Johanna Feary

Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care

Background Comorbidities associated with systemic inflammation including cardiovascular disease (CVD), stroke and diabetes mellitus (DM) are common among individuals with chronic obstructive pulmonary disease (COPD). A study was undertaken to quantify the burden of comorbidity and to determine the risk of first acute arteriovascular events among individuals with COPD. Methods The computerised primary care records of 1 204 100 members of the general population aged ≥35 years on 25 February 2005 were searched for recordings of each disease. Data were analysed using multivariate logistic regression. Cox regression was used to determine whether individuals with COPD were at increased risk of acute myocardial infarction (MI) and stroke. Results Cross-sectional analyses showed that physician-diagnosed COPD was associated with increased risks of CVD (OR 4.98, 95% CI 4.85 to 5.81; p<0.001), stroke (OR 3.34, 95% CI 3.21 to 3.48; p<0.001) and DM (OR 2.04, 95% CI 1.97 to 2.12; p<0.001). In the follow-up analyses, after adjusting for confounding by sex and smoking status and stratifying for age, the greatest increase in the rate of acute arteriovascular events was found in the youngest age groups; the HR for acute MI was 10.34 (95% CI 3.28 to 32.60; p<0.001) and for stroke the HR was 3.44 (95% CI 0.85 to 13.84; p<0.001) compared with the oldest age group. Conclusion Individuals with COPD are substantially more likely to have pre-existing CVD, DM or a previous stroke and are at high risk of acute arteriovascular events. National COPD guidelines and models of care need to adapt to provide an integrated approach to addressing these comorbidities.

Experimental hookworm infection: a randomized placebo-controlled trial in asthma

Background Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.

Atopy and current intestinal parasite infection: a systematic review and meta‐analysis

To cite this article: Feary J, Britton J, Leonardi‐Bee J. Atopy and current intestinal parasite infection: a systematic review and meta‐analysis. Allergy 2011; 66: 569–578.

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study

Background Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.

Immunologic Profiles of Persons Recruited for a Randomized, Placebo-Controlled Clinical Trial of Hookworm Infection

Data from epidemiologic studies suggest that hookworm infections, in establishing an immunologic phenotype conducive to parasite survival, may protect against the development of allergic disease. We describe immunologic findings from a clinical study designed to investigate the safety of iatrogenic hookworm infection in participants with allergic rhinitis. The low, relatively safe level of hookworm infection used in this study was immunogenic, inducing eosinophilia and a significant specific IgG response. Importantly, no potentiation of IgE responses to the environmental allergens to which the participants were sensitized was seen. However, no evidence of systemic immune regulation was seen in infected participants. This finding may indicate that the level of infection or the frequency of infection may have to be altered in future trials to induce a therapeutically conducive immunologic phenotype.

Chronic obstructive pulmonary disease in sub-Saharan Africa: a systematic review.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a major global health problem. Although COPD is the sixth most common cause of mortality in low- and middle-income countries, most research comes from high-income countries. We set out to systematically review existing published research on COPD in sub-Saharan Africa to identify knowledge gaps and opportunities for further research. METHODS A literature search of MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases, published reviews, reference lists from included publications and abstracts from major thoracic medicine conference proceedings within the previous 2 years was performed using a protocol-driven search strategy. Texts were screened for inclusion by two independent reviewers. Studies were included if they met the following criteria: 1) COPD was an outcome, and 2) the population included people from sub-Saharan Africa. There were no language restrictions. FINDINGS Our search identified 688 studies: 41 were duplicates, 638 were excluded, and 9 met our inclusion criteria. Included studies were all cross-sectional, and included 3673 people from four sub-Saharan African countries. Estimates of COPD prevalence varied between 4% and 25%. Only one study used population-based representative sampling and an adequate case definition. Assessment of risk factors was limited. CONCLUSIONS There is little existing research on COPD in sub-Saharan Africa. Prevalence estimates varied, reflecting the range of populations studied, inconsistent diagnostic criteria and variable methods and methodological quality. Population-representative studies using appropriate case definitions are needed to define the epidemiology of COPD in sub-Saharan Africa and to inform the development of prevention and management strategies for the future.

Dietary supplements and asthma: another one bites the dust

No effect of selenium supplementation on symptoms of asthma Throughout history, clinical observation and clinical trials have identified links between nutritional deficiency and disease. For example, scurvy was described by Hippocrates over 2000 years ago, and native cultures have known its cause and cure for centuries. The first intervention study to demonstrate the successful treatment of scurvy with citrus fruits was published in 1753 by Captain James Lind in “ A Treatise of the Scurvy ”. Moving forward to the 20th century, one of the resounding achievements in this field has been identification of the importance of folic acid supplements in the prevention of spina bifida, leading to an overall reduction in incidence in the Western world. The possibility that nutritional factors may play a similarly important role in the aetiology of chronic respiratory disease is therefore intriguing and has recently attracted a great deal of interest. The aetiology of asthma remains unclear, but it is widely accepted that environmental factors play a major role and, of these, diet is a potentially important contender. Evidence for this arises from the observations that the prevalence of asthma increases as societies move from a rural subsistence towards a more Western lifestyle; this is associated, among other factors, with a change in dietary pattern including adoption of a more processed and “convenience-orientated” diet. The result of this dietary change is an overall increase in the intake of refined sugars, fats and additives, and a relative reduction in the intake of complex carbohydrates and micronutrients. This change is a relatively modern phenomenon, occurring in the UK …

Antigen-driven basophil activation is indicative of early Necator americanus infection in IgE-seronegative patients

BACKGROUND Parasitic worms induce a strong, polarized T(H)2-type immune response. The kinetics of gastrointestinal nematode-induced T(H)2-type responses, especially in the context of primary infection, have been extensively studied in experimental infection models but not in human subjects. OBJECTIVE We sought to determine the kinetics of basophil sensitization in subjects infected with Necator americanus during the first 12 weeks after infection. METHODS Thirty nonasthmatic subjects with allergic rhinoconjunctivitis were randomized in a double-blind manner to cutaneous administration of either 10 hookworm infective larvae or histamine placebo. Blood samples were taken at regular intervals for 12 weeks, and basophil activation was determined in whole blood by measuring CD63 and CD203c levels on stimulation with N americanus excretions/secretions. Parasite-specific immunoglobulin responses were assessed by means of ELISA and Western blotting. RESULTS Median values reflecting basophil activation (CD203c/CD63 double-positive cells) in the excretion/secretion-stimulated infected group steadily increased after week 4, consistently achieving statistical significance compared with the placebo group between 6 and 12 weeks after infection. Only parasite-specific IgM levels increased significantly during this period, whereas total and parasite-specific IgE levels did not differ between groups. CONCLUSION Basophils are sensitized early in the context of a low-dose primary infection with N americanus in the absence of measurable total and specific IgE serum level increase.

Laboratory animal allergy: a new world.

Purpose of reviewIn recent years there has been a dramatic shift in the world of animal research whereby genetically modified mice have largely supplanted rats, and individually ventilated cages have been introduced to house delicate experimental animals in place of traditional open cages. Although laboratory animal allergy remains an important cause of occupational asthma, the risks associated with contemporary practice and consequently the opportunities for primary and secondary prevention are largely unknown. Recent findingsAlthough there is clear confirmation of a widespread increase in animal experiments using mice, the evidence-base on the associated risks has lagged. Individually ventilated cages reduce ambient levels of mouse urinary protein in air but task-based exposures are unquantified. Immunological techniques to identify sensitization to mouse proteins are poorly standardized. The available evidence suggests that modern practices are, in most cases, associated with a reduced incidence of animal sensitization. SummaryThere is a paucity of data to inform evidence-based practice in methods to control the incidence of laboratory animal allergy under the prevailing research environment; a better understanding of the relationship between exposures and outcome is urgently needed. As exposures decline, the relative importance of individual susceptibility will become prominent.

Occupational Hypersensitivity Pneumonitis: What Is the Evidence, When to Think of It, and What to Do

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a relatively rare condition with a variable natural history (acute, subacute, or chronic) and fairly nonspecific features. Patients present with pulmonary symptoms with or without constitutional disturbance. HP can be caused by >300 different agents, which broadly comprise microbial agents (bacteria, fungus), animal antigens, and chemicals, and exposure to these agents may occur in occupational settings—the focus of this article—or elsewhere. HP, particularly due to occupational exposures, is underdiagnosed due to a lack of awareness of the condition and difficulties in identifying and confirming the diagnosis. Bird fancier’s lung and farmer’s lung have historically been the most common causes of HP. More recently, metalworking fluids used in engineering have emerged as an increasingly common etiological agent for occupational HP and several outbreaks have been reported. Making a diagnosis of occupational HP is crucial both for the individual, so as to remove them from exposure and maximize the chance of a full recovery, and for the employer, so that they can identify other cases and put into place strategies to prevent further cases. There is no single gold standard test used to confirm HP, and a combination of a careful occupational exposure history, clinical history, radiology, and immunology findings can help ascertain a diagnosis. Certain key questions can be useful in eliciting a work-related pattern to symptoms.