P Cullinan

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

Allergen and dust exposure as determinants of work-related symptoms and sensitization in a cohort of flour-exposed workers; a case–control analysis

OBJECTIVESnTo 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.nnnMETHODSnA 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.nnnRESULTSnIncidence 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.nnnCONCLUSIONSnIn 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.

An outbreak of asthma in a modern detergent factory

The striking decrease in the occurrence of protease-induced occupational asthma in the detergent Industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in size to those reported in the 1960s, in a modem European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-Induced allergy and asthma.

Environmental associations with eczema in early life

Backgroundu2003Although atopic eczema (AE) is a common disease, little is known about its causes.

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.

Cryptogenic fibrosing alveolitis and lung cancer: the BTS study

Background: The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). Methods: Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. Results: 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; pu200a=u200a0.02). Conclusions: These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

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.

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 5u2005yrs 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.

Early allergen exposure and atopic eczema.

Backgroundu2002 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 2u2003years 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.