Wytske J. Fokkens

Type 1-like immune response is found in children with respiratory syncytial virus infection regardless of clinical severity

The immunological response of infants younger than six months to infection with respiratory syncytial virus (RSV) was studied in relation to clinical severity. IL‐6 and IL‐8 were found more frequently and at higher levels in the plasma samples of more severely ill patients and no significant differences were found in the levels of cytokines differentiating between Type 1 and Type 2 responses. Cellular infiltrates in nasopharyngeal washings consisted mainly of polymorphonuclear granulocytes and monocytes. Eosinophils, IgE positive cells and tryptase positive cells were found sporadically. Analyses of RSV stimulated T cell cultures established from peripheral blood mononuclear cells, for intracellular and secreted cytokines showed that, irrespective of clinical severity, the responses were dominated by the production of IFN‐γ, and that only low levels of IL‐4 and IL‐10 were detectable. Collectively these data do not indicate an association between clinical severity and a Type 2‐like T cell response. J. Med. Virol. 62:267–277, 2000.

Dynamics of mast cells in the nasal mucosa of patients with allergic rhinitis and non‐allergic controls: a biopsy study

Mast cell degranulation is thought to be an important component of the pathogenesis of allergic rhinitis. Quantitative studies on mast cells in nasal mucosa after allergen exposure have given widely divergent results, ranging from an overall decrease via redistribution to an overall increase. We investigated this problem by employing a combination of anti‐IgE and toluidine blue staining of biopsy specimens. In allergic patients anti‐IgE was found to identify all mast cells and toluidine blue to detect mast cells that were not (totally) degranulated.

Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation ☆ ☆☆

BACKGROUNDnAllergic inflammation is regulated by the local production and release of several cytokines.nnnOBJECTIVESnThis study was designed to assess the changes in mRNA cytokine-positive cells after allergen provocation and to compare these cytokines with tissue eosinophilia as a marker of allergic inflammation.nnnMETHODSnA grass pollen allergen provocation study was conducted in autumn, out of the hay fever season. Nasal mucosal biopsy specimens were taken before provocation and 1 hour, 24 hours, and 1 week after allergen provocation. Eosinophils and mRNA-positive cells (in situ hybridization for IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFN-gamma, RANTES, and TNF-alpha) were assessed in the biopsy specimens.nnnRESULTSnAfter allergen provocation, an increase in cell number was found for eosinophils and cells expressing mRNA for the chemokines IL-8 and RANTES and for the TH2 cytokines IL-10 and IL-13. Significant correlations were found between eosinophils and RANTES and eosinophils and IFN-gamma in the early phase and between eosinophils and IL-5 and eosinophils and RANTES in the late phase. The increase in eosinophils and IL-10 and IL-13 mRNA-positive cells could still be observed 1 week after allergen provocation.nnnCONCLUSIONSnNasal allergen provocation induced significant tissue eosinophilia and a significant increase in IL-8, IL-13, and RANTES mRNA-positive cells. A significant increase in eosinophils and IL-10 and IL-13 mRNA-positive cells compared with baseline can still be observed 1 week after a single allergen provocation.

Antigen presenting cells in the nasal mucosa of patients with allergic rhinitis during allergen provocation

Background The role of antigen presenting cells (APC) in allergic rhinitis is underexposed. Allergen presentation to T lymphocytes is probably an important aspect of the pathophysiological mechanism of allergic rhinitis.

Fluticasone propionate aqueous nasal spray does not influence the recurrence rate of chronic rhinosinusitis and nasal polyps 1 year after functional endoscopic sinus surgery

Background Local corticosteroids are widely used in the treatment of nasal polyps and chronic rhinosinusitis both before and after nasal surgery. Their efficacy after functional endoscopic sinus surgery (FESS) has not been fully established by placebo‐controlled trials.

Dynamics of nasal eosinophils in response to a nonnatural allergen challenge in patients with allergic rhinitis and control subjects: a biopsy and brush study

BACKGROUNDnEosinophils are thought to play an important role in the symptomatology and pathophysiology of allergic rhinitis. Most quantitative studies on eosinophils in nasal mucosa have focused on the dynamics of eosinophils in the acute and late phases of the allergic reaction by using different cell sampling techniques. Little is known about the dynamics of eosinophils during a more prolonged period of allergen exposure and the activation of eosinophils induced by allergen challenge.nnnOBJECTIVEnThe aim of this study was to investigate the dynamics and activation of the eosinophils in the nasal mucosa of patients with an isolated grass pollen allergy during an out-of-season 2-week allergen exposure, mimicking the natural grass pollen season.nnnMETHODSnSeventeen patients with isolated grass pollen allergy and four control subjects were challenged daily with the allergen during a 2-week period in the winter. Nasal brush specimens were obtained before provocation and each day during the provocation period. Biopsy specimens were obtained once before, six times during, and once after the provocation period. Preparations made of nasal brush and nasal biopsy specimens were stained with the monoclonal antibody BMK 13 and Giemsa stain as paneosinophil markers and with the monoclonal antibody EG2 to identify activated eosinophils.nnnRESULTSnWe found significant increases in the total number of eosinophils and the number of activated eosinophils in the epithelium and lamina propria. These increases were most explicit in the second week. BMK 13 was found to be a paneosinophil marker superior to Giemsa staining.nnnCONCLUSIONnEosinophils are not only involved in the acute and late phases of the allergic reaction but are probably even more involved in the chronic phase.

Characterization and quantification of cellular infiltrates in nasal mucosa of patients with grass pollen allergy, non-allergic patients with nasal polyps and controls.

Little is known about cellular infiltrates in nasal mucosa and the differences between these infiltrates in allergic and non-allergic patients. A reproducible and objective method making use of monoclonal antibodies for the quantification and characterization of cellular infiltrates in biopsy specimens of nasal mucosa is described. This method was used to study quantitative differences in cellular infiltrates in the epithelium and lamina propria of the nasal mucosa of patients with isolated grass pollen allergy, non-allergic patients with nasal polyps, and controls. A surprisingly wide variation was found in all groups. In all groups the T lymphocytes were much more numerous than the B lymphocytes. The number of CD8+ cells exceeded the number of CD4+ cells in the epithelium but in the lamina propria the numbers were approximately equal. Significant differences between the three groups were found with respect to the number of CD1+, IgE+, neutrophils and cytoplasmic IgG4+ cells. No significant differences were found in the numbers of CD4+, CD8+, CD14+, CD22+, HLA-DR+, IgG1-3+ cells or eosinophils. The use of biopsy in combination with monoclonal antibodies is an easy and well-tolerated method to study immunological reactions in the nasal mucosa. The results of this study indicate a possible role for a T-cell-mediated response in allergic rhinitis.

Recruitment of CD1a+ Langerhans cells to the nasal mucosa in seasonal allergic rhinitis and effects of topical corticosteroid therapy.

Background: Local antigen presentation may be necessary for both primary and recall T‐cell responses to grass pollen in hay fever patients. We examined the effect of seasonal allergen exposure on nasal mucosal antigen‐presenting cell (APC) populations and the effects of topical corticosteroid therapy.

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.

Thoughts on the pathophysiology of nonallergic rhinitis

Nonallergic noninfectious rhinitis is a diagnosis by exclusion, meaning that a number of poorly defined nasal conditions that have in common allergy and infection as a cause of the rhinitis have been excluded. The etiology of some subgroups of nonallergic noninfectious rhinitis, like nonallergic rhinitis with eosinophilia (NARES) and drug-induced rhinitis, are quite well defined, but in the majority of the patients, the etiology and pathophysiology are unknown. These patients are classified as idiopathic rhinitis patients. A careful determination of the intensity of the symptoms combined with modern diagnostic tools enables us to discriminate idiopathic rhinitis patients from normal controls. This review discusses the possible pathophysicologic mechanisms of nonallergic noninfectious rhinitis, with emphasis on idiopathic rhinitis.