Basophils and mast cells at the centre of the immunological response.
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Basophils↗
Biomedical subjects
W J Fokkens
Publications and source records attributed to W J Fokkens.
Allergic rhinitis and its impact on otorhinolaryngology.
Allergic rhinitis (AR) is a disease with growing impact on everyday medical practice, as its prevalence has steadily increased during the last decades. Immunoglobulin-E (IgE)-mediated airway inflammation may manifest itself as AR, asthma or both. Allergic inflammation in upper and lower airways is now considered as one airway disease, with manifestation of symptoms in upper, lower or global airway. This insight into allergic inflammation of the whole respiratory tract has consequences for the diagnostic and therapeutic approach of affected patients, as highlighted in the ARIA document. In contrast to asthma, the link between AR and associated conditions in the upper airways like rhinosinusitis, nasal polyps, recurrent viral infections, adenoid hypertrophy, tubal dysfunction, otitis media with effusion and laryngitis remains less explored. It is however of utmost importance to consider the aetiological role of IgE-mediated inflammation of the nasal mucosa in several diseases of the upper respiratory tract, as they represent a large body of patient population seen by the general practitioner as well as the paediatrician, allergologist and otorhinolaryngologist. We here aim at reviewing the current literature on the relationship between AR and conditions in upper airways frequently encountered in everyday clinical practice, and highlight the need for further studies exploring the role of allergic inflammation in the development of these diseases.
Adenoids↗
The 'best method' of topical nasal drug delivery: comparison of seven techniques.
OBJECTIVE: To determine whether there is a 'best' technique for delivering drugs to the middle meatus. DESIGN: Single-blind cross-over study in healthy individuals using endoscopic video-imaging. PARTICIPANTS: A dyed test formulation was administered intranasally on seven non-sequential days to ten healthy individuals with no 'nasal' history. The participants were recruited through advertisement. MAIN OUTCOME MEASURES: Comparison of seven different techniques, 20 nostrils and 140 endoscopic videos for the deposition patterns of dyed test formulation. Analysis was possible in 90% of all endoscopic videos. Three head positions were tested for both nasal drops and nasal sprays. RESULTS: Deposition of dyed test formulation near the middle meatus was observed in 43% of all observations. No significant differences were observed in terms of delivery between any of the seven techniques. CONCLUSIONS: Our study suggests there may not be a single 'best' technique for topical nasal drug delivery. A more individual approach to topical nasal drug treatment, taking anatomy and head position into account would seem to be more appropriate.
Administration, Intranasal↗
Reduced nasal IL-10 and enhanced TNFalpha responses during rhinovirus and RSV-induced upper respiratory tract infection in atopic and non-atopic infants.
Rhinovirus and respiratory syncytial virus (RSV) are the most prevalent inducers of upper respiratory tract infections (URTI) in infants and may stimulate immune maturation. To estimate the amount of immune stimulation, nasal immune responses were examined during rhinovirus and RSV-induced URTI in infants. Nasal brush samples were taken from infants (2-26 months; 57% atopic family) with rhinovirus-induced URTI (N=20), with RSV-induced URTI (N=7), and with rhinovirus-induced rhinitis (N=11), from children with asymptomatic rhinovirus infection (N=7) and from eight non-infected children. Numbers of nasal brush cells positive for Th1-, Th2-, regulatory and proinflammatory cytokines were measured by immunohistochemistry or by measuring protein levels using a cytometric bead array analysis. During rhinovirus and RSV-induced URTI, fewer regulatory cytokine IL-10 positive cells were found compared to non-infected children. This fall was accompanied by an increase in levels of the Th1 cytokine TNFalpha. IL-10 responses were inversely related to TNFalpha responses. No enhanced responses were observed for IFNgamma, IL-12 and IL-18. Cytokine responses were comparable in children with rhinovirus-induced URTI and in children with rhinitis, while responses in asymptomatic rhinovirus-infected children were located between those for symptomatic and asymptomatic rhinovirus-infected children. Cytokine responses did not depend on the age of the child or atopy in the family. In conclusion, reduced nasal IL-10 responses during URTI in infants could facilitate the induction of a TNFalpha response. TNFalpha in turn could replace the immature production of IL-12, IL-18 and IFNgamma during URTI to induce an effective clearance of the viral infection and which could stimulate the maturation of Th1 cytokine production in infancy.
Child, Preschool↗
Age- and infection-related maturation of the nasal immune response in 0-2-year-old children.
BACKGROUND: The hygiene hypothesis suggests that exposure to micro-organisms influences development of the immune system in children. METHODS: In this study, we examined nasal immune responses in the first 2 years of life in relation to age of children and the number of viral infections they have experienced. Nasal brushes were taken during rhinovirus- (n = 20) or respiratory syncytial virus (RSV)-induced (n = 7) upper respiratory tract infections (URTI), and of controls (n = 40). RESULTS: The number of macrophages were higher during URTI and increased with age. The number of T lymphocytes increased with age in controls and were higher during URTI at all ages. We found an age-related decrease in the number of interleukin (IL)-4- and IL-10-positive cells in controls, while the number of IL-12-positive cells remained unchanged. Changes in T lymphocyte and IL-4 cell number were stronger related to the age of the child than to the number of respiratory infections, while the opposite was true for macrophages. CONCLUSIONS: In infants, we found an infection- and age-related increase respectively for nasal macrophages and T lymphocytes during URTI. Furthermore, the number of IL-4- and IL-10-positive cells decreased with age. Whether this maturation reflects a natural age-related maturation, the degree of exposure to respiratory infections, or possibly both, could not be resolved and needs further study.
Age Distribution↗
Evaluation of an intranasal house dust mite provocation model as a tool in clinical research.
BACKGROUND: As a result of the all-year-round exposure to house dust mite (HDM), perennial rhinitis patients never have a clear symptom-free period. In this study, we investigated whether, despite these symptoms, we can still use nasal HDM provocations to study perennial allergic rhinitis and the effects of treatment. METHODS: In a parallel-group study, after 1 week treatment with either fluticasone propionate aqueous nasal spray (FPANS) or placebo, 20 patients, allergic to HDM, registered symptoms (nasal obstruction, rhinorrhoea, sneezing, pruritus and eye symptoms) using three different scoring methods [Lebel, categorical and visual analogue scale (VAS)] and peak nasal inspiratory flow (PNIF) after HDM provocations. Provocations were performed with 1000 biological units/ml and 24 h later with 10,000 biological units/ml of HDM. Before and after the provocations, nasal mucosa biopsies were taken for immunohistochemical staining to determine the number of eosinophils. RESULTS: House dust mite provocations resulted in an increase in symptoms and a decrease in PNIF. Even at high-dose provocation, the FPANS group registered significantly lower symptoms than the placebo group for nasal blockage, sneezing, eye symptoms, and PNIF in both early and late phases. FPANS also suppressed rhinorrhoea during the late phase and the influx of eosinophils in the lamina propria. CONCLUSION: Despite the high background of symptoms, allergic responses can be induced in this perennial rhinitis model. The VAS score seems most suited to detect these changes and the suppression of symptoms by 7 days of FPANS treatment. Epithelial eosinophilia at baseline was correlated positively with the severity of the reaction after the first provocation.
Administration, Intranasal↗
Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.
Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.
Administration, Inhalation↗
Desloratadine reduces systemic allergic inflammation following nasal provocation in allergic rhinitis and asthma patients.
BACKGROUND: Preclinical studies have demonstrated that some second-generation antihistamines have anti-inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass-pollen-allergic rhinitis and asthma. METHODS: Twenty-six subjects with grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season. On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and bronchial biopsies were taken for immunohistochemical evaluation, and blood samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow and peak expiratory flow, were also measured at specified times. RESULTS: The number of circulating eosinophils decreased during DL treatment, and there was a reduced increase in circulating eosinophils after NP in these subjects. There was also a significant reduction in early bronchial clinical response. There was no significant lessening in the severity of the nasal symptoms. Nasal and bronchial mucosal inflammation parameters did not alter under DL treatment. CONCLUSION: These data suggest that treatment with DL reduces systemic eosinophilia and prevents the increase in circulating eosinophils after NP. DL also significantly reduces the early bronchial clinical response to NP. However, airway mucosal inflammation is not altered by 1 week of treatment.
Adult↗
Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate.
Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation, Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid onset of action and excellent safety and efficacy profiles. Having recently received approval for the treatment of nasal polyposis, data indicate that MFNS may also be effective in rhinosinusitis.
Anti-Allergic Agents↗
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.
Aged↗
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. OBJECTIVE: This double-blind placebo-controlled randomized study was performed in order to investigate whether fluticasone propionate aqueous nasal spray (FPANS) reduces the recurrence rate of nasal polyps and chronic rhinosinusitis during the first year after FESS. PATIENTS AND METHODS: The trial looked at 162 patients aged 18 years and older requiring FESS for chronic rhinosinusitis or nasal polyps. After FESS combined with peri-operative systemic corticosteroids, patients were randomized and given FPANS 400 microg b.i.d., FPANS 800 microg b.i.d. or placebo b.i.d. for the duration of 1 year. Patients were withdrawn from the trial (but still included in the study for statistical purposes) if there were recurrent or persistent diseases, defined as progressive regrowth of nasal polyps, recurrent signs and symptoms of chronic sinusitis combined with abnormalities on computed tomography scan and persistent complaints for at least 2 months after FESS. RESULTS: A significant reduction of symptoms was seen after FESS. After 1 year, 46 patients had been withdrawn from the trial because of recurrent diseases and 32 patients because of persistent symptoms. No differences in the number of patients withdrawn because of recurrent or persistent diseases were found between the patients treated with FPANS and patients treated with placebo. We were also unable to find a positive effect of FPANS compared with placebo in several subgroups such as patients with nasal polyps, high score at FESS or no previous sinus surgery. CONCLUSION: This placebo-controlled study does not show that treatment with FPANS up to 1 year after FESS had a positive effect compared with placebo.
Administration, Intranasal↗
Perennial rhinitis in the under 4s: a difficult problem to treat safely and effectively? A comparison of intranasal fluticasone propionate and ketotifen in the treatment of 2-4-year-old children with perennial rhinitis.
To compare the safety and efficacy of fluticasone propionate aqueous nasal spray (FPANS) and oral ketotifen in children aged 2-4 years with perennial rhinitis. A randomized, multicentre, double-blind, double dummy, placebo-controlled study. Paediatric patients between the ages of 2-4 years with perennial rhinitis. Rhinitis symptoms score (parent-rated), clinical evaluation of symptoms (investigator-rated) and adverse event profiles during the treatment period. Patients treated with FPANS had a significant reduction in both the total night-time rhinitis symptom assessment for weeks 4-6 (p-value 0.036), and the total daytime rhinitis symptom score over the same period (p-value 0.049). Generally, except for nasal itching/rubbing over weeks 1-3, the patients taking FPANS had lower recorded symptom scores for all individual symptoms measured. Nasal blockage, in particular, was significantly reduced over the 4-6 week period (p-value 0.027). The overall investigator-rated clinical evaluation showed substantial improvement or improvement in nine of 12 of the children taking FPANS compared with four of 14 taking ketotifen. Finally, there were no reports of serious adverse events, the incidence of drug-related adverse events was low and there was no statistical difference between the groups. FPANS may be an appropriate treatment to control the symptoms of rhinitis in children between 2 and 4 years old.
Administration, Intranasal↗
The diagnosis and management of chronic cough.
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Adult↗
Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection.
Respiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus-specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV-specific cellular immune response in infants with a laboratory-confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2-22 months) in comparison with infants with non-RSV mediated URTI (n = 9, mean age 9.3 months, range 4-18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1-6 months). RSV-specific cytokine-producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T-cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) responses were detected in all three groups. Frequencies of RSV-specific T-cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non-RSV URTI group. The absence of vigorous virus-specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease.
Cytokines↗
Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study.
BACKGROUND: 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. METHODS: Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. RESULTS: The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. CONCLUSIONS: We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.
Administration, Intranasal↗
Nasal corticosteroids, first choice in moderate to severe allergic rhinitis. What prevents general practitioners from using them?
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Administration, Intranasal↗
Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways.
BACKGROUND: Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma. OBJECTIVE: The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma. METHODS: Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system. RESULTS: In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P < or = 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02). CONCLUSIONS: This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.
Adolescent↗
Inflammatory cells seem not to be involved in idiopathic rhinitis.
Mucosal inflammatory cellular infiltrates are correlated with nasal complaints in symptomatic allergic rhinitis. Some authors suggest inflammation of a neurogenic or immunogenic nature as an underlying disorder for idiopathic rhinitis (IR). We looked at the possible involvement of inflammatory cells in the pathogenesis of IR. Nasal biopsies were taken from sixty-five IR patients with significant nasal complaints and from twenty healthy controls with no nasal complaints. Inflammatory cells were quantified using monoclonal antibodies directed against lymphocytes, antigen-presenting cells, eosinophils, macrophages, monocytes, mast cells and other IgE-positive cells. No significant differences were found, for any cell, between IR patients and controls. We conclude that inflammatory cells do not seem to play an important role in this meticulously characterised group of IR patients.
Adolescent↗