Nasal Lavage Fluid Levels Research Articles

Effects of Mometasone Furoate Nasal Spray on Patients with Seasonal Grass Pollinosis

Objective: Seasonal grass pollinosis has recently become a major problem because many people suffer from this allergy. In this study, we evaluate the clinical effects of mometasone for seasonal grass pollinosis, the changes of chemical mediators in nasal lavage fluid, and their correlation with the clinical response. Method: Twenty patients were treated with mometasone from May to August 2009. To assess the clinical response, we focused on the changes of symptoms shown by the allergy diary of each patient. We also investigated the correlation of ECP, VEGF, and eotaxin levels in nasal lavage fluid with the severity of symptoms. Results: There was a significant reduction of the symptom score, medication score, and symptom medication score after administration of mometasone, and also ECP, VEGF, and eotaxin levels showed significant reduction in nasal lavage fluid. We found a significant correlation with VEGF and nasal symptoms. Conclusion: These results may allow us to speculate that mometasone furoate nasal spray is effective for the treatment of patients with seasonal grass pollinosis and also useful to improve QOL of these patients.

Nasal lavage CCL24 levels correlate with eosinophils trafficking and symptoms in chronic sino-nasal eosinophilic inflammation

The aim of our study was to measure CCL24 (eotaxin-2) levels in nasal lavage fluid of patients with different forms of sinonasal chronic eosinophilic inflammation to verify the relationship with nasal hypereosinophilia and symptoms. Patients with nasal hypereosinophilia were randomly recruited and grouped in persistent allergic rhinitis, non-allergic rhinitis with eosinophilia syndrome (NARES) and chronic rhinosinusitis with polyps. Non rhinitic volunteers were recruited as controls. CCL24 concentration was measured by `Quantikine Human CCL24 Immunoassay`. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped by inferior turbinate. CCL24 levels measured in patient groups were significantly higher compared to control group with the highest levels in NARES patients. Eotaxin- 2 levels were significantly correlated to severity of symptoms and to the percentage of eosinophils in nasal tissue. We revealed high levels of CCL24 in all patient groups showing a significant correlation with the degree of eosinophilia and clinical symptoms. A prolonged accumulation of CCL24 inside the nasal mucosa may sustain the process of unspecific self-perpetuating eosinophil recruitment pathognomonic of these patients.

Eotaxin, but not IL-8, is increased in upper and lower airways of allergic rhinitis subjects after nasal allergen challenge

The aim of this study was to assess the impact of a single nasal allergen challenge (NAC) on levels of eotaxin and IL-8 and the inflammatory cells in upper and lower airways of allergic rhinitis (AR) patients. Twenty-four AR patients and 12 control subjects entered a sequential nasal placebo challenge and NAC study, out of the pollen season. Nasal lavage fluid (NLF) was obtained at baseline, 15 minutes, and 1, 5, and 24 hours postchallenge. Before and 24 hours after placebo/allergen challenge induced sputum was performed. NLF and induced sputum were evaluated for total cell count (TCC) and differential cell count and analyzed for concentrations of eotaxin and IL-8 using ELISA method. NAC in AR subjects was associated with significantly increased sputum (p = 0.008) and NLF (p < 0.001) eotaxin levels. Post-NAC IL-8 levels were significantly increased in NLF (p < 00001) but not in sputum (p = 0.080) of AR subjects. Increased eotaxin levels in NLF positively correlated with the increased TCC and eosinophils. Positive correlations were also found between NLF increased eotaxin level and sputum TCC, eosinophils, and macrophages. NAC is associated with the increased levels of eotaxin in lower airways of AR subjects. Allergen-induced secretion of eotaxin in nasal mucosa of AR subjects is involved in determining the cellular character of both upper and lower airway inflammation.

Immunomodulatory Role of Histamine H2 Receptor in Allergen‐Specific Immunotherapy

The purpose of this pilot study was to investigate the effects of HR2 on allergen-specific immunotherapy in a mouse model of allergic rhinitis. An in vivo study using an animal model. Catholic Research Institutes of Medical Science. Fifty mice were divided into 5 groups: control, allergic rhinitis (AR), immunotherapy (IT), immunotherapy with HR2 agonist (HI), and immunotherapy with HR2 antagonist (HB). All mice except for the control group were sensitized with ovalbumin (OVA). After 1 week, mice in the IT, HI, and HB groups underwent immunotherapy by intradermal injections of OVA. During immunotherapy, the HI group was injected with HR2 agonist, whereas the HB group was injected with HR2 antagonist. All sensitized mice were challenged with intranasal OVA. After the final challenge, allergic behavior was evaluated. Interleukin (IL)-13, interferon-γ, IL-10, and transforming growth factor (TGF)-β levels in nasal lavage fluid (NALF), as well as OVA-specific IgE levels in serum, were measured. The number of eosinophils in lamina propria was evaluated. The levels of serum OVA-specific IgE and IL-13 in NALF were significantly increased in the HB group compared with the IT group (P < .05). Also, the tissue eosinophil counts were higher in the HB group than in the IT group (P < .05). HR2 antagonist impaired OVA-specific immunotherapy in mice. Although confirmation of this preliminary result is needed, these findings suggest that HR2 receptors may have inhibitory effects on immune tolerance. The authors suggest that application of this property could enhance the efficiency of allergen-specific immunotherapy.

Effect of 5-aminosalicylate on allergic rhinitis model in mice

Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in allergic rhinitis. It has been reported that 5-aminosalicylate (5-ASA) has an affinity for PPARgamma, but the effects of 5-ASA on the nasal symptoms of allergic rhinitis are unclear. This study aimed to clarify the effects of 5-ASA on nasal symptoms in an allergic rhinitis model in mice. Female BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum) on days 0, 5, 14 and 21. Seven days later, mice were sensitized by the intranasal application of OVA thrice a week. 5-ASA was also administered orally after instillation of the antigen from day 28. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms-sneezing and nasal rubbing. In addition, serum OVA-specific immunoglobulin E (IgE) antibody, interleukin (IL)-4, and IL-10 levels in nasal lavage fluid and histamine sensitivity were determined. Repeated oral administration of 5-ASA attenuated the progression of nasal symptoms in sensitized mice in a dose-dependent manner. Additionally, 5-ASA prevented an increase in histamine sensitivity. Finally, 5-ASA inhibited both OVA-specific IgE antibody and IL-4 production; however, it had no effect on IL-10 levels. These results indicate that 5-ASA has a prophylactic effect on allergic rhinitis.

Immunostimulatory sequence oligdeoxynucleotide/cholera toxin B conjugate: a novel allergen-independent intranasal vaccine for allergic rhinitis

Recent studies have shown that by acting as strong TH1 response-inducing adjuvants, DNA immunostimulatory sequence oligdeoxynucleotides (ISS-ODNs) can be used in the treatment of allergic diseases, and efforts are being made to enhance these TH1 adjuvant actions. To determine whether intranasally delivered ISS-ODN/cholera toxin B (CTB) conjugate has enhanced antiallergic effects in an allergic rhinitis mouse model. BALB-c mice were sensitized with ovalbumin. Chemical conjugation of ISS-ODN and CTB was performed. After a single local intranasal administration of 50 microg of ISS-ODN or high- and low-dose (50- and 5-microg) ISS-ODN/CTB conjugate, we measured the allergic response in terms of sneezing events, eosinophil infiltration in the nasal mucosa, serum ovalbumin specific IgE and IgG2a levels, and TH1 and TH2 cytokine levels in nasal lavage fluid and spleen cell cultures. A single local administration of 50 microg of ISS-ODN did not suppress the allergic phenotype. However, 50 and 5 microg of ISS-ODN/CTB conjugate significantly attenuated allergic symptoms, eosinophil infiltration in the nasal mucosa, and interleukin 4 production from nasal lavage fluid and cultured splenocyte supernatant compared with the allergic control. Serum specific IgG2a and interleukin 12 production in nasal lavage fluid and spleen cell cultures was significantly increased. In a mouse model of allergic rhinitis, a single intranasal delivery of low-dose ISS-ODN/CTB conjugate effectively protects previously sensitized mice from allergic hypersensitivity responses. With further research, ISS-ODN/CTB conjugate may serve as a new allergen-independent intranasal vaccine for the treatment of allergic rhinitis.

Assessment of smoking status based on cotinine levels in nasal lavage fluid

Cotinine is a principal metabolite of nicotine with a substantially longer half-life, and cotinine levels in saliva, urine or serum are widely used to validate self-reported smoking status. The nasal cavity and olfactory system are directly exposed to tobacco smoke in smokers and in non-smokers who live with or work around smokers. However, despite the potential for a direct impact of tobacco smoke on the nasal epithelium and olfactory neurons, no prior studies have assessed cotinine levels in nasal mucus. We sought to determine whether cotinine levels in nasal lavage fluid (NLF) would provide a reasonable estimate of smoke exposure. We assayed cotinine using a competitive immunoassay in NLF from 23 smokers, 10 non-smokers exposed to tobacco smoke (ETS) and 60 non-smokers who did not report smoke exposure. NLF cotinine levels were significantly higher in smokers than in non-smokers, regardless of their exposure to ambient tobacco smoke. Cotinine levels in this small group of exposed non-smokers were not significantly different than those of non-exposed non-smokers. A cutoff of 1 ng/ml provided a sensitivity of 91% and a specificity of 99% for smoking status in this sample. Data were consistent with self-reported smoking status, and a cutoff of 1.0 ng/ml NLF cotinine may be used to classify smoking status. While saliva is the most easily obtained body fluid, NLF can be used to provide an objective and precise indication of smoking status and more directly reflects smoke exposure in the nasal and olfactory mucosa.

Correlation of Quality of Life with Clinical Parameters and Eosinophilic Cation Protein Levels in Children with Allergic Rhinoconjunctivitis

Background: Systemic and mucosal roles of eosinophils in the pathogenesis of allergic rhinoconjunctivitis (AR) are known. The aim of this study was to investigate the relationship of clinical parameters and quality of life with eosinophilic cationic protein (ECP) in grass pollen-sensitive children with seasonal AR. Methods: This study included 31 children with AR and 18 healthy controls aged between 5 and 15 years. ECP levels in nasal lavage fluid and serum were measured. AR symptom scores were calculated and the pediatric rhinoconjunctivitis quality of life questionnaire (PRQLQ) was filled in for all patients. Results: Mean serum and nasal ECP levels (ng/ml) were significantly higher in the patient group (p < 0.05 for both). In the AR group, the mean clinical symptom score was 7.3 ± 2.2, while the total PRQLQ score, activity limitation, symptoms and emotional function domains were 2.5 ± 0.9, 3.0 ± 1.1, 2.5 ± 1.2 and 2.6 ± 1.1, respectively. The total clinical symptom score and disease duration showed a significant correlation with the total PRQLQ score (p = 0.00 and 0.003, respectively). However, neither nasal lavage nor serum ECP levels were significantly correlated with symptom score, duration of disease, PRQLQ total score or domains (p > 0.05 for all). Conclusion: These results may indicate the absence of a correlation between clinical status and quality of life and levels of ECP in tissues with allergic inflammation.

Rosiglitazone Attenuates Allergic Inflammation and Inhibits Expression of Galectin-3 in a Mouse Model of Allergic Rhinitis

Peroxisome proliferator activated receptor gamma (PPAR-gamma) agonists are involved in the regulation of inflammatory responses and recent studies suggest that PPAR-gamma ligands may have potential for the treatment of allergic airway disease. This study investigated the effect of the PPAR-gamma agonist, rosiglitazone, on nasal mucous allergic inflammation and galectin-3 gene expression in a murine model of allergic rhinitis (AR mice). Rosiglitazone resulted in a statistically significant attenuation of the increased numbers of inflammatory cells and Th2 cytokine levels in nasal cavity lavage fluid of AR mice. Furthermore, the expression of galectin-3 in the nasal mucosa of AR mice was statistically significantly increased. Overexpression of galectin-3 was markedly suppressed by rosiglitazone treatment. These data suggest that the PPAR-gamma agonist, rosiglitazone, may have potential in the development of therapies for allergic rhinitis.

Reduction of Substance P in Nasal Lavage Fluid after Allergen Challenge of Mugwort Allergic Patients during Allergen Immunotherapy

Allergen specific immunotherapy (ASIT) may impact neuropeptides released into nasal lavage fluid (NLF) including substance P (SP). 15 subjects (8 females and 7 males) mean age 33.0 ± 7.8 years with symptoms during the previous mugwort pollen season were treated with ASIT as pre-seasonal weekly injections of a mugwort pollen allergoid (Allergovit) for 3 years. All had both positive skin prick tests to mugwort pollen allergen and elevated specific IgE to mugwort pollen (Phadia). The control group consisted of 9 untreated subjects. Nasal mugwort allergen challenge with subsequent lavage performed 15 minutes post-challenge was done by the method of Naclerio. The concentration of SP in NLF was determined by RIA (Incstar, USA). Nasal symptoms during the pollen seasons were recorded. Reduction of symptom scores occurred during the three years of ASIT. Levels of SP in NLF after nasal mugwort challenge in both groups prior to therapy were similar: ASIT group - SP 55.1 ± 15.5 pg/ml versus control group- 54.3 ± 10.1 pg/ml. SP levels in NLF 15 minutes after mugwort allergen challenge were significantly less after 1 year of ASIT versus controls (47.4 ± 14.0 pg/ml versus 53.6 ± 6.8 pg/l) with modest further decrease in SP levels in post-challenge NLF after 2 years of ASIT (42.2 ± 9.6 pg/ml versus 51.2 ± 9.2 pg/ml) and 3 years of ASIT (41.6 ± 18.3 pg/ml versus 51.8 ± 7.6 pg/ml). SP may play a role in nasal allergic responses to mugwort pollen. Decreased release of SP upon nasal allergen challenge occurs with each year of ASIT suggesting that ASIT reduces allergen-induced SP release.

Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis

BackgroundTNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge.MethodsHealthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α2-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.ResultsNasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f. sham challenge). Similarly, α2-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.ConclusionTNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.

Cysteinyl‐leukotrienes in nasal lavage fluid in children with asthma

The aim of this study was to investigate repeatability of cysteinyl-leukotrienes (cys-LT) measurements in nasal lavage fluid (NLF) and to determine if cys-LT levels in NLF are related to asthma severity in children. As a second outcome, we investigated if cys-LT in NLF reflect lower airway inflammation as assessed by exhaled NO measurement. To assess the repeatability of cys-LT measurements, two NLF samples were obtained from eight healthy controls 24 h apart. Sixty-nine asthmatic children (mean age; range: 12.8; 7.3-17.7 yr), which were grouped according to asthma severity were studied cross-sectionally on one occasion. Cys-LT in NLF were analyzed using a specific enzyme immunoassay, exhaled NO, and pulmonary function parameters were measured. The coefficient of repeatability for the repeated cys-LT measurements was 1.45 pg/ml. Cys-LT levels in NLF differed significantly between asthma severity groups (p < 0.001): mild intermittent: [median (IQR)] 6.88 pg/ml (2.00-27.87); mild persistent: 21.09 pg/ml (4.50-84.67); and moderate persistent asthmatics: 36.41 pg/ml (11.03-118.40). Concentration of cys-LT in NLF and exhaled NO was positively correlated (r = 0.85; p < 0.001). In conclusion, concentration of cys-LT in NLF correlates with asthma severity in children and is related to lower airway inflammation.

Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms and signs of allergic rhinitis

Conclusions. Intranasal microemulsion treatment can attenuate allergen challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We hypothesize that the mechanism of action involves modification of the allergen–mucosa interaction. The present observation suggests a novel principle for prevention in allergic rhinitis. Objective. To evaluate a specific microemulsion as a treatment for allergic rhinitis in an acute allergen challenge model. Patients and methods. Patients with allergic rhinitis were examined out of the pollen season. Treatment with a single dose of a specific microemulsion was given in a single-blind, placebo-controlled, and crossover design using a nasal pool device. Nasal allergen challenges were carried out and symptoms of allergic rhinitis were scored. Furthermore, nasal lavages were performed and levels of the plasma protein α2-macroglobulin were measured as an index of exudative inflammation. Results. The allergen challenges produced significant increases in nasal symptoms (p=0.007) and in nasal lavage fluid levels of α2-macroglobulin (p=0.008). The challenge-induced symptoms as well as the plasma exudation were attenuated by treatment with the microemulsion (p=0.016 and 0.012, respectively, compared with placebo).

Signal transduction and oxidative processes in sinonasal polyposis

Nasal polyposis is characterized by impaired regulation of nasal tissue growth and is associated with chronic inflammation, sinus infections, and low levels of nitric oxide (NO). Based on its critical role in mediating cell growth and antimicrobial function, decrease of NO levels has been implicated in the pathogenesis of nasal polyposis. We sought to evaluate mechanisms for the low NO level in polyposis, including factors regulating NO synthase (NOS) expression and activity and NO consumptive processes in nasal epithelial cells and nasal lavage fluid. Eighteen patients with nasal polyposis and 8 healthy control subjects were studied. Nasal brushings, nasal lavage fluid, and nasal biopsy specimens were collected and analyzed. NO metabolite levels (nitrite and nitrate) in nasal lavage fluid from patients with polyps were less than those in control subjects, but activation of signal transduction and inducer of transcription 1, which regulates inducible NOS gene expression and protein expression, was present at higher levels in polyp than in healthy control tissue. Levels of arginine, methylarginine, and endogenous NOS inhibitors were similar between polyp and control tissue. In contrast, superoxide dismutase activity of polyp tissues was lower than that seen in control tissue and associated with increased nitrotyrosine, a biomarker of oxidant consumptive products of NO. Taken together, these data suggest that the nasal polyp environment is characterized by abnormalities in NO metabolism that might predispose to altered regulation of tissue growth and infection. Identification of NO metabolic abnormalities might lead to novel treatments for sinonasal polyposis targeted against the pathways identified within this study.

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.

Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma

Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium. To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline. We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls. In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients. Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.

Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses

Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).

Aspergillus fumigatus Challenge Increases Cytokine Levels in Nasal Lavage Fluid

Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-4, IL-6, interferon [IFN]-γ) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1β levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-α levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects

Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects.

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.