Nonallergic rhinitis: therapeutic options.

PURPOSE OF REVIEW: The purpose of this review is to briefly discuss methods for classifying Nonallergic rhinitis (NAR), the current understanding of its immunopathogenesis, scientific evidence-based treatment options along with anecdotal clinical experience for selecting different treatment regimens for these challenging patients. RECENT FINDINGS: NAR also known as idiopathic rhinitis, irritant-induced rhinitis and vasomotor rhinitis is a heterogeneous condition that has been classified many different ways, but currently there is no consensus on definition for this condition due to its poorly elucidated mechanism(s) of action. A typical patient presents with nasal congestion, postnasal drainage with or without a cough associated with, to a lesser extent, some degree of sneezing, itching, and rhinorrhea. Recent studies have proposed more specific approaches for characterizing rhinitis subtypes. It is speculated that this condition is due to an autonomic imbalance resulting in an overactive parasympathetic and perhaps an underactive sympathetic nervous system. Our poor understanding of NAR mechanism(s) of action has significantly hindered progress in developing novel therapies for this condition. SUMMARY: Further investigation is required to understand the neurogenic signaling pathways that lead to this aberrant response. Until we have selective therapies for NAR, treatment requires selecting the medication or combination of medications best suited to the symptomatic needs of the patient.

When sneezing indicates the cell type.

BACKGROUND: Nasal hyperreactivity is the symptomatic expression of vasomotor rhinitis. This study describes a typical nasal reaction, represented by a "volley of sneezes" found in some patients during nasal endoscopy, and to assess the possible correlation between hyperreactivity and a particular clinical and cytological condition. METHODS: We studied 671 rhinological subjects, 344 male, mean age 35.7 ± 13.76 standard deviation (SD) years. All were submitted to medical histories and clinical and instrumental investigations (skin prick test, nasal endoscopy, and nasal cytology). While performing endoscopy, particular attention was paid to the possible signs of nasal hyperreactivity, in particular "volley of sneezes" both during and immediately after the diagnostic procedure. RESULTS: Out of 671 endoscopies performed, 130 (17.1%) patients presented signs of hyperreactivity during and/or immediately after nasal endoscopy. The ratio of positive vasomotor reaction was 10.6% in the nasal polyposis (NP) group, 19% in the allergic rhinitis (AR) group, 70.6% (p < 0.01) in nonallergic rhinitis with mast cells (NARMA), 76% (p < 0.01) in nonallergic rhinitis with eosinophils and mast cells (NARESMA), and 83% (p < 0.01) in nonallergic rhinitis with eosinophils (NARES). In the AR subjects hyperreactivity was more frequent during the pollen season, compared to the period of absence of pollen (87.5% vs 12%). CONCLUSION: The onset of hyperreactivity (sneezing) can be considered an important "sign" in nasal symptomatology, whose sensitivity and specificity for nonallergic "cellular" rhinitis are 79% and 93%, respectively.

Enhanced nerve growth factor expression by mast cells does not differ significantly between idiopathic and allergic rhinitis.

BACKGROUND: The role of neurotrophins in allergic rhinitis (AR) has been well studied, but it has not been evaluated in idiopathic rhinitis (IR). OBJECTIVE: We aimed to evaluate the nasal ß-nerve growth factor (ß-NGF) expressions of mast cells in patients with AR and IR. METHODS: Seventeen patients with house dust mites-induced persistent moderate/severe allergic rhinitis (mean age: 29.7 ± 11.96), 14 patients with idiopathic rhinitis (mean age, 29.3 ± 10.62), and 16 healthy controls (29.9 ± 11.57) were included in the study. Nasal biopsy specimens were taken from the posterior part of the inferior turbinate from all of the study subjects. Nasal ß-nerve growth factor and its receptors, pan-neurotrophin receptor p75, and tyrosine kinase A (trkA) were assessed with an immunofluorescence assay. Mast cells were determined by both an immunofluorescence assay and immunohistochemistry as tryptase-positive cells. RESULTS: The ß-NGF, trkA, and p75 receptor counts were significantly higher in AR and IR patients than in the control group (P < .001, for each), but they were not different between AR and IR patients. Similarly, the ratio of ß-NGF+ mast cells/total mast cells and the ratio of ß-NGF+ mast cells/total ß-NGF+ cells in AR and IR patients was found to be elevated when compared with the control group (P < .001, P < .001, P < .001, and P = .046, respectively); furthermore, the 2 ratios were not statistically different between the 2 patient groups. CONCLUSION: The increase in ß-NGF-expressing mast cells does not differ between idiopathic and allergic rhinitis. Therefore, we propose that mast cells do play a role in the pathogenesis of IR as important as in that of AR.

Immunohistochemical localization of 3-nitrotyrosine in the nasal respiratory mucosa of patients with vasomotor rhinitis.

CONCLUSION: This study demonstrates that, in the nasal respiratory mucosa of patients with vasomotor rhinitis, oxidative stress following peroxynitrite formation is confined to the respiratory epithelium. This suggests that the role of peroxynitrite in vasomotor rhinitis differs from its role in other diseases of the respiratory tract. The results of this study also support the concept that different pathogenetic mechanisms are probably involved in vasomotor rhinitis. OBJECTIVE: Previous studies indicated that nitric oxide (NO) is involved in the pathogenesis of vasomotor rhinitis, strong expression of NO synthase being detected in the smooth muscle cells of the cavernous sinuses and in the respiratory epithelium. However, most adverse effects of high levels of NO originate from the reaction of NO with superoxide anions to form peroxynitrite. Therefore, in this study we evaluated the involvement of peroxynitrite in the pathogenesis of vasomotor rhinitis. MATERIAL AND METHODS: Sites of peroxynitrite formation were identified by immunolabelling for 3-nitrotyrosine (3NT), its footprint in tissues. Samples of nasal mucosa were obtained from vasomotor rhinitis patients and from control subjects who had undergone corrective surgery of the nasal septum. All samples were obtained by reduction of the inferior turbinate. RESULTS: Examination of specimens from vasomotor rhinitis patients revealed that 3NT is absent in epithelium with a normal appearance, cells of the subepithelial connective tissue, the glands and the blood vessels, including the cavernous sinuses. In contrast, intense 3NT immunolabelling was found in the disrupted respiratory epithelium. 3NT was not present in any of the specimens from control subjects.

[An assessment of the immune status of the mucosal membranes in chronic rhinosinusitis]. / Otsenka immunnogo statusa slizistykh obolochek pri khronicheskom rinosinusite.

The authors studied immune status of upper respiratory tracts mucosa in patients with different forms of chronic rhinosinusitis (purulent, polypous, vasomotor) in comparison to control subjects. An original complex of laboratory diagnostic techniques is proposed which can assess functional condition of the defense barriers of the upper respiratory tract mucosa in chronic inflammation, estimate impairment of specific and nonspecific resistance. This facilitates choice of optimal scheme of pathogenetic therapy of chronic inflammation in the upper respiratory tracts.

[The evaluation of cellular immunity in patients with allergy to pollen]. / Ocena odpornosci komórkowej u chorych na pylkowice.

The study comprised 180 patients with pollinosis, 30 patients with vasomotor rhinitis and 30 healthy male adults. The skin reactions of cellular immunity were determined by Multitest CMI. The numbers of lymphocytes T and numbers of CD4 and CD8 lymphocytes were determined under influence of histamine or clemastinum and histamine or cimetidine and histamine. There were statistically significant decrease of percentage of CD8 lymphocytes in patients with pollinosis after addition of histamine. Statistically significant increase of percentage of CD8 lymphocytes after the addition of H2 receptor blocker indicated that blocking of this receptor neutralized the effect of histamine on the CD8 lymphocytes. Author observed increase of Multitest CMI skin reactions (particularly for antigens: Streptococcus and Proteus mirabilis).

A comparative immunological study of vasomotor rhinitis and pollinosis.

Differentiation between pollinosis and vasomotor rhinitis creates great diagnostic difficulties. The aim of this study was to conduct comparative immunological clinical studies contrasting these two distinct diseases. Thirty-one subjects with untreated pollinosis and 29 subjects with untreated symptoms of rhinitis were tested, determining their T and B lymphocyte counts and the counts of their subpopulations, the levels of immunoglobulin A, M, G, D and E, both separately and in total, and levels of both basal and whole histamine. The control group was comprised of 30 healthy subjects. The results of this study show that these two diseases differ from each other (p < 0.05) in the recorded levels of basal histamine, total IgE, and IgG, IgM and IgD, as well as the count of T-RFC lymphocytes, T lymphocytes with receptors for Fc IgG and B lymphocytes with superficial receptors for IgG. The most useful laboratory methods for diagnosing the difference between pollinosis and vasomotor rhinitis appear to be the determination of levels of basal histamine and IgD in the blood.

Mast cells, eosinophils and IgE-positive cells in the nasal mucosa of patients with vasomotor rhinitis. An immunohistochemical study.

Vasomotor rhinitis (VMR) is a disorder of unknown pathogenesis. Forty patients with VMR were carefully selected on the basis of inclusion and exclusion criteria proposed by Mygind and Weeke. Nasal biopsy specimens were taken in the patient group as well as in a group of ten controls. Brush cytology was also taken in the VMR group. Inflammatory cells were identified and counted in the nasal mucosa, with the use of immunohistochemical techniques and a panel of monoclonal antibodies. Eosinophils were studied with the use of BMK13, EG2, and Giemsa. Mast cells were studied with anti-chymase (B7), anti-tryptase (G3) and toluidine blue. Sections were stained with IgE as well. There was no significant difference in the number of eosinophils, mast cells and IgE-positive cells between the two groups. Additionally, in contrast with other reports, in sections that were double-stained with anti-chymase and anti-tryptase, single chymase-positive cells were found.

[The treatment of atopic rhinitis in children with an accelerated variant of specific immunotherapy]. / Lechenie atopicheskogo rinita u detei uskorennym variantom spetsificheskoi immunoterapii.

An intensified course of specific immunotherapy (36 days) has been tried in 72 children with atopic vasomotor rhinitis. The age of the patients ranged from 5 to 15 years. The effectiveness of the treatment was assessed by nasal mucosa function, cellular and humoral immunity measured throughout the treatment and 6 moths after it. Good results were obtained in 71.1% of the patients, satisfactory in 24.4%, unresponsive children made up 4.2%. No complications occurred. During the treatment adverse reactions were noted in 11 children. Short-term discontinuation of the allergen administration corrected the situation. Clinical, functional and immunological findings permitted the authors to conclude on the expediency of a short-term specific immunotherapy in atopic rhinitis management in children.

[Comparative value of skin tests and IgE antibodies in the serum in patients with chronic vasomotor rhinitis]. / Uporedne vrednosti koznog testiranja i IgE antitela u serumu obolelih od hronicnog vazomotornog rinitisa.

In order to assess values of skin testing and determination of pulp, as a credible indicator considering sensibilisation of an organism, 61 patients suffering from chronic vasomotor rhinitis were tested. By application of "prick" test, skin test results were positive in 30 patients and negative in 31. Presence of specific IgE antibodies in the serum was assessed in all patients by "ELISA" test. In 51 patients (83.6%) both kinds of findings corresponded. In 26 patients both skin parameters were negative while in 10 patients (16.40%) findings did not correspond. It was established that for Dermatophagodies pteronyssinus specific IgE antibodies are determined in serum when pap is 5 mm wide. Grasp pollen always caused strong local reactions, regularly more than 10 mm. Considerably high levels of IgE antibodies was also established while other pollens did not show such correspondence.

Relationship between IgE and IgG antibodies in type I allergy.

Serum samples of human patients with immediate type allergy were examined for both IgE (by radioallergosorbent test) and IgG (by enzyme immunoassay) antibodies to several of the common inhalant and food allergens. The results show a statistically significant correlation between the titers of anti-allergen antibodies of both isotypes. The data indicate that immune stimulation in atopic individuals is not restricted to the IgE isotype, but equally affects the IgG-producing antibody systems. The statistical relationship observed may either be due to common pathways in the production of both antibody classes in atopic people, or may be explained by preferential binding of allergens to circulating IgE-IgG immune complexes.

[Cellular immunity in pollinosis patients]. / Sostoianie kletochnogo immuniteta u bol'nykh pollinozom.

A study of 107 patients with pollinosis with exacerbation during the spring-summer season revealed T-lymphopenia, increased number of 0-lymphocytes, reduction of the level of "active" and theophyllin-sensitive lymphocytes and histamin-sensitive cells. The number of low-differentiated B-cells increased, the number of autorosette-forming lymphocytes decreased. The revealed changes may be interpreted as secondary immunological insufficiency (relative hyposuppressor variant).

[Indicators of the activity of the immune system during laser therapy of vasomotor rhinitis]. / Pokazateli aktivnosti immunnoi sistemy pri lazernoi terapii vazomotornogo rinita.

Helium-neon laser LH-75 was used to treat 60 inbred mice and 62 patients with vasomotor rhinitis. The patients were given 10 laser sessions. In animals, all responses of T-lymphocytes were modified. Cyclic changes that developed during laser irradiation were accompanied by immunity suppression or activation. In patients, the count of T- and B-lymphocytes and the leucocyte migration inhibition reaction were measured. The patients with vasomotor rhinitis showed a significant increase of T-lymphocytes and a higher capacity of T-cells to form the migration inhibition factor. The efficacy of laser therapy of vasomotor rhinitis became optimal on irradiation day 6 or 7 and reached a maximum on day 10.