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P Cullinan

Publications and source records attributed to P Cullinan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Occupational distribution and geographic clustering of deaths certified to be cryptogenic fibrosing alveolitis in england and wales.

STUDY OBJECTIVES: The etiology of cryptogenic fibrosing alveolitis (CFA) remains largely obscure, although a 1996 report suggested an increased risk from occupational exposure to metal and wood dusts. Using data from death certificates in England and Wales, we sought evidence of any relationship between occupation and CFA and of the extent of any temporospatial clustering of place of birth and place of death as possible evidence of a geographically related environmental factor. DESIGN AND SETTING: Data on occupation and address (postal code) were obtained from certificates of men and women dying as a result of CFA between 1981 and 1990 and were compared with national mortality statistics. Place of birth data were extracted from certificates for deaths between 1993 and 1995, the only available years, and were compared with national birth statistics. MEASUREMENTS AND RESULTS: Standardized mortality ratios (SMRs) were raised (p<0.05) in the following four occupational groups: members of the armed forces (SMR, 217.8); miners and quarrymen (SMR, 142.0); service, sports, and recreation workers (SMR, 118.6); and electrical and electronic workers (SMR, 146.6). Of these four groups, the latter group might be worth testing in a future study. There was statistical evidence of geographic clustering in postal code sectors for the recorded place of death, but the high-rate areas were different in men and women. Deaths were increased for those subjects born in urban areas, although these did not follow a clear geographic pattern. CONCLUSIONS: Overall, these analyses provide little evidence of any important contribution from environmental factors to the etiology of CFA and suggest that more consideration be given to alternative concepts of causation.

Adolescent↗
PubMed2001

Clusters, classification and epidemiology of interstitial lung diseases: concepts, methods and critical reflections.

The present article reports on two conceptual and methodological issues concerning interstitial lung disease (ILD) about which there is a lot of misunderstanding and contradiction: the investigation of epidemics and clusters and the classification and epidemiology of ILD. In general, an epidemic is the occurrence of cases of an illness in excess of normal expectancy. The investigation of an epidemic often demands a number of sequential studies: first descriptive, then aetiological. Clusters consist of an increase in incidence of much smaller magnitude, perhaps excluding the possibility that this is merely a result of chance. In recent years, more valid statistical methods for the assessment of clusters have developed. For interstitial lung disease in particular, different classifications exist that are sometimes inconsistent and may change with time. All diseases require a process of ascertainment, whereby they are identified, classified and perhaps registered. The two most employed epidemiological techniques for testing aetiological hypotheses are the cohort and case-referent approaches.

Age Factors↗
PubMed2001

Interstitial lung diseases: an epidemiological overview.

Epidemiological studies on interstitial lung diseases (ILDs) may be schematically subdivided into the following major types: 1) quantifications of disease, broken down into incidence, prevalence and mortality data; 2) identification of aetiological factors; and 3) clinical epidemiological studies. Epidemiological data may be obtained from different sources or population groups, using different study designs such as systematic national statistics, population-based data and registries, and large case series of specific diseases. Differences in results between epidemiological studies may be due to real differences in incidence, but may also be due to changes in disease definitions and classifications, differences in the epidemiological design of the studies, or even registration bias. Comparative epidemiological data of different ILDs are almost limited to the general population study in Bernalillo County and to national mortality statistics, which should be interpreted with great caution. Also, some, mostly national registries of the different ILDs have been carried out by specific medical profession groups (especially pulmonologists), which clearly underestimate the real incidence of ILDs, but in which the comparison of the relative frequencies is probably accurate. Based on all these comparative studies, sarcoidosis and idiopathic pulmonary fibrosis appear to be the most frequent ILDs, followed by hypersensitivity pneumonitis and ILD in collagen vascular disease, when classical pneumoconioses are not included. There is also a relatively large group of nonspecific fibrosis. Much more data have been published on the epidemiology of specific forms of interstitial lung disease. Most information is available on the epidemiology of sarcoidosis, and those data are probably the most accurate. Data on idiopathic pulmonary fibrosis have the disadvantage of the recent changes in definition and classification of this disease. Hypersensitivity pneumonitis has been studied epidemiologically, especially in some exposure groups such as farmers and pigeon breeders, and in some regions in North America, UK, France and Scandinavia. Estimates of frequencies of interstitial lung disease in collagen vascular disease or of drug-induced interstitial lung disease are less accurate and more variable, depending on diagnostic criteria. Notwithstanding the aforementioned problems, this report tries to provide a balanced overview of the epidemiology of different interstitial lung diseases.

Humans↗
PubMed2000

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.

Adolescent↗
PubMed2000

Effect of lung-volume-reduction surgery in patients with severe emphysema.

BACKGROUND: Although many patients with severe emphysema have undergone lung-volume-reduction surgery, the benefits are uncertain. We conducted a randomized, controlled trial of the surgery in patients with emphysema. Patients with isolated bullae were excluded because such patients are known to improve after bullectomy. METHODS: Potentially eligible patients were given intensive medical treatment and completed a smoking-cessation program and a six-week outpatient rehabilitation program before random assignment to surgery or continued medical treatment. After 15 patients had been randomized, the entry criteria were modified to exclude patients with a carbon monoxide gas-transfer value less than 30 percent of the predicted value or a shuttle-walking distance of less than 150 m, because of the deaths of 5 such patients (3 treated surgically and 2 treated medically). RESULTS: Of the 174 subjects who were initially assessed, 24 were randomly assigned to continued medical treatment and 24 to surgery. At base line in both groups, the median forced expiratory volume in one second (FEV1) was 0.75 liter, and the median shuttle-walking distance was 215 m. Five patients in the surgical group (21 percent) and three patients in the medical group (12 percent) died (P=0.43). After six months, the median FEV1 had increased by 70 ml in the surgical group and decreased by 80 ml in the medical group (P=0.02). The median shuttle-walking distance increased by 50 m in the surgical group and decreased by 20 m in the medical group (P=0.02). There were similar changes on a quality-of-life scale and similar changes at 12 months of follow-up. Five of the 19 surviving patients in the surgical group had no benefit from the treatment. CONCLUSIONS: In selected patients with severe emphysema, lung-volume-reduction surgery can improve FEV1, walking distance, and quality of life. Whether it reduces mortality is uncertain.

Adrenergic beta-Agonists↗
PubMed2000

Total and specific IgE (house dust mite and intestinal helminths) in asthmatics and controls from Gondar, Ethiopia.

BACKGROUND: The role, if any, of parasitosis in the development of asthma remains incompletely understood; both 'protective' and 'predictive' associations have been reported. We report a study which examined immunoglobulin (Ig) E responses to two common helminths in asthmatics living in Ethiopia. OBJECTIVE: To compare the frequencies of specific IgE antibodies to Ascaris and Necator species and to Der p 1 among 84 adult asthmatics and a referent group of nonasthmatics. METHODS: A case-control analysis. RESULTS: Total IgE levels were not different between the two groups. The presence of specific IgE to Der p 1 was strongly associated with asthma (P = 0.001). Raised levels of Ascaris-(P = 0.010) and Necator- (P = 0.001) specific IgE antibodies were more common among referents; there were no associations between specific IgE production to Der p 1 and either of the two parasites. CONCLUSION: These findings confirm the association between Der p 1 sensitization and asthma among urban, adult Ethiopians. While they also indicate a negative relationship with two indicators of helminth infestation it appears that this is not mediated through the immunological response to common aeroallergens.

Adolescent↗
PubMed2000

Sensitization to oilseed rape is not due to cross-reactivity with grass pollen.

BACKGROUND: Oilseed rape is an important crop grown in the UK which can cause specific immunological sensitization with clinical symptoms in a relatively small number of the general population. Individuals with immunoglobulin (Ig) E-mediated allergy to oilseed rape have also been found to be sensitized to other pollen allergens, most frequently being grass pollen. Cross-reactivity between common grass and oilseed rape would have important implications, especially as their flowering period coincides. OBJECTIVE: We have investigated whether the cosensitization found in individuals sensitized to both oilseed rape and grass pollen is due to cross-reactivity. METHODS: Cross-reactivity between oilseed rape and grass pollen was determined using RAST, RAST inhibition, Western blotting and inhibition studies with Western blotting. RESULTS: Competitive RAST inhibition studies between pollen of oilseed rape and grass failed to show any cross-reactivity between the pollen types. Self-inhibition with oilseed rape resulted in 90% inhibition, whereas there was less than 10% inhibition with grass pollen. Western blotting revealed allergens of similar molecular weight in both oilseed rape and grass pollen. Despite allergens of similar molecular weights being present in both pollen types, inhibition immunoblot studies confirmed that the allergens in the two allergens were immunologically distinct. CONCLUSION: The allergens of oilseed rape and grass pollen, although similar in molecular weights, are immunologically distinct and there is no evidence of cross-reactivity between them. Individuals allergic to grass pollen will not necessarily develop a specific nasal or airway response to inhaled oilseed rape pollens.

Adult↗
PubMed2000

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV(1)) were recorded and histamine provocative concentration causing a 20% fall in FEV(1) (PC(20)) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.

Adult↗
PubMed2000

Epidemiology of familial sarcoidosis in the UK.

BACKGROUND: The last comprehensive epidemiological studies on familial sarcoidosis in the UK were more than 25 years ago, reporting another affected family member in 1.7% of index cases. A significant proportion of like-sex over unlike-sex pairs, an excess of mother-child over father-child associations, and a preponderance of monozygous over dizygous twins was noted. Another study reported ethnic heterogeneity in familial disease. This study was undertaken to identify the risk ratio (lambda(S)) for siblings of familial sarcoidosis in the UK, to determine if the previous epidemiological findings have persisted, and to reassess whether ethnic heterogeneity prevails in familial disease. METHOD: Questionnaires were sent to 406 index patients. RESULTS: Two hundred and sixty eight replies (66%) were received. Twenty four of the original 406 index patients (5.91%) were found to have at least one other relative (first, second or third degree) with biopsy proven sarcoidosis. A lambda(S) value of 36-73 was calculated indicating significant familial clustering of the disease. Ethnically the families comprised 62.5% Caucasian, 29.2% Afro-Caribbean, and 8.3% Asian. Mean age at diagnosis was 39.8 years for women and 40.9 years for men with a male to female ratio of 1:1.7. This differed for the Asian families in which all the affected members were male. Three sets of female twins (two monozygous and one dizygous) were included. There was an equal distribution of like-sex (primarily female) and unlike-sex families as well as mother-child and father-child pairs. Pulmonary involvement was predominant irrespective of ethnicity, as was the need for corticosteroid treatment. CONCLUSIONS: These results support the theory that a shared determinant (either genetic or environmental) is operating in familial sarcoidosis and suggest that this determinant is similar for all ethnic groups.

Adult↗
PubMed2000

Airway inflammation after controlled exposure to diesel exhaust particulates.

Epidemiologic evidence suggests a link between morbidity and mortality and levels of particulate matter in the atmosphere. We studied the inflammatory response to inhalation of diesel exhaust particulates (DEP) in normal volunteers. DEP were collected from the exhaust of a stationary diesel engine and were resuspended in an exposure chamber. Ten nonsmoking healthy volunteers were exposed for 2 h at rest to a controlled concentration of DEP (monitored at 200 microg/m(3) particulate matter of less than 10 microm aerodynamic diameter [PM(10)]) or air in a double-blind, randomized, crossover study. Exposures were followed by serial spirometry and measurement of pulse, blood pressure, exhaled carbon monoxide (CO), and methacholine reactivity, as well as sputum induction and venesection for up to 4 h after exposure, and a repeat of all these procedures at 24 h after exposure. There were no changes in cardiovascular parameters or lung function following exposure to DEP. Levels of exhaled CO were increased ater exposure to DEP, and were maximal at 1 h (air: 2.9 +/- 0.2 ppm [mean +/- SEM]; DEP: 4.4 +/- 0.3 ppm; p < 0.001). There was an increase in sputum neutrophils and myeloperoxidase (MPO) at 4 h after DEP exposure as compared with 4 h after air exposure (neutrophils: 41 +/- 4% versus 32 +/- 4%; MPO: 151 ng/ml versus 115 ng/ml, p < 0.01), but no change in concentrations of inflammatory markers in peripheral blood. Exposure to DEPs at high ambient concentrations leads to an airway inflammatory response in normal volunteers.

Adult↗
PubMed1999

Amiodarone-associated thyroid dysfunction: risk factors in adults with congenital heart disease.

BACKGROUND: Amiodarone is widely used in adults with congenital heart disease, but no systematic study has been published on its effects on thyroid function in these patients. A retrospective study was performed to examine the frequency of amiodarone-associated thyroid dysfunction in adults with congenital heart disease and to identify any contributing factors. METHODS AND RESULTS: All adults (16 to 60 years old) with congenital heart disease were identified from a database if they had no preexisting thyroid disease, had taken amiodarone for >/=6 months, and were currently followed up by 1 consultant (J.S.). Ninety-two patients were found and evaluated for thyroid status and cardiac complications. A case-control analysis was performed, with patients matched for duration of amiodarone therapy. Of the 92 patients (age, 34.9+/-10.2 years; range, 18 to 60 years), 36% developed thyroid dysfunction: 19 became hyperthyroid and 14 hypothyroid. Female sex and complex cyanotic heart disease were significant risk factors for developing thyroid dysfunction (odds ratios, 3.0 and 7.00; P=0.04 and 0.01, respectively). Previous Fontan-type surgery also appeared to be a risk factor for developing thyrotoxicosis (odds ratio, 4.0; P=0.17), and amiodarone >200 mg/d a risk factor for thyroid dysfunction (odds ratio, 4.0; P=0.60). CONCLUSIONS: Amiodarone-associated thyroid dysfunction is common in adults with congenital heart disease. Women and those with complex cyanotic lesions are at particular risk, as patients may be who have had Fontan-type surgery or are taking >200 mg/d of amiodarone. Amiodarone should be used only when other antiarrhythmics are ineffective or contraindicated. Vigilance is required to detect and treat thyroid dysfunction.

Adolescent↗
PubMed1999

A prospective study of wound infection in coronary artery surgery.

OBJECTIVE: The incidence of wound infection in coronary artery surgery is low, but there is an appreciable mortality associated with sternal infection. In other fields of surgery there is evidence that an all disposable paper gown and drape system has protective advantages over a fabric system. Using an established wound scoring system (ASEPSIS), we investigated this in a prospective, randomised trial of patients undergoing cardiac surgery. METHODS: 505 patients undergoing isolated coronary artery surgery in a single hospital over an 18 month period were randomised to either a disposable, paper drape system or re-usable fabric drapes. Allocation was stratified according to whether or not the patient had had previous coronary artery surgery. Patients were followed for 3 months. Total infection scores for each wound were calculated from daily scores collected in hospital together with the scores at six weeks and three months. RESULTS: The two randomised groups were otherwise well matched. Full follow-up information was available for 464 (92%) patients. There was no evidence of any difference in rates of sternal or leg wound infection between the two groups (P = 0.87 and 0.62, respectively). Women were more likely to have infected sternal wounds (P = 0.17) and significantly more likely to have infected leg wounds (P = 0.04). Patients with sternal wound infections had a significantly higher body mass index (P = 0.001). High Parsonnet scores and increased time on ventilation were significantly associated with leg wound but not sternal infections. For both wound sites, patients with infections had spent longer in the operating theatre. CONCLUSION: In a randomised controlled study of patients undergoing coronary artery surgery we found that the use of paper drapes and gowns conferred no benefit over a reusable fabric in terms of post-operative wound infection. Although females and diabetics are more likely to experience this complication, an important additional risk factor is an extended operating time.

Coronary Disease↗
PubMed1999

Allergen exposure, atopy and smoking as determinants of allergy to rats in a cohort of laboratory employees.

This study aimed to examine the relationship between exposure to rat urinary allergens, atopic status, smoking and the development of allergic symptoms and specific sensitization. It is a case-referent analysis of a cohort of 342 newly employed laboratory animal workers. Cases comprised persons developing symptoms of laboratory animal allergy or a positive skin prick test to rat urinary allergens; each was matched with up to two asymptomatic referents. Subjects were assigned to categories of exposure based on measurements of airborne rat urinary allergens. Of the cases, 80% reported that their symptoms started within 2 yrs of employment. The odds ratio (OR) for development of each symptom type (respiratory, eye or nose and skin) and of an immediate skin test reaction was increased in those with direct contact with rats. A gradient of increasing OR for the development of any such symptom across exposure categories was found; for respiratory symptoms and skin test reactions the OR for subjects in the highest exposure category were lower than those in intermediate categories, a pattern attenuated when the analysis was confined to outcomes developing within 2 yrs of first exposure. Atopy increased the OR of most outcomes as did cigarette smoking, although there was no evidence of a relationship between smoking and the development of a specific skin test reaction. In conclusion, allergen exposure was confirmed as the most important determinant of laboratory animal allergy; by implication, measures to reduce exposure may be the most effective means to reduce its incidence.

Adult↗
PubMed1999

Interaction of HLA phenotype and exposure intensity in sensitization to complex platinum salts.

The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characterized exposure. We investigated the workforce of a large platinum refinery exposed to ammonium hexachloroplatinate (ACP) to test the hypothesis that the development of IgE-associated sensitization to ACP was influenced by human leukocyte-associated antigen (HLA) phenotype, especially in those with lower ACP exposure. We performed HLA typing in 44 cases with a positive skin prick test to ACP, and 57 nonsensitized referents matched on age, race, duration of employment, and category of ACP exposure. An HLA-DR3 phenotype was more common among cases (odds ratio [OR] 2.3), and more so in those with low (OR infinite) than with high exposure (OR 1.6); HLA-DR6 was less common among the cases (OR 0.4), an association also stronger in the low-exposure group (OR 0.1 versus 0.5). These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the workplace, disease incidence will increasingly be determined by genetic susceptibility.

Adult↗
PubMed1999

Domestic aeroallergen exposures among infants in an English town.

A multicentre, prospective cohort study of childhood asthma was established in three European countries; the purpose of the project is the examination of factors which modify the relationship between allergen exposure in infant life and subsequent atopy and asthma. Dust samples were collected from the homes of 643 infants in a single town in the UK (the first cohort) and assayed for house dust mites (Der p 1) and cat allergen (Fel d 1) concentrations by enzyme-linked immunosorbent assay. A questionnaire with potential relevance to the development of atopy and asthma was completed. A wide variation in exposure to both allergens was observed. Carpeted, double-glazed or damp living rooms, and those sampled in the winter months, had higher levels of Der p 1, but these features did not predict Fel d 1 concentrations. Measures of high home occupancy were positively related to Der p 1 concentrations; and inversely with levels of Fel d 1, a finding which could not be explained by cat ownership. Homes in which one or more persons smoked had significantly lower concentrations of Der p 1, but not Fel d 1. There were no consistent differences in allergen levels between homes where one or more parent or sibling was either atopic or asthmatic. These findings indicate complex interactions among domestic, behavioural and seasonal factors and early allergen exposure in British children.

Air Pollution, Indoor↗
PubMed1999

Determinants of chronic infection with Staphylococcus aureus in patients with bronchiectasis.

Staphylococcus aureus is an uncommon pathogen in bronchiectasis not caused by cystic fibrosis (CF). The object of this study was to identify characteristics that cause patients to be prone to infection with S. aureus. The study population consisted of patients with bronchiectasis attending the authors' unit, excluding those with a diagnosis of overt CF. All patients had a high resolution computer tomographic scan (HRCT) of the thorax which demonstrated bronchiectasis. Cases that were currently chronically infected with S. aureus (isolated consecutively on more than two occasions >3 months apart) were identified (n = 12) and compared with 74 control patients who had not been chronically infected with S. aureus. Patients were carefully evaluated to determine the aetiology of their disease. Odds ratios (OR) and 95% confidence intervals (CI) as measures of the association between disease characteristics and chronic infection with S. aureus were calculated. The results for patients chronically infected by S. aureus demonstrated significant associations with allergic bronchopulmonary aspergillosis (ABPA; OR = 8.8, 95% CI 1.8-41.9), atypical variants of CF (OR = 12.0, 95% CI 1.8-81.7) or equivocal sweat sodium values (OR = 4.0, 95% CI 1.0-15.3). The associations persisted when the analysis was based on cases (n = 28) in whom S. aureus had ever been isolated from sputum. In the latter analysis there was also a significant association with predominant upper zone disease on HRCT. These results suggest that patients with bronchiectasis in whom S. aureus is isolated from sputum should be carefully evaluated to exclude allergic bronchopulmonary aspergillosis or atypical cystic fibrosis.

Adult↗