Mandibulotomy access to tumour sites: fewer complications for postoperative compared with preoperative radiotherapy.

The purpose of this study was to compare complication rates at the mandibulotomy site between patients receiving preoperative radiotherapy (RT) and those receiving postoperative RT during treatment for oral and oropharyngeal cancer where the surgical procedure required a mandibular osteotomy to gain access to the tumour. Sixty-four consecutive patients treated during the period 2000-2015 were available for analysis. Their medical records were reviewed retrospectively. All patients were followed for at least 1year postoperatively. A subgroup of patients received RT on several occasions or long before the mandibulotomy, therefore the statistical comparisons focused on the two groups of patients receiving RT on one occasion and within 6 months prior to or following surgery. Seventeen patients presented a total of 29 complications, yielding an overall complication rate of 27%. Orocutaneous fistula was the most common complication. Patients who received RT preoperatively presented a higher complication rate (9/15; 60%) when compared to those who received RT postoperatively (2/31; 6.5%) (odds ratio 21.8, P<0.001). This study demonstrated fewer complications in the mandibulotomy area exposed to postoperative RT compared with preoperative RT. It is therefore suggested that, when possible, RT should be given postoperatively if combination treatment with RT and surgery, including a mandibulotomy, is planned.

C-type Lectin Receptor Expression on Human Basophils and Effects of Allergen-Specific Immunotherapy.

Basophils are emerging as immunoregulatory cells capable of interacting with their environment not only via their characteristic IgE-mediated activation, but also in an IgE-independent manner. Basophils are known to express and respond to stimulation via TLR2, TLR4, DC-SIGN and DCIR, but whether basophils also express other C-type lectin receptors (CLRs) is largely unknown. In this study, we investigate the CLR expression profile of human basophils using multicolour flow cytometry. As FcRs as well as some CLRs are associated with allergen recognition and shown to be involved in subsequent immune responses, the expression of CLRs and FcRs on peripheral blood basophils, as well as their frequency, was monitored for 1 year in subjects undergoing subcutaneous allergen-specific immunotherapy (AIT). Here, we show that human basophils express CLECSF14, DEC205, Dectin-1, Dectin-2 and MRC2. Furthermore, we demonstrate that the frequencies of basophils expressing the allergy-associated CLRs Dectin-1 and Dectin-2 were significantly reduced after 1 year and 8 weeks of AIT, respectively. In contrast, the frequency of basophils positive for FcγRII, as well as the fraction of total basophils, significantly increased after 1 year of AIT. The herein demonstrated expression of various CLRs on basophils, and their altered CLR and FcR expression profile upon AIT, suggest yet unexplored ways by which basophils can interact with antigens and may point to novel immunoregulatory functions targeted through AIT.

Diversity of immunoglobulin E-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis.

BACKGROUND: The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. OBJECTIVE: To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). METHODS: The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4 ± 3.2%; CRS, 7.0 ± 4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE. CONCLUSION AND CLINICAL RELEVANCE: We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease.

TRPV1-mediated itch in seasonal allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). AIM OF THE STUDY: To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. METHODS: Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms were monitored after each challenge and compared with symptoms reported following corresponding sham challenges. Symptoms recorded after challenge prior to pollen season were also compared with challenge-induced symptoms during pollen season. RESULTS: The TRPV1, TRPA1 and TRPM8-activators produced sensory symptoms dominated by pain and smart. During seasonal allergen exposure, but not prior to season, TRPV1-activators also induced itch. Furthermore, the seasonal challenge to the TRPV1-activator olvanil was associated with rhinorrhoea. CONCLUSION: Patients with allergic rhinitis feature an increased itch response to TRPV1 stimulation at seasonal allergen exposure. We suggest that this reflects part of the hyperresponsiveness that characterizes on-going allergic rhinitis. Intervention with the TRPV1-signalling pathway may offer potential treatments of this condition.

Incidence and remission of self-reported allergic rhinitis symptoms in adults.

BACKGROUND: A few studies have examined the incidence and remission of allergic rhinitis (AR) in the same general population. METHODS: A questionnaire focused on respiratory symptoms and airway diseases was mailed out in 1992 and in 2000 to the same subjects. Of 4933 subjects, in 1992 aged 20-59 years, 4280 (86.8%) answered at both occasions. AR was defined on self-reported AR and a simultaneous report of nasal symptoms provoked by exposure either to tree-, grass-pollen, furred animals or house dust. Multiple logistic regression adjusted for age and gender was used to analyze potential predictors, reported in 1992, for incidence and remission of AR. RESULTS: The prevalence of AR increased from 12.4% in 1992 to 15.0% in 2000. The incidence of AR from 1992 to 2000 was 4.8%, while 23.1% of the cases with AR in 1992 stated no AR symptoms in 2000 indicating remission. The highest incidence was seen in the youngest age group (20-29 years), whereas remission was highest in the oldest age group (50-59 years). Asthma symptoms during the last year (as reported in 1992) predicted increased incidence of AR and less chance for remission, 1.89 (95%CI 1.08-3.31) and 0.52 (0.31-0.87), respectively. Family histories of AR or asthma predicted increased incidence of AR 1.99 (1.42-2.80) and 1.62 (1.10-2.37), respectively, but were not associated with chance for remission, OR = 1.23 (0.81-1.87) and 0.94 (0.60-1.48). CONCLUSION: This study showed that AR became more common between 1992 and 2000, but also indicated remission in about 20% of the cases within the 8-year period, particularly in older ages. Asthma seems to be associated with higher risk for AR as well as less chance for remission, while heredity of asthma (or AR) may only be associated with the risk for the development and not remission of AR.

Obstructive airways diseases, smoking and use of inhaled corticosteroids in southern Sweden in 1992 and 2000.

OBJECTIVE: To examine the prevalence of obstructive pulmonary diseases, respiratory symptoms, smoking habits and pulmonary medication in an adult population, and to compare the results with a study performed in the same geographical area in 1992. DESIGN: In 2000, a postal questionnaire was sent to a randomly selected population of 5179 subjects aged 20-59 years living in southern Sweden. RESULTS: The participation rate was 71.3%. Self-reported asthma was reported by 8.5% of all respondents (vs. 5.5% in 1992, P < 0.001) and 14.5% of females aged 20-29 years. Self-reported chronic bronchitis and/or emphysema and/or chronic obstructive pulmonary disease (CBE/COPD) was reported by 3.6% (vs. 4.6% in 1992, non-significant) with the highest prevalence (5.7%) in the 50-59 year cohort. Smoking decreased from 33.3% in 1992 to 28.4% in 2000 (P < 0.05). About 46% of asthmatics reported nocturnal respiratory symptoms, and 69% reported having had asthma symptoms in the last 12 months. Use of inhaled steroids increased in subjects with asthma and CBE/COPD from 19.4% to 36.5% (P < 0.05) and from 8.6% to 30.0% (P < 0.05), respectively. CONCLUSIONS: Self-reported asthma increased significantly between 1992 and 2000, but the prevalence of CBE/COPD was unchanged. The high proportion of reported symptoms in asthmatics despite an increased use of steroids suggests that further efforts are needed to improve asthma treatment.

Blockade of CTLA-4 promotes airway inflammation in naive mice exposed to aerosolized allergen but fails to prevent inhalation tolerance.

In subjects not developing allergy, inhalation of nonpathogenic protein antigens causes no harm and is associated with tolerance induction. Repeated exposure to aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and induces inhalation tolerance in experimental animals. The present study explored the role of the inhibitory T-cell receptor CTLA-4, in preventing inflammation and in establishing inhalation tolerance in response to a protein antigen. Naive BALB/c mice were injected intraperitoneally with anti-CTLA-4 monoclonal antibody or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA over 10 or 20 consecutive days. OVA-specific IgE levels and the inflammatory response in airway tissues were assessed 2 days after last exposure. The OVA-specific IgE response was also evaluated in mice subjected to a subsequent immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice were made tolerant by 10 days of OVA aerosol exposure and were then subjected to an immunogenic OVA challenge combined with CTLA-4 blockade or control IgG treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary inflammatory response. In contrast, 10 days of OVA exposure combined with blockade of CTLA-4 led to development of eosinophilic lung infiltrates, BAL fluid eosinophilia, goblet cell hyperplasia and increased OVA-specific IgE. By 20 days of OVA exposure and blockade of CTLA-4, the inflammatory response remained. Mice exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA-specific IgE responses to subsequent immunogenic OVA challenge. Blockade of CTLA-4 during the period of OVA aerosol exposure did not prevent this suppression of the OVA-specific IgE response. Neither did blockade of CTLA-4 during immunogenic OVA challenge alter the allergen-specific IgE response. Our results indicate that in vivo blockade of CTLA-4 modulates the initial immune response to a protein antigen allowing the development of allergen-induced airway inflammation in naive mice. However, this initial exaggerated immune response is followed by the induction of inhalation tolerance, demonstrating that CTLA-4 signalling is not decisive in this process. Our findings also show that once inhalation tolerance is established it may not be disrupted by blockade of CTLA-4.

Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation.

BACKGROUND: In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. OBJECTIVE: To determine the degranulation status of circulating eosinophils in common allergic diseases. METHODS: Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg-Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. RESULTS: Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89-98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). CONCLUSION: In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ.

Secretoneurin is released into human airways by topical histamine but not capsaicin.

BACKGROUND: The neuropeptide secretoneurin, with potential relevance to leukocyte trafficking, is present in nerves of the nasal mucosa in allergic rhinitis and may be released in response to allergen and histamine exposure. There is no information on the occurrence and mechanisms of release of secretoneurin in healthy human airways. METHODS: The presence of secretoneurin in nasal biopsies and its release in response to nasal capsaicin and histamine challenges were examined. Symptoms and lavage fluid levels of fucose were recorded as markers of effects in part produced by neural activity. Bronchial histamine challenges followed by sputum induction and analysis of secretoneurin were also carried out. RESULTS: Nerves displaying secretoneurin immunoreactivity abounded in the nasal mucosa. Nasal capsaicin challenge produced local pain (P <0.05) and increased the levels of fucose (P <0.05), but failed to affect the levels of secretoneurin. Nasal histamine challenge produced symptoms (P <0.05) and increased the mucosal output of secretoneurin (P <0.05) and fucose (P <0.05). Bronchial histamine challenge increased the sputum levels of secretoneurin (P <0.05). CONCLUSIONS: We conclude that secretoneurin is present in healthy human airways and that histamine evokes its release in both nasal and bronchial mucosae. The present observations support the possibility that secretoneurin is involved in histamine-dependent responses of the human airway mucosa.

Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure.

Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure. A total of 23 patients scored symptoms q.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively. Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure increased this degranulation (87+/-1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge. In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis.

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide). METHODS: During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.

Influence of heavy traffic, city dwelling and socio-economic status on nasal symptoms assessed in a postal population survey.

BACKGROUND: The association between social position, living environment and nasal symptoms is inconsistent. We wanted to test how living environment, occupation and social position were associated with nasal symptoms. METHODS: In a postal survey study of a random sample of 12,079 adults, aged 20-59 years living in the southern part of Sweden the relationship between nasal symptoms, socio-economic status and environmental factors was analysed. RESULTS: The response rate was 70% (n = 8469) of whom 33% reported significant nasal symptoms. Nasal discharge, thick yellow discharge, a blocked nose, sneezing and itching were strongly associated with living close to heavy traffic or living in cities. Most of the nasal symptoms provoked by extrinsic factors were more frequently reported among subjects who lived close to heavy traffic and in cities. Apart from thick yellow discharge and nasal symptoms provoked by damp/cold air which were more common in the socio-economic position "low" no relation to the socio-economic group was found. The prevalence of self-reported hay fever was neither affected by site of living nor by socio-economic status. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by non-allergic factors were linked to chronic bronchitis/emphysema CBE. CONCLUSIONS: To conclude, we found a strong relation between geographical site and the prevalence of self-reported nasal symptoms which emphasizes the environment as a risk factor for nasal symptoms. Only by merging the socio-economic groups into "low" and "middle/high" an association to nasal symptoms was apparent. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by "non allergic factors" were linked to CBE.

Hypertonic saline increases secretory and exudative responsiveness of human nasal airway in vivo.

Hypertonic saline (HS) is used in sputum induction studies. However, little is known about the physiological effects of HS on human airways in vivo. The present study takes advantage of the fact that the airway effects of topical challenges may be accurately examined in the readily accessible nasal airway. The present study specifically examines whether exposure to HS affects histamine challenge-induced exudation of plasma (alpha2-macroglobulin) and methacholine-induced secretion of mucin (fucose). Isotonic saline and HS (27 and 45 g x L(-1)), with and without concomitant histamine challenges, and with and without preceding methacholine challenges, were administered onto the nasal mucosa in 16 healthy subjects. Lavage fluid levels of alpha2-macroglobulin and fucose were analysed. Histamine produced a significant mucosal output of plasma (alpha2-macroglobulin). HS itself did not evoke exudation of alpha2-macroglobulin, but it significantly increased the plasma exudation effect of histamine. Methacholine produced a significant nasal mucosal output of fucose. HS also increased the mucin secretion (fucose), and it enhanced the secretory effect of methacholine. The authors concluded that hypertonic saline alone evokes mucinous secretion in human nasal airways in vivo and that it also enhances the exudative and secretory effects of histamine and methacholine, respectively. Through different mechanisms the HS exposure may also improve the recovery of soluble indices in human nasal airways. Whether or not the present findings are translatable to human bronchial airways remains to be examined.

Effects of rhinovirus-induced common colds on granulocyte activity in allergic rhinitis.

OBJECTIVE: To explore the activities of mast cells, eosinophils, and neutrophils in patients with allergic rhinitis developing common colds and increased responsiveness to allergen following nasal rhinovirus inoculation. METHODS: We have revisited a nasal lavage material obtained from 17 patients who were successfully inoculated with rhinovirus outside the pollen season and received nasal allergen challenges before and after inoculation. We have examined indices of mast cell activity (tryptase), eosinophil degranulation (eosinophil peroxidase; EPO), and neutrophil activation (myeloperoxidase; MPO). RESULTS: Allergen challenges performed before rhinovirus inoculation increased the nasal output of EPO. Notably, this response was significantly greater after rhinovirus inoculation (cf. before inoculation). The output of MPO was also increased following allergen challenge after, but not before, rhinovirus inoculation. Nasal lavage fluid levels of tryptase were increased following allergen challenge similarly before and after rhinovirus inoculation. Also, the viral infection did not affect the baseline levels of tryptase. CONCLUSIONS: The present data demonstrate that rhinovirus infections activate both eosinophils and neutrophils, but that they may not affect mast cell activity. We suggest that common colds in part through stimulation of granulocyte activity potentiate the airway inflammation in allergic diseases.

Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis.

BACKGROUND: Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. OBJECTIVE: To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. METHODS: Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. RESULTS: All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. CONCLUSION: The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.

Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment.

BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. METHODS: Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. RESULTS: At baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.

Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis.

Acute and late phase (dual) symptomatic responses after allergen challenge commonly occur in allergic asthma. The aim of the present study was to explore the occurrence of allergen challenge-induced biphasic responses in patients with chronic perennial allergic rhinitis living in an area with high house dust mite (HDM) exposure. Fifteen patients with perennial rhinitis and evident allergy to HDM participated. Nasal challenges with HDM and sham were performed on separate days in a crossover design. Nasal symptoms, forced expiratory volume in 1 s (FEV1) and orally exhaled nitric oxide were recorded every hour for up to 8 h after each challenge. Alpha2-macroglobulin and eosinophil cationic protein (ECP) were analysed in hourly nasal lavages, and nasal histamine provocations were carried out after 8 h. HDM, but not sham, caused an immediate increase in nasal symptoms which gradually abated over the 8-h period. No reoccurrence of nasal late phase symptoms was seen. HDM, but not sham, induced an early increase in alpha2-macroglobulin and ECP levels: both indices remained elevated for up to 3 h after challenge. HDM challenge evoked hyper-responsiveness to histamine expressed as increased nasal symptoms (p < 0.05; HDM vs sham). No differences in exhaled nitric oxide or FEV1 were demonstrated at any one time point between the HDM- and sham-challenged days. It is concluded that nasal symptomatic and exudative late phase responses may not be a general feature, even in subjects with perennial rhinitis challenged with high, symptom-provoking, doses of HDM allergen.

Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema.

Little information is available on associations between rhinitis and chronic bronchitis/emphysema (CBE). Self-reported upper airway symptoms, asthma, and CBE were examined in 12,079 adults living in southern Sweden. The response rate was 70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported bronchial disease were generally more common among smokers than nonsmokers. There was little overlap between asthma and CBE, but 46% of those with asthma and 40% of those with CBE had significant nasal symptoms. Best predicting factors (odds ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and damp/cold air, respectively. One-third of an adult, southern Swedish population, had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were frequently found to coexist with both asthma and chronic bronchitis/emphysema, suggesting that pan-airway engagement is common in both diseases. Differing associations between types of nasal symptoms and allergic and irritant triggers of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema, emphasize the different natures of these bronchial diseases.