The rising incidence of idiopathic pulmonary fibrosis in the U.K.

BACKGROUND: Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the U.K. and U.S.A. Death registrations and primary care data were used to determine the current trends in IPF incidence in the U.K. 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 U.K. continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the U.K.

Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study.

BACKGROUND: Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to assess the association between maternal asthma and gestational exposure to asthma medications with risk of congenital malformation in offspring. METHODS: A matched case-control study was performed using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery. RESULTS: 5124 cases of liveborn children with major congenital malformations and 30,053 controls were included in the study. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR 1.10, 95% CI 1.01 to 1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR 1.06, 95% CI 0.94 to 1.20). In assessing teratogenicity of medications, no increased risk of malformation was found with gestational exposures to short- or long-acting beta agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculo-skeletal system malformation associated with cromone exposure. CONCLUSIONS: Gestational exposure to commonly used asthma medications was found to be safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.

The impact of the 2004 NICE guideline and 2003 General Medical Services contract on COPD in primary care in the UK.

BACKGROUND: The introduction of the NICE guideline on COPD and the inclusion of COPD in the new Quality and Outcomes Framework (QOF) were designed to improve the care of people with COPD in primary care in the UK. AIM: We have investigated whether these initiatives have had an impact on the prevalence of COPD, the recording of spirometry data and the use of combined inhaled corticosteroid/long-acting beta-agonist inhalers. DESIGN: We analysed data from The Health Improvement Network for the year before and after the introduction of the NICE guideline. METHODS: Data were analysed using logistic regression. RESULTS: The prevalence of COPD in 2003 was 1.27%, and this increased by 14-1.45% in 2005. The risk of COPD was strongly related to age, male gender, socioeconomic disadvantage and living in the North of England, Scotland and Wales. People with COPD had an increased mortality (adjusted rate ratio for 2003 is 2.38, 95% confidence interval 2.30-2.47). The presence of recorded spirometry data in people with COPD increased from 18% in 2003 to 62% in 2005, and FEV1 was consistently a strong predictor of survival. The use of combination inhalers in people with moderate to severe COPD also increased markedly during the study. CONCLUSION: Following the introduction of the NICE guideline for COPD and the new QOF, there has been an increase in the prevalence of COPD in general practice and a large increase in spirometry data and prescriptions for combination inhalers. This represents significant progress for people with COPD.

Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids are used increasingly to treat people with COPD, but the extent to which these drugs increase the risk of fracture is unclear. AIM: To quantify the dose-response relationship between fracture risk and inhaled corticosteroids in people with COPD, independent of the effects of percent predicted FEV(1) and oral corticosteroids. DESIGN: Nested case-control study. METHODS: Cases and controls were COPD patients aged > or =40 years or more at diagnosis, with a FEV(1) measurement recorded in The Health Improvement Network database, up to 5 July 2005. Cases (people with a fracture event after 1 January 1998, n = 1235) were assigned up to four controls (n = 4598), matched by gender and general practice. RESULTS: Mean FEV(1) was 57.5% in cases, and 58.5% in controls. Inhaled corticosteroids had been prescribed in 69% of cases (median dose 269 mcg/day) and 66% (226 mcg/day) of controls. Oral corticosteroids had been prescribed in 60% of cases (median annual prescription rate 0.6) and 56% of controls (also 0.6 per year). Risk of fracture increased with increasing mean daily doses of inhaled corticosteroid (p for trend 0.007), and was most marked in those whose daily dose was > or =1600 mcg (OR 1.80, 95% CI 1.04-3.11). This effect was virtually unchanged by adjustment for mean percent predicted FEV(1) and annual prescription rate for oral corticosteroids (OR for highest dose exposure 1.74, 95% CI 1.00-3.01). DISCUSSION: Our findings add to the evidence that the use of inhaled corticosteroids is associated with a small increase in fracture risk, particularly at higher doses.

Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?

BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. AIM: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. RESULTS: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Does the presence of connective tissue disease modify survival in patients with pulmonary fibrosis?

OBJECTIVES: Previous studies into the survival differences between individuals with idiopathic pulmonary fibrosis and those with connective tissue disease associated pulmonary fibrosis (CTD-PF) have yielded mixed results. The aim of this study is to compare the survival of individuals with CTD-PF to those with idiopathic pulmonary fibrosis clinical syndrome (IPF-CS) using data derived from The Health Improvement network, a large primary care database in the UK. METHODS: Incident cases of CTD-PF and IPF-CS between the years 2000-2009 were identified. Survival analysis was performed using Kaplan-Meier methods, stratified by type of connective tissue disease. Cox regression was then used to compare mortality rates between the groups, adjusting for age, gender and year of diagnosis. RESULTS: A total of 324 cases of CTD-PF and 2209 cases of IPF-CS were followed up over a mean period of 2.3 years. During this period, 113 (34.9%) cases of CTD-PF and 1073 (48.6%) cases of IPF-CS died. The mortality rates for cases with CTD-PF and IPF-CS were 123.6 per 1000 person years (95%CI: 102.8-148.9) and 229.8 per 1000 person years (95% CI: 216.4-244.0) respectively. After adjusting for age, sex and year of diagnosis, cases with CTD-PF had a better prognosis compared to those with IPF-CS (HR 0.76,95%CI: 0.62-0.92). CONCLUSION: The prognosis of individuals with CTD-PF appears to be significantly better than those with IPF-CS, but remains an important cause of death in patients with connective tissue disease, and requires more effective treatment options.

The incidence of pneumonia using data from a computerized general practice database.

Despite being widely recognized as a significant public health problem there are surprisingly few contemporary data available on the incidence of pneumonia in the UK. We conducted a general population-based cohort study to determine the incidence of pneumonia in general practice in the United Kingdom. Data were obtained from The Health Improvement Network (THIN) - a computerized, longitudinal, general practice database. Recorded diagnoses of pneumonia between 1991 and 2003 were used to calculate the incidence of pneumonia stratified by year, sex, age group and deprivation score. The overall incidence of pneumonia was 233/100 000 person-years [95% confidence interval (CI) 231-235] and this rate was stable between 1991 and 2003. The incidence of pneumonia was slightly lower in females compared to males [age-adjusted incidence rate ratio (IRR) 0.88, 95% CI 0.86-0.89]. Pneumonia was most common in children aged <4 years and adults aged >65 years. There was an increased incidence of pneumonia with higher levels of socioeconomic disadvantage such that people living in the most deprived areas of the United Kingdom were 28% more likely to get pneumonia than those in the least deprived areas (age- and gender-adjusted IRR 1.28, 95% CI 1.24-1.32). In conclusion, pneumonia is an important public health problem and the incidence of pneumonia is higher in people at the extremes of age, men and people living in socially deprived areas.

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.

Fertility rates in women with asthma, eczema, and hay fever: a general population-based cohort study.

The protective association between having older siblings and the risk of subsequent allergic disease may be due to decreased fertility among women with allergic disease. In this study, the authors compared fertility rates among women with asthma, eczema, or hay fever with those in the general female population. Computerized primary-care data from the United Kingdom were used to conduct a cohort analysis of 491,516 women. General fertility rates and age-specific fertility rates for 1994-2004 were estimated. Using Poisson regression, the authors compared fertility rates among women with asthma, eczema, or hay fever with rates in women without these diagnoses. Fertility rates were 53.0 and 52.3 livebirths per 1,000 person-years in women with and without asthma, respectively. The fertility rate ratio for women with asthma compared with women without asthma was 1.02 (95% confidence interval (CI): 1.00, 1.04) after adjustment for age, smoking, body mass index, and socioeconomic status. Equivalent fertility rate ratios for eczema and hay fever were 1.15 (95% CI: 1.13, 1.17) and 1.08 (95% CI: 1.06, 1.10), respectively. The authors found no evidence that the fertility rates of women with asthma, eczema, or hay fever are lower than those of women in the general population.

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.

Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study.

BACKGROUND: Adrenal insufficiency, a well recognised complication of treatment with oral corticosteroids, has been described in association with inhaled corticosteroid use in over 60 case reports. The risk of adrenal insufficiency in people prescribed an oral or inhaled corticosteroid in the general population is not known. A study was undertaken to quantify the association between adrenal insufficiency and oral and inhaled corticosteroid exposure. METHODS: A case-control study was performed using computerised general practice data from The Health Improvement Network. RESULTS: From a cohort of 2.4 million people, 154 cases of adrenal insufficiency and 870 controls were identified. There was a dose related increased risk of adrenal insufficiency in people prescribed an oral corticosteroid with an odds ratio of 2.0 (95% CI 1.6 to 2.5) per course of treatment per year. Adrenal insufficiency was associated with a prescription for an inhaled corticosteroid during the 90 day period before the diagnosis with an odds ratio of 3.4 (95% CI 1.9 to 5.9) and this effect was dose related (p for trend <0.001). After adjusting for oral corticosteroid exposure, this odds ratio was reduced to 1.6 (95% CI 0.8 to 3.2) although the dose relation remained (p for trend 0.036). CONCLUSION: People prescribed an oral or inhaled corticosteroid are at a dose related increased risk of adrenal insufficiency although the absolute risk is small. This analysis suggests that the increased risk in people prescribed an inhaled corticosteroid is largely due to oral corticosteroid exposure, but inhaled corticosteroids may have an effect when they are taken at higher doses.

Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study.

BACKGROUND & AIMS: Previous studies have raised concern about reduced fertility and increased adverse pregnancy-related events in women with celiac disease, but none has estimated overall fertility compared with the general female population. METHODS: We compared computerized primary care data for 1521 women with celiac disease with data for 7732 age- and practice-matched women without celiac disease. We estimated population-based rates of fertility and adverse pregnancy outcomes. RESULTS: Crude fertility rates were 48.2 and 47.7 live births per 1000 person-years for women with and without celiac disease, respectively (rate ratio, 1.01; 95% confidence interval, 0.90-1.14). Age-specific fertility rates showed that women with celiac disease had lower fertility when younger but higher fertility when older compared with women without celiac disease. This increase in relative fertility with increasing age held whether women had treated or untreated celiac disease. Risks of cesarean section (odds ratio, 1.33; 95% confidence interval, 1.03-1.70) and miscarriage (rate ratio, 1.31; 95% confidence interval, 1.06-1.61) were moderately higher in women with celiac disease, but risks of assisted birth, breech birth, preeclampsia, postpartum hemorrhage, ectopic pregnancy, stillbirth, and termination were similar. CONCLUSIONS: Overall, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age. Although our findings may reflect a disease effect, the age shift in fertility rates and the increase in cesarean section risk is consistent with socioeconomic or educational advantages of women with celiac disease.