Overcoming barriers to intranasal corticosteroid use in patients with uncontrolled allergic rhinitis

Introduction

Allergic rhinitis causes a variety of symptoms, including nasal congestion, sneezing, rhinorrhea, postnasal drip, nasal and ocular itching, and watery eyes.¹ Classification is based on the pattern (eg, seasonal, perennial, or episodic), frequency (intermittent or persistent), and severity (mild or moderate/severe) of symptoms.^1,2 Among individuals with self-reported nasal symptoms,³ the 12-month prevalence of allergic rhinitis was estimated at 30%, corresponding to ~90 million Americans. Notably, only 22% of individuals in this survey reported a physician diagnosis of allergic rhinitis, suggesting that the disorder is being largely self-managed without physician oversight.³

National surveys evaluating the burden of allergic rhinitis on affected individuals have found that approximately three-quarters of respondents consider nasal congestion to be bothersome or extremely bothersome.^4,5 Other highly bothersome symptoms included runny nose (by 69% of respondents), red, itchy eyes (68%), and postnasal drip (65%).^4,5

As with the overall population of allergy sufferers, the majority of allergy symptoms experienced by children and adolescents are attributable to allergic rhinitis.³ The symptom profile in children is comparable with that in adults, with both children and their parents reporting nasal congestion as the most common and the most bothersome symptom.⁶ In the Pediatric Allergies in America survey,⁶ parents of children with allergic rhinitis reported a 30% decrease in productivity at school and home when allergy symptoms were at their worst. Children with allergies were also significantly more likely to avoid school or social activities compared to children without allergies (P<0.001).

Nasal congestion and other allergy symptoms have a notable impact on the quality of life, work productivity, sleep quality, the ability to perform daily activities, and medical costs, particularly when uncontrolled.^7–12 For example, employed individuals reported that their work productivity was reduced by ~25% on days when their symptoms were at their worst.^4,5 Allergic rhinitis sufferers typically self-recognize their symptoms and then initiate management with over-the-counter (OTC) medications;¹³ 82% of those managing their allergic rhinitis symptoms with OTC medications report that they required minimal or no guidance from their physicians. Since most individuals are self-managing their symptoms outside of direct physician’s care, pharmacists are well positioned, when needed, to provide guidance and advice regarding the management and treatment of allergic rhinitis symptoms.

Pathophysiology of allergic rhinitis

Allergic rhinitis is caused by immunoglobulin E (IgE)-mediated responses to inhaled allergens, which trigger a series of immunological and biochemical events that produce the clinical symptoms characteristic of the disorder (Figure 1).¹⁴ The process of allergic sensitization involves uptake of the allergens by antigen-presenting cells in nasal tissues, subsequent presentation to other immune response cells, and production of allergen-specific IgE. The IgE binds to high-affinity FceRI receptors on the surface of nasal mast cells and circulating basophils, thereby sensitizing them to the offending allergen but not yet causing any symptoms.^14–16 Upon re-exposure, the offending allergen is recognized by IgE on sensitized mast cells and basophils, which induce early- and late-phase responses that lead to the clinical symptomatology of allergic rhinitis. Within minutes, the allergen–IgE interaction causes degranulation of the sensitized cells, leading to the release/production of mediators, including histamine, tryptase, leukotrienes, and prostaglandins. Histamine activates H₁ receptors on sensory nerve endings to cause sneezing and nasal secretion, as well as both H₁ and H₂ receptors on mucosal blood vessels to cause nasal congestion. The leukotrienes act on receptors located on blood vessels and mucus glands to induce nasal congestion and mucus secretion. The symptoms produced by this immediate hypersensitivity reaction typically last for ~1 hour and then dissipate.^14,15 Approximately 50% of patients with allergic rhinitis then experience a late-phase response that may persist for hours after allergen exposure.¹⁴ The late-phase response is characterized by the influx and activation of multiple inflammatory cells, including T cells, eosinophils, basophils, neutrophils, and monocytes, as well as by an increase in mast cell number in the nasal submucosa and epithelium, and is thought to be mediated by cytokines and chemokines released by the local activation of Th2 cells. Nasal congestion is the most prominent symptom during the late-phase response.^14–16

Figure 1 Pathophysiological steps leading to allergic rhinitis symptoms. Note: Based on Figure 2 of Pathophysiology of allergic and nonallergic rhinitis. Sin B, Togias A. 2011. Proc Am Thorac Soc. 2011;8(1):106–114.14 Abbreviations: EOS, eosinophil; GM-CSF, granulocyte-macrophage colony-stimulating factor; IgE, immunoglobulin E; IL, interleukin; Th2, helper T-cell type 2.

Allergic rhinitis can be classified as intermittent (≤4 days/week or ≤4 weeks/year) or persistent (>4 days/week and >4 weeks/year) and as mild (normal sleep, no impairment of daily activities, normal work and school, and no troublesome symptoms) or moderate to severe (abnormal sleep, impairment of daily activities, impairment of work and school activities, or troublesome symptoms).² Symptoms also may be classified according to their temporal pattern as seasonal, perennial/year-round, or episodic (eg, following exposure to a home with pets).¹ These classifications can help to identify the most appropriate treatment options on an individual basis.

Overview of current treatment guidelines

Multiple drug classes are available by prescription or OTC for the treatment of allergic rhinitis. To help guide the selection of appropriate medications, several professional organizations have issued practice guidelines, including the Allergic Rhinitis and its Impact on Asthma (ARIA) working group,^2,17 the American Academy of Allergy, Asthma & Immunology (AAAAI) and American College of Allergy, Asthma & Immunology (ACAAI) jointly,¹⁸ and the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF).¹

Each set of practice guidelines recognizes that intranasal corticosteroids (INCSs) are the most effective medication class for controlling allergic rhinitis symptoms (Table 1).^1,2,18 The high efficacy of INCSs is attributed to their ability to modulate the pathophysiology of allergic rhinitis, including the release of multiple mediators and cytokines as well as the recruitment and infiltration of activated inflammatory cells to the nasal mucosa.¹ Accordingly, INCSs are effective at attenuating both early- and late-phase symptoms, including nasal congestion and hyperresponsiveness. The onset of action usually occurs within 12 hours of administration but may commence as early as 3–4 hours after use,¹⁸ which is slower than the onset of antihistamines.^2,18 Continued daily use of INCSs may be needed in order to achieve maximum efficacy; although as-needed INCS dosing is less effective than continuous dosing, it may be an appropriate option for some patients with intermittent symptoms.¹ Local INCS side effects include nasal irritation/dryness, epistaxis, taste and smell disturbances, and, rarely, nasal septal perforation, which can be minimized with proper technique during administration.^1,18–24 Headache is a common systemic side effect with INCSs; cataracts and/or glaucoma may occur but are rare.^1,19–23 In general, the second-generation INCSs, including mometasone furoate, fluticasone propionate, ciclesonide, and fluticasone furoate, have very low (<1%) systemic bioavailability, which is postulated to limit the risk for clinically significant systemic side effects.²⁴ Evidence regarding potential effects on growth suppression with INCSs continues to evolve with the availability of data from more robust study designs, which has underscored the need for a thorough evaluation of safety and the balance of benefits and risks when used in children.²⁵ Additional long-term studies are needed to determine the effect of INCSs during childhood on final adult height.²⁵

Table 1 Relative efficacy of medication classes by allergic rhinitis symptom, symptom frequency, and symptom severity Notes: Seidman MD, Gurgel RK, Lin SY, et al; Guideline Otolaryngology Development Group. AAO-HNSF. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg. 2015;152(1 Suppl):S1–S43. Copyright © 2015. Adapted with Permission from SAGE Publications, Inc.1 For each medication class, the plus symbols indicate its relative effectiveness (+++, most effective) against the various symptoms and its relative role in treatment (++, highest recommendation) based on symptom frequency and severity.

Oral antihistamines are effective against histamine-mediated allergic rhinitis symptoms, including rhinorrhea, sneezing, nasal itching, and ocular symptoms.² Agents in this class are less effective against nasal congestion (Table 1). Oral antihistamines can be categorized into first-generation and second-generation agents. Use of the former (eg, diphenhydramine and chlorpheniramine) may be limited by sedation and mucosal dryness reflecting their ability to cross the blood–brain barrier and their anticholinergic effects, whereas second-generation agents (eg, fexofenadine, cetirizine, levocetirizine, loratadine, and desloratadine) exhibit selectivity for the H₁ receptor and minimal penetration across the blood–brain barrier.¹ Although not as effective as the INCSs, an oral antihistamine may be sufficient for patients with mild-to-moderate symptoms of allergic rhinitis or intermittent symptoms, offering the advantages of lower cost and a more rapid onset of action.¹ When indicated, each set of guidelines recommends a second-generation oral antihistamine in order to minimize the risk of sedation, performance impairment, and anticholinergic side effects.^1,17,18

Intranasal antihistamines are more effective than oral antihistamines for nasal congestion and at least as effective in controlling other allergic rhinitis symptoms^1,18 but, again, not as effective as INCSs^1,18 in providing relief of nasal symptoms.^18,26 Agents in this class may benefit patients who fail oral antihistamines or cannot otherwise tolerate them. Advantages include a rapid onset of action within 15–30 minutes and targeted delivery of higher antihistamine dosages to nasal tissues while minimizing systemic side effects. The most common side effects are bitter taste, epistaxis, headache, somnolence, and nasal burning.¹

Allergic rhinitis sufferers may experience ocular symptoms in addition to nasal congestion, as previously described. Ocular antihistamines and mast cell stabilizers are also available and may be used to alleviate concomitant symptoms of allergic conjunctivitis.²⁷

The orally administered leukotriene antagonist (LTRA), montelukast, is the only US Food and Drug Administration-approved LTRA for the treatment of allergic rhinitis in adults and children; other available LTRAs have not been adequately studied in allergic rhinitis.¹ Limitations compared with oral antihistamines include higher cost, prescription-only availability, and potential for side effects including headache and rare neuropsychiatric events.^1,11 Although LTRAs are not recommended as primary therapy for allergic rhinitis, they may be beneficial for patents with both allergic rhinitis and asthma.^1,18

Combination therapy may be suggested when monotherapy does not adequately control allergic rhinitis symptoms.¹ For patients already on an INCS, an intranasal antihistamine can be added, or, alternatively, treatment can be switched to a combination product containing both medications, such as azelastine/fluticasone propionate. Similarly, temporary addition of an intranasal decongestant (eg, oxymetazoline), with use limited to 3–5 days in order to avoid rebound nasal congestion, represents another therapeutic approach.^1,17 An oral antihistamine or LTRA should not be added to an INCS, as clinical trials have shown no benefit from these combinations. Options for patients already using an oral antihistamine include switching to an INCS or an intranasal antihistamine, or adding an oral decongestant. The latter approach, however, is associated with an increased risk of side effects. Similarly, an INCS should not be added to an oral antihistamine because large clinical trials have not demonstrated a benefit of an INCS with an oral antihistamine compared to an INCS alone.¹ For patients inadequately controlled by an intranasal antihistamine, the addition of an INCS (a combination product currently available only via prescription) is the only recommended option based on current evidence.

Allergen-specific immunotherapy should be considered for patients who respond inadequately to available pharmacologic options.^1,18 This approach aims to increase immune tolerance through repetitive, controlled exposure to the offending allergen(s) and may be considered for patients with persistent symptoms despite pharmacological therapy.¹

Barriers to the use of INCS

Although current practice guidelines recognize that INCSs are the most effective agents available for the treatment of allergic rhinitis, a large online survey found that only 30% of patients in the USA with severe nasal congestion were actually receiving INCS therapy.⁷ However, it is important to note that the survey was conducted in 2004, prior to the OTC availability of INCSs in the USA (the first of which became available in 2014) and before the most recent treatment guidelines emphasizing their use. At present, multiple INCS products (including several OTC options) that are comparable in efficacy are available (Table 2).^{19–23,28–33} Nevertheless, patient perceptions, beliefs, and preferences as well as formulation characteristics and cost may be barriers to the initiation of and adherence to INCS therapy. Fear of side effects has been reported more often for INCSs than for oral antihistamines (48 vs 33%) among patients with allergic rhinitis. The most common specific fears with INCSs were habituation (ie, loss of response due to frequent use), damage to mucous membranes, and side effects on other organs, whereas the most common fear with oral antihistamines was fatigue.³⁴ In another survey, few respondents thought that INCSs were unsafe but most did not use their INCSs because they feared a loss of effectiveness if used too much.³⁵

Table 2 Intranasal corticosteroids approved for allergic rhinitisa Notes: aIndications, dosage, and prescription status may vary by country. bApproved by US Food and Drug Administration for OTC use as of August 2016; OTC product is anticipated to be available commercially in 2017. Abbreviations: BC, benzalkonium chloride; BID, twice daily; HFA, hydrofluoroalkane; OTC, over-the-counter; QD, once daily; Rx, prescription; TID, three times daily.

Sensory attributes of an intranasal spray – including scent/odor, immediate taste, aftertaste, throat rundown, nose runout, burning, and feel of the spray in the nose and throat – may influence patient adherence. Among individuals with allergic rhinitis in US allergy/immunology clinics,³⁶ patient preference for an INCS decreased with increasing intensity of each of these sensory attributes, with the most important attributes identified as aftertaste, immediate taste, throat rundown, and nose runout. Notably, 77% of the respondents indicated that they would be able to adhere to a daily regimen for 3 months if the INCS had the lowest level of each sensory attribute, compared to only 4% of respondents if given an INCS with moderate levels of the sensory attributes (P<0.01).³⁶ Moreover, patients indicated a willingness to pay more to avoid sensory attributes of INCS sprays, particularly aftertaste, throat rundown, and nose runout.³⁷

Numerous studies of sensory perceptions and patient preferences for INCS products (Table 3)^38–46 have illustrated that patients can detect significant differences in sensory attributes and specify preference for one product over another. High preference was shown across studies for several products, including fluticasone furoate, mometasone furoate, and triamcinolone acetonide aqueous spray. Fluticasone furoate was preferred over mometasone furoate after treatment for 2 weeks,³⁸ and triamcinolone acetonide was preferred over mometasone furoate in several single-dose studies.^42,45,46 Notably, fluticasone furoate was preferred over fluticasone propionate in terms of having less odor/scent, causing less nose runout/throat rundown, and having less aftertaste.³⁹ Thus, even though a patient may not have liked the sensory attributes of fluticasone propionate in the past, this should not preclude the use of fluticasone furoate given the differences in sensory perception. Finally, practice guidelines recognize that patient preference should be considered when recommending an INCS product.^1,2

Table 3 Comparison of sensory attributes and patient preferences among INCS products Abbreviations: AR, allergic rhinitis; BDP, beclomethasone dipropionate; BUD, budesonide; CO, crossover; DB, double-blind; FF, fluticasone furoate; FP, fluticasone propionate; INCS, intranasal corticosteroids; MC, multicenter, MF, mometasone furoate; PC, placebo-controlled; PG, parallel group; R, randomized; SAR, seasonal allergic rhinitis; SB, single-blind; TAA, triamcinolone acetonide.

Role of the pharmacist in the self-management of allergic rhinitis symptoms

Many patients with allergic rhinitis attempt to self-manage their symptoms, and some will seek advice from pharmacists about choosing appropriate OTC products. Pharmacists should ask the patient to describe his/her symptoms in order to confirm that the patient is suffering from allergic rhinitis, including whether a medical diagnosis of hay fever, allergic rhinitis, or asthma has previously been identified. Establishing the history of symptoms (including the onset and temporal pattern, frequency, severity, and duration) and evaluating the exacerbating or mitigating factors and the therapies that have already been tried are critical factors in helping the patient select the proper treatment for their symptoms.⁴⁷ In addition, inquiring about other medical comorbidities or the use of other medications may help to identify which treatment approach is optimal for a particular patient.² The presence of two or more of the following symptoms lasting >1 hour on most days is suggestive of allergic rhinitis: watery anterior rhinorrhea, sneezing, nasal congestion, and nasal itching; conjunctivitis may also be present. The presence of symptoms in only one nostril, nasal congestion without other symptoms, mucopurulent rhinorrhea, postnasal drip with thick mucus and/or no anterior rhinorrhea, pain, recurrent epistaxis, and loss of the sense of smell are not usually associated with allergic rhinitis. Such patients should be referred to a physician for further evaluation and treatment.^1,2,18

The American Pharmacists Association algorithm for the self-care of allergic rhinitis (Figure 2)⁴⁸ outlines a suggested approach to treatment recommendations for individuals with symptoms consistent with intermittent or persistent allergic rhinitis who are appropriate candidates for self-treatment. Exclusions for self-treatment include the presence of symptoms of nonallergic rhinitis; otitis media, sinusitis, bronchitis, or other infection; undiagnosed or uncontrolled asthma (eg, wheezing and shortness of breath); chronic obstructive pulmonary disease; or other lower respiratory disorder, and those who have experienced severe or unacceptable side effects of treatment. For children younger than 12 years and pregnant or lactating women, self-treatment is acceptable only if a physician has diagnosed allergic rhinitis and approved the use of OTC treatment.

Figure 2 Treatment recommendations for the self-care of allergic rhinitis. Note: Posted with permission of the American Pharmacists Association from Krinsky DL, Ferreri SP, Hemstreet BA, et al. Handbook of Nonprescription Drugs. 18th ed. Washington, DC: American Pharmacists Association; 2015:174.48 Abbreviations: ADR, adverse drug reactions; AH, antihistamine; AR, allergic rhinitis; HCP, healthcare provider; INCS, intranasal corticosteroid; Rx, prescription.

When possible, pharmacists should advise the use of nonpharmacological measures for the avoidance of known allergens and environmental control.^1,18,47 Patients should be encouraged to avoid or minimize exposure to allergens that trigger allergic rhinitis symptoms. For severe seasonal symptoms caused by outdoor allergens, such as pollen, measures might include staying inside air-conditioned buildings with windows and doors closed, particularly on sunny, windy days with low humidity.¹⁸ For indoor allergens (dust mites and mold), multifaceted environmental controls (eg, reduction of moisture, use of protective bed covers, washing of bedding and soft toys, use of acaricides, and removal of carpets) may be beneficial where practicable. For pet dander, measures include the avoidance or removal of animal allergens from the household.¹⁸

Pharmacists are often the primary source to provide medication counseling to patients with allergic rhinitis.⁴⁹ To guide treatment recommendations, it is important to discuss patient preferences and goals of treatment, which may include providing symptom relief, preventing symptom recurrence, and improving or restoring the quality of life and ability to function.¹⁸ Based on this information along with the symptom profile, including frequency and severity, the pharmacist should provide counseling regarding available OTC treatment options.

Several OTC INCS products are available, differing in terms of formulation, number of sprays required per dose, age range approved for use, and, to some extent, dosing frequency (Table 2). The characteristics of nasal spray formulations may influence patient preferences. Additives and preservatives can irritate nasal mucosal membranes, thereby influencing comfort of use, and can confer an unpleasant odor or taste. Formulations containing phenylethyl alcohol may have a strong odor⁴³ and cause a feeling of dryness after administration.⁴⁶ Formulations containing benzalkonium chloride as a preservative may have a bitter taste.⁴³ Formulations delivering smaller volumes may have less nose runout and throat rundown.

The pharmacist should clarify any potential misperceptions about INCSs that could be a barrier to their appropriate use when indicated and, after recommending a product, provide counseling regarding its proper use, treatment expectations, and instructions on when to consult a physician. With INCSs, some benefit may be achieved within 3–4 hours,¹⁸ but these medications provide optimal symptom control when used continually for several days. Moreover, patients should be instructed to continue using the INCS to maintain symptom control and not simply resort to a use-as-needed approach. For seasonal sufferers, treatment should be maintained during the allergy season.

Counseling regarding proper medication self-administration, including priming the device and using proper spray technique, in turn, may improve adherence and facilitate better symptom control.^29,33,50 Although the directions differ somewhat for each product, in general, the recommended technique involves several steps to ensure proper administration (Figure 3).^48,51 Each OTC product includes specific step-by-step directions for dosing and administration; these should be reviewed with the patient.^29,33,50

Figure 3 General instructions for the use of intranasal corticosteroid sprays. Note: Posted with permission of the American Pharmacists Association from Krinsky DL, Ferreri SP, Hemstreet BA, et al. Handbook of Nonprescription Drugs. 18th ed. Washington, DC: American Pharmacists Association; 2015;187.48

A number of prescription-to-OTC switches have occurred in the INCS category over the past several years, providing the general public with greater access to these products. Additional prescription-to-OTC switches may occur in the future, which would expand access to options that allow easier or more preferable drug dosage delivery and self-administration. For example, fluticasone furoate, which was recently approved for OTC treatment of seasonal and perennial allergic rhinitis in the USA,⁵² is a scent- and alcohol-free formulation with minimal throat/nose drip provided in a nasal device that contains a side-actuated mist-release button with a cap that prevents the button from being pressed accidentally.³² The OTC product (FLONASE^® Sensimist™ Allergy Relief; GlaxoSmithKline Consumer Healthcare, Research Triangle Park, NC, USA) is expected to become available in the USA in 2017.⁵²

Conclusion

Given the prevalence of allergic rhinitis and symptom burden associated with the condition, many patients will opt for self-management and seek advice from pharmacists. Pharmacists, in turn, must keep abreast of the latest clinical evidence related to the prevention and treatment of symptoms, including product efficacy and nuances in product formulation.

In addition to suggesting strategies for avoiding exposure to allergens and irritants, pharmacists are often asked for recommendations regarding which OTC products to use. Current practice guidelines recognize that INCSs are the most effective medications for controlling allergic rhinitis symptoms including nasal congestion,^1,2,18 which is consistently identified in national surveys as the most bothersome symptom.^4,5 By asking a series of questions, pharmacists can establish if the patient has allergic rhinitis and identify the temporal pattern, frequency, and severity of symptoms.² This information is important for identifying when an INCS is the best choice; examples include patients with persistent and moderate-to-severe symptoms, patients suffering from predominantly nasal congestion, or patients whose symptoms disrupt their sleep or interfere with their work or school activities. To implement successful INCS use, pharmacists may have to address and help resolve several barriers, including concerns about safety or loss of response due to frequent use, and recognize that patient preferences and formulation characteristics are important considerations. All available INCS products have comparable efficacy and safety;¹ however, differences in sensory attributes, formulation characteristics, or spray bottle features may be important factors that influence patient adherence to therapy.

By educating and collaborating with patients to set appropriate treatment goals, pharmacists can play an important role in improving symptom control and quality of life in patients with allergic rhinitis.

Acknowledgments

Medical writing assistance was provided by Barry M Weichman, PhD, and Diane Sloan, PharmD, of Peloton Advantage and was funded by GlaxoSmithKline Consumer Healthcare. GlaxoSmithKline Consumer Healthcare provided a full review of the article.

Disclosure

The author reports no conflicts of interest in this work.

References

1.		Seidman MD, Gurgel RK, Lin SY, et al; Guideline Otolaryngology Development Group. AAO-HNSF. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg. 2015;152(1 suppl):S1–S43.
2.		Members of the Workshops. ARIA in the pharmacy: management of allergic rhinitis symptoms in the pharmacy. Allergic rhinitis and its impact on asthma. Allergy. 2004;59(4):373–387.
3.		Nathan RA, Meltzer EO, Derebery J, et al. The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey. Allergy Asthma Proc. 2008;29(6):600–608.
4.		Bielory L, Skoner DP, Blaiss MS, et al. Ocular and nasal allergy symptom burden in America: the allergies, immunotherapy, and rhinoconjunctivitis (AIRS) surveys. Allergy Asthma Proc. 2014;35(3):211–218.
5.		Allergies in America: a landmark survey of nasal allergy sufferers. Executive summary. HealthSTAR Communications, Inc, in partnership with Schulman, Ronca & Bucuvalas, Inc.: 1–45. Available from: http://www.worldallergy.org/UserFiles/file/Allergies%20in%20America%20(AIA)%20-%20Adult%20Executive%20Summary.pdf. Accessed March 30, 2017.
6.		Meltzer EO, Blaiss MS, Jennifer DM, et al. Burden of allergic rhinitis: results from the pediatric allergies in America survey. J Allergy Clin Immunol. 2009;124(suppl 3):S43–S70.
7.		Shedden A. Impact of nasal congestion on quality of life and work productivity in allergic rhinitis: findings from a large online survey. Treat Respir Med. 2005;4(6):439–446.
8.		Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4–S10.
9.		Canonica GW, Mullol J, Pradalier A, Didier A. Patient perceptions of allergic rhinitis and quality of life: findings from a survey conducted in Europe and the United States. World Allergy Organ J. 2008;1(9):138–144.
10.		Blaiss MS. Allergic rhinitis: direct and indirect costs. Allergy Asthma Proc. 2010;31(5):375–380.
11.		Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011;378(9809):2112–2122.
12.		Thompson A, Sardana N, Craig TJ. Sleep impairment and daytime sleepiness in patients with allergic rhinitis: the role of congestion and inflammation. Ann Allergy Asthma Immunol. 2013;111(6):446–451.
13.		Fromer LM, Blaiss MS, Jacob-Nara JA, Long RM, Mannion KM, Lauersen LA. Current allergic rhinitis experiences survey (CARES): consumers’ awareness, attitudes and practices. Allergy Asthma Proc. 2014;35(4):307–315.
14.		Sin B, Togias A. Pathophysiology of allergic and nonallergic rhinitis. Proc Am Thorac Soc. 2011;8(1):106–114.
15.		Bernstein DI, Schwartz G, Bernstein JA. Allergic rhinitis: mechanisms and treatment. Immunol Allergy Clin North Am. 2016;36(2):261–278.
16.		Wheatley LM, Togias A. Clinical practice. Allergic rhinitis. N Engl J Med. 2015;372(5):456–463.
17.		Brozek JL, Bousquet J, Baena-Cagnani CE, et al; Global Allergy and Asthma European Network; Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126(3):466–476.
18.		Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(2 suppl):S1–S84.
19.		Beconase AQ [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2015.
20.		Nasonex [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2013.
21.		Rhinocort Aqua [package insert]. Wilmington, DE: AstraZeneca; 2010.
22.		Flixonase [summary of product characteristics France]. Cedex, France: GlaxoSmithKline Laboratory; 2013.
23.		Nasacort [summary of product characteristics France]. Gentilly, France: Sanofi Aventis France; 2016.
24.		Sastre J, Mosges R. Local and systemic safety of intranasal corticosteroids. J Investig Allergol Clin Immunol. 2012;22(1):1–12.
25.		Skoner DP. The tall and the short: repainting the landscape about the growth effects of inhaled and intranasal corticosteroids. Allergy Asthma Proc. 2016;37(3):180–191.
26.		Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2002;89(5):479–484.
27.		Mounsey AL, Gray RE. Topical antihistamines and mast cell stabilizers for treating allergic conjunctivitis. Am Fam Physician. 2016;93(11):915–916.
28.		QNASL [package insert]. Horsham, PA: Teva Respiratory, LLC; 2014.
29.		FDA. Rhinocort Allergy (OTC Product) Approved Label; 2016. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020746Orig1s034lbl.pdf. Accessed May 25, 2016.
30.		Omnaris [package insert]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; 2013.
31.		Zetonna [package insert]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; 2014.
32.		Veramyst [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2015.
33.		FDA. Nasacort Allergy 24HR (OTC product) Approved Label; 2013. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020468Orig1s035lbl.pdf. Accessed May 25, 2016.
34.		Hellings PW, Dobbels F, Denhaerynck K, Piessens M, Ceuppens JL, De Geest S. Explorative study on patient’s perceived knowledge level, expectations, preferences and fear of side effects for treatment for allergic rhinitis. Clin Transl Allergy. 2012;2(1):9.
35.		Valovirta E, Ryan D. Patient adherence to allergic rhinitis treatment: results from patient surveys. Medscape J Med. 2008;10(10):247.
36.		Mahadevia PJ, Shah S, Leibman C, Kleinman L, O’Dowd L. Patient preferences for sensory attributes of intranasal corticosteroids and willingness to adhere to prescribed therapy for allergic rhinitis: a conjoint analysis. Ann Allergy Asthma Immunol. 2004;93(4):345–350.
37.		Mahadevia P, Shah S, Mannix S, et al. Willingness to pay for sensory attributes of intranasal corticosteroids among patients with allergic rhinitis. J Manag Care Pharm. 2006;12(2):143–151.
38.		Yonezaki M, Akiyama K, Karaki M, et al. Preference evaluation and perceived sensory comparison of fluticasone furoate and mometasone furoate intranasal sprays in allergic rhinitis. Auris Nasus Larynx. 2016;43(3):292–297.
39.		Meltzer EO, Andrews C, Journeay GE, et al. Comparison of patient preference for sensory attributes of fluticasone furoate or fluticasone propionate in adults with seasonal allergic rhinitis: a randomized, placebo-controlled, double-blind study. Ann Allergy Asthma Immunol. 2010;104(4):331–338.
40.		Khanna P, Shah A. Assessment of sensory perceptions and patient preference for intranasal corticosteroid sprays in allergic rhinitis. Am J Rhinol. 2005;19(3):316–321.
41.		Meltzer EO, Bardelas J, Goldsobel A, Kaiser H. A preference evaluation study comparing the sensory attributes of mometasone furoate and fluticasone propionate nasal sprays by patients with allergic rhinitis. Treat Respir Med. 2005;4(4):289–296.
42.		Stokes M, Amorosi SL, Thompson D, Dupclay L, Garcia J, Georges G. Evaluation of patients’ preferences for triamcinolone acetonide aqueous, fluticasone propionate, and mometasone furoate nasal sprays in patients with allergic rhinitis. Otolaryngol Head Neck Surg. 2004;131(3):225–231.
43.		Shah SR, Miller C, Pethick N, Uryniak T, Jones MK, O’Dowd L. Two multicenter, randomized, single-blind, single-dose, crossover studies of specific sensory attributes of budesonide aqueous nasal spray and fluticasone propionate nasal spray. Clin Ther. 2003;25(8):2198–2214.
44.		Lumry W, Hampel F, LaForce C, Kiechel F, el-Akkad T, Murray JJ. A comparison of once-daily triamcinolone acetonide aqueous and twice-daily beclomethasone dipropionate aqueous nasal sprays in the treatment of seasonal allergic rhinitis. Allergy Asthma Proc. 2003;24(3):203–210.
45.		Bunnag C, Suprihati D, Wang DY. Patient preference and sensory perception of three intranasal corticosteroids for allergic rhinitis. Clin Drug Investig. 2003;23(1):39–44.
46.		Bachert C, El-Akkad T. Patient preferences and sensory comparisons of three intranasal corticosteroids for the treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2002;89(3):292–297.
47.		Bousquet J, Khaltaev N, Cruz AA, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(suppl 86):8–160.
48.		Scolaro KL. Colds and allergy. In: Krinsky DL, Ferrari SP, Hemstreet B, et al., editors. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. 18th ed. Washington, DC: American Pharmacists Association; 2015:171–196.
49.		Kuehl BL, Abdulnour S, O’Dell M, Kyle TK. Understanding the role of the healthcare professional in patient self-management of allergic rhinitis. SAGE Open Med. 2015;3:2050312115595822.
50.		FDA. Flonase Allergy Relief (OTC Product) Approved Label; 2014. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205434Orig1s000Lbl.pdf. Accessed May 25, 2016.
51.		Benninger MS, Hadley JA, Osguthorpe JD, et al. Techniques of intranasal steroid use. Otolaryngol Head Neck Surg. 2004;130(1):5–24.
52.		GSK. FDA Approves Flonase® Sensimist™ Allergy Relief [press release]; 2016. Available at: https://us.gsk.com/en-us/media/press-releases/2016/fda-approves-flonase-sensimist-allergy-relief/. Accessed: September 8, 2016.