Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults

Journal of Allergy and Clinical Immunology (JACI) 127 (1), 72-80.e2 (Jan 2011)

Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI 

BACKGROUND Immunotherapy for allergic rhinoconjunctivitis (ARC) in North America is generally administered subcutaneously, but alternative formulations might be safer and more convenient. Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data. 

OBJECTIVEWe sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet (AIT) treatment in North American subjects with ARC. 

METHODS Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were randomized to once-daily 2,800 bioequivalent allergen units of standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 standardized quality tablet, containing approximately 15 μg of Phl p 5) or placebo approximately 16 weeks before the 2009 grass pollen season (GPS). The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS. Rhinoconjunctivitis Quality of Life Questionnaire with standardized activities (RQLQ[S]) scores, Phl p 5-specific IgG4 levels, and IgE-blocking factor levels were additional end points. Adverse events (AEs) were monitored for safety. 

RESULTS Relative to placebo, grass AIT treatment improved total combined scores by 20% (P = .005), daily symptom scores by 18% (P = .02), and RQLQ(S) scores by 17% (P = .02). Daily medication scores were improved by 26% and trended toward significance (P = .08). Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS (P <.001). Grass AIT treatment was safe and well tolerated. The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise. In the grass AIT group, 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction (local site reactions, chest discomfort, and rash). 

CONCLUSIONS Timothy grass AIT treatment (cross-reactive with related Pooideae grasses) was demonstrated to be effective, generally safe, and well tolerated in North American adults with grass pollen-induced ARC.

Effectiveness criteria for the topical application of glucocorticosteroids to the treatment of exudative otitis media associated with allergic rhinitis

Vestnik Otorinolaringologii (5), 32-34 (2010)

Poliakova SD, Popova EA 

We undertook comparative analysis of ciliotoxic effect of glucocorticosteroids frequently used for catheterization of the eustachian tube in patients presenting with exudative otitis media and concomitant allergic rhinitis. It was shown that the recovery of transport function of ciliary epithelium and appreciable clinical effect of the treatment were achieved by the application of mometasone furoate. Dexamethasone was next to mometasone in terms of efficiency whereas hydrocortisone produced much lower beneficial effect. It is concluded that, taking into account high bioavailability of dexametasone and hydrocortisone (>80%) and contraindications to their intranasal administration, the preference should be given to medications with lower bioavailability.

Treatment of allergic rhinitis

American Family Physician 81 (12), 1440-6 (Jun 2010)
Sur DK, Scandale S;


Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition.

Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease.

Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.

Ear-acupressure for allergic rhinitis: a systematic review

Clinical Otolaryngology 35 (1), 6-12 (Feb 2010)

Zhang CS, Yang AW, Zhang AL, Fu WB, Thien FU, Lewith G, Xue CC

BACKGROUND: Allergic rhinitis affects 10-40% of the population globally with a substantial health and economic impact on the community.
OBJECTIVE OF REVIEW: To assess the effectiveness and safety of ear-acupuncture or ear-acupressure for the treatment of allergic rhinitis by reviewing randomised controlled trials and quasi-randomised controlled trials.
TYPE OF REVIEW: This review followed the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. SEARCH STRATEGY: A total of 21 electronic English and Chinese databases were searched from their respective inceptions to April 2008. Key words used in the search included the combination of ear, auricular, acupuncture, acupressure, acupoint, allergic, allergy, rhinitis, hayfever, randomised clinical trial and their synonyms. EVALUATION METHOD: The methodological quality was assessed using Jadad's scale. The effect size analysis was performed to explore the difference between interventional groups. RESULTS: Ninety-two research papers were identified and seven of them referring to five studies met the inclusion criteria. All included studies involved ear-acupressure treatment. These studies mentioned randomisation, but no details were given. None of the five studies used blinding or intention-to-treat analysis. Ear-acupressure was more effective than herbal medicine, as effective as body acupuncture or antihistamine for short-term effect, but it was more effective than anti-histamine for long-term effect.
CONCLUSIONS: The benefit of ear-acupressure for symptomatic relief of allergic rhinitis is unknown due to the poor quality of included studies

Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis

Journal of Allergy and Clinical Immunology (JACI) (Apr 2010)

Prenner BM, Lanier BQ, Bernstein DI, Shekar T, Teper A

BACKGROUND: Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses.

OBJECTIVE: We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR.

METHODS: Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 mug once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire.

RESULTS: MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (-0.34, P = .026, coprimary end point), instantaneous TNSSs (-0.88, P<.001, coprimary end point), reflective TOSSs (-0.44, P = .005), and reflective TNSSs (-1.06, P<.001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo (P<.05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo (P<.001). MFNS was well tolerated.

CONCLUSION: This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.

Is there a role for leukotriene antagonists in the prevention of recurrent nasal polyps?

Current Opinion in Allergy and Clinical Immunology 10 (3), 200-5 (Jun 2010)

Rasp G

PURPOSE OF REVIEW: The aim of this review is to provide the current available data for leukotriene receptor antagonists in the treatment of nasal polyps, the use in the postoperative therapy single or as an add-on to standard treatments.

RECENT FINDINGS: Surgical treatment of nasal polyps was refined in the last 30 years by the introduction of functional endoscopic sinus surgery and nasal endoscopy for monitoring nasal polyp patients. As the relapse is the main challenge and as nasal steroids only delay it, a more efficient treatment is needed. Leukotriene antagonists have effects on asthma and allergic rhinitis; preliminary data show some benefits in nasal polyps.

SUMMARY: In the surgery of nasal polyps, recurrence is the main problem. Steroids are the current standard therapy, but the limitations are obvious. The role of leukotrienes in the disorder of nasal polyps is well established now, and with the antagonists available, interest rose in treating nasal polyps. A total of 356 patients took part in several studies involving leukotriene antagonists in the nasal polyp population. Some studies have minor levels of evidence; the data show positive effects for patients in preoperative and postoperative studies and medical treatments. There were benefits as an add-on to steroids and data from allergic rhinitis studies also show possible synergism with antihistamines. There are hints for a positive effect on eosinophil inflammation, clinical symptom scores, nasal airflow, sneezing and postnasal drip. Although some effects are shown, more controlled studies are necessary for reliable data.

Congestion and sleep impairment in allergic rhinitis

Current Allergy and Asthma Reports 10 (2), 113-21 (Mar 2010)

 Craig TJ, Sherkat A, Safaee S;

Allergic rhinitis is a prevalent disease in developed nations, and its prevalence has been increasing throughout the world. Nasal congestion is the most common and bothersome symptoms of rhinitis.

Congestion is associated with sleep-disordered breathing and is thought to be a key cause of sleep impairment in individuals with rhinitis. The end result is a decrease in quality of life and productivity and an increase in daytime sleepiness. Treatment with intranasal corticosteroids has been shown to reduce nasal congestion.

Data on sleep-related end points from clinical trials of intranasal corticosteroids indicate that this reduction is associated with improved sleep, reduced daytime fatigue, and improved quality of life. Other therapies, such as montelukast, also have a positive influence on congestion and sleep.

This review examines nasal congestion and the associated sleep impairment of allergic rhinitis patients. It explores the adverse effects of disturbed sleep on quality of life and how these conditions can be reduced by therapies that decrease congestion.

Drug-induced rhinitis

Clinical and Experimental Allergy 40 (3), 381-4 (Mar 2010)
Varghese M, Glaum MC, Lockey RF

Background: Rhinitis is characterized by inflammation of the mucous membranes lining the nose and can be divided into two categories, allergic and non-allergic. Drug-induced is a type of non-allergic rhinitis.

Objective A review of the literature was conducted. Very little is known about this topic and there are no publications to date solely devoted to drug-induced rhinitis.

Methods A PubMed and Medline search was conducted using a combination of the keywords; drug, medication, rhinitis, congestion, rhinorrhea, sneezing, pruritus, vasomotor, reflex, neurogenic, allergic and non-allergic. Medications that were found in the search were then cross-referenced with the physicians desk reference and Epocrates. The final literature search was conducted in August 2009.

Results Three categories of drug-induced rhinitis exist based on the mechanism of action. These include local inflammatory, neurogenic and idiopathic types. Rhinitis medicamentosa, a form of drug-induced rhinitis, has unique characteristics.

Conclusion When possible, the offending medication should be discontinued or substituted. Although there are no established treatment recommendations for drug-induced rhinitis other than avoidance, clinical experience suggests that it would be reasonable to initiate use of an intranasal corticosteroid spray to treat symptomatically. The addition of an intranasal antihistamine in combination with use of an intranasal corticosteroid may be considered as step-up therapy if the intranasal corticosteroid alone is not effective.

Rhinitis and sinusitis

Journal of Allergy and Clinical Immunology (JACI) 125 (2 Suppl 2), S103-15 (Feb 2010)
Dykewicz MS, Hamilos DL

Rhinitis and sinusitis are among the most common medical conditions and are frequently associated. In Western societies an estimated 10% to 25% of the population have allergic rhinitis, with 30 to 60 million persons being affected annually in the United States. It is estimated that sinusitis affects 31 million patients annually in the United States. Both rhinitis and sinusitis can significantly decrease quality of life, aggravate comorbid conditions, and require significant direct medical expenditures. Both conditions also create even greater indirect costs to society by causing lost work and school days and reduced workplace productivity and school learning.
Management of allergic rhinitis involves avoidance, many pharmacologic options, and, in appropriately selected patients, allergen immunotherapy. Various types of nonallergic rhinitis are treated with avoidance measures and a more limited repertoire of medications. For purposes of this review, sinusitis and rhinosinusitis are synonymous terms.
An acute upper respiratory illness of less than approximately 7 days' duration is most commonly caused by viral illness (viral rhinosinusitis), whereas acute bacterial sinusitis becomes more likely beyond 7 to 10 days.

Although the mainstay of management of acute bacterial sinusitis is antibiotics, treatment of chronic sinusitis is less straightforward because only some chronic sinusitis cases have an infectious basis.

Chronic rhinosinusitis (CRS) has been subdivided into 3 types, namely CRS without nasal polyps, CRS with nasal polyps, and allergic fungal rhinosinusitis. Depending on the type of CRS present, a variety of medical and surgical approaches might be required

Overexpression of glucocorticoid receptor-beta in severe allergic rhinitis

Auris Nasus Larynx (Feb 2010)
Ishida A, Ohta N, Koike S, Aoyagi M, Yamakawa M;

OBJECTIVE: To clarify the role of glucocorticoid receptor-beta in resistance to glucocorticoid therapy for allergic rhinitis, we studied 37 tissue samples from 20 patients with severe allergic rhinitis, and samples from age-matched controls.
METHODS: Patients were treated with intranasal fluticasone for 6 months and inferior turbinectomy was performed for patients with poor response to glucocorticoid treatment. The expression of glucocorticoid receptor-alpha (GR-alpha), glucocorticoid receptor-beta (GR-beta), and nuclear factor-kappaB (NF-kappaB) in nasal mucosa was studied immunohistochemically.
RESULTS: GR-alpha and NF-kappaB were expressed to a similar extent in patients and controls, but GR-beta was expressed significantly more in patients, resulting in an increased GR-beta/GR-alpha ratio.
CONCLUSION: Our findings suggest that GR-beta plays an important role in resistance to glucocorticoid therapy for allergic rhinitis, and its expression might be used as an additional parameter indicating steroid resistance in allergic rhinitis

The role of neurotrophins in the pathophysiology of allergic rhinitis

Current Opinion in Allergy and Clinical Immunology (Nov 2009) 
 Raap U, Braunstahl GJ

PURPOSE OF REVIEW: Allergic rhinitis is characterized by allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. In this regard, neurotrophins are prime candidates as mediators of neuronal and immunological plasticity and they will be the focus of the current review.
RECENT FINDINGS: Neurotrophins including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are expressed in the nasal mucosa. The majority of NGF expression has been found in eosinophil granulocytes, the glandular apparatus and peripheral nerves. As shown recently, nasal allergen provocation upregulates BDNF expression in nasal mucosa and NGF expression on peripheral nerves and nasal lavage in patients with allergic rhinitis. In this regard, increased BDNF expression positively correlates with the maximum increase in total nasal symptom score. The neurotrophin receptors including pan-neurotrophin receptor p75, tyrosine kinase A (trkA) and trkB are expressed in nasal tissue. TrkA is expressed on endothelial, p75 on peripheral nerves and trkB on nasal mucosa mast cells that decreases after allergen provocation. The expression of these neurotrophin receptors is increased on peripheral blood eosinophils in allergic rhinitis compared with nonatopic controls. Further, BDNF and NGF exert immunomodulatory functions on eosinophils of patients with allergic rhinitis. Finally, eosinophils of patients with allergic rhinitis are capable of BDNF and NGF production.
SUMMARY: Neurotrophins represent prime candidates in upper airway pathophysiology in allergic rhinitis. Research on neurotrophins in allergic rhinitis is thus becoming a progressively more exciting field and may reveal new and promising therapeutic options for the future.