With the judicious use of inhaled corticosteroids, β2 agonists, and leukotriene modifiers, most patients with asthma are easily controlled and managed. However, approximately 5% of asthmatics do not respond to standard therapy and are classified as "difficult to control." [1] Typically, these are patients who complain of symptoms interfering with daily living despite long-term treatment with inhaled corticosteroids in doses up to 2,000 μg daily. Many factors can contribute to poor response to conventional therapy, and especially for these patients, a systematic approach is needed to identify the underlying causes. First, the diagnosis of asthma and adherence to the medication regimen should be confirmed. Next, potential persisting exacerbating triggers need to be identified and addressed. Concomitant disorders should be discovered and treated. Lastly, the impact and implications of socioeconomic and psychological factors on disease control can be significant and should be acknowledged and discussed with the individual patient. Less conventional and novel strategies for treating corticosteroid-resistant asthma do exist. However, their use is based on small studies that do not meet evidence-based criteria; therefore, it is essential to sort through and address the above issues before reverting to other therapy.

The possibility of producing local hyposensitization by administering allergens via mucosal routes was envisaged at the beginning of 1900, and local nasal immunotherapy has been extensively studied since the 1970s. Presently, there are 21 randomized controlled trials being conducted with the most common allergens, consistently showing the clinical efficacy of local nasal immunotherapy for rhinitis. Other advantages are that it has an optimal safety profile and can be self-administered at home by the patient. Moreover, there are several data from animal models and from humans that confirm the immunomodulatory effect of intranasally administered antigens. On the other hand, local nasal immunotherapy seems to be effective only on rhinitis symptoms and requires a particular technique of administration. For these reasons, its clinical use is progressively declining in favour of the sublingual route although nasal immunotherapy is validated in official documents and remains a viable alternative to injection.

The aggregation of high-affinity immunoglobulin E (IgE) receptors (FcεRI) on mast cells is a critical event in the initiation of an allergic reaction. Coengagement of FcεRI with immunoglobulin G (IgG) low-affinity receptor FcγRIIB/CD32 inhibits degranulation and the release of inflammatory mediators from mast cells and has therefore been proposed as a new therapeutic approach for the treatment of allergies. In this study, we investigated whether FcγRIIB, besides inhibiting degranulation, negatively regulates other signalling pathways downstream of FcεRI. For this, we determined the phosphorylation and/or expression of proteins involved in the regulation of mast-cell apoptosis. Coaggregation led to an attenuation of Akt phosphorylation but did not inhibit phosphorylation of transcription factor Foxo3a or its proapoptotic target, Bim. Similarly, FcεRI-dependent expression of the prosurvival gene A1 was not affected by coaggregation. Our data demonstrate that coengagement of FcεRI and FcγRIIB inhibits degranulation but not the signalling pathways regulating Bcl-2 family members Bim and A1.

Neutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, the src family of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils.

Purpose

To retrospectively examine the relation between skin test reactivity, venom-specific immunoglobulin E (IgE) antibody levels, and severity of clinical reaction in patients with insect venom allergy.

Method

Thirty-six patients (including 15 females) who presented with a history of allergic reactions to insect stings were assessed. The mean age at the time of the reactions was 33.4 ± 15.1 years (range, 4-76 years), and patients were evaluated 43.6 ± 90 months (range, 1-300 months) after the reactions. Clinical reactions were scored according to severity, from 1 (cutaneous manifestations only) to 3 (anaphylaxis with shock). These scores were compared to scores for skin test reactivity (0 to 5, indicating the log increase in sensitivity from 1 μg/mL to 0.0001 μg/mL) and radioallergosorbent test (RAST) levels (0 to 4, indicating venom-specific IgE levels, from undetectable to >17.5 kilounits of antigen per litre [kUA/L]).

Results

No correlation was found between skin test reactivity (Spearman's coefficient = 0.15, p = .377) or RAST level (Spearman's coefficient = 0.32, p = .061) and the severity of reaction. Skin test and RAST scores both differed significantly from clinical severity (p < .05), but there was a significant correlation between skin test reactivity and RAST score (p = .042). There was no correlation between skin test reactivity and time since reaction (Spearman's coefficient = 0.18, p = .294) nor between RAST and time since reaction (r = 0.1353, p = .438). Elimination of patients tested more than 12 months after their reaction still produced no correlation between skin test reactivity (p = .681) or RAST score (p = .183) and the severity of the clinical reaction.

Conclusion

In venom-allergic patients (in contrast to reported findings in cases of inhalant IgE-mediated allergy), there appears to be no significant correlation between the degree of skin test reactivity or levels of venom-specific IgE (determined by RAST) and the severity of the clinical reaction.

Complementary and alternative medicine and dietary supplements are often used by patients. A detailed examination of each preparation used by four patients was carried out. Seven such preparations with the potential to cause bleeding, cardiovascular and central nervous system side effects, and allergic food reactions are described. They were taken by both Asian and Caucasian patients, were purchased locally, and were used for allergic and nonallergic disorders. Inquiry into their use is important to prevent potential adverse and allergic reactions. There should be a higher standard of regulation for such products.

The medical history is the gateway to the diagnosis of occupational asthma. The medical history should indicate whether a patient's asthma began during a work period and whether the asthma worsens during work periods or improves on days when the patient is off work or on holidays. A suspicion of sensitizer-induced occupational asthma will increase if the patient was exposed to a recognized respiratory sensitizer in the workplace at the time of the onset of symptoms or if the patient had associated symptoms of allergic rhinitis and conjunctivitis. A history of accidental high respiratory irritant exposure shortly before the initial onset of symptoms would raise the possibility of irritant-induced occupational asthma. Although such features of the history are sensitive indicators of occupational asthma, they are not specific and should therefore be followed by further investigations to confirm the diagnosis of asthma and its relation to the workplace exposure. The earlier the diagnosis is suspected and investigated, the better the outcome is likely to be for the patient.

Adverse food reactions are abnormal responses to ingested foods. Reactions vary from immunologic to nonimmunologic immune reactions and can be either immunoglobulin E (IgE) mediated or non-IgE mediated. Food-induced IgE-mediated reactions range from localized urticaria to anaphylaxis and have been well studied. However, in comparison, there has been significantly less research into non-IgE-mediated food reactions. Non-IgE-mediated reactions can cause respiratory, gastrointestinal, and cutaneous symptoms. The most recent evidence suggests that these reactions are probably T-cell mediated as evidenced in lymphocyte proliferation assays. This review will explore the symptoms and testing methods of the most common non-IgE-mediated reactions.

Background

There is increased emphasis on the role of indoor allergens in asthma.

Objective

To examine the spectrum of skin test reactivity (sensitization) to indoor allergens and its correlation with asthma severity in Jeddah, Saudi Arabia.

Methods

Asthmatic patients referred to the allergy clinic at King Abdulaziz University Hospital (KAUH) in Jeddah were studied. Measures of clinical severity were adopted from national and international asthma guidelines. The degree of sensitization was assessed by the wheal size (positive ≥ 3 mm) from standard skin-prick tests for the following common indoor inhalant allergens: house dust mites (Dermatophagoides pteronyssinus [Dp] and Dermatophagoides farinae [Df]), cat, and cockroach.

Results

Skin test results from 113 of 151 (74.8%) asthmatic patients were positive for one or more allergens. The patients' ages ranged between 9 and 63 years (mean, 30 ± 13 years), and females constituted 65.5%. The predominant asthma severity level was moderate persistent (55.8%), followed by mild persistent (33.6%). The prevalences of sensitization to indoor allergens were as follows: Dp, 87% (3-25 mm [mean, 7 mm]); Df, 84% (3-20 mm [mean, 7 mm]); cat, 44% (3-15 mm [mean, 6 mm]); and cockroach, 33% (3-12 mm [mean, 4 mm]). Higher asthma severity levels were significantly correlated with the number of allergens with positive sensitization (R = 0.3, p < .001) and with the degree of sensitization to house dust mites (Dp [degrees of freedom {df} = 16, p < .001] and Df [df = 17, p < .01]) but not to cat (df = 10, p < .24) or cockroach (df = 8, p < .36).

Conclusions

Immunoglobulin E-mediated skin test reactivity to indoor allergens, particularly to house dust mites, was common in asthmatic patients from Jeddah at KAUH. Increased sensitization was associated with higher levels of asthma severity, which is compatible with the literature. This emphasizes the importance of identifying sensitization to relevant indoor allergens in the clinical evaluation of asthmatic persons.

Angioedema is a common presentation with a broad differential, including rare disorders with which an allergist must be familiar. Our objective was to report a case of swelling of the hands and feet mimicking angioedema with hepatomegaly in a 4-year-old girl. The patient was evaluated for painful swelling of the hands and feet after exposure to sun. Examination revealed edema and erythema of the extremities and hepatomegaly. Laboratory evaluation included elevated liver transaminases and plasma protoporphyrin, with normal urine porphyrins. Liver biopsy confirmed the diagnosis of erythropoietic protoporphyria, a disorder of heme biosynthesis in which patients may present with photosensitivity and angioedema. It is important for allergists to recognize this entity in patients with cutaneous disorders of unclear etiology in order to prevent possible life-threatening sequelae.

The objective of this study was to investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from southern Brazil. A cross-sectional study was carried out with the International Study of Asthma and Allergies in Childhood phase III written questionnaire. The questionnaire was self-applied by 2,948 randomly selected schoolchildren aged 13 to 14 years. The lifetime prevalence rates of symptoms were as follows: wheezing, 40.8%; rhinitis, 40.7%; eczema, 13.6%; self-reported asthma, 14.6%; rhinitis, 31.4%; eczema, 13.4%. Rhinitis was reported by 55% of adolescents with current asthma (60% females vs 46.9% males). Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema than boys had. Atopic eczema was reported by 42.7% of girls and 31.4% of boys with asthma. The prevalence rates were statistically significant for symptoms of asthma, rhinitis, and atopic eczema in females. However, there were no statistically significant differences between the sexes in regard to reported asthma and bronchospasm induced by exercise.

Background

Guidelines for the diagnosis and management of asthma have been published over the last 15 years; however, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies, particularly in children, have highlighted the need to incorporate new information into the asthma guidelines. The objectives of this article are to review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Report and its 2001 update, with a major focus on pediatric issues.

Methods

The diagnosis of asthma in young children and prevention strategies, pharmacotherapy, inhalation devices, immunotherapy, and asthma education were selected for review by small expert resource groups. The reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published through December 2004 were subsequently reviewed by the individual expert resource groups.

Results

This report evaluates early-life prevention strategies and focuses on treatment of asthma in children, emphasizing the importance of early diagnosis and preventive therapy, the benefits of additional therapy, and the essential role of asthma education.

Conclusion

We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This document is a guide for asthma management based on the best available published data and the opinion of health care professionals, including asthma experts and educators.