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1.  The anti-inflammatory effects of levocetirizine - are they clinically relevant or just an interesting additional effect? 
Levocetirizine, the R-enantiomer of cetirizine dihydrochloride has pharmacodynamically and pharmacokinetically favourable characteristics, including rapid onset of action, high bioavailability, high affinity for and occupancy of the H1-receptor, limited distribution, minimal hepatic metabolism together with minimal untoward effects. Several well conducted randomised clinical trials have demonstrated the effectiveness of levocetirizine for the treatment of allergic rhinitis and chronic idiopathic urticaria in adults and children. In addition to the treatment for the immediate short-term manifestations of allergic disease, there appears to be a growing trend for the use of levocetirizine as long-term therapy. In addition to its being a potent antihistamine, levocetirizine has several documented anti-inflammatory effects that are observed at clinically relevant concentrations that may enhance its therapeutic benefit. This review will consider the potential or otherwise of the reported anti-inflammatory effects of levocetirizine to enhance its effectiveness in the treatment of allergic disease.
PMCID: PMC2804563  PMID: 20066054
2.  Hodgkin's lymphoma presenting with markedly elevated IgE: a case report 
Markedly elevated IgE as a manifestation of a lymphoproliferative disorder has been only rarely reported.
Case Presentation
We present the case of a 22 year old female referred to the adult Allergy & Clinical Immunology clinic for an extremely elevated IgE level, eventually diagnosed with Hodgkin's lymphoma. She had no history of atopy, recurrent infections, eczema or periodontal disease; stool was negative for ova & parasites. Chest X-ray revealed large bilateral anterior mediastinal masses that demonstrated prominent uptake on gallium scan. Mediastinal lymph node biopsy was consistent with Hodgkin's lymphoma, nodular sclerosing subtype, grade I/II.
Although uncommon, markedly elevated IgE may be a manifestation of a malignant process, most notably both Hodgkin's and Non-Hodgkin's lymphomas. This diagnosis should be considered in evaluating an otherwise unexplained elevation of IgE.
PMCID: PMC2794847  PMID: 20016775
3.  Stem cells, inflammation and allergy 
Recently, many studies have suggested a potential role for early hematopoietic progenitor cell and hematopoietic stem cell (HSC) recruitment and differentiation in the development of allergy and inflammation. This is based largely on evidence that stem cells or CD34+ progenitor cells are recruited to the site of inflammation in allergic diseases, likely through many of the same adhesion and chemokine receptors used for stem cell homing to the bone marrow (PSGL-1, CXCL12, alpha4-beta1 integrin, CD44, etc). Once at the site of inflammation, it has been suggested that stem cells could participate in the perpetuation of inflammation by maturing, locally, into inflammatory cells in response to the growth factors released in situ. Here we provide a brief review of the evidence to suggest that hematopoietic stem and progenitor cells (versus mature hematopoietic lineages) are, indeed, recruited to the site of allergic inflammation. We also discuss the molecules that likely play a role in this process, and highlight a number of our novel observations on a specific role for the stem cell antigen CD34 in this process.
PMCID: PMC2804275  PMID: 20066174
4.  Treating rhinitis in the older population: special considerations 
Rhinitis in the elderly is a common but often neglected condition. Structural changes in the nose associated with aging, predisposes the elderly to rhinitis. There are a number of specific factors that affect medical treatment of the elderly including polypharmacy, cognitive dysfunction, changes in body composition, impairment of liver and renal function and the cost of medications in the face of limited resources. Rhinitis in the elderly can be placed in several categories and treatment should be appropriate for each condition. The most important aim is to moisten the nasal mucosa since the nose of the elderly is so dry. Great caution should be used in treatment with first generation antihistamines and decongestants. Medications generally well tolerated by the elderly are second generation antihistamines, intra-nasal anti-inflammatory agents, leukotriene modifiers and iprapropium nasal spray.
PMCID: PMC2794852  PMID: 20016692
5.  Importance of basophil activation testing in insect venom allergy 
Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, there are still many questions and controversies regarding immunotherapy, like selection of the appropriate allergen, safety and long term efficacy.
Literature review was performed to address the role of basophil activation test (BAT) in diagnosis of venom allergy.
In patients with positive skin tests or specific IgE to both honeybee and wasp venom, IgE inhibition test can identify sensitizing allergen only in around 15% and basophil activation test increases the identification rate to around one third of double positive patients. BAT is also diagnostic in majority of patients with systemic reactions after insect stings and no detectable IgE. High basophil sensitivity to allergen is associated with a risk of side effects during VIT. Persistence of high basophil sensitivity also predicts a treatment failure of VIT.
BAT is a useful tool for better selection of allergen for immunotherapy, for identification of patients prone to side effects and patients who might be treatment failures. However, long term studies are needed to evaluate the accuracy of the test.
PMCID: PMC2794846  PMID: 20016774
6.  Urticaria and infections 
Urticaria is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. In spontaneous acute urticaria there is no doubt for a causal relationship to infections and all chronic urticaria must have started as acute. Whereas in physical or distinct urticaria subtypes the evidence for infections is sparse, remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Current summarizing available studies that evaluated the course of the chronic urticaria after proven Helicobacter eradication demonstrate a statistically significant benefit compared to untreated patients or Helicobacter-negative controls without urticaria (p < 0.001). Since infections can be easily treated some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori. This review will update the reader regarding the role of infections in different urticaria subtypes.
PMCID: PMC2804274  PMID: 20066173
7.  Introduction of oral vitamin D supplementation and the rise of the allergy pandemic 
The history of the allergy pandemic is well documented, enabling us to put the vitamin D hypothesis into its historical context. The purpose of this study is to compare the prevalence of rickets, vitamin D supply, and allergy prevalence at 50-year intervals by means of a retrospective analysis of the literature since 1880.
English cities in 1880 were characterized by an extremely high rickets prevalence, the beginning of commercial cod liver oil production, and the near absence of any allergic diseases. By 1930 hay fever prevalence had risen to about 3% in English-speaking countries where cod liver oil was preferentially used for the treatment of rickets. In 1980 vitamin D was used nation-wide in all industrialized countries as supplement to industrial baby food, thus eradicating nearly all cases of rickets. At the same time the allergy prevalence reached an all-time high, affecting about 30% of the population.
Time trends are therefore compatible with the vitamin D hypothesis although direct conclusions cannot be drawn. It is interesting, however, to note that there are at least two earlier research papers linking synthesized vitamin D intake and allergy (Reed 1930 and Selye 1962) published prior to the modern vitamin D hypothesis first proposed in 1999.
PMCID: PMC2794851  PMID: 20016691
8.  Imitators of exercise-induced bronchoconstriction 
Exercise-induced bronchoconstriction (EIB) is described by transient narrowing of the airways after exercise. It occurs in approximately 10% of the general population, while athletes may show a higher prevalence, especially in cold weather and ice rink athletes. Diagnosis of EIB is often made on the basis of self-reported symptoms without objective lung function tests, however, the presence of EIB can not be accurately determined on the basis of symptoms and may be under-, over-, or misdiagnosed. The goal of this review is to describe other clinical entities that mimic asthma or EIB symptoms and can be confused with EIB.
PMCID: PMC2794850  PMID: 20016690
9.  Determinants in early life for asthma development 
A reliable screening test in newborns for the subsequent development of bronchial asthma (BA) has not been found yet. This is mainly due to the complexity of BA, being made up by different types and underlying mechanisms. In different studies, a number of risk factors for BA have been identified. These include a positive family history of BA, passive smoking (also during pregnancy), prematurity (including pulmonary infections, RDS and BPD), early viral respiratory infections (such as RSV-bronchiolitis), male gender, early lung function abnormalities and atopic constitution. The major risk factor for persistent BA is an underlying allergic constitution. Therefore, early symptoms and markers of allergy (i.e. The Allergic March) and a positive family history for allergy should be considered as important risk factors for the development of BA.
PMCID: PMC2794849  PMID: 20016777
10.  Diagnostic evaluation of food-related allergic diseases 
Food allergy is a serious and potentially life-threatening problem for an estimated 6% of children and 3.7% of adults. This review examines the diagnostic process that begins with a patient's history and physical examination. If the suspicion of IgE-mediated food allergy is compelling based on the history, skin and serology tests are routinely performed to provide confirmation for the presence of food-specific IgE antibody. In selected cases, a provocation challenge may be required as a definitive or gold standard reference test for confirmation of IgE mediated reactions to food. Variables that influence the accuracy of each of the diagnostic algorithm phases are discussed. The clinical significance of food allergen-specific IgE antibody cross-reactivity and IgE antibody epitope mapping of food allergens is overviewed. The advantages and limitations of the various diagnostic procedures are examined with an emphasis on future trends in technology and reagents.
PMCID: PMC2776233  PMID: 19946406
11.  Pollen allergens do not come alone: pollen associated lipid mediators (PALMS) shift the human immue systems towards a TH2-dominated response 
Pollen allergy is characterized by a TH2-biased immune response to pollen-derived allergens. However, pollen-exposed epithelia do not encounter pure allergen but rather a plethora of protein and non-protein substances. We demonstrated that pollen liberate lipids with chemical and functional similarities to leukotriens and prostaglandins - the pollen associated lipid mediators (PALMs). To date, two main groups of PALMs have been characterized: The immunostimulatory PALMs activating innate immune cells such as neutrophils and eosinophils, and the immunomodulatory E1-phytoprostanes blocking IL-12 production of dendritic cells, resulting in the preferential induction of TH2 responses. This article reviews our work in the field of PALMs and their effects on cells of the innate and adoptive immune system. From recent results a general picture starts to emerge in which PALMs (and possibly other pollen-associated substances) may - independently from protein allergens - propagate an overall TH2 favoring micromilieu in pollen exposed tissue of predisposed individuals.
PMCID: PMC2776232  PMID: 19946407
12.  AACI is now an open access journal 
It is our pleasure to welcome you to the new website of Allergy, Asthma & Clinical Immunology (AACI).
PMCID: PMC2776231
13.  The role of Probiotics in allergic diseases 
Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders.
PMCID: PMC2776230  PMID: 19946408
14.  How safe are the biologicals in treating asthma and rhinitis? 
A number of biological agents are available or being investigated for the treatment of asthma and rhinitis. The safety profiles of these biologic agents, which may modify allergic and immunological diseases, are still being elucidated. Subcutaneous allergen immunotherapy, the oldest biologic agent in current use, has the highest of frequency of the most serious and life-threatening reaction, anaphylaxis. It is also one of the only disease modifying interventions for allergic rhinitis and asthma. Efforts to seek safer and more effective allergen immunotherapy treatment have led to investigations of alternate routes of delivery and modified immunotherapy formulations. Sublingual immunotherapy appears to be associated with a lower, but not zero, risk of anaphylaxis. No fatalities have been reported to date with sublingual immunotherapy. Immunotherapy with modified formulations containing Th1 adjuvants, DNA sequences containing a CpG motif (CpG) and 3-deacylated monophospholipid A, appears to provide the benefits of subcutaneous immunotherapy with a single course of 4 to 6 preseasonal injections. There were no serious treatment-related adverse events or anaphylaxis in the clinical trials of these two immunotherapy adjuvants. Omalizumab, a monoclonal antibody against IgE, has been associated with a small risk of anaphylaxis, affecting 0.09% to 0.2% of patients. It may also be associated with a higher risk of geohelminth infection in patients at high risk for parasitic infections but it does not appear to affect the response to treatment or severity of the infection.
Clinical trials with other biologic agents that have targeted IL-4/IL-13, or IL-5, have not demonstrated any definite serious treatment-related adverse events. However, these clinical trials were generally done in small populations of asthma patients, which may be too small for uncommon side effects to be identified. There is conflicting information about the safety TNF-alpha blocking agents, which have been primarily used in the treatment of rheumatoid arthritis, with serious infections, cardiovascular disease and malignancies being the most frequent serious adverse events. An unfavorable risk-benefit profile led to early discontinuation of a TNF-blocking agent in a double-blind placebo controlled of severe asthmatics.
In summary, the risk of anaphylaxis and other treatment-related serious events with of all of the biological agents in this review were relatively small. However, most of the clinical trials were done in relatively small patient populations and were of relatively short duration. Long term studies in large patient populations may help clarify the risk-benefit profile of these biologic agents in the treatment of asthma.
PMCID: PMC2794848  PMID: 20016776

Results 1-14 (14)