Henk Blom

Idiopathic rhinitis, the ongoing quest

The term rhinitis in daily practice is used for nasal dysfunction causing symptoms‐like nasal itching, sneezing, rhinorrhea and or nasal blockage. Chronic rhinitis can roughly be classified into allergic, infectious or nonallergic/noninfectious. When allergy, mechanical obstruction and infections have been excluded as the cause of rhinitis, a number of poorly defined nasal conditions of partly unknown aetiology and pathophysiology remain. The differential diagnosis of nonallergic noninfectious rhinitis is extensive. Although the percentage of patients with nonallergic noninfectious rhinitis with a known cause has increased the last decades, still about 50% of the patients with nonallergic noninfectious rhinitis has to be classified as suffering from idiopathic rhinitis (IR), or rather e causa ignota. Specific immunological, clinical and sometimes radiological and functional tests are required to distinguish known causes. Research to the underlying pathophysiology of IR has moved from autonomic neural dysbalans to inflammatory disorders (local allergy), the nonadrenergic noncholinergic (NANC) sensory peptidergic neural system and central neural hyperaesthesia, still without solid ground or proof. This review summarizes the currently known causes for nonallergic noninfectious rhinitis and possible treatments. Also possible pathophysiological mechanisms of IR are discussed.

Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double‐blind randomized application regimen study

Background:u2002 In a recent study, we showed that intranasal capsaicin spray gives a significant and long‐term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double‐blind double‐dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective.

Allergic rhinitis and inflammation: the effect of nasal corticosteroid therapy

Topical corticosteroids have proved to be effective in the treatment of allergic rhinitis. The symptomatology of allergic rhinitis is considered to be the result of the accumulation and activation of inflammatory cells and cytokine release and hence the efficacy of corticosteroids is associated with their anti‐inflammatory action. New advances in allergic inflammation now suggest that not only mast cells and eosinophils but also T‐lymphocytes and antigen‐presenting dendritic cells, play an important role in the inflammatory reaction. The effect of topical fluticasone propionate on cellular infiltration in the nasal mucosa is examined, with an emphasis on two studies performed in Rotterdam, The Netherlands. The cells influenced most by corticosteroid therapy were Langerhans cells (antigen‐presenting cells), which were almost completely eradicated, possibly resulting in diminished antigen presentation, and eosinophils. There was a reduction in the number of epithelial mast cells, but the number of T‐lymphocytes only decreased following high doses of corticosteroid therapy or long‐term treatment. However, T‐lymphocyte function was influenced, as shown by the reduction in the T‐helper, (ThJ‐related cytokines, interleukin (1L)‐4 and IL‐5. Topical corticosteroid therapy had no effect on the accumulation of macrophages. The reduction in antigen presentation, and the decrease in T‐lymphocyte stimulation and cytokine production, may cause a reduced influx of eosinophils and other inflammatory cells, resulting in diminished symptomatology.

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.

Fixation with Carnoy's fluid reduces the number of chymase-positive mast cells : not all chymase-positive mast cells are also positive for tryptase

Mast cells in the nasal mucosa can be studied by means of monoclonal antibodies (mAb) against tryptase (T+MC) and chymase (C+MC). Fixation with acetone gives more positive cells than does fixation with Carnoys fluid. In frozen biopsy specimens of allergic nasal mucosa fixed with acetone, the number of T+MC equals that of C+MC. When fixed with Carnoys fluid, however, the number of T+MC is larger than the number of C+MC. The decrease in both T+MC and C+MC resulting from fixation with Carnoys fluid is time‐related and depends on the type of mAb used. Carnoy fixation time gives a decrease in the number of C+MC within 1 min, whereas the number of T+MC decreases only after 10 min. Within 1 min, the number of C+MC decreases to a level where continued fixation no longer gives further decreases in the number of cells. Two populations of mast cells can be distinguished here: one sensitive and the other insensitive to Carnoys fluid. When double‐staining is used, fixation with acetone gives three populations of mast cells: one positive for tryptase (T+C‐MC), another positive for tryptase and chymase (T+C+MC), and a third one positive for chymase (T‐C+MC). These three populations were found in lymph node, spleen, thymus, dermis, lung parenchyma, small intestinal submucosa, and nasal mucosa.

The effect of fluticasone propionate aqueous nasal spray on nasal mucosal inflammation in perennial allergic rhinitis

Mast cell degranulation, and the subsequent recruitment of infiltrating inflammatory cells, such as eosinophils, into the nasal mucosa has long been considered the most important model to explain allergic rhinitis. Several studies show a decrease in the number of eosinophils and possibly also mast cells during local corticosteroid treatment. Over the last decade, a new model to explain allergic inflammation has evolved. In this model, Langerhans’cells and T‐cells play an important role. Langerhans’cells possess a high affinity receptor for IgE. In patients with allergic rhinitis, allergen provocation results in stimulation of T‐cells by the IgE‐positive Langerhans’cells. The T‐cells produce a number of cytokines which stimulate IgE production as well as the inflammatory reaction. The number of T‐cells is not usually influenced by corticosteroid treatment; however, the function of the T‐cells, shown by the spectrum of cytokines produced, is clearly influenced. The cells that are most dramatically affected by local corticosteroid treatment are the Langerhans’cells, which completely disappear during treatment. This decrease suggests that there is a reduction in antigen presentation. The subsequent decrease in T‐cell stimulation may result in a reduction of the reactions that are dependent on T‐cell‐derived mediators.

NOVEL HEAD AND NECK CANCER SURVIVAL ANALYSIS APPROACH: RANDOM SURVIVAL FORESTS VERSUS COX PROPORTIONAL HAZARDS REGRESSION

Electronic patient files generate an enormous amount of medical data. These data can be used for research, such as prognostic modeling. Automatization of statistical prognostication processes allows automatic updating of models when new data is gathered. The increase of power behind an automated prognostic model makes its predictive capability more reliable. Cox proportional hazard regression is most frequently used in prognostication. Automatization of a Cox model is possible, but we expect the updating process to be time‐consuming. A possible solution lies in an alternative modeling technique called random survival forests (RSFs). RSF is easily automated and is known to handle the proportionality assumption coherently and automatically. Performance of RSF has not yet been tested on a large head and neck oncological dataset. This study investigates performance of head and neck overall survival of RSF models. Performances are compared to a Cox model as the “gold standard.” RSF might be an interesting alternative modeling approach for automatization when performances are similar.

A visual analog scale can assess the effect of surgical treatment in children with chronic otitis media with effusion

BACKGROUNDnThe OM-6 survey is a validated and multinationally accepted instrument to measure the treatment effect of otitis media in children. Routine use of the OM-6 in a busy general practice is not always possible and can lead to incomplete returned surveys. A simplified method is favoured when the aim is a continuous process of complete treatment-outcome-data collection. This study tests if a VAS can quantify how much a child suffers from chronic otitis media and how much this changes due to surgical treatment. The change in overall OM-6 scores due to surgical treatment, functions as the gold reference standard. Furthermore, this study tests if the VAS is faster to use than the OM-6 and if it leads to an improvement in complete data collection.nnnMETHODSnProspective cohort follow-up study of 175 consecutive children with chronic otitis media in a paediatric otolaryngology practice in a metropolitan area. Data collected included patients age, gender, clinical presentation, type of surgical procedure performed, overall OM-6 score and VAS score (at initial presentation and at follow-up), time needed to complete an OM-6 survey and VAS separately and number of incorrect OM-6 surveys and VAS questions returned.nnnRESULTSnThe VAS scores and overall OM-6 scores show a good, positive correlation at baseline (Spearmans rho=0.71). This correlation improves at follow-up, one and 6 months after intervention (rho=0.73 and rho=0.80, respectively). The change in VAS scores and overall OM-6 scores, interpreted as change due to surgical intervention, show a good positive correlation at follow-up (rho=0.70 and rho=0.77, respectively). The VAS is almost three times faster than the OM-6 (28s versus 81s). More than 13% of OM-6 surveys were returned incomplete. All VAS questions were returned correct.nnnCONCLUSIONSnThe VAS can be used as a simplified method for routine surgical treatment effect analysis in children with chronic otitis media.