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Anaphylaxis: past, present and future

Anaphylaxis is a clinical emergency, and recent reports suggest increased prevalence. A diverse set of primary genetic and environmental influences may confer susceptibility to anaphylactic reactions.

Anaphylaxis presents diagnostic and therapeutic challenges. It often manifests with a broad array of symptoms and signs that might be similar to other diseases. The management of anaphylaxis consists of emergency treatment of acute episodes as well as preventive strategies to avoid recurrences. Treatment is complicated by its rapid onset and progression, presence of concurrent diseases or medications, and need for long-term allergen avoidance. Health care professionals must be able to recognize the signs of anaphylaxis, treat an episode promptly and appropriately, and provide preventive recommendations.

Recognizing the gaps in our understanding and management of anaphylaxis may help identify promising targets for future treatment and prevention and areas that require further study.

Days with severe symptoms: an additional efficacy endpoint in immunotherapy trials

In immunotherapy trials, primary and secondary endpoints often focus on average symptom and medication scores during the pollen season or on days with low symptoms and low medication use. Thus, there is a need for endpoints describing the treatment effect on the most troublesome days in the pollen season.

Aims of the study:  A possible additional efficacy endpoint, days with severe symptoms during the pollen season, was investigated using data from a multicentre, double-blind, randomized, placebo-controlled trial of the SQ-standardized grass allergy immunotherapy tablet (AIT) (Grazax, Phleum pratense, 75 000 SQ-T/2,800 BAU, ALK, Hørsholm, Denmark).

Methods:  The trial included 634 subjects (NGrass AIT = 316; NPlacebo = 318) with grass pollen-induced rhinoconjunctivitis. Six different definitions of a day with severe symptoms were suggested. The number of days with severe symptoms was analysed and odds ratios were calculated.

Results:  The number and percentage of days with severe symptoms differed between definitions, but overall the analysis of days with severe symptoms showed consistent results (odds ratios: 2.0–3.4) for the different definitions. All definitions showed a reduced risk of having days with severe symptoms in the grass AIT group when compared to the placebo group.

Conclusions:  Days with severe symptoms during the pollen season is a relevant additional efficacy endpoint, which can be used in immunotherapy trials to support the clinical interpretation of commonly used efficacy endpoints.

What are the ‘ideal’ features of an adrenaline (epinephrine) auto-injector in the treatment of anaphylaxis?

Anaphylaxis is a systemic allergic reaction that often involves respiratory symptoms and cardiovascular collapse, which are potentially life-threatening if not treated promptly with intramuscular adrenaline.

Owing to the unpredictable nature of anaphylaxis and accidental exposure to allergens (such as peanuts and shellfish), patients should be prescribed intramuscular adrenaline auto-injectors and carry these with them at all times. Patients also need to be able to use their auto-injectors correctly while under high stress, when an anaphylactic attack occurs. Despite this, an alarming number of patients fail to carry their auto-injectors and many patients, carers of children with known anaphylaxis and healthcare professionals do not know how to use the device correctly, despite having had training.

Currently available auto-injector devices have various limitations that may impede their use in the management of anaphylaxis. There is also a lack of validated assessment criteria and regulatory requirements for new devices.

This review describes the different delivery systems used in currently available auto-injectors and discusses the key barriers to the use of adrenaline auto-injectors, with the goal of identifying the ‘ideal’ features/characteristics of such devices in the emergency treatment of anaphylaxis that will ensure ease of use, portability and accurate delivery of a life-saving drug.

Vaccination of adults with asthma and COPD

Vaccines play a major role in preventing potentially life-threatening diseases. More attention is now focused on the adult population, particularly as they age, as a reservoir for vaccine-preventable diseases.

Adults with comorbid conditions such as asthma and chronic obstructive pulmonary disease (COPD) are considered to be at higher risk for invasive diseases, many of which are preventable through routine vaccination.

This article reviews the pertinent literature for the use of vaccines in the management of adult patients with asthma and COPD.

Fatty acids in breast milk and development of atopic eczema and allergic sensitisation in infancy

One of the explanations for the increasing prevalence of atopic diseases is a relative low perinatal supply of n-3 fatty acids. However, this does not explain the protective effects of whole-fat dairy products or high levels of transfatty acids in breast milk, observed in some studies.

We evaluated the role of perinatal supply of fatty acids in the early development of atopic eczema and allergic sensitisation.

Methods:  Fatty acids, including n-3 long-chain polyunsaturated fatty acids (LCPs) as well as ruminant fatty acids (rumenic acid, cis-9,trans-11-C18:2 conjugated linoleic acid; and vaccenic acid, trans-11-C18:1), were determined in breast milk sampled at 1 month postpartum from 310 mother–infant pairs in the KOALA Birth Cohort Study, the Netherlands. Children were followed for atopic outcomes until 2 years of age.

Results:  Higher concentrations of n-3 LCPs as well as ruminant fatty acids were associated with lower risk of (1) parent-reported eczema, (2) atopic dermatitis (UK Working Party criteria), and (3) sensitisation at age 1 year (as revealed by specific serum IgE levels to cow’s milk, hen’s egg and/or peanut). In multivariable logistic regression analysis, the inverse associations between ruminant fatty acid concentrations in breast milk and atopic outcomes were found to be independent from n-3 LCPs.

Conclusions:  The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations.

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