Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.

In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.

This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.

The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.

Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.

The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

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Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

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Allergic Rhinitis and Its Impact on Asthma

Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma

National Asthma Education and Prevention Program.

Chironomid larvae (red midge larvae) are often used by aquarists as fish food. Their hemoglobins can cause IgE-mediated allergic diseases in exposed and unexposed people. The aim of this study was to find out the prevalence of positive skin tests to chironomids in patients suffering from rhinitis and/or bronchial asthma in Ciudad Real (Spain). A total of 465 patients were submitted to skin prick tests with chironomids in addition to common inhalant allergens. The patients with positive skin prick test (wheal > or = 3 mm) to these larvae answered a questionnaire. Skin prick tests with Acarus siro, shrimp, cockroach and mosquito (Culex pipiens) were carried out. Serum levels of total IgE and anti-Chironommus thummi, anti-Dermatophagoides pteronyssinus, anti-shrimp, and anti-mosquito (Aedes communis) IgE were determined. Conjunctival or nasal provocation tests were carried out with chironomids. Of the 465 patients skin tested, 19 showed a positive skin prick test with chironomids, corresponding to 4.1% of all patients and 6% of the atopic patients. None were monosensitized. Significant correlations were found between skin prick test results with chironomids and mites (p < 0.005). Of the 19 patients, 15 had positive skin prick test with the common mosquito C. pipiens. Seven patients showed elevated anti-D. pteronyssinus IgE, six elevated anti-shrimp IgE, and 10 showed elevated anti-A. communis IgE. Provocation tests with chironomids were positive in 14 patients (four nasal and 10 conjunctival tests). Conjunctival provocation tests were carried out in 16 controls and were positive in three; all three showed positive skin prick test with chironomids. One patient had occupational allergy from the larvae (aquarist). After mosquito bites, five patients showed immediate wheal reactions and one patient suffered an anaphylactic reaction after several mosquito bites. Only two patients remembered having been in contact with chironomids as fish food. We found hypersensitivity to these larvae in patients without apparent contact to them. These patients could have become sensitized in various ways, including: 1) inhaling particles of chironomids or others that are cross-reactive with them; 2) exposure to products used as fish food containing chironomids; and, 3) through cross-reactivity with other allergens such as mites, shrimp or mosquitoes.

Hypersensitivity to chironomid larvae.

Background
Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as the pollen food syndrome. This study aims to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins.

Methods
The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2, and Mal d 4) were measured in-vitro using PBMCs from 26 Spanish grass allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in-vivo using two different mouse strains (BALB/c and C3H).

Results
Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and two immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes, and further influenced by additional genetic factors, likely to be MHC II.

Conclusion
The strength, prevalence and cross reactivity of T-cell responses towards Phl p 12 is comparable to the major allergen Phl p 1, which supports the hypothesis that T-cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with the pollen-food syndrome.

This article is protected by copyright. All rights reserved.

Strong and frequent T‐cell responses to the minor allergen Phl p 12 in Spanish patients IgE‐sensitized to Profilins

Background: The family Dermestidae belongs to the order Coleoptera. Occupational allergy has been described in museum personnel. A 31-year-old male wool worker presenting rhinoconjunctivitis and asthma episodes probably linked to exposure to Dermestidae-infected wool was investigated.



Methods: Extracts prepared either from insect bodies or from dust from parasitized wool were used for skin prick testing (SPT), conjunctival and bronchial provocation tests and in vitro determinations.



Results: SPT and provocation tests were positive to both extracts. PEFR measurement demonstrated the association between the patient's symptoms and occupational exposure to Dermestidae. Specific IgE to both extracts was detected and immunoblotting revealed several protein bands from 5 to 200 kDa that were reactive to IgE from the patient's serum.



Conclusions: Dermestidae exposure in wool workers when handling parasitized wool can be a cause of IgE-mediated rhinoconjunctivitis and asthma.

Occupational rhinoconjunctivitis and asthma in a wool worker caused by Dermestidae spp.

The surface coating of iron oxide nanoparticles drives their intracellular trafficking and degradation in endolysosomes differently depending on the cell type.

In the last decades have emerged new technological platforms that allow evaluation of genes, transcripts, proteins, or metabolites of a living being, so-called omics sciences. More importantly, new technics for their integration have provided access to a complete set of information of the current conditions and features of a specific biological sample in a precise moment. Thus, omic sciences are now considered an essential tool for patient stratification in base to their severity, to understand disease progression and to identify new biomarkers. Severe patients, that are out of control, provide an excellent model to understand disease evolution and to identify new intervention and biomarkers strategies. Here we discuss the use of metabolomics to understand severity in allergic diseases in a strategy that opens new insights as well as identify new biological systems relevant for allergy progression. Metabolomics strategies are based in parallel evaluation of different allergy severity models by mean of untargeted analysis that allows the identification of potential biomarkers. Overlapping of different biomarkers in multiple models, provides information of general as well as specific biological systems involved in each model. Later a selected panel of biomarkers will be used in a target method to explore the diagnosis potential to stratify allergic patients.

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Domingo Barber

Papers

Hypersensitivity to chironomid larvae.

Strong and frequent T‐cell responses to the minor allergen Phl p 12 in Spanish patients IgE‐sensitized to Profilins

Occupational rhinoconjunctivitis and asthma in a wool worker caused by Dermestidae spp.

The surface coating of iron oxide nanoparticles drives their intracellular trafficking and degradation in endolysosomes differently depending on the cell type.

Metabolomics strategies to discover new biomarkers associated to severe allergic phenotypes