Andrew W. Fogarty

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.

Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial

Background: Increased dietary vitamin E intake is associated with a reduced incidence of asthma, and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction. A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma. Methods: 72 participants from a clinical trial register of adults with asthma were randomised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled, double blind parallel group clinical trial. Inclusion criteria included age 18–60 years, maintenance treatment of at least one dose of inhaled corticosteroid per day, a positive skin prick test to one of three common allergens, and bronchial hyperresponsiveness to methacholine (defined as a dose provoking a 20% fall in forced expiratory volume in 1 second (FEV1) (PD20) of 12.25 μmol). Secondary outcomes were FEV1, forced vital capacity, mean morning and evening peak flow, symptom scores, bronchodilator use, and serum immunoglobulin E levels. Results: In the primary intention to treat analysis the change in PD20 was similar in the vitamin E and placebo groups with a mean difference of +0.25 doubling doses of methacholine (95% confidence interval −0.67 to +1.16 greater with vitamin E). There was no effect of vitamin E supplementation on any other measure of asthma control, either in the intention to treat or per protocol analysis. There was also no effect of vitamin E supplementation on serum immunoglobulin levels. Conclusion: Dietary supplementation with vitamin E adds no benefit to current standard treatment in adults with mild to moderate asthma.

Dietary vitamin E, IgE concentrations, and atopy.

Vitamin E inhibits IgE responses to allergic stimuli in animals. We investigated the relation between dietary vitamin E intake and serum IgE concentrations and atopy, measured as allergen skin sensitisation, in a random sample of 2633 adults. Higher concentrations of vitamin E intake were associated with lower serum IgE concentrations and a lower frequency of allergen sensitisation. These findings may explain the beneficial effect of dietary vitamin E on the incidence of asthma.

Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo‐controlled trial

Background Epidemiological studies suggest that higher intakes of dietary vitamin C and magnesium may be associated with a reduced risk of asthma.

The Association between Idiopathic Pulmonary Fibrosis and Vascular Disease : A Population-based Study

RATIONALE Previous studies have suggested that people with idiopathic pulmonary fibrosis (IPF) may be at increased risk of vascular disease. OBJECTIVES To quantify the risk of cardiovascular disease before and after a diagnosis of IPF. METHODS We used computerized primary care data from the Health Improvement Network to quantify the relative risk of having a cardiovascular event (acute coronary syndrome, angina, atrial fibrillation, deep-vein thrombosis, and cerebrovascular accident) either before or after having a diagnosis of IPF in comparison to age, sex, and community-matched general population control subjects. MEASUREMENTS AND MAIN RESULTS Our study included 920 incident case subjects of IPF (mean age at diagnosis, 71 yr; 62% male) and 3,593 matched control subjects. There was an increased risk of acute coronary syndrome (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.15-2.03), angina (OR, 1.84; 95% CI, 1.48-2.29) and deep-vein thrombosis (OR, 1.98; 95% CI, 1.13-3.48) in the period before the diagnosis of IPF. During the follow-up period, there was a marked increased risk of acute coronary syndrome (rate ratio [RR], 3.14; 95%CI, 2.02-4.87) and deep-vein thrombosis (RR, 3.39; 95% CI, 1.57-7.28). None of these estimates were confounded by smoking habit or modified by age or sex. CONCLUSIONS People with IPF have an increased risk of vascular disease in comparison with the general population. This effect is most marked for acute coronary syndrome and deep-vein thrombosis after the diagnosis of IPF has been made.

Systemic inflammation and decline in lung function in a general population: a prospective study

Background: An increase in levels of C-reactive protein (CRP), a marker of systemic inflammation, is associated with reduced forced expiratory volume in 1 s (FEV1), supporting the hypothesis that the pathophysiology of chronic obstructive pulmonary disease has a systemic inflammatory component. However, few large studies have assessed the relationship between systemic inflammation as measured by CRP and decline in lung function prospectively in a randomly selected population. Methods: In 1991, data were collected on FEV1 and forced vital capacity (FVC) and a blood sample was taken from 2442 randomly selected adults in a community-based cohort. In 2000 these measures were repeated in 1301 individuals. The level of serum CRP was analysed in these samples from 1991 and 2000. Results: In cross-sectional analyses of data from 1991 and 2000, serum CRP levels were inversely related to FEV1 and FVC. After adjustment for smoking and other confounders, the difference in FEV1 was reduced by −9 ml (95% CI –13 to –5) and –7 ml (95% CI –13 to –2) for each mg/l increment in serum CRP in 1991 and 2000, respectively. There was no significant association between baseline serum CRP levels and decline in FEV1 and FVC over 9 years. Conclusions: Although serum CRP levels are inversely associated with lung function in cross-sectional studies, there was no effect of a marker of systemic inflammation on decline in lung function over 9 years.

Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review

As idiopathic pulmonary fibrosis emerges as an important public health problem, there is a need to coordinate data on incidence and mortality globally. This study aims to systematically assess all available studies to investigate the global burden of disease. Medline and Embase databases were searched systematically for all population-based studies of incidence or mortality of idiopathic pulmonary fibrosis. Clinical case series and prevalence studies were excluded. The search was supplemented using the Google search engine, hand-searching of references and conference abstracts. Data were extracted independently by two authors using a pre-specified proforma, with assessment of methodological quality. 34 studies were identified, providing data from 21 countries from 1968–2012. 28 studies reported incidence data and eight reported mortality data. In studies from the year 2000 onwards, we estimated a conservative incidence range of 3–9 cases per 100 000 per year for Europe and North America. Incidence was lower in East Asia and South America. The majority of studies showed an increase in incidence over time. The incidence of idiopathic pulmonary fibrosis is increasing worldwide and rates are coming together across countries. Current data suggest incidence is similar to that of conditions such as stomach, liver, testicular and cervical cancers. Incidence of IPF varies worldwide but seems to be increasing to rates around 3–9 per 100 000 per year http://ow.ly/KSeMZ

In-Hospital Mortality after Surgical Lung Biopsy for Interstitial Lung Disease in the United States. 2000 to 2011

RATIONALE Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks. Most currently available mortality data are derived from case series and may not be generalizable to broader populations. OBJECTIVES To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United States. METHODS Data were obtained from the 2000-2011 Nationwide Inpatient Sample. Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies. Lung resections and cases of lung cancer were excluded. Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosis. MEASUREMENTS AND MAIN RESULTS We estimated there to be around 12,000 surgical lung biopsies performed annually for interstitial lung disease in the United States, two-thirds of which were performed electively. In-hospital mortality was 1.7% for elective procedures but significantly higher for nonelective procedures (16.0%). Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease-related interstitial lung disease were risk factors for increased mortality. CONCLUSIONS In-hospital mortality after elective surgical lung biopsy for interstitial lung disease is just under 2% but significantly higher for nonelective procedures. Identified risk factors for death should be taken into account when counseling patients on whether to pursue a histologic diagnosis.

Use of Self-controlled Analytical Techniques to Assess the Association Between Use of Prescription Medications and the Risk of Motor Vehicle Crashes

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

Effects of Helicobacter pylori, geohelminth infection and selected commensal bacteria on the risk of allergic disease and sensitization in 3-year-old Ethiopian children

Background Epidemiological studies have suggested that gastro‐intestinal infections including Helicobacter pylori, intestinal microflora (commensal bacteria) and geohelminths may influence the risk of asthma and allergy but data from early life are lacking.