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Biomedical subjects

P Cullinan

Publications and source records attributed to P Cullinan.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adolescent↗
PubMed2006

The prognosis of occupational asthma due to detergent enzymes: clinical, immunological and employment outcomes.

BACKGROUND: Little is known about the prognosis of occupational asthma induced by high molecular weight proteins. OBJECTIVE: Our objective was to measure the clinical, immunological and employment outcomes of individuals with occupational asthma induced by detergent enzymes. METHODS: We undertook a workforce-based follow-up study in 35 (78%) of the 45 ex-employees from a single factory with occupational asthma. In each case the diagnosis was supported by evidence of specific sensitization and characteristic changes in peak flow or a positive response to specific bronchial provocation testing. RESULTS: This group had left the factory on average 37 months before study. On review 25 (71%) reported chest symptoms during the last month. Compared with when working at the factory, most (86%) reported that their symptoms had improved. Twenty continued to attend their general practitioner for respiratory symptoms and 19 still used asthma medications. Since leaving the factory 16 (46%) and four (11%) had found full-time or part-time employment, respectively; of these 16 found they were paid less than when they worked at the factory. The remaining 15 subjects had not had any paid employment. All but two had positive skin prick tests to one or more three detergent enzymes. The estimated half-life of serum-specific IgE antibodies was 20 months for protease, and 21 months for cellulase and amylase. CONCLUSIONS: Population-based follow-up studies of the prognosis of occupational asthma are rare but probably avoid the bias in clinic-derived surveys. This study demonstrates that 3 years after the avoidance of exposure with detergent enzymes most patients continue to be troubled by, albeit improved, symptoms and experience difficulty in re-employment.

Adult↗
PubMed2006

Bolus thrombolytic infusion during prolonged refractory cardiac arrest of undiagnosed cause.

Acute myocardial infarction (AMI) and pulmonary embolism (PE) account for about 70% of cardiac arrest. Although thrombolytic therapy is an effective therapy for both AMI and PE, it is not routinely recommended during cardiopulmonary resuscitation (CPR) for fear of life threatening bleeding complications. Numerous case reports and retrospective studies have suggested a beneficial effect of thrombolytics in cardiac arrest secondary to AMI and PE; however, we present a case of successful use of bolus thrombolytics during CPR in a patient with undifferentiated cardiac arrest (undiagnosed cause) after prolonged conventional resuscitation without success.

Adult↗
PubMed2005

Improving rate of decline of FEV1 in young adults with cystic fibrosis.

BACKGROUND: CF is characterised by a progressive decline in lung function; reductions in this decline are often used as a measure of success in clinical trials. With improvements in treatment it may be that there has been a temporal shift in the pattern of the disease. METHODS: 318 patients born in five successive cohorts and attending a specialist clinic with at least two routine measurements of lung function made between the ages of 18 and 22 were included. The declines in their lung function were estimated and compared. RESULTS: The mean (SE) slopes for percentage predicted forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were -1.53 (0.36)% and -1.27 (0.34)%, respectively (NS). The annual deterioration in FEV(1) was -2.49%, -1.99% -2.20%, -1.65%, and -0.65% from the earliest to the most recent birth cohort; a similar pattern was observed for changes in FVC. There were no differences between male and female patients. Patients infected with Pseudomonas had a greater average decline in FEV(1) (-1.6% v -1.1%). CONCLUSIONS: The rates of decline in lung function in young adults with CF have diminished with successive birth cohorts. This has important implications for the design of clinical studies in this disease.

Adolescent↗
PubMed2005

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.

Adolescent↗
PubMed2005

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.

Asthma↗
PubMed2005

Evidence based guidelines for the prevention, identification, and management of occupational asthma.

BACKGROUND: Occupational asthma is the most frequently reported work related respiratory disease in many countries. This work was commissioned by the British Occupational Health Research Foundation to assist the Health and Safety Executive in achieving its target of reducing the incidence of occupational asthma in Great Britain by 30% by 2010. AIM: The guidelines aim to improve the prevention, identification, and management of occupational asthma by providing evidence based recommendations on which future practice can be based. METHODS: The literature was searched systematically using Medline and Embase for articles published in all languages up to the end of June 2004. Evidence based statements and recommendations were graded according to the Royal College of General Practitioner's star system and the revised Scottish Intercollegiate Guidelines Network grading system. RESULTS: A total of 474 original studies were selected for appraisal from over 2500 abstracts. The systematic review produced 52 graded evidence statements and 22 recommendations based on 223 studies. DISCUSSION: Evidence based guidelines have become benchmarks for practice in healthcare and the process used to prepare them is well established. This evidence review and its recommendations focus on interventions and outcomes to provide a robust approach to the prevention, identification, and management of occupational asthma, based on and using the best available medical evidence. The most important action to prevent cases of occupational asthma is to reduce exposure at source. Thereafter surveillance should be performed for the early identification of symptoms, including occupational rhinitis, with additional functional and immunological tests where appropriate. Effective management of workers suspected to have occupational asthma involves the identification and investigation of symptoms suggestive of asthma immediately they occur. Those workers who are confirmed to have occupational asthma should be advised to avoid further exposure completely and early in the course of their disease to offer the best chance of recovery.

Adult↗
PubMed2005

The changing distribution of occupational asthma: a survey of supermarket bakery workers.

In the UK, since the mid 1980s, supermarkets have accounted for an increasing volume of bread production. Occupational asthma among employees who produce bread from raw ingredients in supermarkets has not been previously investigated. A cross-sectional survey was undertaken involving 239 (71%) employees from 20 different supermarket bakeries. The work-related symptoms were investigated by using questionnaires and measuring the radioallergosorbent test serum-specific immunoglobulin (Ig)E to flour and fungal alpha-amylase. A total of 89 employees underwent whole-shift personal measurement of dust exposure. The geometric mean dust exposure for bakers was 1.2 mg x m(-3), which was higher than for other bakery employees. A total of 37 (15%) employees also reported work-related chest symptoms. Serum IgE to flour was present in 24 (11%) employees and to fungal alpha-amylase in nine (4%) employees. The combination of work-related chest symptoms and specific IgE was found in six (9%) bakers, one (4%) manager and two (3%) assistants. One-quarter of all employees, but half of bakers and managers, had previously worked for different, mainly small, bakeries. This population of bakery workers has important levels of sensitisation and work-related respiratory symptoms, despite low levels of dust exposure. Changes in the location and process of bread manufacture have led to a change in the distribution of bakers' asthma in the UK.

Asthma↗
PubMed2004

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.

Adult↗
PubMed2004

Determination of the T cell epitopes of the lipocalin allergen, Rat n 1.

BACKGROUND: Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail. OBJECTIVE: We undertook a cross-sectional study of a large population of individuals exposed to laboratory rats to determine the proliferative responses of peripheral blood mononuclear cells (PBMCs) to the major rat allergen, Rat n 1. METHODS: Eighty-three cases (defined by a positive skin prick test (SPT) > or =3 mm and/or a positive RAST > or =2% binding) and 274 referents without specific IgE to rats were tested for their proliferative responses of PBMCs to rat allergen. Cytokine release to rat urinary protein was examined in 28 sensitized and 42 non-sensitized exposed individuals. RESULTS: Proliferation to rat urinary protein was weak in all individuals. Four regions within Rat n 1 were identified as containing potential immunodominant T cell epitopes and three of these co-localized within the conserved regions of the lipocalin molecule. All four regions within Rat n 1 overlapped considerably with the characterized epitopes of the lipocalin allergen, Bos d 2. IL-5 and ratios of IL-5/IFN-gamma were significantly increased in cases. CONCLUSION: The response to Rat n 1 is remarkably similar to the cow lipocalin allergen Bos d 2. T cell epitopes within lipocalins appear to co-localize with the conserved regions of the molecule. LAA is characterized by an increased production of IL-5. Investigation of other lipocalin allergens will provide further information about the allergenicity of this group of proteins.

Allergens↗
PubMed2004

Concentrations and determinants of NO2 in homes of Ashford, UK and Barcelona and Menorca, Spain.

UNLABELLED: This study examined indoor nitrogen dioxide (NO2) concentrations in Ashford, Kent (UK), Menorca Island and Barcelona city (Spain) and the contribution of their most important indoor determinants (e.g. gas combustion appliances and cigarette smoking). The homes examined (n = 1421) were those from infants recruited for the Asthma Multicentre Infants Cohort Study, which aimed to assess, using a standard protocol, the effects of pre- and post-natal environmental exposures in the inception of atopy and asthma. Indoor NO2 was measured using passive filter badges placed on a living room wall of the homes for between 7 and 15 days. Homes in the three centers had significantly different concentrations of indoor NO2, with those in Barcelona showing the highest levels (median NO2 levels: 5.79, 6.06 and 23.87 p.p.b. in Ashford, Menorca and Barcelona, respectively). Multiple regression analysis showed that the principal indoor determinants of NO2 concentrations in the three cohorts were the heating/cooking fuel used in the house (gas fire increased average NO2 concentrations by 1.27-fold and gas cooker by 2.13 times), parental cigarette smoking and season of measurement. Those variables significantly related to indoor NO(2) accounted for 23, 14 and 39% of the variation in indoor NO2 concentration in Ashford, Barcelona and Menorca, respectively. In all the cohorts combined, 52% of the variation could be explained in this way. Although outdoor NO2 was not measured concurrently, its additional contribution was estimated. In conclusion, despite differences in indoor NO2 mean concentrations probably reflecting different outdoor NO2 level, home factors affecting indoor NO2 values and their specific contributions were constant across the three cohorts. PRACTICAL IMPLICATIONS: This study found that principal determinants associated to indoor NO2 in three different sites of Europe: Ashford (UK), Barcelona and Menorca (Spain) were the energy source present in the home and cigarette smoking, despite these areas presented different climates, levels of outdoor contamination, housing characteristics and ventilation behavior. It is suggested that interventions in homes of these three centers will need to address principally cigarette smoking and gas combustion appliances. These latter factors require institutional intervention, while cigarette smoking mainly require personal changes.

Adult↗
PubMed2004

The introduction of solids in relation to asthma and eczema.

BACKGROUND: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy. AIMS: To explore whether late introduction of solids is protective against the development of asthma, eczema, and atopy. METHODS: A total of 642 children were recruited before birth and followed to the age of 5(1/2) years. Main outcome measures were: doctor's diagnosis of eczema ever, atopy according to skin prick test results against inhalant allergens, preschool wheezing, transient wheezing, all defined at age 5-5(1/2) years. Introduction of solids as main exposure measure was assessed retrospectively at age 1 year. RESULTS: There was no evidence for a protective effect of late introduction of solids for the development of preschool wheezing, transient wheezing, atopy, or eczema. On the contrary, there was a statistically significant increased risk of eczema in relation to late introduction of egg (aOR 1.6, 95% CI 1.1 to 2.4) and milk (aOR 1.7, 95% CI 1.1 to 2.5). Late introduction of egg was furthermore associated with a non-significant increased risk of preschool wheezing (aOR 1.5, 95% CI 0.92 to 2.4). There was no statistical evidence of feeding practices playing a different role in the development of asthma and eczema after stratification for parental asthma and atopy status. CONCLUSIONS: Results do not support the recommendations given by present feeding guidelines stating that a delayed introduction of solids is protective against the development of asthma and allergy.

Age Factors↗
PubMed2004

Occupational asthma caused by cellulase and lipase in the detergent industry.

Three employees from two different detergent companies were investigated for occupational asthma, using skin prick tests, serum specific IgE, and specific bronchial challenge. Two were challenged with lipase and one with cellulase. All three cases had immunological evidence of sensitisation to the detergent enzymes with which they worked. Bronchial challenge in each provoked a reproducible dual asthmatic response, which reproduced their work related symptoms. These are the first reported cases of occupational asthma attributable to cellulase and lipase in the detergent industry. Four of the most common enzymes used in this industry have now been reported to cause occupational asthma; continued vigilance and caution are needed when working with these or other enzymes.

Adult↗
PubMed2004

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.

Allergens↗
PubMed2004

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.

Adult↗
PubMed2004

Clinical aspects of occupational asthma.

In about 1 in 10 cases, new or recurrent asthma in adulthood will be caused by work. In many cases the asthma will arise from the action of non-specific airway irritants on a background of bronchial hyperreactivity; in others the mechanism is one of hypersensitivity to a specific agent for which the label ''occupational asthma'' is generally reserved. Some 300 different workplace agents are capable of inducing asthma but most cases are attributable to a far smaller number to which exposure is incurred in a few high-risk occupations. The clinical diagnosis of occupational asthma is usually straightforward; problems occur in patients with pre-existing asthma or in those with unusual exposures, especially if these are to low molecular weight agents. Management is more difficult since there are often important employment and other social issues to be taken into account.

Asthma↗