St. Joseph’s Regional Medical Center
Pharmacy Times Office of Continuing Professional Education is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 2.0 contact hours (0.2 CEUs) under the ACPE universal activity number 0290-0000-13-156-H01-P. The activity is available for CE credit through October 11, 2015.
The following contributors have no relevant financial relationships with commercial interests to disclose.
Judy V. Lum, MPA, and Steve Lin, PharmD
An anonymous peer reviewer was part of the content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose.
Allergic rhinitis (AR) is commonly regarded as a frustrating reminder of the change in seasons, but AR is actually a prevalent disease state with serious consequences. Although the condition affects many people nationwide, determination of its actual incidence is variable, primarily due to reliance on physician diagnosis and the lack of reporting of AR in widespread national surveys.1
Estimates, however, do suggest that up to 40 million Americans are affected by this condition.2,3
Symptoms of AR may be categorized as seasonal allergic rhinitis (SAR), which is primarily related to outdoor allergens such as pollen and mold, and perennial allergic rhinitis (PAR), which is most frequently caused by indoor allergens such as dust mites and animal dander.4
When AR is further stratified into these 2 subtypes, approximately 40% of individuals with AR have PAR, 20% have SAR, and the remaining 40% report having PAR with seasonal worsening.3
The frequency of AR increases through the early years of life, reaches a peak in youth and adolescence, and begins to decline in older patients.5
Up to 24% of adults and 42% of children are affected by AR, making the disease one of the most common chronic conditions in children younger than 18 years.1,6
With such a high prevalence, and a frequency that is increasing in both the adult and pediatric populations, AR can lead to significant negative outcomes for patients.1
In a large study of 2500 adults with AR, 66% of patients indicated that AR had effects on their daily lives.2
Among allergy sufferers, one-third reported missing work due to nasal allergies, and 35% indicated that their nasal symptoms caused moderate hindrance to their employment.3
Additionally, symptoms of AR have been shown to cause sleep disturbances, potentially leading to negative effects on mental health, including depression, anxiety, and alcohol abuse. Further, a cross-sectional survey of 15,000 households found that, compared with normal controls, patients with AR experience decreased quality of sleep and a 10-times greater frequency of microarousals due to increased nasal discharge, decreased air entry through the upper airway, and disordered breathing.2
In adults, sleep disturbances can result in daytime drowsiness, and in children, these effects on sleep have been related to impairments in learning abilities, attention, and behavior.3
Aside from its negative effects on patient quality of life, AR is also associated with a significant increase in health care expenditures. In a national survey of health care utilization, cosponsored by the Agency for Health Care Research and Quality and National Center for Health Statistics, medical spending for AR in the United States, which included inpatient hospital care, ambulatory care, and medication purchases, was estimated to be $11.2 billion in 2005, nearly double the value in 2000.7
However, this figure does not include indirect costs, such as decreased productivity and missing work, which can lead to additional, significant financial impact.2,7
In children, an estimated 10,000 students miss school due to the symptoms of AR on any given day.2
The impact of other medical conditions associated with AR is another consequence of the disease that is often unaccounted for in the calculations of its costs. Evidence from epidemiologic studies has consistently demonstrated that many patients with rhinitis, particularly moderate to severe disease, are likely to suffer from asthma as well. Evidence also suggests that there is a link between AR, sinusitis, and conjunctivitis.8
Other conditions that may be present in those affected with AR include otitis media and chronic cough; however, that relationship is less well defined.4
The appropriate management of symptoms related to AR would prevent the development of such comorbidities, as well as the associated burden that is placed on patients with this chronic condition.
A higher incidence of AR may be seen in patients with higher socioeconomic status, nonwhite patients, patients who reside in areas of higher pollution, and patients born during the pollen season. Several studies suggest that the risk of rhinitis is increased in children who were introduced to food or formula earlier in life, had mothers who smoked during the first years of the child’s life, experienced early exposure to animals, and have higher serum IgE levels (more than 100 IU/mL before 6 years of age). Some evidence points to the development of the "hygiene hypothesis," which theorizes that children who have been exposed to bacterial pathogens early in life are less likely to develop allergies.4
These risk factors may help elucidate the predisposing components of AR and provide options for prevention of the disease in the future.5
Pathophysiology and Symptoms
The cascade of events that characterize AR can be divided into 3 components: (1) allergic sensitization, (2) early-phase response, and (3) late-phase response. Typically, due to actions by the glands, blood vessels, nerves, epithelium, and immune-mediated responses, the human nose is able to humidify and clean inhaled air.9
In genetically predisposed patients, a well-coordinated immune response causes the signs and symptoms of AR.1
The first stage, or sensitization, occurs in patients when allergens enter the nose and are presented to CD4+ T lymphocytes, which prompts the release of interleukins and cytokines. The release of cytokines, as well as the direct interaction of T cells with B cells, leads to the differentiation of B cells into plasma cells, which secrete allergen-specific immunoglobulin E (IgE). The allergen-specific IgE then binds to mast cells and basophils, which thereby sensitizes patients to the presenting allergen.10
On re-exposure to these allergens, the IgE, which is bound to mast cells and basophils, recognizes the allergen and causes the degranulation and activation of these cells. Numerous inflammatory mediators are then released, including histamines, cytokines, proteases, prostaglandin D2, and leukotrienes (LTC4
, and LTE4
These inflammatory mediators also lead to the recruitment of other cytokines and the involvement of the mucosal glands, sensory nerves, and vasculature.10
The symptoms of the early phase are a result of these interactions and include sneezing, substantial rhinorrhea, pruritus, and some nasal congestion.9
In the late-phase response, which occurs 4 to 8 hours after the early response, additional inflammatory mediators are signaled for involvement, including basophils, neutrophils, macrophages, eosinophils, and T lymphocytes. The release of these products contributes to an increase in nasal congestion, which predominates at this stage, and continued symptoms of sneezing and nasal drainage. 10
Mediators also act on the nasal vasculature, enhancing edema. The release of several cytokines and circulation to the central nervous system produces the symptoms of weakness, lethargy, and irritability.1
Inflammatory mediators that are released during this late phase are the culprits responsible for epithelial damage, which is characteristic of patients with chronic disease.9
As described in the stages described above, the clinical signs and symptoms of AR are paramount to its appropriate identification and diagnosis and may be classified as mild or moderate/severe and as intermittent or persistent in frequency (Table 1).11
The symptomatology of AR is defined as 2 or more of the following for more than 1 hour on most days: watery rhinorrhea, sneezing, nasal obstruction, and/or nasal pruritus, with or without ocular symptoms, such as irritation and watering of the eyes. Collecting a patient history of potential triggers for AR should be considered, with common outdoor allergens including pollen and mold, and major indoor allergens including insects, mites, animal dander, and fungi.4
On physical examination of the patient, providers may observe wheezing, otitis, and sinus pain. For patients with more severe disease who do not respond to the avoidance of allergens and initial medication therapy, allergy skin testing may be considered to identify specific allergen triggers.12
Management Strategies for Allergic Rhinitis
A successful treatment plan for alleviating and managing the symptoms of AR combines pharmacologic treatment with nonpharmacologic measures that prevent or minimize contact with allergens and/or irritants that may exacerbate symptoms. Nonpharmacologic management of AR may provide symptomatic relief and reduce the need for medications in patients, particularly those who are affected seasonally.11
Guidelines developed in collaboration with the World Health Organization recommend the identification and avoidance of allergens when practical. However, the evidence does not suggest that any 1 intervention alone will lead to substantial symptom reduction.4
Recommendations have included the minimization of exposure to pollen or mold, which are major allergens for patients with seasonal rhinitis, by keeping windows and doors closed during pollen season. Additionally, if air conditioning is used, closing the outdoor vents and utilizing a small-particle filter may be beneficial. Outdoor activities should also be minimized on sunny days with low humidity and high winds, as pollen counts tend to increase on those types of days. For patients with indoor allergies, such as sensitivity to dust mites, methods to reduce exposure include reducing the use of carpets, maintaining a level of humidity between 35% to 50%, washing the bedding in hot water, avoiding stuffed toys and upholstered furniture, and placing mattresses, box springs, and pillows in allergy-proof coverings. For patients with allergies to pets, minimization of exposure is the primary recommendation.9
In many of these instances, avoidance is not practical for patients, but a reduction to exposure of exacerbating allergens may limit symptoms and the need for pharmacotherapy.
Since allergen avoidance alone rarely results in a complete mitigation of symptoms, many patients with AR require drug therapy for management and prevention. A myriad of pharmacologic treatment options for symptomatic relief exist (eg, anti-inflammatory agents) and may be considered either for acute symptom relief or for long-term treatment of the underlying causes of disease. A complete patient evaluation and history of the frequency and severity of allergic symptoms may help guide the appropriate selection and use of drug therapy. Pharmacologic agents indicated for the management of symptoms associated with AR include intranasal and systemic corticosteroids, antihistamines, decongestants, cromolyn, anticholinergics, and leukotriene receptor antagonists (Table 2).8,11,13,14
The goals of therapy for AR should be to minimize the impact of symptoms on an individual’s quality of life or to completely alleviate symptoms, when possible.
Oral antihistamines represent the most commonly prescribed agents indicated for the treatment of mild, intermittent symptoms of AR.9
Additionally, many of the agents in this drug class are readily available without a prescription, making them desirable for patients who require acute symptomatic relief. Histamine is a known inflammatory mediator that produces increased mucous secretion, vascular permeability, and smooth muscle contraction, and may also contribute to the symptoms of AR.15
) receptor antagonists exert their effects by blocking the inflammatory action of histamine at these receptor sites in the respiratory tract, thereby mitigating the symptoms of sneezing, nasal discharge or rhinorrhea, congestion, pruritus, and ocular irritation.11
Although first-generation oral antihistamines have long been used for the acute relief of ocular and nasal symptoms, with an onset of relief estimated to occur 15 to 30 minutes after administration, their sedating effects and potential for interactions with cytochrome P450 isoenzymes relegate them as second-line therapy. Second-generation, nonsedating oral H1
receptor antagonists (eg, cetirizine, fexofenadine, levocetirizine, loratadine, desloratadine) are preferred as initial therapy for mild, intermittent symptom relief due to their rapid onset of effect and lack of anticholinergic and sedative properties. 12
All second-generation oral antihistamines are considered to have similar effects on alleviating symptoms of AR and can be used as needed for short-term symptomatic relief. The disadvantages of oral antihistamines include (1) for optimal effect, these agents may need to be used on a scheduled, rather than as needed; (2) they may only have a moderate effect on alleviating symptoms of nasal congestion; and (3) sedation may occur with oral antihistamines at therapeutic doses (eg, cetirizine).8
For individuals with moderate to severe symptoms, oral antihistamines may be of value as add-on therapy when alternative agents are also used based on their complementary mechanisms of action.
Intranasal antihistamine therapy with either azelastine or olopatadine provides the localized delivery of a higher concentration of medication with fewer systemic side effects.16
These agents are considered safe and effective for the treatment of nasal symptoms of pruritus, sneezing, and discharge, and also have a rapid onset of effect, generally within 15 minutes. Disadvantages of the intranasal antihistamines include (1) higher costs relative to oral antihistamine therapy; (2) prescription-only availability; (3) lower efficacy compared with intranasal corticosteroids (INSs); (4) use that is limited to the relief of nasal symptoms; and (5) the risk of sedation, particularly with azelastine.8,12,17,18
Intranasal antihistamine therapy may be considered as an alternative to oral antihistamine therapy for individuals with mild seasonal symptoms of AR or for patients with persistent symptoms despite oral antihistamine use.12,13
For the treatment of both intermittent (eg, seasonal) and persistent (eg, perennial) symptoms, a trial of oral antihistamine therapy is preferred to intranasal antihistamine use due to patient preference and the bitter taste associated with intranasal antihistamines.12
Ocular antihistamines, which are available over the counter (eg, ketotifen, Zatidor, Zyrtec Itchy Eye; naphazoline and pheniramine, Naphcon-A) or by prescription (eg, azelastine, Optivar; olopatadine, Pataday, Patanol), can be useful for individuals with localized ocular symptoms. These agents may be instilled 1 to 4 times daily according to manufacturer labeling and are generally well tolerated, with common side effects that include transient ocular irritation and headache.14
INSs are currently the most potent treatment option for individuals with moderate to severe SAR and PAR, producing the greatest effects on symptomatic relief for nasal congestion, ocular irritation, rhinorrhea, and sneezing.9,19
Agents in this class work by inhibiting the local inflammatory response in the upper airways, specifically, which results in local vasoconstriction, reduced mucosal edema, suppression of inflammatory mediator production (eg, cytokineformation), and inhibition of infiltration by inflammatory cells.9
Clinical efficacy does not seem to vary among available agents, and current guidelines recommend the use of these agents for both children and adults with AR based on their favorable safety profiles.9,12
Localized nasal irritation and epistaxis have been reported with the use of INSs, with nasal septal perforation a rare but serious side effect.9
When counseling a patient on the use of INSs, underscoring the importance of good technique is essential to minimizing the risk of adverse effects related to medication use. Growth suppression and systemic side effects in children have not been reported with the use of these agents at recommended doses.9
A downside to the use of INSs is the slower onset of relief compared with oral or intranasal antihistamines; the onset of therapeutic effects may require 3 to 12 hours, depending on the agent that is used, with maximal benefit typically not seen for several days following continuous use.8,9
Clinical studies have shown that as-needed use of INSs, while effective for the treatment of SAR, may not be as effective as continuous inhaler use.9
Based on the expected pharmacokinetics of agents in this drug class, it may be prudent to recommend initiating treatment prior to the start of the expected allergy season for individuals with SAR. Although agents in this class are currently available by prescription only, a recent FDA Advisory Committee meeting has approved the prescription-to- OTC switch of triamcinolone acetonide (Nasacort AQ) nasal spray (see "New and Emerging Treatment Options" below).20
Systemic oral corticosteroid therapy, on the other hand, is associated with significant adverse event and safety concerns and should be reserved only for individuals with severe symptoms refractory to other drug therapies.8,9
Short-term oral treatment may be indicated for individuals with symptoms of intractable rhinitis or nasal polyposis.9
Intranasal cromolyn sodium has been a long-available OTC agent for the treatment of intranasal symptoms associated with AR, but has since been supplanted by the use of the intranasal and oral antihistamines, as well as INSs for symptomatic relief. Intranasal cromolyn works by inhibiting mast cell degranulation and has been shown to be effective for the episodic relief of AR symptoms.9
Although cromolyn has a favorable safety profile, including side effects such as intranasal irritation, stinging, burning, and sneezing, its disadvantages include the requirement for 3 to 6 applications per day and a delayed effect (requiring up to 2 to 4 weeks to achieve maximum results), which may limit patient adherence and tolerability.12,14
The prescription-only intranasal anticholinergic, ipratropium bromide, may be considered for short-term relief for individuals with persistent symptoms of AR, particularly rhinorrhea.12
As an anticholinergic, ipratropium works by drying nasal secretions, but the agent does not relieve sneezing, congestion, pruritus, or the ocular symptoms of AR. Disadvantages to its use include the need for multiple daily administrations (2 to 4 times per day) and the potential for causing dry nose and epistaxis and exacerbating other medical conditions (eg, glaucoma, urinary retention). 8,14
Decongestants, whether administered intranasally or orally, treat symptoms of nasal congestion by functioning as agonists at adrenergic receptor sites in the nasal mucosa to cause local vasoconstriction. 16,21
Although decongestants are available over the counter and are associated with a rapid (within 10 minutes for intranasal products) onset of relief, decongestants have several limitations. Oral decongestant agents can cause systemic adverse effects, including hypertension, insomnia, nervousness, agitation, and tachycardia.8,14
Topically administered decongestants, when used continuously for more than 3 days, can cause rhinitis medicamentosa or rebound vasodilation and have been associated with localized nasal irritation and discharge.9,14
The use of decongestant therapy could be considered for individuals with severe nasal congestion as a method of providing short-term, symptomatic relief.12
Finally, the leukotriene receptor antagonist montelukast (Singulair), which is available by prescription only, may be considered for children and adults with symptoms of PAR and SAR.12
Although there are 2 other agents within this drug class (eg, zafirlukast, Accolate; zileuton, Zyflo; Zyflo CR), montelukast is unique in that it is the only agent approved for use in the treatment of AR. Montelukast exerts its effect by inhibiting the cysteinyl leukotriene receptor, thereby inhibiting the production and release of these potent inflammatory mediators from the nasal mucosa following exposure to an allergen. 14
The leukotriene receptor antagonist is well tolerated and approved for use in children as young as 6 months, and it may alleviate both nasal and ocular AR symptoms.8,14
Montelukast may cause headache and has rarely been associated with serious central nervous system adverse effects, including abnormal dreams, aggressive behavior, agitation, and suicidal ideation.8,14
Further, the cost of montelukast may be significantly more than that of other treatments.
In patients for whom pharmacotherapy results in significant side effects or inadequate symptom control, allergen immunotherapy offers effective treatment for AR. Evidence from numerous randomized double-blind clinical trials have demonstrated reductions in symptoms and medication use, as well as an improvement in quality-of-life scores through subcutaneous and sublingual (not approved in the United States) therapy, 2 of the most common routes of administration for allergy immunotherapy.22
In allergen immunotherapy, IgE-specific antibody tests are administered to an individual to determine relevant allergens. Subcutaneous administration is the only approved route for allergen immunotherapy in the United States; however, sublingual administration has gained widespread use in Europe and in several other countries. After the identification of patient-specific allergens, extracts are administered to the patient in increasing doses: 1 to 3 times per week. On determination of the maintenance dose, which may require 8 to 28 weeks, the patient is administered a maintenance dose every 2 to 4 weeks for approximately 3 to 5 years.22,23
Adverse effects of subcutaneous administration include injection site reactions, such as swelling and induration, and rarely, systemic reactions, including anaphylaxis. Local reactions may be managed with the application of ice packs, topical antihistamines, or topical corticosteroids. Anaphylaxis should be managed with epinephrine, whereas more minor systemic reactions may be treated with antihistamines and systemic corticosteroids.23
New and Emerging Treatment Options
Despite the various modalities currently available for the treatment of AR, novel therapies with improved efficacy and safety profiles are still moving through the development pipeline. Specifically, agents that target the inhibition of histamine at the H3
receptor sites are in development, which, compared with H1
receptor antagonists, may be associated with an improved effect on nasal symptoms related to AR.24,25
Intranasal beclomethasone (Qnasl) and ciclesonide (Zetonna) represent 2 new INS agents that are approved for the treatment of SAR and PAR in patients 12 years and older.14
These new agents differ from existing INSs in that they are formulated as dry nasal aerosols that utilize hydrofluroalkane propellants. Unfortunately, to date, no comparative studies have been conducted to evaluate the efficacy of this type of intranasal drug delivery over conventional aqueous intranasal spray delivery.26-28
An intranasal combination product containing azelastine and fluticasone (Dymista) has also recently received approval for the treatment of SAR in patients 12 years and older.14
Further, an FDA advisory panel has recently recommended that prescription-only triamcinolone acetonide nasal spray (Nasacort AQ) become available over the counter for the temporary relief of nasal symptoms associated with AR in adults and children 2 years and older.20
This product is likely to become available on pharmacy shelves as early as 2014, mandating that pharmacists be familiar with the role of the INS agents in the treatment of AR symptoms.
The Role of the Pharmacist
Often, the management of AR begins in the aisles of local pharmacies. Due to the overwhelming incidence of AR symptoms that are estimated to affect the global population, as well as the undeniable impact of AR on an individual's quality of life, pharmacists must understand the nonpharmacologic lifestyle interventions for allergen avoidance in addition to the role of pharmacotherapy and immunotherapy for appropriately managing this condition. Pharmacists are able to coach patients on the importance of adherence to therapy, contribute to symptomatic relief, and ultimately improve patient quality of life. To achieve these ends, an initial management strategy may be developed in the pharmacy in conjunction with patient preferences.29
Medication adherence must take into account patient factors such as expectations of treatment, treatment factors, and high medication costs.29
More than 50% of the total cost of treatment for AR is related to the cost of prescription medications. A survey from 2 sources has also estimated that up to $1.5 billion was spent on OTC medications in the United States during 2008 alone.7
By balancing the benefits of treatment with the side effects and complexity associated with medication use, pharmacists may help guide patients toward optimal treatment adherence. Patient counseling on the proper use of prescription medications, such as INSs, antihistamines, and OTC medications, should always be included in the treatment plan.29
Patients may present to the pharmacy with complaints that are consistent with AR under a variety of circumstances, such as experiencing an initial episode or symptoms of another disease state (eg, viral infection, deviated septum, sinusitis); based on the duration and severity of a patient’s presenting symptoms, a referral to a physician may be necessary. Complaints for which patients should seek further management include unilateral symptoms, rhinorrhea with mucus, pain, loss of smell, and/or epistaxis. If the symptoms are suggestive of new onset or uncontrolled asthma, or the symptoms do not improve after initial management by OTC methods (2 to 4 weeks), patients should also be referred. Patients who are pregnant, breast-feeding, or younger than 12 years should be treated under the direction of a physician for the use and monitoring of selected pharmacotherapy.29
Through collaboration with patients and physicians, pharmacists are able to ensure an informed understanding of medication use and management strategies for adverse effects, which will ultimately help patients to remain adherent to their prescribed therapies and to achieve optimal control of their AR.
Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001;108:S2-S8.
Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007;28:3-9.
Blaiss MS, Meltzer EO, Derebery J, Boyle JM. Patient and healthcare-provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28:S4-S10.
Bousquet J, Khaltaev N, Cruz AA, et al. ARIA (allergic rhinitis and its impact on asthma) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy. 2008;63(suppl 86):8-160.
Jones N. Allergic rhinitis: aetiology, predisposing and risk factors. Rhinology. 2004;42:49-56.
Borish L. Allergic rhinitis: systemic inflammation and implications for management. J Allergy Clin Immunol. 2003;112:1021-1031.
Blaiss MS. Allergic rhinitis: direct and indirect costs. Allergy Asthma Proc. 2010;31:375-380.
Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011;378:212-222.
Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122:S1- S84.
Rosenwasser LJ. Current understanding of the pathophysiology of allergic rhinitis. Immunol Allergy Clin N Am. 2011;31:433-439.
Brozek JL, Bousquet J, Baena-Cagnani CE, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126:466-476.
Bahls C. In the clinic: allergic rhinitis. Laine C, Goldman DR, Wilson JF, eds. Allergic rhinitis. Ann Intern Med.2007;146:ITC4-ITC16.
Sur DK, Scandale S. Treatment of allergic rhinitis. Am Fam Physician. 2010;81:1440-1446.
DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. www .micromedexsolutions.com. Accessed August 23, 2013.
Howarth PH, Salagean M, Dokic D. Allergic rhinitis: not purely a histamine-related disease. Allergy. 2000;55:7-16.
Bousquet J, Van Cauwenberge P, Khaltaev N; ARIA Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108(5 suppl):S147-S334.
Corren J, Storms W, Bernstein J, et al; Azelastine Cetirizine Trial No. 1 (ACT 1) Study Group. Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with SAR. Clin Ther. 2005;27:543-553.
Berger WE, White MV; Rhinitis Study Group. Efficacy of azelastine nasal spray in patients with an unsatisfactory response to loratadine. Ann Allergy Asthma Immunol. 2003;91(2):205-211.
Spector SL, Nicklas RA, Chapman JA, et al. Symptom severity assessment of allergic rhinitis: part 1. Ann Allergy Asthma Immunol. 2003;91:105-116.
Sanofi US. FDA Advisory Committee recommends approval of Sanofi's Nasacort® AQ nasal spray for over-the-counter use. http://sanofi.mediaroom.com/2013- 07-31-FDA-Advisory-Committee-Recommends- Approval-of-Sanofis-Nasacort-AQ-Nasal-Spray-for- Over-the-Counter-Use. Accessed August 25, 2013.
Price D, Bond C, Bouchard J, et al. International Primary Care Respiratory Group (IPCRG) Guidelines: management of allergic rhinitis. Prim Care Respir J. 2006;15:58- 70.
Burks AW, Calderon MA, Casale T, et al. Update on allergy immunotherapy: American academy of allergy, asthma and immunotherapy/European academy of allergy and clinical immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131:1288-1296.
Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter update. J Allergy Clin Immunol. 2011;127(1 suppl):S1-S15.
Barchuk WT, Salapatek AM, Ge T, D’Angelo P, Liu X. A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion [published online 2013]. J Allergy Clin Immunol. 2013. pii: S0091-6749(13)00756-2. doi: 10.1016/j. jaci.2013.05.001.
Hanuskova E, Plevkova J. The role of histamine H4 receptors as a potential targets in allergic rhinitis and asthma. Open J MolIntegrative Physiol. 2013;3:6-14.
Meltzer EO, Jacobs RL, LaForce CF, et al. Safety and efficacy of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with perennial allergic rhinitis. Allergy Asthma Proc. 2012;33:249-257.
Ratner P, Jacobs R, Mohar D, et al. Evaluation of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol, 80 or 160 μg once daily, for the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2010;105:471-479.
Berger WE, Mohar DE, Laforce C, et al. A 26-week tolerability study of ciclesonide nasal aerosol in patients with perennial allergic rhinitis. Am J Rhinol Allergy. 2012;26:302-307.
Bousquet J, Van Cauwenberge P, Khaltaev N, et al. ARIA in the pharmacy: management of allergic rhinitis symptoms in the pharmacy. Allergy. 2004;59:373-387.