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.

/pdf/allergic-rhinitis-and-its-impact-on-asthma-aria-2008-update-13eqfzaw4u.pdf

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

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

World Health Organization; GA(2)LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Background: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. Objective: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. Methods: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. Results: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. Conclusion: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.

/pdf/allergic-rhinitis-and-its-impact-on-asthma-aria-guidelines-3pawic20n9.pdf

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American Col- lege of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology have jointly accepted responsibility for establishing ''Allergen immunotherapy: A practice parameter third update.'' This is a complete and com- prehensive document at the current time. The medical environ- ment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individ- ual, including those who served on the Joint Task Force, is authorizedtoprovideanofficial AAAAIorACAAIinterpretation ofthesepracticeparameters.Anyrequestforinformationaboutor an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. A current list of published practice parameters of the Joint Task Force on Practice ParametersforAllergyandImmunologycanbefoundinTableE1 in this article's Online Repository at www.jacionline.org. Disclosure ofpotentialconflictofinterest:L.Coxisaconsultant forGenentech/Novartis, Hollister-Stier, and Stallergenes; is a speaker for Novartis; has received research support from Stallergenes; is on the Board of Directors for the American Board of Allergy and Immunology; and is on the US Food and Drug Administration (FDA)'s Allergenic Product Advisory Committee. H. Nelson is a consultant for Merck and Planet Biopharmaceuticals, is a Data and Safety Monitoring Board member of DBV Technologies, and has received research support from ALK-AbellM. Nelson has re- ceivedresearchsupportfromtheDepartmentofDefense,isaspeakerfortheAmerican College of Allergy, Asthma & Immunology (ACAAI), and is a member of the FDA's AdvisoryCommitteeonAllergicProducts.R.Weberisonthespeakers'bureauforAs- traZeneca and Genentech, has received research support from Novartis and Glaxo- SmithKline, and is Committee Chair of the ACAAI. D. I. Bernstein is a consultant and on the advisory board for ALK America, is on the advisory board for Merck, and has received research support from Merck and Schering-Plough. J. Blessing- Moore is a speaker for Merck-Schering/AstraZeneca, Novartis, TEVA, and Meda Alcon and has received research support from Meda. D. A. Khan is a speaker for As- traZeneca and Merck, has received research support from the Vanberg Family Foun- dation and the Sellars Family Foundation, is Conjoint Board Review Chair for the ACAAI,andisapastpresidentoftheTexasAllergy,AsthmaandImmunologySociety. D. M. Lang is a speaker and consultant for GlaxoSmithKline; is a speaker for Astra- Zeneca, Merck, TEVA, Sanofi-Aventis, and Genentech/Novartis; and has received re- search support from Genentech/Novartis. R. A. Nicklas is a fellow for the ACAAI. J. Oppenheimer is a consultant and has provided lectures for AstraZeneca, Merck, and GlaxoSmithKline; and has received research support from AstraZeneca, Merck, Glax- oSmithKline, and Genentech. J. M. Portnoy is a speaker for Phadia, Merck, and CSL Behring; hasreceived researchsupportfromtheUSDepartment ofHousingandUrban Development;andisa board memberof theACAAI board of regents.S.L. Spector has received research support from Genentech, GlaxoSmithKline, Schering-Plough, Aventis, Novartis, Pharmaxis, Boehringer Ingelheim, AstraZeneca, Johnson & John- son, Xyzal, Alcon, Centocor, Sepracor, UCB, Amgen, Capnia, and IVAX. S. Tilles isaspeakerforAlcon; isontheadvisoryboard forALK,Ista,Merck,andStallergenes; has received research support from Alcon, Amgen, Amphastar, Astellas, Boehringer Ingelheim,Ception,Genentech,Icagen, MAP Pharma, MEDA, Merck, Novartis, Rox- ane, and Sepracor; is Associate Editor of Allergy Watchand Annals of Allergy; and is a task force member for the Joint Task Force for Practice Parameters. D. Wallace is a speaker and advisor for Alcon, is a speaker for Merck and Sanofi-Aventis, and is President-Elect of the ACAAI. The rest of the authors have declared that they have no conflict of interest.

/pdf/allergen-immunotherapy-a-practice-parameter-third-update-1itlwly1yo.pdf

Allergen immunotherapy: A practice parameter third update

Background
Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease.

Objectives
To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients.

Search methods
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006.

Selection criteria
All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo.

Data collection and analysis
Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events.

Main results
We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities.

Authors' conclusions
This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

/pdf/allergen-injection-immunotherapy-for-seasonal-allergic-41pan5fuyh.pdf

Allergen injection immunotherapy for seasonal allergic rhinitis

Background Few studies have investigated the use of specific immunotherapy (SIT) for childhood seasonal allergic asthma. Objective We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen ( Phleum pratense Alutard SQ; ALK-Abello, Horsholm, Denmark) in children with seasonal allergic asthma. Methods A randomized, double-blind, placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16 years) with a history of seasonal allergic asthma sensitized to grass pollen ( P pratense ) and requiring at least 200 μg of inhaled beclomethasone equivalent per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded. The primary outcome measure was a combined asthma symptom-medication score during the second pollen season. Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen, sputum eosinophilia, exhaled nitric oxide, and adverse events. Results Thirty-nine subjects were enrolled. Thirty-five subjects provided data for analysis. The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo ( P = .04). There were also significant reductions in cutaneous ( P = .002), conjunctival ( P = .02), and bronchial ( P = .01) reactivity to allergen after SIT compared with that after placebo. The 2 groups had similar levels of airway inflammation, despite a trend toward less inhaled steroid use in the active group. No serious adverse events were reported, and no subjects withdrew because of adverse events. Conclusion The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen.

https://www.jacionline.org/article/S0091-6749(05)02522-4/pdf

Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma

Background: Health-related quality of life (HRQOL) questionnaires currently being used to evaluate allergic disease are organ-specific. They therefore fail to take account of the systemic aspects of allergic disease. Objective: To develop and validate a pediatric HRQOL questionnaire for allergic disease (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ) that encapsulates problems related to the eyes, ears, nose, lungs, skin, emotions, and everyday activities. Methods: In the development phase, 77 subjects (6 to 16 years of age), with seasonal or perennial allergic problems, were asked how much they were bothered by each different area of HRQOL impairment. The highest scoring areas were used to construct the PADQLQ. In the validation phase of the study, 36 subjects (8 to 16 years of age) with seasonal allergic rhinoconjunctivitis, seasonal allergic asthma, and/or cutaneous manifestations of grass pollen allergy were assessed before and during the pollen season. Results: The PADQLQ contains 26 questions. In addition to standard symptoms (eg, rhinitis), it incorporates multiorgan symptoms that are usually overlooked (eg, hearing problems). The PADQLQ demonstrated good cross-sectional and longitudinal validity, showing a high degree of correlation with symptom scores and quality of life as measured by a visual analogue scale and two-organ specific questionnaires. The PADQLQ showed good within-subject reliability and a small minimal important difference (0.33; 95% CI, 0.11 to 0.54 on a 7-point scale). Conclusions: The PADQLQ has good cross-sectional and longitudinal validity, making it a potentially useful outcome measure in the evaluation of systemic treatments such as antihistamine medications and immunotherapy in children with multisystem allergic disease.

Development of a quality-of-life assessment for the allergic child or teenager with multisystem allergic disease.

Summary
Background Allergic disease has been shown to impair health-related quality of life (HRQL). The relationship between HRQL and either allergen exposure or allergic inflammation has not been previously assessed.

Objective To assess the relationship between HRQL and both grass pollen exposure and airway inflammation using the Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ). This is a novel questionnaire previously developed to assess the multi-system aspects of allergic disease.

Methods Eighty-four subjects, aged 6–17 years, with seasonal allergic rhinoconjunctivitis, asthma and/or cutaneous manifestations were assessed before and during the grass pollen season. They were assessed with the PADQLQ, a visual analogue scale (VAS) to assess quality of life, symptom diary and exhaled nitric oxide (FENO).

Results HRQL, as measured by the PADQLQ, significantly correlated with the average pollen count in the previous week (regression coefficient 0.038, 95% confidence interval (CI) 0.027–0.049, P<0.001). The PADQLQ score was also found to be significantly associated with airway inflammation as measured by FENO (regression coefficient 0.410, 95% CI 0.175–0.646, P=0.001). Additionally, PADQLQ showed a high degree of correlation with symptom scores and quality of life as measured by a VAS, good within-subject reliability and a small minimal important difference (0.20, 95% CI −0.09 to 0.49 on a seven-point scale).

Conclusion HRQL is related to both allergen load and allergic inflammation and the PADQLQ has excellent cross-sectional and longitudinal validity with respect to quality of life and symptoms.

Impairment in quality of life is directly related to the level of allergen exposure and allergic airway inflammation.

AAAAI 60th Anniversary Meeting Denver, Colorado March 7–March 12, 2003 Program and abstract of paper to be presented during scientific sessionsGrass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma*

Background: Exhaled nitric oxide (NO) has been proposed as a marker of airway eosinophilic inflammation in asthma. There is currently a paucity of longitudinal data relating it to allergen exposure and asthma symptoms. Methods: Forty four children (6–16 years) with seasonal allergic asthma were sequentially followed before and during the grass pollen season. Asthma symptoms, lung function, NO levels, and pollen counts were recorded. The relationship between exhaled NO and both the pollen levels and asthma control were assessed longitudinally, comparing a subject’s measurements with their previous ones. Results: The median exhaled NO concentration was significantly increased during the pollen season (6.2 v 9.2 parts per billion (ppb), p Conclusions: The results suggest that, within a longitudinal model, the exhaled NO concentration is related to preceding allergen exposure and asthma control. It may be clinically more useful to compare exhaled NO values with a subject’s previous values than to compare them with a population based normal range.

https://thorax.bmj.com/content/thoraxjnl/59/9/752.full.pdf

Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthma

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