Joe West

Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK

Background: Idiopathic pulmonary fibrosis (IPF) and sarcoidosis are common diagnoses in patients attending chest clinics, but little is known about the epidemiology of these diseases. We used data from a general practice database to provide information on the current incidence of IPF and sarcoidosis in the UK. Methods: Data were extracted for all patients with a diagnosis of IPF or sarcoidosis between 1991 and 2003. The whole population of the database was used to calculate disease incidence stratified by age, sex, region, and time period. Poisson regression was used to compare the incidence between populations and Cox regression was used to compare survival between populations. Results: 920 cases of IPF (mean age 71 years, 62% male) and 1019 cases of sarcoidosis (mean age 47 years, 47% male) were identified. The overall incidence rate per 100 000 person-years was 4.6 for IPF and 5.0 for sarcoidosis. The incidence of IPF increased progressively between 1991 and 2003 (p<0.00001), and was highest in Northern England and Scotland (p<0.0001). The survival of patients with IPF was stable over time. In contrast, the incidence of sarcoidosis was highest in London, West Midlands and Northern Ireland and remained stable over time. Conclusions: The incidence of IPF has more than doubled between 1990 and 2003; this is not due to the ageing of the UK population or an increased ascertainment of milder cases. The incidence of sarcoidosis has not changed during this time period. Our findings suggest that more than 4000 new cases of IPF and 3000 new cases of sarcoidosis are currently diagnosed each year in the UK.

The rising incidence of idiopathic pulmonary fibrosis in the UK

Background Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the UK and USA. Death registrations and primary care data were used to determine the current trends in IPF incidence in the UK. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study. Methods Age- and stratum-specific death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratified by age, sex and geographical region, and survival rates between calendar periods were compared. Results Annual death certificate recording of IPF-CS rose sixfold across the study period from 0.92 per 100 000 in the 1968–1972 calendar periods to 5.10 per 100 000 in the 2006–2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100 000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England. Conclusions The incidence of IPF-CS in primary care and registered deaths from this cause in the UK continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the UK.

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England

Objective: To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK. Methods: The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45–76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants’ serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour. Results: The seroprevalence of undetected coeliac disease in this general population sample aged 45–76 was 1.2% (95% confidence interval (CI) 0.9–1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being “good or excellent” (odds ratio (OR) 1.76 (95% CI 0.90–3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14–0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3–7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5–8.2)) compared with EMA negative participants. Conclusions: Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45–76 years, a value similar to several other countries. Those affected report “better health” but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.

Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study

Objective To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. Design Retrospective historical cohort study. Setting Computerised medical records from the health improvement network, a large population based UK general practice database. Participants Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. Main outcome measures Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. Results 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). Conclusions Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.

Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study.

BACKGROUND Patients with inflammatory bowel disease who develop deep vein thrombosis or pulmonary embolism often have active disease at the time of thromboembolism. We therefore aimed to quantify the risk of venous thromboembolism prospectively during different activity phases of inflammatory bowel disease. METHODS From the General Practice Research Database, we matched patients with prospectively recorded inflammatory bowel disease from November, 1987, until July, 2001 with up to five controls by age, sex, and general practice. A flare was defined as the period 120 days after a new corticosteroid prescription. We used Cox regression analysis with time-varying covariates to accommodate changes in the state of inflammatory bowel disease, and whether patients were at high risk of venous thromboembolism after hospitalisation. FINDINGS 13 756 patients with inflammatory bowel disease and 71 672 matched controls were included in the analysis, and of these 139 patients and 165 controls developed venous thromboembolism. Overall, patients with inflammatory bowel disease had a higher risk of venous thromboembolism than did controls (hazard ratio 3.4, 95% CI 2.7-4.3; p<0.0001; absolute risk 2.6 per 1000 per person-years). At the time of a flare, however, this increase in risk was much more prominent (8.4, 5.5-12.8; p<0.0001; 9.0 per 1000 person-years). This relative risk at the time of a flare was higher during non-hospitalised periods (15.8, 9.8-25.5; p<0.0001; 6.4 per 1000 person-years) than during hospitalised periods (3.2, 1.7-6.3; p=0.0006; 37.5 per 1000 person-years). INTERPRETATION Trials of primary prophylaxis of venous thromboembolism are warranted to find out whether this important complication can be prevented. FUNDING National Association for Colitis and Crohns Disease.

Malignancy and mortality in people with coeliac disease: population based cohort study

Abstract Objective To quantify the risks of malignancy and mortality in people with coeliac disease compared with the general population. Design Population based cohort study. Setting General practice research database. Participants 4732 people with coeliac disease and 23 620 matched controls. Main outcome measures Hazard ratios for malignancy and mortality. Results Of the 4732 people with coeliac disease, 134 (2.8%) had at least one malignancy and 237 (5.0%) died. The overall hazard ratios were: for any malignancy 1.29 (95% confidence interval 1.06 to 1.55), for mortality 1.31 (1.13 to 1.51), for gastrointestinal cancer 1.85 (1.22 to 2.81), for breast cancer 0.35 (0.17 to 0.72), for lung cancer 0.34 (0.13 to 0.95), and for lymphoproliferative disease 4.80 (2.71 to 8.50). The increased risk was primarily in the first year after diagnosis, with the risk for only lymphoproliferative disease remaining significantly raised thereafter. After excluding events in the year after diagnosis, the hazard ratio for malignancy was 1.10 (0.87 to 1.39) and for mortality was 1.17 (0.98 to 1.38), giving absolute excess rates of 6 and 17 per 10 000 person years, respectively. Conclusions People with coeliac disease have modest increases in overall risks of malignancy and mortality. Most of this excess risk occurs in the year of follow up after diagnosis. People with coeliac disease also have a noticeably reduced risk of breast cancer. The mechanism of this merits further attention as it may provide insights into the cause of this common malignancy.

Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux

Background and aims: While patients with Barrett’s oesophagus develop oesophageal adenocarcinoma more frequently than the general population, it has controversially been suggested that gastro-oesophageal reflux (GORD) itself is a more important determinant of risk. In order to assess the validity of this suggestion, we examined the risk of oesophageal cancer in patients with Barrett’s and with GORD compared with the general population in a community based cohort study. Methods: Cohorts of patients with Barrett’s (n = 1677), oesophagitis (n = 6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were selected from the General Practice Research Database. The last three cohorts were matched to the Barrett’s cohort by general practitioner practice, age, and sex. Cox’s regression analysis was used to calculate relative risks for oesophageal cancer. Standardised incidence ratio methodology was used to estimate the relative risks for oesophageal adenocarcinoma. Results: A total of 137 oesophageal cancers were identified, of which 94 prevalent cases were excluded. The hazard ratios for oesophageal cancer were 10.6 (5.1–22.0), 2.2 (0.9–5.2), and 1.7 (0.7–4.5) in the Barrett’s, oesophagitis, and reflux cohorts compared with the reference cohort, respectively. The corresponding relative risks for oesophageal adenocarcinoma were 29.8 (9.6–106), 4.5 (1.04–19.6), and 3.1 (0.6–14.2). Conclusion: Barrett’s oesophagus increases the risk of oesophageal cancer approximately 10 times and oesophageal adenocarcinoma approximately 30 times compared with the general population. There is only a modestly increased risk of oesophageal cancer in patients with reflux who have no record of Barrett’s oesophagus. Our findings therefore do not support the suggestion that gastro-oesophageal reflux disease itself predisposes to cancer.

Recent advances in coeliac disease

The management of coeliac disease is an increasing part of a gastroenterologist’s workload. Recent prevalence studies suggest ∼1% of the general UK population have positive coeliac serology, which combined with increasing population and primary care awareness is leading to more and more referrals. The majority of contemporary referrals are now initially diagnosed by highly sensitive and specific serological tests followed by readily performed endoscopic biopsy (fig 1). Consequently, we now identify many more patients with no or only mild clinical symptoms, making the classical scenario of diarrhoea/steatorrhoea and weight loss a comparative rarity. Much of the early data on clinical aspects of classical coeliac disease (that is, published pre ∼1990) may not be applicable to contemporary coeliac disease. These changes in clinical practice have been paralleled by a dramatic increase in our knowledge of disease pathogenesis, making coeliac disease the best understood human “autoimmune” disorder. In this review article, we present selected major recent advances in both clinical and basic science aspects of coeliac disease, focusing on the many high quality studies published within the last five years. Figure 1  Contemporary and classical diagnosis of coeliac disease. In the past, coeliac disease was mainly diagnosed after clinical presentation. This remains the description of disease in many textbooks. Nowadays, many more patients are referred on the basis of positive serological tests. Endoscopy and “routine” duodenal biopsy (without prior suspicion of coeliac disease) may also lead to diagnosis. *Serology, duodenal histology, HLA-DQ genotyping. Adapted from Green et al 2005.106 ### General population based prevalence studies of undetected coeliac disease Several serological screening studies from Europe, South America, Australasia, and the USA have shown that approximately 0.5–1% of these populations may have undetected coeliac disease. The most consistent estimate reported from the largest population based studies is approximately 1%. The prevalence is even higher in first and second degree relatives of people with coeliac …

The epidemiology of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional condition of the bowel that is diagnosed using clinical criteria. This paper discusses the nature of the diagnostic process for IBS and how this impacts epidemiological measurements. Depending on the diagnostic criteria employed, IBS affects around 11% of the population globally. Around 30% of people who experience the symptoms of IBS will consult physicians for their IBS symptoms. These people do not have significantly different abdominal symptoms to those who do not consult, but they do have greater levels of anxiety and lower quality of life. Internationally, there is a female predominance in the prevalence of IBS. There is 25% less IBS diagnosed in those over 50 years and there is no association with socioeconomic status. IBS aggregates within families and the genetic and sociological factors potentially underlying this are reviewed. Patients diagnosed with IBS are highly likely to have other functional disease and have more surgery than the general population. There is no evidence that IBS is associated with an increased mortality risk. The epidemiological evidence surrounding these aspects of the natural history is discussed.

Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971-2001.

In the last two decades, mortality from primary liver cancer has increased in the UK. We aimed to determine whether the incidence trends for these cancers were similar and in particular if the increasing occurrence of cholangiocarcinoma has continued. We calculated directly age-standardised incidence rates (using the European standard population) by subsite and histological type for all cancers of the liver, gallbladder and biliary tract in England and Wales from 1971 to 2001, using cancer registry data. The incidence of cancers of the liver, gallbladder and biliary tract increased, with the greatest rise, around 12-fold, in intrahepatic bile duct cancers. The rate of liver cell cancer increased by around 45% in males, but by <10% in females. There were marked reductions in the incidence of gallbladder and extrahepatic bile duct cancer. Cholangiocarcinoma increased around 16-fold and became the most common type of primary liver cancer in females, while hepatocellular carcinoma remained the commonest type in males. The age-specific incidence rates showed that intrahepatic bile duct cancer continued to increase throughout the 1990s in those aged 75 and over, while liver cell cancer decreased in the older age groups. In conclusion, there were increases in the incidence of primary liver cancer, which have been particularly dramatic for intrahepatic bile duct cancer, over the last three decades of the 20th century in England and Wales. There has been a halving in the incidence of gallbladder cancer and a reduction of a third in extrahepatic bile duct cancer.