Latest developments in the management of allergic rhinitis.

Allergic rhinitis (AR) is the most common chronic atopic disease, and it is associated with considerable costs and comorbidities. The management of AR includes environmental control measures, pharmacotherapy, and immunotherapy. This article discusses several developments and findings that have recently emerged in these three areas. The effectiveness of traditional methods of mitigating allergen exposure, such as the use of impermeable dust mite-proof bedding covers, has been rendered debatable. Exposure to environmental factors, such as household pets, is known to provoke exacerbation of allergic disease but now is proposed to have protective effects in certain settings. Changes in the choices of pharmacotherapy continue to occur as antileukotrienes and derivatives of certain antihistamines are added to the armamentarium against AR. However, a critical review of the clinical trials involving these drugs suggests that the changes are not necessarily incremental. Innovative methods of immunomodulation are currently being developed, with the objective of optimizing efficacy and safety. These include alternative routes or forms of delivering immunotherapy and other novel approaches in altering the pathobiology of AR.

The effects of the nasal antihistamines olopatadine and azelastine in nasal allergen provocation.

BACKGROUND: Olopatadine, an antihistamine used in allergic conjunctivitis, is under development as a nasal preparation for the treatment of allergic rhinitis. OBJECTIVES: To evaluate the efficacy of olopatadine in suppressing symptoms and biomarkers of the immediate reaction induced by nasal allergen provocation and to compare olopatadine with azelastine in the same model. METHODS: The study was approved by the Johns Hopkins University institutional review board, and all subjects gave written consent. We studied 20 asymptomatic subjects with seasonal allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%. In a third exploratory phase, olopatadine, 0.1%, was compared with topical azelastine, 0.1%, in a patient-masked design. Efficacy variables were the allergen-induced sneezes, other clinical symptoms, and the levels of histamine, tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in nasal lavage fluids. RESULTS: Both concentrations of olopatadine produced significant inhibition of all nasal symptoms, compared with placebo. Olopatadine, 0.1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine, albumin, and lysozyme. The effects of olopatadine, 0.1%, were comparable to those of azelastine, 0.1%. CONCLUSIONS: Olopatadine, at 0.1% and 0.2% concentrations, was effective in suppressing allergen-induced nasal symptoms. At 0.2%, olopatadine provided evidence suggestive of inhibition of mast cell degranulation.

The role of the nervous system in rhinitis.

The nose provides defensive and homeostatic functions requiring rapid responses to physical and chemical stimuli. As a result, it is armed with a complex nervous system that includes sensory, parasympathetic, and sympathetic nerves. Sensory nerves transmit signals from the mucosa, generating sensations, such as pruritus; motor reflexes, such as sneezing; and parasympathetic and sympathetic reflexes that affect the glandular and vascular nasal apparatuses. Reflexes directed to the nose are also generated by inputs from other body regions. Hence all symptoms that constitute the nosologic entity of rhinitis can be triggered through neural pathways. In addition, neural signals generated in the nose can influence distal physiology, such as that of the bronchial tree and the cardiovascular system. Neural function can be chronically upregulated in the presence of mucosal inflammation, acutely with an allergic reaction, or even in the absence of inflammation, as in cases of nonallergic rhinitis. Upregulation of the nasal nervous system can occur at various levels of the reflex pathways, resulting in exaggerated responses (neural hyperresponsiveness), as well as in increased capacity for generation of neurogenic inflammation, a phenomenon that depends on the release of neuropeptides on antidromic stimulation of nociceptive sensory nerves. The molecular mechanisms of hyperresponsiveness are not understood, but several inflammatory products appear to be playing a role. Neurotrophins, such as the nerve growth factor, are prime candidates as mediators of neural hyperresponsiveness. The many interactions between the nervous and immune systems contribute to nasal physiology but also to nasal disease.

Localization of nerve growth factor and its receptors in the human nasal mucosa.

BACKGROUND: Nerve growth factor (NGF) is a pluripotent mediator, the levels of which are elevated in nasal lavage fluids of individuals with allergic rhinitis at baseline. Levels of NGF increase after allergen challenge. OBJECTIVE: In the current study, we tested the hypotheses that mast cells are the main source of human nasal NGF, and that NGF can potentially affect mucosal elements other than nerves. METHODS: Immunostaining with antibodies against NGF, tryptase, CD3, eosinophil cationic protein, and the high-affinity (tyrosine kinase A) and low-affinity (p75) receptors for NGF was performed by using human nasal turbinate sections. RESULTS: Double immunofluorescence staining demonstrated NGF in only 2% (median) (1.3, 2.3; 25th, 75th percentiles) of mast cells, 0.2% (0, 0.4) of T cells, but in 62.2% (56.5, 68) of activated eosinophils. With immunohistology, NGF expression was consistently strongest in the submucosal glands and lesser in the epithelial lining. Both high-affinity and low-affinity receptors for NGF were localized not only on nerves, as expected, but also on nasal epithelium, submucosal glands, and some interstitial cells, but not on vascular endothelium. CONCLUSION: This study demonstrates that submucosal glands, nasal epithelium, and eosinophils constitute the major sources of NGF in the human nasal mucosa. That NGF receptors are found in cells other than nerves supports the notion that the role of this neurotrophin is broader than simple modulation of the sensorineural system. CLINICAL IMPLICATIONS: The distribution of NGF and its receptors and its established release during allergic reactions suggest that this factor participates in the pathophysiology of allergic rhinitis.