Aim and scopePediatric Allergy and Immunology publishes original contributions and comprehensive reviews related to the understanding and treatment of immune defi ciency, allergic infl ammatory and infectious diseases in children. Other areas of interest include development of specifi c and accessory immunity, and the immunological interaction during pregnancy and lactation between mother and child. As the journal is intended to promote communication between scientists engaged in basic research and clinicians working with children, both clinical and experimental work will be published.

Summary:Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called 'idiopathic' (previously 'vasomotor') rhinitis. Allergic rhinitis affects approximately 1 in 4 of the population of westernised countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptive immunity together with environmental factors is likely to play major roles. In allergic rhinitis, initial allergen exposure and sensitization involves antigen presenting cells, T and B lymphocytes and results in the generation of allergen-specific T cells and allergen specific IgE antibodies. On re-exposure to relevant allergens crosslinking of IgE on mast cells results in the release of mediators of hypersensitivity such as histamine and immediate nasal symptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 T lymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phase allergic response. Evidence for nasal priming and whether or not remodelling may be a feature of allergic rhinitis will be reviewed. The occurrence of so-called 'local' allergic rhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE mediated) rhinitis will be considered in the context of inflammatory and non-inflammatory disorders.Key words: Allergic rhinitis, non-allergic rhinitis, pathogenesis, priming, remodelling, Word count: 237. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Page 2 of 39 Clinical & Experimental Allergy Introduction:Rhinitis is a common heterogeneous chronic disorder in both children and adults that is defined as an inflammation of the nasal mucosa and characterised by the presence of one or more nasal symptoms that includes sneezing, itching, nasal discharge and nasal blockage.Allergic rhinitis is the most common form of non-infectious rhinitis that is associated with an IgE-mediated immune response against environmental allergens [1]. There are a number of rhinitis phenotypes that may be classified as shown in Table 1.The International Study of Asthma and Allergies in Childhood (ISAAC) revealed an increased worldwide trend of rhinitis with an average prevalence of 8-15% in children [2,3], with a prevalence in the general population ranging from 10-40% in industrialised countries [4][5][6][7]. Studies of the natural history of rhinitis in children have shown a prevalence of 2.8% and 11.8% at 4 years and 18 years of age for non-allergic rhinitis and, respectively, 3.4% and 27.3% for allergic rhinitis. The adjusted prevalence rate in adults was found to be 9.6% for non-allergic rhinitis and 29.8% for alle...

IMPORTANCE Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. OBJECTIVE To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. DESIGN, SETTING, AND PARTICIPANTSA randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.INTERVENTIONS Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 μg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 μg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). MAIN OUTCOMES AND MEASURESTotal nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. RESULTS Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [P = .75]).CONCLUSIONS AND RELEVANCE Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.