Romanian Journal of Rhinology, Vol. 3, No. 9, January - March 2013 LITERATURE REVIEW The concept of control in allergic rhinitis: a new perspective Florin-Dan Popescu Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania ABSTRACT The concept of disease control has recently been discussed for allergic rhinitis. The disease severity and control are distinct, yet related concepts. Allergic rhinitis control may be defined in several ways. A simple visual analog scale and the Rhino-Con- junctivitis Allergy-Control-Score are currently discussed. The treatment algorithm for allergic rhinitis in relation to control may be adapted from the state-of-the-art ARIA guidelines. Allergic rhinitis management driven by the level of control demands a close partnership relation between the physician and the patient. Several unmet needs must also be taken into account regard- ing the control of allergic rhinitis. The concept of control in this allergic inflammatory disease offers a new perspective for its assessment and therapeutic approach. KEYWORDS: allergic rhinitis, severity, control INTRODUCTION • complex environmental modification strategies to reduce allergen exposure, The purpose of Allergic Rhinitis and its Impact on • allergen-specific immunotherapy and/or anti- Asthma (ARIA), the world health initiative on allergic rhi- inflammatory pharmacologic therapies for pa- nitis, is to educate and implement evidence-based man- tients with respiratory allergies, agement of allergic rhinitis in conjunction with asthma. • evaluating the control of the respiratory allergies. ARIA is a non-governmental organization working in col- Misinterpretation of the results for diagnostic tests or laboration with the World Health Organization. in assessing the control level by non-specialists can lead According to ARIA documents, allergic rhinitis is to inappropriate diagnosis and/or management. Con- defined as an immune-mediated inflammatory disease versely, the under-appreciation of the severity of respira- of the nasal mucosa, induced after allergen exposure tory allergy can lead to life-endangering under-treatment by an IgE-mediated hypersensitivity reaction in the or the lack of potentially specific immunotherapy2. nose, clinically characterized by suggestive symptoms Allergic rhinitis classification consisted previously into of sneezing, nasal itching, rhinorrhea and nasal ob- seasonal, perennial and occupational forms, but this subdivi- struction. Rhinitis symptoms occur during two or sion is nowadays considered not satisfactory because1,3: more consecutive days for more than one hour on • in certain regions, pollens and molds are peren- most days1. nial allergens, Allergic rhinitis requires the demonstration of IgE- • weather/climatic changes modify the timing, dis- mediated hypersensitivity. The role of the allergy spe- tribution, quantity and quality of pollens as aero- cialist, in the multidisciplinary approach together with allergens, ENT specialists, resides especially in2: • traveling creates different exposure conditions to • performing and interpreting allergic history, aeroallergens in different times of the year, • in vivo and in vitro allergy testing (avoiding uneval- • symptoms to perennial aeroallergens may not al- uated risks for the patient or wrong evaluations), ways be present all year round, • assessment of allergen cross-reactivities and aller- • lifestyle, building and inhabited conditions influ- gic inflammation, ence indoor aeroallergen exposure, Corresponding author: Florin-Dan Popescu, MD, PhD, Associate Professor, Head of Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Address: “Nicolae Malaxa” Clinical Hospital, 12 Sos. Vergului, Bucharest, Sector 2, Romania email: [email protected] 34 Romanian Journal of Rhinology, Vol. 3, No. 9, January - March 2013 • many patients are sensitized to several different PHARMACOTHERAPEUTIC APPROACH allergens, • nonspecific irritants, such as air pollution, may Pharmacotherapeutic approach of inflammation in al- aggravate symptoms. lergic rhinitis includes nowadays several classes of intrana- State-of-the-art ARIA guidelines recently classified sal and oral drugs, generally considered effective and safe. allergic rhinitis1: Intranasal glucocorticosteroids are recommended for 4 according to evolution of symptoms: the treatment of allergic rhinitis because they have po- < intermittent allergic rhinitis tent anti-inflammatory effects by activating the glucocor- • less than 4 days per week or ticoid receptor, to directly or indirectly regulate the tran- • for less than 4 consecutive weeks; scription of the target genes. Glucocorticosteroids availa- < persistent allergic rhinitis ble for intranasal administration in allergic rhinitis are • more than 4 days per week and (in alphabetical order): beclomethasone dipropionate, • lasting more than 4 consecutive weeks; budesonide, ciclesonide, flunisolide, fluticasone propio- 4 according to the severity of symptoms: nate, fluticasone furoate, mometasone furoate, triamci- < mild allergic rhinitis nolone acetonide1. Although new-generation, oral non- • normal sleep, sedating H1-antihistamines and antileukotrienes possess • no impairment of school or work activities, anti-inflammatory effects, intranasal glucocorticosteroids • no impairment of daily activities, leisure, sport, are the most effective anti-inflammatory medication for con- • symptoms present, but not troublesome; trolling symptoms of allergic rhinitis1,9. < moderate-severe allergic rhinitis New generation intranasal halogenated glucocorti- • sleep disturbance, costeroids, fluticasone furoate and mometasone furoate, • impairment of school or work activities, have high affinity for the glucocorticoid receptor com- • impairment of daily activities, leisure, sport, pared with other corticosteroid molecules10. Such new • troublesome symptoms. second-generation agents, currently in use, have favor- A modified ARIA criterion (m-ARIA) for the allergic able pharmacokinetic characteristics that minimize sys- rhinitis severity classification is a validated useful clini- temic bioavailability compared with older representa- cal tool to discriminate moderate from severe forms, in tives11. Yearlong therapy with either fluticasone furoate both treated and untreated patients. The m-ARIA clas- or mometasone furoate nasal sprays reveals no mucosal sification categorizes allergic rhinitis severity into: atrophy as well as reduction in inflammation12. • mild allergic rhinitis (no affected items), Fluticasone furoate represents a molecular evolution • moderate allergic rhinitis (1-3 affected items), of fluticasone propionate and there is scientific evi- • severe allergic rhinitis (all four affected items)4. dence of therapeutic advantages over fluticasone pro- The classical clinical phenotypes of seasonal and peren- pionate. A literature review, achieved through PubMed nial rhinitis cannot be used interchangeably with those and Medline research methods, supports the clinical from ARIA classification, “intermittent” and “persistent” efficacy of fluticasone furoate versus placebo in reduc- being not synonymous with “seasonal” and “perennial”. ing nasal and ocular symptoms related to allergic rhi- Severe chronic upper airway disease is defined by pa- nitis, with a good safety profile13. tients whose symptoms are inadequately controlled de- Because intranasal glucocorticosteroids are consid- spite pharmacologic treatment based on guidelines5,6. ered first-line treatment for moderate-to-severe allergic Endotypes are subtypes of allergic rhinitis, considered rhinitis, to guide clinical decision-making, it was evaluated an inflammatory disorder, which are defined by distinct a therapeutic index (TIX) for such drugs reflecting effi- pathobiological mechanisms. Using the level of concor- cacy and safety, using a Medline search (1966 to June dance between allergic symptoms induced on exposure 2009), identifying all placebo-controlled randomized trials to pollen in a pollen challenge chamber, some allergic and reports for safety issues. Three parameters each for rhinitis endotypes reflect concordantly low versus high efficacy: patient rated total nasal symptom score (TNSS), total symptom scores in both the natural season and the patient rated total ocular symptom score (TOSS), patient pollen challenge chamber, respectively, while another or physicians global assessment (PGA), and safety: epista- endotype presents greater total symptom scores in the xis, long term side effects on growth or cortisol levels (ob- natural season than in the pollen challenge chamber7. servation period at least 6 month), systemic ocular side Moreover, by assessing nasal inflammation, using cellular effects such as glaucoma or an increased ocular pressure (GATA-3 T lymphocyte, eosinophil, mast cell numbers) were defined. The highest value of therapeutic index and allergic inflammation soluble markers (IL-5, eosino- score obtained for mometasone furoate indicates its high ef- phil cationic protein), persistent allergic rhinitis is char- ficacy and low potential of adverse events14. acterized by a significantly greater eosinophilic and pre- Systemic glucocorticosteroids should not be consid- dominantly Th2 cell-mediated nasal inflammatory profile ered usually for the treatment of allergic rhinitis, due compared with intermittent allergic rhinitis8. to their adverse effects. They can be used only for few Popescu The concept of control in allergic