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1.  Bilateral inverted papilloma: A report of two cases and review of the current literature 
Inverted papilloma is locally aggressive tumour which typically presents as a unilateral nasal polyp. Whilst it has a malignant potential it rarely transforms and in its benign form the main concern originates from its locally aggressive nature and substantial propensity to recur. Bilateral disease can also be due to inverted papilloma, sometimes due to direct extension of the tumour, but it can also occur as two distinct lesions. Here we report two cases of bilateral involvement, review the current literature and highlight some important issues on the management and follow-up of this well known neoplasm.
doi:10.1007/s12070-010-0079-4
PMCID: PMC3450237  PMID: 23120732
Inverted papilloma; Paranasal sinus neoplasm; Bilateral
2.  Time trends in allergic disorders in the UK 
Thorax  2007;62(1):91-96.
Background
Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma.
Methods
A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality.
Results
Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio‐oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991.
Conclusions
The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
doi:10.1136/thx.2004.038844
PMCID: PMC2111268  PMID: 16950836
trend; allergic disease; epidemiology
3.  Temporal associations between daily counts of fungal spores and asthma exacerbations 
Background
Outdoor aeroallergens are one of a number of environmental factors thought to precipitate asthma exacerbations.
Aims
To investigate the short term associations between daily fungal spore concentrations and indicators of daily asthma exacerbations in a large urban population.
Methods
Daily counts of visits for asthma to family physicians and hospital accident and emergency (A&E) departments and emergency hospital admissions in London 1992–93 were compiled. Daily concentrations of fungal spores (30 species), daily average temperature, humidity, and concentrations of pollen and outdoor air pollution were also compiled. The analysis was restricted to the period when fungal spores were most prevalent (June to mid October). Non‐parametric regression time series methods were used to assess associations controlling for seasonality, day of week, and meteorological factors. The sensitivity of the findings to the inclusion of pollen and air pollution into the models was also assessed.
Results
In children aged 0–14 years the relative risks for increases in the number of A&E visits and hospital admissions associated with changes in fungal spore concentrations from the lower to upper quartiles were 1.06 (95% CI 0.94 to 1.18) and 1.07 (0.97 to 1.19) respectively. The addition of pollen or air pollutants had little impact on the observed associations. A number of individual spore taxa, in particular Alternaria, Epicoccum, Agrocybe, Mildews, and both coloured and colourless Basidiospores and Ascospores, were associated with increases in the number of emergency visits and hospital admissions for asthma, although the precision of these estimates were low. No evidence was found for associations in adults.
Conclusions
Fungal spore concentrations may provoke or exacerbate asthma attacks in children resulting in visits to A&E departments and emergency hospital admissions. These findings were unlikely to be due to confounding by other environmental factors. The associations were comparable to those observed for ambient air pollution from similarly designed studies.
doi:10.1136/oem.2005.024448
PMCID: PMC2078167  PMID: 16551756
aeroallergens; asthma exacerbations; time series
4.  Lack of association of MYO9B genetic variants with coeliac disease in a British cohort 
Gut  2006;55(7):969-972.
Background and aims
Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)‐DQ2 and ‐DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3′ region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation.
Methods
Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3′ haplotype block (exons 15–27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity.
Results
UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease.
Conclusions
Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.
doi:10.1136/gut.2005.086769
PMCID: PMC1856329  PMID: 16423886
coeliac disease; myosin IXB; MYO9B
5.  Childhood asthma in South London: trends in prevalence and use of medical services 1991–2002 
Thorax  2006;61(5):383-387.
Background
Hospital admission rates for asthma in Britain rose during the 1980s and fell during the 1990s, but less is known about recent trends in the prevalence of asthma.
Methods
In 1991 and 2002 the same questionnaire was distributed to parents of all school pupils in year 3 (aged 7–8 years) in the London borough of Croydon. Parents of currently wheezy children were then invited for home interview (100% targeted in 1991, 66% in 2002).
Results
The prevalence of wheeze during the previous year increased from 12.9% in 1991 to 17.8% in 2002 (prevalence ratio 1.39 (95% CI 1.23 to 1.56)). Increases were observed in frequent (1.54 (95% CI 1.16 to 2.03)) and infrequent attacks, severe speech limiting episodes (2.25 (95% CI 1.34 to 3.77)), and night waking (1.36 (95% CI 1.07 to 1.72)), and in the reported use of steroids (19.9% v 64.1% of currently wheezy children). Nevertheless, the proportions reporting a visit to the GP at his/her surgery for wheeze in the previous year (prevalence ratio 1.15 (95% CI 0.91 to 1.45)) or an outpatient visit (0.98 (95% CI 0.49 to 1.94)) changed little and an increase in reported casualty attendance (1.66 (95% CI 0.89 to 3.07)) was non‐significant.
Conclusions
There is evidence of an increase in the prevalence of asthma among British primary school children between 1991 and 2002. The absence of a corresponding increase in health service utilisation data may reflect more widespread prophylactic treatment and/or changes in the use and provision of medical services.
doi:10.1136/thx.2005.043646
PMCID: PMC2111176  PMID: 16449274
asthma; prevalence; children; medical services
6.  Maternal age of menarche is not associated with asthma or atopy in prepubertal children 
Thorax  2005;60(10):810-813.
Background: Maternal sex hormones in pregnancy can theoretically influence the developing fetal immune system and modulate the subsequent development of atopic disorders. Early onset of menarche has been linked to increased oestrogen levels in adult women. A study was undertaken to examine the association between early onset menarche in pregnant women and asthma and atopic status of their children at 7 years of age.
Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study in which pregnant women, resident in Avon (UK), were recruited on the basis of an expected date of delivery between 1 April 1991 and 31 December 1992. Maternal age at menarche was assessed from prenatal questionnaires administered to the women. Clinical outcomes in the children were based on mothers' responses to self-completion questionnaires and included asthma, eczema, and hay fever. The atopic status of the child was objectively assessed by skin prick tests to a panel of common aeroallergens at the age of 7 years. Analyses used multivariable logistic regression with a diverse range of possible confounders.
Results: Complete data were available on 5765 woman and child pairs. The prevalence of ever reported asthma to 7 years was 20.4%, eczema 58.6%, hay fever 12.1%, and atopy (defined as any positive (>2 mm weal) response) was present in 20.6%. There were no significant differences in mean age of menarche between mothers of children with and without each of the primary outcomes. Adjusted odds ratios (95% CI) for the latest age of menarche (16+ years) compared with the lowest (<12 years) reference group were 1.41 (1.00 to 1.99) for asthma, 0.98 (0.73 to 1.91) for eczema, 0.95 (0.62 to 1.44) for hay fever, and 0.98 (0.68 to 1.42) for atopy.
Conclusion: No consistent association was found between maternal age at menarche and asthma, eczema, hay fever or atopy in their children during early childhood.
doi:10.1136/thx.2004.037093
PMCID: PMC1747209  PMID: 16055625
7.  Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood 
Thorax  2008;63(11):974-980.
Background:
Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.
Methods:
Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age.
Results:
Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.
Conclusions:
The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
doi:10.1136/thx.2007.093187
PMCID: PMC2582336  PMID: 18678704
8.  Timing of routine immunisations and subsequent hay fever risk 
Archives of Disease in Childhood  2005;90(6):567-573.
Background: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy.
Aims: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk.
Methods: Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression.
Results: Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations.
Conclusions: Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.
doi:10.1136/adc.2004.051714
PMCID: PMC1720414  PMID: 15908618
9.  Polymorphisms in the PTPN22 region are associated with psoriasis of early onset 
The British Journal of Dermatology  2008;158(5):962-968.
Background
Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset ≤ 40 years) usually have a strong genetic component to the disease.
Objectives
The purpose of this study was to investigate the role of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I psoriasis.
Patients and methods
Thirteen single nucleotide polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis and 566 normal controls.
Results
The rs2476601 (R620W) SNP, widely associated with other inflammatory autoimmune diseases, showed no evidence of association with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604) demonstrated significant association with Type I psoriasis and were subsequently genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414 and rs3789604 were also significantly associated with Type I psoriasis in the combined datasets (P = 0·003 and P = 0·0002, respectively); furthermore carriage of both risk alleles was also significantly associated (P = 0·002).
Conclusions
This study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604) in the PTPN22 region with Type I psoriasis, providing evidence for a role of this gene in Type I psoriasis that is not conferred by the R620W variant previously associated with a number of inflammatory diseases.
doi:10.1111/j.1365-2133.2008.08482.x
PMCID: PMC2342636  PMID: 18341666
Psoriasis; PTPN22; genetic association; linkage disequilibrium
10.  Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children 
Aims: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC).
Methods: Between 1992 and 1996, each centre studied random samples of children aged 13–14 and 6–7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account.
Results: In Western Europe (57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% (95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude (positively) and mean annual outdoor temperature (negatively).
Conclusions: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.
doi:10.1136/oem.2002.006809
PMCID: PMC1740799  PMID: 15208377
11.  Asthma and swimming pools: statistical issues 
doi:10.1136/oem.2003.011205
PMCID: PMC1740770  PMID: 15090674
12.  Role of outdoor aeroallergens in asthma exacerbations: epidemiological evidence 
Thorax  2004;59(4):277-278.
doi:10.1136/thx.2003.019133
PMCID: PMC1763797  PMID: 15047944
13.  Periorbital swelling: the important distinction between allergy and infection 
Emergency Medicine Journal : EMJ  2004;21(2):240-242.
doi:10.1136/emj.2002.004051
PMCID: PMC1726299  PMID: 14988362
14.  Dentures may be radiolucent 
Emergency Medicine Journal : EMJ  2003;20(6):562-563.
doi:10.1136/emj.20.6.562
PMCID: PMC1726223  PMID: 14623855
15.  Acute effects of winter air pollution on respiratory function in schoolchildren in southern England 
Aim: To investigate the acute health effects of winter outdoor air pollution (nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), sulphate (SO42-) ,and particles (PM10)) on schoolchildren in an area of southern England where levels of SO2 had been reported to be high.
Methods: A total of 179 children, aged 7–13, from three schools (two urban and one rural location), were included. Peak expiratory flow rate (PEFR) and presence or absence of upper respiratory infections were recorded on 63 school days from 1 November 1996 to 14 February 1997. Air pollution and meteorological data were taken from monitors at each school site. The analysis regressed daily PEFR on pollutant level adjusting for confounders and serial correlation and calculated a weighted pooled estimate of effect overall for each pollutant. In addition, large decrements in PEFR were analysed as a binary outcome. Same day, lag 1, lag 2, and a five day average of pollutant levels were used.
Results: There were no clear effects of any pollutant on mean PEFR. In addition, we analysed large PEFR decrements (a binary outcome), observing consistent negative associations with NO2, SO42-, and PM10, although few lag/pollutant combinations were significant: odds ratios (95% CI) for five day average effect: NO2 24 h average 1.043 (1.000 to 1.089), SO42- 1.090 (0.898 to 1.322), PM10 1.037 (0.992 to 1.084). The observed effects of PM10 (only) were stronger in wheezy children (1.114 (1.057 to 1.174)). There were no consistent negative associations between large decrements and ozone or SO2 .
Conclusions: There is no strong evidence for acute effects of winter outdoor air pollution on mean PEFR overall in this area, but there is evidence for negative effects on large PEFR decrements.
doi:10.1136/oem.60.2.82
PMCID: PMC1740463  PMID: 12554833
16.  Comparative epidemiology of atopic and non-atopic wheeze and diagnosed asthma in a national sample of English adults 
Thorax  2002;57(11):951-957.
Background: There is debate as to whether asthma has distinct atopic and non-atopic forms and whether in epidemiological studies asthma cases should be defined by a physician diagnosis or by self-reported asthma symptoms.
Methods: A total of 24 952 people aged 11 and over were surveyed as part of the 1995–6 health surveys for England. Participants were asked if they had experienced wheezing in the past year and if they had ever been given a diagnosis of asthma by a doctor. Serum total IgE and house dust mite (HDM) specific IgE were measured.
Results: Wheeze in the past year without an asthma diagnosis was more common in men and older age groups, whereas wheeze with an asthma diagnosis was more common in women and younger people. Both types of wheeze were more common in the lower social classes, among ex-smokers and current smokers, and in urban areas. Thirty two percent of people reporting wheezing and 22% of those with diagnosed asthma had neither raised total IgE nor HDM IgE. Among the non-atopic subjects the prevalence of wheeze rose with age and lower social class, largely due to an increase in wheeze without diagnosed asthma. In contrast, among atopic subjects there was no overall trend with age or social class, but wheeze with diagnosed asthma decreased with age.
Conclusions: Clear epidemiological differences are evident between adult wheeze with and without an asthma diagnosis and between atopic and non-atopic wheeze. Subjects with diagnosed asthma are more likely to be atopic, but the results challenge the premise that adult asthma is almost always associated with some IgE mediated reaction.
doi:10.1136/thorax.57.11.951
PMCID: PMC1746228  PMID: 12403877
17.  Molecular epidemiology of tuberculosis in London 1995–7 showing low rate of active transmission 
Thorax  2002;57(7):617-622.
Background: Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of Mycobacterium tuberculosis has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of M tuberculosis in London and subpopulations of the community with high rates of recent transmission.
Methods: M tuberculosis isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS6110 restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable.
Results: RFLP patterns were obtained for 2042 isolates with more than four copies of IS6110; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0–19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering.
Conclusions: Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.
doi:10.1136/thorax.57.7.617
PMCID: PMC1746370  PMID: 12096206
18.  Ischaemic heart disease and Cag A strains of Helicobacter pylori in the Caerphilly heart disease study 
Heart  2001;86(5):506-509.
OBJECTIVE—To look for the presence of the more virulent strains of Helicobacter pylori (H pylori) in men who developed ischaemic heart disease over a 10 year period and in controls.
DESIGN—The Caerphilly prospective heart disease study recruited 2512 men aged 45-59 years during 1979-83. Western blot analysis or enzyme linked immunosorbent assay (ELISA) was performed on serum taken from those who subsequently died of ischaemic heart disease, or developed non-fatal myocardial infarction, to determine H pylori and Cag A status. Similar information was available on age matched controls.
RESULTS—During the first decade of the study, 312 men died of ischaemic heart disease or developed non-fatal myocardial infarction. Serum was available from 172 of these (55%). There was no evidence of an association between Cag A seropositivity and incident ischaemic heart disease or ischaemic heart disease mortality, either before or after adjustment for potential confounders (adjusted odds ratios 1.18 (95% confidence interval (CI) 0.76 to 1.85) and 1.13 (95% CI 0.61 to 2.07), respectively). Further, the odds ratios for ischaemic heart disease incidence and ischaemic heart disease mortality by H pylori seropositivity did not appear to depend on the presence or absence of Cag A strains (p = 0.76 and 0.77, respectively).
CONCLUSIONS—In this cohort of middle aged men, followed over a 10 year period, there is little evidence of an association between Cag A seropositivity and either incident ischaemic heart disease or ischaemic heart disease mortality.


Keywords: ischaemic heart disease; epidemiology; infection; Helicobacter pylori
doi:10.1136/heart.86.5.506
PMCID: PMC1729961  PMID: 11602541
19.  Pharyngeal pouch (Zenker's diverticulum) 
Postgraduate Medical Journal  2001;77(910):506-511.
Pharyngeal pouches occur most commonly in elderly patients (over 70 years) and typical symptoms include dysphagia, regurgitation, chronic cough, aspiration, and weight loss. The aetiology remains unknown but theories centre upon a structural or physiological abnormality of the cricopharyngeus. A diagnosis is easily established on barium studies. Treatment is surgical via an endoscopic or external cervical approach and should include a cricopharyngeal myotomy. Unfortunately pharyngeal pouch surgery has long been associated with significant morbidity, partly due to the surgery itself and also to the fact that the majority of patients are elderly and often have general medical problems. External approaches are associated with higher complication rates than endoscopic procedures. Recently, treatment by endoscopic stapling diverticulotomy has becoming increasingly popular as it has distinct advantages, although long term results are not yet available. The small risk of developing carcinoma within a pouch that is not excised remains a contentious issue and is an argument for long term follow up or treating the condition by external excision, particularly in younger patients.


Keywords: Zenker's diverticulum; surgical procedures: endoscopic; surgical stapling
doi:10.1136/pmj.77.910.506
PMCID: PMC1742115  PMID: 11470929
20.  Fungal and other spore counts as predictors of admissions for asthma in the Trent region 
OBJECTIVES—The importance of airborne fungal and other spores in provoking asthma attacks is uncertain. Panel studies have generated evidence that suggests a link between outdoor spore counts and severity of asthma. There have been no population based time series studies relating outdoor exposure to spores with incidence of attacks of asthma.
METHODS—Outcomes were hospital admissions for asthma on 2002 days during 1987-94, for children and adults in the Trent region of England. Predictors were daily counts of 25 spore taxa from volumetric traps in Derby on the same and previous day. Admissions for asthma were adjusted for weekly, seasonal, and longer term trends by log linear autoregressive models. Spore counts on 6 days of asthma epidemics were also examined.
RESULTS—When spore counts for individual taxa were analysed as quantitative variables, two positive and two negative correlations (out of a possible 100) were significant at the 5% level. When spore counts were dichotomised at the 90th percentile, one negative and eight positive correlations (out of 100) were significant at the 5% level. All significantly positive associations related to admissions among children, but none involved the total spore count. However, total spores were above the 90th percentile on four of the six epidemic days (odds ratio (OR) 9.92, 95% confidence interval (95% CI) 1.41 to 109.84), but epidemics occurred on only four of 343 days with high total moulds.
CONCLUSIONS—There was some evidence that exceptional rates of admission for asthma tend to occur on days with high total mould spore counts, but no specific taxon was consistently implicated. The predictive power was insufficient to support a public warning system.


Keywords: asthma; hospital admissions; moulds; fungi; spore counts; aeroallergens; log linear autoregression
doi:10.1136/oem.57.11.786
PMCID: PMC1739878  PMID: 11024204
21.  Which spirometric indices best predict subsequent death from chronic obstructive pulmonary disease? 
Thorax  2000;55(9):785-788.
BACKGROUND—Previous epidemiological studies have related mortality from chronic obstructive pulmonary disease (COPD) to forced expiratory volumes (FEV1 or FEV0.75) and it is unknown whether other spirometric indices might have greater predictive power.
METHODS—A case-control study of fatal COPD was conducted within a cohort of London civil servants who performed forced expiratory spirograms in 1967-9 and were followed up for mortality over 20years. The spirograms of 143 men who died of COPD (ICD8 491, 492or 519.8) were compared with those of 143 controls individually matched for age, height, and smoking habit who survived longer than their matched case. Flow rates in different parts of the spirogram were compared within case-control pairs and analysed as predictors of fatal COPD by conditional logistic regression.
RESULTS—Within pair case:control ratios of FEV1, mid expiratory flow rates (e.g. FEF50-75) and FEF75-85 were highly intercorrelated (r>0.7) but correlations with FEF85-95 were weaker (r<0.5). All indices except the FEV1/FVC ratio were stronger predictors of death from COPD within the first 10 years than of later deaths (15-19 years). After adjustment for FEV1, mid expiratory flow rates independently predicted fatal COPD but end expiratory flow rates did not. The FEV1 adjusted mortality ratios associated with a 10% decrement in each index were 2.24 (95% CI 1.54 to 3.76) for FEF50-75, 1.20 (95% CI 1.00 to 1.42) for FEF75-85, and 1.10 (95% CI 0.96 to 1.26) for FEF85-95.
CONCLUSION—This study confirms FEV1 and mid expiratory flow rates as powerful predictors of mortality from COPD, and suggests that measurement of end expiratory flow rates would add little extra predictive information.


doi:10.1136/thorax.55.9.785
PMCID: PMC1745857  PMID: 10950899
23.  Epidemiology of pneumothorax in England 
Thorax  2000;55(8):666-671.
BACKGROUND—Little is known of the epidemiology of pneumothorax. Routinely available data on pneumothorax in England are described.
METHODS—Patients consulting in primary care with a diagnosis of pneumothorax in each year from 1991 to 1995 inclusive were identified from the General Practice Research Database (GPRD). Emergency hospital admissions for pneumothorax were identified for the years 1991-4 from the Hospital Episode Statistics (HES) data. Mortality data for England & Wales were obtained for 1950-97. Analyses of pneumothorax rates by age and sex were performed for all data sources. Seasonal and geographical analyses were carried out for the HES data.
RESULTS—The overall person consulting rate for pneumothorax (primary and secondary combined) in the GPRD was 24.0/100 000 each year for men and 9.8/100 000 each year for women. Hospital admissions for pneumothorax as a primary diagnosis occurred at an overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and women, respectively. Mortality rates were 1.26/million per year for men and 0.62/million per year for women. The age distribution in both men and women showed a biphasic distribution for both GP consultations and hospital admissions. Deaths showed a single peak with highest rates in the elderly. There was an urban-rural trend observed for hospital admissions in the older age group (55+ years) with admission rates in the conurbations significantly higher than in the rural areas. Analysis for trends in mortality data for 1950-97 showed a striking increase in the death rate for pneumothorax in those aged 55+ years between 1960and 1990, with a steep decline in the 1990s. Mortality in the younger age group (15-34 years) remained low and constant.
CONCLUSION—There is evidence of two epidemiologically distinct forms of spontaneous pneumothorax in England. The explanation for the rise and fall in mortality for secondary pneumothorax is obscure.


doi:10.1136/thorax.55.8.666
PMCID: PMC1745823  PMID: 10899243
24.  Molecular epidemiology of tuberculosis in London 1995–7 showing low rate of active transmission 
Molecular Pathology  2003;56(2):121-126.
Background: Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of Mycobacterium tuberculosis has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of M tuberculosis in London and subpopulations of the community with high rates of recent transmission.
Methods: M tuberculosis isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS6110 restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable.
Results: RFLP patterns were obtained for 2042 isolates with more than four copies of IS6110; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0–19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering.
Conclusions: Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.
PMCID: PMC1187304
tuberculosis; molecular epidemiology; transmission
25.  Western blotting is useful in the salivary diagnosis of Helicobacter pylori infection 
Journal of Clinical Pathology  2000;53(4):314-317.
Background—The salivary diagnosis of Helicobacter pylori infection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations to H pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children.
Subjects and methods—Paired serum and saliva specimens were obtained from 665 school children aged 9–11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum.
Results—The sensitivity and specificity of salivary ELISA in the 665 specimens was 32 of 50 (64%) and 530 of 691 (87%), respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001).
Conclusion—Salivary western blotting for IgG is useful in the diagnosis of H pylori infection and is superior to ELISA. It also permits the identification of pathogenic strains.
Key Words: Helicobacter pylori • western blotting • enzyme linked immunosorbent assay • salivary specimens
doi:10.1136/jcp.53.4.314
PMCID: PMC1731175  PMID: 10823129

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