rural background. METHODS: A cross-sectional survey of the inhabitants (age >5 years, n = 1657) of Sobotka, a town of 4000 people in south-west Poland: and seven neighbouring villages. We measured and analysed responses to skin prick tests (atopy) and to a standard questionnaire (asthma and hayfever). RESULTS: Atopy was very uncommon (7%) among villagers at all ages but not among townspeople (20%, P < 0.001); the differences were most marked among those aged under 40 years. Asthma and hayfever were similarly distributed, both being very rare among villagers. The differences appear to be explained by the cohort effect of a communal move away from rural life. This interpretation is supported by an ecological correlation (rho = -0.59) between rural populations and childhood wheeze in 22 European countries. CONCLUSION: The very striking differences in the prevalence of allergy between these two neighbouring communities of central Europe reflect the pan-continental population movements that may have been responsible for the emergence of childhood allergies in Europe.

Early allergen exposure and atopic eczema.

BACKGROUND: The relationship between exposure to indoor aeroallergens in early life and subsequent eczema is unclear. We have previously failed to show any significant associations between early life exposure to house dust mite and cat fur allergens and either sensitization to these allergens or wheeze. We have also previously reported a lower prevalence of parent-reported, doctor-diagnosed eczema by age 2 years for children exposed to higher concentrations of house dust mite, but no other associations with other definitions of eczema or for exposure to cat allergen. OBJECTIVES: To extend the exposure-response analysis of allergen exposure and eczema outcomes measured up to age 8 years, and to investigate the role of other genetic and environmental determinants. METHODS: A total of 593 children (92 x 4% of those eligible) born to all newly pregnant women attending one of three general practitioner surgeries in Ashford, Kent, were followed from birth to age 8 years. Concentrations of house dust mite and cat allergen were measured in dust samples collected from the home at 8 weeks after birth. The risk of subsequent eczema as defined by the U.K. diagnostic criteria was determined according to different levels (quintiles) of allergen exposure at birth. RESULTS: By age 8 years, 150 (25 x 3%) children had met the diagnostic criteria for eczema at least once. Visible flexural dermatitis was recorded at least once for 129 (28 x 0%). As in other studies, parental allergic history was positively associated with most eczema outcomes, as were higher maternal education and less crowded homes. No clear linear associations between early exposure to house dust mite or cat allergen were found, regardless of the definition of eczema used. The risk of eczema appeared to increase for the three lowest quintiles of house dust mite allergen exposure (odds ratio, OR 1 x 37 for third quintile compared with first), and then to fall for the two highest quintiles (OR 0 x 66 and 0 x 71) even after controlling for confounding factors. CONCLUSIONS: The lack of any clear exposure-disease relationship between allergens in early life and subsequent eczema argues against allergen exposure being a major factor causing eczema. If the lower levels of eczema at higher levels of house dust mite are confirmed, then interventions aimed at reducing house dust mite in early infancy could paradoxically increase the risk of subsequent eczema.

IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis.

Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection, unresolving inflammation and progressive lung damage. Bronchiectasis can be associated with autoimmune diseases including ulcerative colitis. Defects of both innate and adaptive immunity have been proposed. The airway inflammation is characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils and T cells. Here we investigated two candidate gene polymorphisms that may contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that is implicated in IL-8 binding and neutrophil trafficking as well as the interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of IFNgamma production. These polymorphisms were distributed similarly in the idiopathic bronchiectasis group and controls, suggesting that these two candidate gene polymorphisms are not associated with disease susceptibility.

The effects of farming and birth order on asthma and allergies.

A farm childhood is apparently protective in allergic disease, but studies of this issue in Europe have been confined to particular types of farming practice. This study addressed whether or not this effect was generalisable. A cross-sectional survey of 800 schoolchildren living in rural Crete was undertaken. Standard questions relating to allergic disease were included and atopy was measured through skin-prick tests involving 10 local aeroallergens. The prevalence of atopy was 24%, but associated symptoms were far less common. At all ages, children from farming families had more frequent contact with farm animals (mainly goats), but were no less likely to be atopic. Atopy and seasonal rhinitis were significantly and independently more common among first-born children. This community has an intermediate prevalence of atopy but a very low frequency of allergic disease; farming does not seem to be an important determinant, possibly because it is of the wrong sort. Thus farming effects may be specific to local practices. First-born children in this community also appear to be at increased risk of allergic disease.

Childhood atopy and allergic disease and skin test responses to environmental mycobacteria in rural Crete: a cross-sectional survey.

BACKGROUND: Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease. OBJECTIVE: To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria. METHODS: Eight hundred and six children aged 8-18 years and living in rural Crete--most of whom had had previous BCG immunization--underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I). RESULTS: Twenty-three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children--and those with a BCG scar--there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant. CONCLUSIONS: Our findings, in a population of BCG-immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.

Supermarket baker's asthma: how accurate is routine health surveillance?

BACKGROUND: Regular health surveillance is commonly recommended for workers exposed to occupational antigens but little is known about how effective it is in identifying cases. AIMS: To report one large company's surveillance and compare its findings with those of a standard cross-sectional survey in the same workforce. METHODS: A supermarket company with 324 in-store bakeries producing bread from raw ingredients conducted a three-stage health surveillance programme in around 3000 bakery employees. The first stage involved the administration of a simple respiratory questionnaire. If chest symptoms were present a second questionnaire focusing on their work relationship was administered. If positive a blood sample was requested for the measurement of specific IgE to flour and fungal alpha-amylase. The results were compared to an independent cross-sectional survey of employees in 20 of the company's stores. RESULTS: Two hundred and ninety nine (92%) of the company's bakeries took part in surveillance. The overall employee response for the first stage was 77%; a quarter of those with respiratory symptoms reported that they were work related. Seventy four (61%) of those with work related chest symptoms had a measurement of specific IgE to either flour or fungal alpha-amylase, of whom 30 (41%) had a positive result. Surveillance estimated that 1% of bakery employees (1% bakers, 2% managers, 0.6% confectioners) had work related symptoms with specific IgE. This compared with 4% (7.5% bakers, 3.3% managers, 0% confectioners) in the cross-sectional survey (n = 166, 93% response). CONCLUSION: Comparison with a standard cross-sectional survey suggests that routine surveillance can underestimate the workplace burden of disease. The reasons may include technical or resource issues and uncertainties over confidentiality or the perceived consequences of participation. More research needs to be done looking into the design and efficacy of surveillance in occupational asthma.

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study.

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.

New pregnancies and loss of allergy.

BACKGROUND: Inverse associations between allergic disease and sibship have been consistently described and are frequently explained by purported lower rates of early infection among children from small families. Alternative explanations include the possibility that pregnancy itself determines maternal atopic status. OBJECTIVE: To test the hypothesis that atopy defined by skin prick test (SPT) declines with increasing numbers of pregnancies. METHODS: At enrollment to a birth cohort, mothers were skin prick tested to three common allergens. Seven years later these women underwent a second SPT and provided information on their reproductive histories. At both visits, information on allergic disease was also sought. RESULTS: Twenty five (15%) women who were initially atopic were no longer so at the second visit; loss of hayfever symptoms was reported by 33 (29%) women. Women with higher numbers of intervening pregnancies were more likely to 'lose' their atopy (P=0.05) and symptoms of hayfever (P=0.02); this was not true for asthma. The findings could not be accounted for by maternal age. CONCLUSION: Successive pregnancies may in part determine a mother's atopic state. Since maternal atopy is a risk factor for childhood atopic disease, this process may affect the atopic state of successive children. These findings suggest an alternative explanation for the sibship effect in allergic disease.

Early prescriptions of antibiotics and the risk of allergic disease in adults: a cohort study.

BACKGROUND: It is frequently asserted that antibiotic prescriptions in childhood are associated with the development of allergic disease, especially asthma. A study was undertaken to establish the direction of this relationship. METHODS: A retrospective cohort study of 746 adults was performed in three general practices. Antibiotic prescriptions in the first 5 years of life, collected from contemporary medical records, were related to self-reports of asthma and hay fever and the results of skin prick testing with common aeroallergens. RESULTS: There was no relationship between early antibiotic prescription and atopy, either for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages. The significant associations between prescriptions at ages 4 and 5 and hay fever (OR 1.23 and 1.16, respectively) were explained by coexisting asthma. Relationships between antibiotic use and asthma (allergic or otherwise) were statistically significant and strengthened with increasing age of prescription, but were largely confined to antibiotics prescribed for lower respiratory symptoms. CONCLUSIONS: The reported associations between childhood antibiotic use and asthma are most plausibly explained by "reverse causation"--the tendency for prescriptions to be written for the early manifestations of pre-existing asthma.

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.

Controversies in epidemiology of occupational asthma.

Epidemiology is the study of the distribution, determinants and outcome of disease. In this article, the recently acquired knowledge of the epidemiology of occupational asthma is described, as well as current areas of controversy. Incidence figures obtained from field studies in high-risk workplaces, medicolegal statistics and sentinel programmes indicate that approximately 10% of adult-onset asthma is attributable to the workplace. The strategy to identify cases through questionnaires and tools that address functional, immunological and physiopathological issues needs to be improved. Although few in number and limited to a handful of workplaces, cohort studies found that the risk of developing occupational asthma is determined less by individual susceptibility (e.g. atopy, tobacco smoking, human leukocyte antigen phenotype) and more by the level of exposure to its causes; in general, the higher the exposure, the greater the risk, and, by implication, lowering the level of exposure reduces the incidence of disease. Occupational asthma can be used as a satisfactory model for the development of adult-onset asthma. There is a great need to develop intervention strategies through adequate surveillance programmes in high-risk workplaces.

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.

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.

Analysis of allergens in rat fur and saliva.

BACKGROUND: The fur is an important source of allergens in many mammal species, but this source has not been extensively studied in rats. Rat room dust contains high-molecular-weight allergens that have been found to cross-react with fur and its presumed salivary contaminants. The role of rat fur and saliva as a source of respiratory allergens merits further investigation. The objective was to describe the allergens present in the fur and saliva of male rats. METHODS: Allergen extracts were prepared from the saliva and fur of the pelts from adult male rats. Immunoblotting was used to describe the allergens present in rat fur and saliva with serum from 76 and 25 individuals, respectively. RESULTS: There was considerable variation between the individuals in the binding of IgE to the separated fur and saliva allergens. Immunoblot analysis identified 23 allergens in rat fur. "Major" allergens were found at the "origin", and at 55, 51, 19, and 17 kDa, and "intermediate" allergens at 74, 67 (probably albumin), and 21.5 (diffuse) kDa. Seventeen salivary allergens were described with "major" allergens at 21.5, 19.5, 19, 18, and 17.5 kDa. Many subjects had IgE to the 67 kDa (56%) and 43 kDa (64%) allergens but the density of staining was weak. CONCLUSION: Rat fur and saliva are the sources of many allergens. Fur contained five "major" allergens and was a complex source of allergens of relatively high molecular weight (>22 kDa). The most important salivary allergens have molecular weights of less than 22 kDa. Fur is the most probable source of the high-molecular-weight allergens found in rat room dust.

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.

Current best practice for the health surveillance of enzyme workers in the soap and detergent industry.

This study defines current best practice for the health surveillance of workers who are potentially exposed to enzymes in the manufacture of enzymatic detergent products. It is recommended that health surveillance is performed 6-monthly for the first 2 years and annually thereafter. The health surveillance programme should include a respiratory questionnaire to detect symptoms, assessment of lung function to detect pre-symptomatic changes and an immunological test to detect specific immunoglobulin E (IgE) to enzymes. The International Union Against Tuberculosis and Lung Disease respiratory questionnaire should be used since it has been validated extensively for detecting asthma. Operators should observe the American Thoracic Society performance criteria for spirometers and standardized procedures for conducting spirometry. Since current airborne monitoring techniques for enzymes do not detect short-duration peak exposures, the incidence of employee sensitizations remains the most reliable measure of the integrity of environmental control. The Pepys skin prick test has been validated as a sensitive, specific and practical test for detecting specific IgE to many inhalant allergens including enzymes. For newly sensitized workers, a multi-cause investigation should be conducted to identify potential sources of exposure. Group results of immunological test results assist in the evaluation of workplace control measures, and should be used to monitor the effectiveness of hygiene and engineering programmes and to help prioritize areas for improvement. Positive responses to a questionnaire or abnormal spirometry should be assessed further. Occupational asthma should be excluded in any case of adult-onset asthma that starts or deteriorates during working life. This is particularly important because an accurate diagnosis of occupational asthma with early avoidance of exposure to its cause can result in remission of symptoms and restoration of lung function.

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.