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Paul Cullinan

Publications and source records attributed to Paul Cullinan.

18 recordsLinked to original sources
PubMed2006

Occupational asthma: an assessment of diagnostic agreement between physicians.

OBJECTIVES: To investigate the levels of agreement between expert respiratory physicians when making a diagnosis of occupational asthma. METHODS: 19 cases of possible occupational asthma were identified as part of a larger national observational cohort. A case summary for each case was then circulated to 12 physicians, asking for a percentage likelihood, from the supplied information, that this case represented occupational asthma. The resulting probabilities were then compared between physicians using Spearman's rank correlation and Cohen's kappa coefficients. RESULTS: Agreement between the 12 physicians for all 19 cases was generally good as assessed by Spearman's rank correlation. For all 66 physician-physician interactions, 45 were found to correlate significantly at the 5% level. The agreement assessed by kappa analysis was more variable, with a median kappa value of 0.26, (range -0.2 to +0.76), although 7 of the physicians agreed significantly (p<0.05) with >or=5 of their colleagues. Only in one case did the responses for probability of occupational asthma all exceed the "on balance" 50% threshold, although 12 of the 19 cases had an interquartile range of probabilities not including 50%, implying "on balance" agreement. The median probability values for each physician (all assessing the identical 19 cases) varied from 20% to 70%. Factors associated with a high probability rating were the presence of a positive serial peak expiratory flow Occupation Asthma SYStem (OASYS)-2 chart, and both the presence of bronchial hyper-reactivity and significant change in reactivity between periods of work and rest. CONCLUSIONS: Despite the importance of the diagnosis of occupational asthma and reasonable physician agreement, certain variations in diagnostic assessment were seen between UK expert centres when assessing paper cases of possible occupational asthma. Although this may in part reflect the absence of a normal clinical consultation, a more unified national approach to these patients is required.

Adult↗
PubMed2006

Outcome of occupational asthma after cessation of exposure: a systematic review.

BACKGROUND: Patients with occupational asthma, and their medical advisers, need valid information about the prognosis of their disease. METHODS: A systematic review of the published literature on the symptomatic and functional outcomes of occupational asthma was carried out after avoidance of exposure to the causative agent. Through a full search of electronic and bibliographic sources, original studies documenting complete recovery from asthma (n = 39,1681 patients) or improvement in non-specific bronchial hyper-responsiveness (NSBHR; n = 28,695 patients) were identified. The median duration of follow-up was 31 (range 6-240) months for studies of symptomatic recovery and 37 (6-240) months for studies of NSBHR. Most studies were of patients recruited from special clinics. RESULTS: Reported rates of symptomatic recovery varied from 0% to 100%, with a pooled estimate of 32% (95% CI 26% to 38%). These rates were lower with increasing age (p = 0.019) and among clinic based populations (p = 0.053). Patients with the shortest durations of exposure (< or =76 months) had the highest rate of recovery (36%; 95% CI 25% to 50%), but the effect was not linear. The pooled prevalence of persistent NSBHR at follow-up was 73% (95% CI 66% to 79%). This figure was higher among patients whose disease was due to high-molecular-weight agents (p = 0.006) and, less clearly, those from clinic-based populations (p = 0.561). In between-study comparisons, no clear patterns of improvement relating to total duration of exposure or follow-up were found. From within-study comparisons there was some evidence that a shorter duration of symptoms was associated with a higher rate of symptomatic recovery. CONCLUSION: The available data on the prognosis of occupational asthma are insufficiently consistent to allow confident advice to be given to patients with the disease. Clinicians and epidemiologists with an interest in this disease should consider a collaborative and carefully standardised study of the prognosis of occupational asthma.

Adult↗
PubMed2006

Early-life domestic aeroallergen exposure and IgE sensitization at age 4 years.

BACKGROUND: Although it is widely assumed that childhood sensitization to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups. OBJECTIVE: We sought to assess the role of early exposure to 2 major household aeroallergens (Der p 1 and Fel d 1) in sensitization at the age of 4 years. METHODS: Pregnant women and their children were recruited for the Asthma Multicenter Infant Cohort Study. Three cohorts (Ashford in the United Kingdom and Menorca and Barcelona in Spain) followed the same research protocol. A total of 1611 newborn children were initially included in the cohort, from whose homes we collected dust samples at 3 months of age for 1474; Der p 1 and Fel d 1 levels were measured. Of these children, we obtained blood for specific IgE determination in 1019. RESULTS: The risk of Fel d 1 sensitization increased with exposure in a nonlinear manner. No association was found between specific IgE to Der p 1 and aeroallergen levels of exposure at early life in 2 centers, but a positive association was observed in the third. CONCLUSIONS: The dose-response relationships between allergen exposure and sensitization differ between allergens and might vary between different locales. The hypothesis that sensitization to house dust mite is directly related to levels of allergen exposure might not apply to the general population or to different ranges of exposure. CLINICAL IMPLICATIONS: Aeroallergen avoidance might not have any important effect on the incidence of sensitization.

Air Pollution, Indoor↗
PubMed2006

Modified Th2 responses at high-dose exposures to allergen: using an occupational model.

RATIONALE: The relationships between allergen exposures and allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG- and IgG(4)-specific antibody responses without sensitization or risk of asthma, a process described as a "modified Th2 response." Attenuation of risk of allergy and asthma at high exposure levels has been reported in longitudinal studies of both childhood and occupational asthma. OBJECTIVES: To investigate, using an occupational model, the relationships among estimated exposure to aeroallergens, the production of specific IgE, IgG and IgG(4) antibodies, and the prevalence of associated symptoms. METHODS: Cross-sectional survey of employees exposed to rats at work on six pharmaceutical sites across the United Kingdom. A total of 689 (89%) provided a blood sample and completed a questionnaire. MEASUREMENTS AND MAIN RESULTS: At highest exposure to rats, there was an attenuation of the exposure response for sensitization and symptoms. In contrast, the frequency of individuals producing high quantities of specific IgG and IgG(4) increased with exposure intensity. Ratios of IgG(4)/IgE were highest in those handling the greatest number of rats. Risk of developing work-related chest symptoms was lower for those who produced both specific IgE and IgG(4) compared to those with specific IgE only. CONCLUSIONS: High exposure to rats is associated with lower rates of specific IgE and symptoms but an increased frequency of high specific IgG and IgG(4) production. Specific IgG(4) produced together with specific IgE may reduce the risk of developing work-related chest symptoms compared with when specific IgE is produced alone.

Adolescent↗
PubMed2006

Is occupational asthma to diisocyanates a non-IgE-mediated disease?

BACKGROUND: Exposure to diisocyanates in the workplace is an important cause of occupational asthma. The majority of patients with diisocyanate-induced asthma have no detectable diisocyanate-specific IgE antibodies in serum. There has been much debate as to whether this is due to diisocyanate-induced asthma being mediated by non-IgE mechanisms or whether it is the result of using inappropriate conjugates. OBJECTIVE: We sought to determine whether RNA message for Cepsilon, IL-4, and other associated inflammatory markers could be detected locally within the bronchial mucosa after diisocyanate challenge. METHODS: Fiberoptic bronchoscopic bronchial biopsy specimens were obtained at 24 hours after both a control and an active challenge in 5 patients with positive and 7 patients with negative inhalation test responses to diisocyanates. Using both immunohistochemistry and in situ hybridization, we determined mRNA for Cepsilon, IL-4, IL-5, and other associated inflammatory markers. RESULTS: There was a striking absence of Cepsilon and IL-4 mRNA-positive cells in bronchial biopsy specimens from patients challenged with diisocyanate (Cepsilon median of 0 and interquartile range of 0-1.85; IL-4 median of 0 and interquartile range of 0-0.85). In contrast, there were increased numbers of IL-5-, CD25-, and CD4-positive cells and a trend toward an increase in eosinophils after active challenge with diisocyanate. CONCLUSION: We found a striking absence of both bronchial Cepsilon and IL-4 RNA message after inhalation challenge with diisocyanates, irrespective of whether the challenge test response was positive or negative. We propose that diisocyanate-induced asthma is a non-IgE-mediated disease, at least in patients in whom specific IgE antibodies to diisocyanates are undetectable.

Adult↗
PubMed2005

Prenatal dichlorodiphenyldichloroethylene (DDE) and asthma in children.

Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median = 1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (< 0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk = 2.63 (95% confidence interval 1.19-4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma.

Antigens↗
PubMed2004

A prospective study of Fel d1 and Der p1 exposure in infancy and childhood wheezing.

The impact of domestic exposure to cat allergen (Fel d1) and house dust mite (Der p1) on wheezing from birth to the age of 4 years was investigated in a multicenter prospective birth cohort; 1,611 mothers were recruited before delivery in Ashford, England, and Barcelona and Menorca, Spain. Exposures were gathered via dust sample collection at children's home in their first year of life. Families provided complete outcome data (wheezing status in all 4 years) for 1,289 children. Domestic allergen levels varied substantially between centers. Six hundred three (47%) children never wheezed during their first 4 years of life. Der p1 did not correlate with any type of wheezing outcome. Fel d1 significantly increased the risk of wheezing in 3- and 4-year-olds in comparison to 1-year-olds. Distinct risk profiles were found for wheezing at different ages. Multivariate analysis revealed an interaction between Fel d1 and maternal asthma among children who wheeze in Year 4 (relative risk = 2.77; 95% confidence interval = 1.19-6.46). Our data support the idea that several patterns of wheezing with different risk profiles exist among young children. The effect of Fel d1 exposure varied according to age and maternal asthma.

Animals↗
PubMed2004

Urban air pollution and children's asthma: what do parents and health professionals think?

Our objective was to explore and compare, in the context of other exposures, lay and professional perceptions of the links between urban air pollution and children's asthma. We used a triangulated survey approach, using quantitative questionnaire surveys enriched by qualitative interviews. Derivation of indicators of actual local air quality used modelled air pollution and a geographical information system. Our setting involved families and community health professionals in the London borough of Ealing, and pediatric respiratory specialists across the United Kingdom. Participants included 863 parents of children aged 3-11 years, 151 reporting currently asthmatic children, of whom 20 were extensively interviewed; 98 local general practitioners and 50 practice nurses; and 75 paediatric respiratory consultants and 55 specialist nurses. Main outcome measures involved views about the links between urban air pollution and children's asthma, relative to other triggers. Comparison of assessments of local air quality, with actual pollution levels, was made by parents with and without asthmatic children. Many parents were unsure as to what factors initiate asthma, but the most frequently cited was traffic pollution; it was also considered important in the exacerbation of asthma. Health professionals' assessments were inconsistent: specialists conformed to the dominant literature dismissing strong links between air pollution and asthma, while local clinicians reflected the views of parents in their community. Surrounding parents' views were difficulties defining exposures to urban air pollution, underlying concerns about risks to general health, perceived lack of control, unclear expert opinion, and widely accepted informal "messages" which assumed strong links. Parents with experience of asthma were found to have significantly less accurate (negatively biased) perceptions of local air quality. In conclusion, reactions to uncertainty surrounding associations between asthma and urban air pollution varied: parents' concerns were heightened (and propagated by other influences), specialist clinicians were dismissive, and community clinicians fell between these extremes.

Adult↗
PubMed2004

Nitrogen dioxide is not associated with respiratory infection during the first year of life.

BACKGROUND: Nitrogen dioxide (NO(2)) has been related to respiratory infections in experimental studies but its role remains controversial in general population studies of children. We aim to assess the association between indoor NO(2) and lower respiratory tract infections (LRTI) during the first year of life in a multicentre prospective cohort study. METHODS: Children (n = 1611) were recruited prior to birth for the Asthma Multicentre Infants Cohort Study (AMICS). Three concurrent cohorts (Ashford, Kent [UK]; Barcelona city, and Menorca Island [Spain]) followed the same research protocol. NO(2) was measured with passive diffusion tubes placed in the living room for 2 weeks when infants were approximately 3 months old. Doctor-diagnosed LRTI during the first year of life (as well as antibiotic use) were measured by questionnaire, and in Ashford validated by the examination of clinical records. In Barcelona, direct measurements using nasopharyngeal lavage and cultures within a continuous surveillance system were done. RESULTS: The cumulative rates of LRTI (39% in Ashford, 28% in Barcelona, and 45% in Menorca) were unrelated to NO(2) levels (corresponding medians 6, 46, and 12 ppb, respectively) in all three centres (all odds ratios being around 1). Similarly, the rates of LRTI in Barcelona measured with the continuous record showed no association with NO(2) (all rate ratios being below 1). In addition, there was no association between rate of antibiotics courses per year per child (2.4 in Ashford, 1.7 in Barcelona, 0.9 in Menorca) and NO(2) levels. CONCLUSIONS: Indoor NO(2) at current levels does not seem to be involved in increasing respiratory infections by itself in infants, suggesting that the effects observed in studies on outdoor air are probably due to other copollutants.

Air Pollutants↗
PubMed2003

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

BACKGROUND: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. OBJECTIVE: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. METHODS: We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. RESULTS: HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. CONCLUSION: HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies.

Adolescent↗
PubMed2003

Asthma: environmental and occupational factors.

Asthma is in several ways a difficult disease to study. Generally arising in childhood, its pattern is often one of remission and relapse; at any point there are difficulties in translating its characteristic, clinical features into an operational definition. Geographical and temporal patterns in its distribution - whereby the disease appears to have increased in frequency in more 'westernised' countries -suggest strong environmental determinants in its causation although there are, too, undoubted and important genetic influences on both its incidence and presentation. Recent aetiological research has concentrated on the function of allergen exposure or on the role of early-life microbial contact that may regulate the development of a range of childhood allergies, including asthma. To date the 'hygiene hypothesis' offers the most efficient explanation for the distribution of the disease in time and place although convincing evidence for it remains elusive.

Adolescent↗
PubMed2003

Interpreting the results of the amplified Mycobacterium tuberculosis direct test for detection of M. tuberculosis rRNA.

The Amplified Mycobacterium tuberculosis Direct (AMTD) test detects M. tuberculosis rRNA. By using culture of M. tuberculosis as a gold standard, a number of different diagnostic indices were examined in an attempt to determine the diagnostic performance of the AMTD test and demonstrate how it might usefully be interpreted during the early management of disease.

Data Interpretation, Statistical↗
PubMed2002

Domestic aeroallergen levels in Barcelona and Menorca (Spain).

Exposure to common indoor allergens is known to be associated with sensitization and triggers of asthma. Levels of allergens have been barely described in Mediterranean countries. This study reports domestic allergen levels among the general population of two regions of Spain. Dust samples were collected from living rooms and mattresses in homes of infants in Barcelona (n = 366) and Menorca (n = 475) and assayed for house dust mite (Der p 1) and cat allergen (Fel d 1) concentrations by enzyme-linked immunoabsorbent assay (ELISA). Geometric mean values (95% CI) of Der p 1 were 0.77 micro g/g (0.65, 0.92) in living rooms and 0.68 (0.56, 0.82) in children's mattresses in Barcelona, and 9.06 (7.93-10.34) and 3.12 (2.71-3.59) in Menorca, respectively. Fel d 1 levels were 0.37 micro g/g (0.31, 0.45) and 0.14 (0.12, 0.18) in Barcelona, and 0.42 (0.35, 0.50) and 0.20 (0.18, 0.24) in Menorca. Home characteristics were not consistently related to levels of aeroallergens in either location. Differences in Der p 1 levels in the two locations indicate that levels cannot be extrapolated from one part of a country to another with any certainty. Additionally, allergen reduction measures related to indoor sources must be specific to each location.

Air Pollution, Indoor↗
PubMed2002

Personal exposure and long-term health effects in survivors of the union carbide disaster at bhopal.

Nine years after the Bhopal methyl isocyanate disaster, we examined the effects of exposures among a cross-section of current residents and a subset of those with persistent symptoms. We estimated individual exposures by developing exposure indices based on activity, exposure duration, and distance of residence from the plant. Most people left home after the gas leak by walking and running. About 60% used some form of protection (wet cloth on face, splashing water). Mean and median values of the exposure indices showed a declining trend with increasing distance from the plant. For those subjects reporting any versus no exposure, prevalence ratios were elevated for most respiratory and nonrespiratory symptoms. We examined exposure-response relationships using exposure indices to determine which were associated with health outcomes. The index total exposure weighted for distance was associated with most respiratory symptoms, one measure of pulmonary function in the cross-sectional sample [mid-expiratory flow (FEF)(25-75), p = 0.02], and two measures of pulmonary function in the hospitalized subset [forced expiratory volume (FEV)(1), p = 0.02; FEF(25-75), p = 0.08). Indices that correlated with FEV(1) and forced vital capacity in the hospitalized subset did not correlate with the cross-sectional sample, and most indices (except total exposure) that correlated with the hospitalized subset did not correlate with the cross-sectional sample. Incorporation of distance into every index increased the number of symptoms associated; an improvement was also noted in the strength of the association for respiratory symptoms, but not for pulmonary function. The sum of duration (p = 0.02) and total exposure (p = 0.03) indices independently demonstrated stronger associations with percent predicted FEF(25-75) than the distance variable (p = 0.04). The results show that total exposure weighted for distance has met the criteria for a successful index by being associated with most respiratory symptoms as well as FEF(25-75), features of obstructive airways disease.

Adult↗
PubMedDate not supplied

Smoking cessation and associated factors during pregnancy.

OBJECTIVE: To examine smoking habits before and during pregnancy, as well as factors associated with smoking cessation, in three European settings. METHODS: Women seeking antenatal care in Ashford (UK), Minorca and Barcelona (Spain) were recruited to the Asthma Multicenter Infant Cohort Study (AMICS). Questionnaires inquiring into the smoking habits of each woman and her partner, demographic data, occupation, educational level, number of previous children, breast feeding, alcohol intake, and history of asthma and of other allergic diseases were completed during pregnancy and in the first year after delivery. RESULTS: A total of 1,572 pregnant women were included in the three cohorts. Smoking prior to pregnancy was more common in Barcelona (46.2%) than in Minorca (39.8%) or Ashford (31.6%). Cessation rates during pregnancy also differed: 18% of women in Ashford, 20.4% in Minorca and 31.9% in Barcelona were still smoking during the first trimester. In a multivariate regression model, the factors showing a significant (negative) association with smoking cessation during pregnancy were having older children, having a partner who smoked and starting smoking at a young age. CONCLUSIONS: Baseline smoking habits and changes in smoking habits during pregnancy significantly differed between the three communities studied. Women pregnant with their first child, those who had started smoking at a later age and those whose partners were non-smokers were more likely to stop smoking when pregnant.

Adult↗
PubMedDate not supplied

Bhopal priorities.

Explore the source record for details and available documents.

Accidents, Occupational↗