Notes: In both seasonal and perennial rhinitis there is epithelial mast cell accumulation and tissue infiltration by eosinophils. Activation of these cells can be observed by electron microscopy and by elevated levels of tryptase and eosinophil cationic protein in nasal lavage fluid. Furthermore, seasonal increases in the antigen presenting cell (Langerhans’cell) are also evident. Investigations into the mechanisms involved in cell accumulation and activation reveals upregulation of leucocyte endothelial adhesion molecules and an increase in interleukin-4 (IL-4) in naturally occurring rhinitis, while mRNA for IL-4, IL-5 and granulocyte macrophage colony stimulating factor activity and lavage tumour necrosis factor-alpha (TNFα) levels are increased following local allergen challenge. These cytokines may be derived from a variety of sources, including mast cells, eosinophils and T-lymphocytes, and contribute to the underlying inflammatory process in rhinitis.

Notes: Studies of the pathology of rhinitis and asthma have identified similarities and differences between these two clinical conditions. With regard to symptoms, both the nose and the lower airways respond to neural stimulation by irritant substances, but a major difference is that engorgement of the capacitance vessels is the main cause of nasal obstruction in rhinitis, while muscle constriction is the major determinant of lower airway narrowing. There are also similarities and differences with respect to the role of infiammatory cells. In both conditions there is evidence of allergen-induced mast cell activation, with production of an array of mediators (some mast cell-derived and others originating from a variety of other cell types). Eosinophilia is also characteristic of both diseases — it is prominent even in mild forms of asthma, but is low in pollen-sensitive rhinitics outside of the season. T-cell activation and production of cytokines plays an important role in the development and maintenance of allergic disease, but the level of T-cell activation may differ between asthma and rhinitis. Further research into differences in cellular activity and response to treatment between these two diseases may help define factors which will determine whether atopic disease is expressed in the upper, lower, or both parts of the respiratory tract.

Notes: The mediators released during the allergic inflammatory reaction induce the clinical symptoms of the allergic disease and although there have been numerous studies investigating mediator release in allergen challenge models of allergic rhinitis very few have extended this approach to the study of natural disease.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveThe aim of this investigation was therefore to measure mast cell and eosinophil mediator levels and indices of vascular permeability in naturally occurring rhinitis.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsThree groups of subjects were studied, normal non-rhinitics, seasonal allergic rhinitics in and out of the grass pollen season and perennial allergic rhinitics. Mediators were recovered using the technique of nasal lavage and the levels of tryptase, histamine, eosinophil cationic protein and albumin were determined. In addition, eosinophils were enumerated in nasal smears as an indices of underlying inflammation.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsThe levels of tryptase, eosinophil cationic protein and albumin were significantly higher in the lavage recovered from the symptomatic seasonal allergic rhinitics than when asymptomatic (P = 0.05, P = 0.003, P = 0.009, respectively). These levels of eosinophil cationic protein and albumin were also significantly higher than those of the normal non-rhinitics (P = 0.0008, P = 0.0.003, respectively). In the perennial allergic rhinitics the levels of tryptase, eosinophil cationic protein and albumin were higher than the normal non-rhinitics (P  〈 0.0001, P = 0.0003, P = 0.0001, respectively). The levels of tryptase and histamine were higher in the perennial allergic rhinitics than the seasonal allergic rhinitics (P = 0.0003, P = 0.006, respectively). These changes in mediator levels were accompanied by a significant influx of eosinophils into the nasal mucosa of both the symptomatic seasonal rhinitics, compared with asymptomatic (P = 0.04) and normal controls (P = 0.0006) and the perennial rhinitics compared to normal controls (P = 0.03).〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionThese results indicate that in both naturally occurring seasonal allergic rhinitis and perennial allergic rhinitis mast cell and eosinophil activation occurs and this is accompanied by an increase in vascular permeability. These measurements in lavage fluid provide a method of monitoring the mucosal cellular events in response to therapy.

Notes: Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 μg) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double-blind and cross-over studies on eight non-rhinitic subjects. Thus subjects received either double-placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days. This study, therefore, demonstrates that cholinergic pathways and mast cell release of histamine do not contribute to increase in NAR, rhinorrhoea and plasma protein extravasation induced by bradykinin.

Notes: Background The epithelial accumulation of mast cells is a feature of allergic rhinitis and this has been linked to the expression of the known mast cell chemoattractant transforming growth factor-β (TGF-β) at this site. Little is known concerning the regulation of TGF-β gene expression or protein release by nasal epithelial cells. To address this we have utilized the RPMI 2650 human nasal epithelial cell line, which has some features that closely resemble normal nasal epithelium and has been reported to secrete a TGF-β-like molecule.Objectives To investigate the regulation of TGF-β gene expression and protein secretion in RPMI 2650 nasal epithelial cells following exposure to allergens (house dust mite (HDM) and grass pollen) and mast cell associated T-helper type 2 (Th2) cytokines (IL-4, IL-13, and TNF-α).Methods Light and scanning electron microscopy was used to evaluate the morphology of RPMI 2650 cells in culture, enzyme-linked immunosorbent assay was used to investigate their TGF-β secretory capacity and the identification of the TGF-β isotype(s) involved, flow cytometry was used to demonstrate the presence of TGF-β receptors on the RPMI 2650 cells, and the quantitative real-time TaqMan PCR was used to measure TGF-β gene expression.Results TGF-β2 was identified as the main isotype secreted by the RPMI 2650 cells. HDM allergens and TNF-α increased both TGF-β gene expression and protein release from these cells, whereas grass pollen, IL-4, and IL-13 were without effect.Conclusions The RPMI 2650 nasal epithelial cell line represents a valid in vitro model to evaluate the regulation of TGF-β biology. In this system HDM allergens have stimulatory activity that is fundamentally different from that of grass pollen allergens, and the Th2 cytokines IL-4 and IL-13 are without effect. The ability of TNF-α to up-regulate both TGF-β gene expression and protein release indicates that mast cell–epithelial interactions concerning TGF-β are bi-directional and this may be fundamental to epithelial immunoregulation. The availability of a model system, such as the RPMI 2650 cells, will enable the early evaluation of future novel and targeted interventions directed toward the aberrant responses of upper airway structural cells.

Notes: The traditional viewpoint that inflammation, owing to a genetic T-helper type 2 (Th2)-directed imbalance, is the cause of allergic rhinitis has meant that the potential coexistence of other genetic defects and the relevance of any airway remodelling changes to disease pathogenesis and persistence have received scant attention, and as such remain controversial areas. This is particularly so in view of the limited published work in this field, which has so far reported markedly conflicting findings. This review endeavours to outline what is known about the nature of the remodelling response within the upper airway in allergic rhinitis, in addition to highlighting specific areas where further research is warranted.