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.

Importance of Component Resolved Diagnosis of Vespula/Polistes Allergic Patients

Allergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards TH1-secreting IFN-γ, as well as an induction of IL10+ cTFR and TREG have been observed. TH2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10+ DCREG expressing C1Q and STAB are induced. KLRG1+ IL10+ ILC2 were shown to be induced in AIT in correlation with efficacy. BREG cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients’ compliance to complete the course of treatment.

Biomarkers of AIT: Models of prediction of efficacy

Rationale Lipid transfer proteins (LTP) have been identified as relevant allergens. Their role in latex allergy is unclear. This study aimed to produce a recombinant latex-LTP (rHev b 12) to examine its IgE-binding properties. Methods A recombinant generated Maltose-Binding-Protein (MBP)-rHev b 12 fusion protein was coupled to ImmunoCAP for the determination of specific IgE. 48 sera of atopic patients (14 from Spain, 34 from Germany) with fruit-allergy were examined. 25 of these sera displayed positive latex-specific IgE values. Results rHev b 12-specific IgE was measured in four Spanish peach-allergic patients (CAP-values: 0.88-2.27 kU/L), whereby one had an additional latex-sensitization. Two sera from cherry-allergic German patients with latex-sensitization displayed also rHev b 12-specific IgE antibodies (0.68 and 0.96 kU/L). All other sera and the MBP controls revealed negative results ( Conclusions Latex-LTP (rHev b 12)-specific IgE-binding in peach- and cherry-allergic patients seem to be a result of partially common IgE-binding epitopes with the LTPs of peach (homology to Pru p 3: 65%) and cherry (homology to Pru av 3: 61%). Although rHev b 12 seems to have minor relevance as a latex allergen in Central Europe, its significance as a cross-reactive allergen in Mediterranean countries like Spain has to be kept in mind.

Specific IgE-binding of rHev b 12 is restricted to fruit-allergic patients

Rationale We evaluated the profile of sensitization to different natural and recombinant natural rubber latex (NRL) allergens among health care workers (HCWs). Methods Thirty-nine HCWs allergic to NRL with respiratory and/or cutaneous symptoms as demonstrated by positive skin tests (ALK-Abello) and challenges tests were studied. Specific IgE to whole NRL extract (CAPk82) and different latex allergens was measured using CAP-FEIA (Pharmacia). Results Ten percent of the sera were negative to all determinations. The percentage of positive results was as follows: k82 (82%); mix rHev b1,5,6,8 (79%); in 30 sera both measurements were positive and in 6 both were negative, in 2 cases k82 was positive and mix negative, and in 4 cases k82 negative and mix positive. rHev b1 was positive 1/32 (3%), and 6/6 to nHev b2 (100%), 5 of these sera were negative to the recombinant mix, rHev b5 and rHev b6.01, but all them were positive to k82; 11/33 rHev b5 (33%); 23/33 rHev b6.01 (70%); 7 sera were positive to rHev b5 and rHev b6.01 and 6 were negative to both; 4/29 rHev b8 (14%); 0/9 rHev b9, 0/11 rHev b10, 1/10 rHev b11 (10%) and 1/6 rHev b13 (17%). Five sera were k82(-) and some recombinants(+). Conclusions Hev b6.01 and Hev b5 are major allergens recognized by our population of HCWs. Hev b2 also seems an important allergen in some patients. CAPk82 shows a good diagnostic sensitivity similar to the recombinant mix, but the use of a panel of allergens is necessary for in vitro diagnosis in some HCWs allergic to NRL.

Profile of sensitization to individual latex allergens among health care workers allergic to natural rubber latex

Background Panallergens like profilin are proteins that have very similar sequences and structure. People can develop IgE specific to these highly cross reactive panallergens. The purpose of this study was to determine the prevalence of profilin sensitivity and the contribution to multiple allergen skin test responses. Sensitivity to profilin was established by IgE binding to purified profilins. Possible effects on skin test results were studied by including Queen Palm (QP) allergen in the skin prick testing panel as a possible source of profilin. QP is a species with a low probability of pollen exposure.

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Domingo Barber

Papers

Importance of Component Resolved Diagnosis of Vespula/Polistes Allergic Patients

Biomarkers of AIT: Models of prediction of efficacy

Specific IgE-binding of rHev b 12 is restricted to fruit-allergic patients

Profile of sensitization to individual latex allergens among health care workers allergic to natural rubber latex

Skin prick tests to multiple pollens and prevalence of IgE specific to profilin.