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Allergic rhinitis (AR) is a multifactorial disease characterized by paroxysmal symptoms of sneezing, rhinorrhea, postnasal drip and nasal congestion. For over a century, subcutaneous allergen immunotherapy (SCIT) has been recognized as the most effective therapy to date that may modify the underlying disease course and provide long-term benefits for individuals refractory to pharmacotherapy. However, over the past 25 years, there has been substantial growth in developing alternative therapies to traditional SCIT. Areas covered: This article will review the most current literature focusing on advancements of AR therapies. Novel AR therapies that are currently under investigation include: the addition of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody (mAb), to SCIT; altering the method of delivery of allergen immunotherapy (AIT) including sublingual (SLIT), epicutaneous (EIT), intralymphatic (ILIT), intranasal (INIT) and oral mucosal immunotherapy (OMIT); use of capsaicin spray; novel H3 and H4 antihistamines; activation of the innate immune system through Toll-like receptor agonists; and the use of chemically altered allergens, allergoids, recombinant allergens and relevant T-cell epitope peptides to improve the efficacy and safety of AIT. Expert opinion: These promising novel therapies may offer more effective and/or safer treatment options for AR patients, and in some instances, induce immunologic tolerance.

In this study, 18 synthetic naphthalene derivatives were tested for their inhibitory effects on the activation of neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristic acetate (PMA). Some of these compounds showed significant antiinflammatory activities. In general, esterification of 1-naphthalene to compound 14 (2-hydroxymethyl-1-naphthol diacetate; TAC) enhanced the antioxidant activity. Compound 15, N,N-bis(2-hydroxy-1-naphthylmethyl) amine, has moderate inhibitory activity on neutrophils stimulated with fMLP as compared to Mannich bases of naphthylene derivatives. Either substitution at 1 or 2 position, except TAC, disfavored the inhibitory effects evoked by PMA stimulation. The influence of these compounds on the release of granule enzyme lysozyme-induced by fMLP was measured. TAC had the highest potency on the inhibition of lysozyme release from rat neutrophil degranulation. The effects of TAC on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were also investigated with the aid of the whole-cell patchclamp technique. TAC caused an inhibitory effect on voltage-dependent L-type Ca 2þ current (I Ca,L ) with an IC 50 value of 0.8 mM. The inhibitory effect of TAC on I Ca,L may not be caused by its inhibition of superoxide formation. Such an effect may, also in part, affect neuronal function. Drug. Dev. Res. 60: 261-269, 2003.

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RATIONALE: ABPA occurs predominantly in individuals with asthma or CF. Standard treatment for ABPA includes oral corticosteroids and, occasionally, antifungal agents. It has been reported that omalizumab, a monoclonal anti-IgE antibody, can be an effective treatment for CF patients with ABPA. METHODS: We performed a retrospective chart review on three adolescent CF patients who were diagnosed with ABPA and treated with omalizumab. Patients 1 and 2 presented with pulmonary exacerbations, diminishing FEV 1 , and abnormal chest radiographs. Pseudomonas aeruginosa and Aspergillus fumigatus were detected in bronchoalveolar lavage fluid from patient 1, and Mycobacterium spp. and A. fumigatus from patient 2. Patient 3 was previously diagnosed with ABPA at age 8 and received a trial of omalizumab treatment after unsatisfactory response to standard therapy. Symptoms improved and omalizumab was maintained for 3 years. Three years later, his lung function deteriorated. New infiltrates were noted on chest radiograph, and sputum cultures showed A. fumigatus. RESULTS: Additional investigation revealed skin test positivity to A. fumigatus and presence of A. fumigatus specific IgE and IgG in all 3 patients, suggesting ABPA diagnosis. Corticosteroids were withheld due to concomitant bacterial infection in patients 1 and 2, and history of corticosteroid-induced hypertension in patient 3. Treatment with omalizumab injection every 2 weeks was initiated and led to a substantial clinical improvement. After 3 months of therapy, FEV 1 increased from baseline in all 3 patients. CONCLUSIONS: Omalizumab may be an effective, alternative therapy for ABPA in CF patients who fail to respond to systemic corticosteroids or have contraindications to its use.