Increase In Nasal Symptoms Research Articles

Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Background:Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential.Aim:To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications.Materials and Methods:Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP).Results:Intranasal challenge of OVA resulted in significant induction (P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly (P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited (P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased (P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited (P < .05) by apigenin. It also significantly ameliorated (P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA.Conclusion:Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

Saikosaponin A ameliorates nasal inflammation by suppressing IL-6/ROR-γt/STAT3/IL-17/NF-κB pathway in OVA-induced allergic rhinitis

Allergic rhinitis (AR) is a type I hypersensitivity immune response and is a common chronic allergic respiratory disorder characterized by one or more nasal symptoms. Despite many studies on AR therapy, the drugs of treatment for AR remain limited in effect. In the present study, we aimed to elucidate the effects of saikosaponin A (SSA) on nasal inflammation, T helper (Th)2 and Th17 cytokines, retinoic acid-related orphan nuclear receptor (ROR)-γt, signal transducer and activator of transcription (STAT)3, and nuclear factor (NF)-κB signalings in ovalbumin (OVA)-induced AR mice model. OVA-induced AR mice exhibited increase in nasal symptoms, histological alteration, OVA-specific immunoglobulin (Ig)E/IgG1, ROR-γt, STAT3 and NF-κB signalings. However, the administration of SSA significantly decreased allergic symptoms including nasal rubbing and sneezing. Additionally, histological alterations such as mucosa layer thickness, goblet cell hyperplasia, eosinophils and mast cell infiltration in nasal tissues dramatically improved by treatment with SSA. Also, SSA treatment decreased the levels of OVA-specific IgE/IgG1 in serum and the levels of Th2 and Th17 cytokines such as interleukin (IL)-6 and IL-17 in nasal lavage fluid (NALF). Moreover, SSA inhibited the activation of transcription factor ROR-γt, STAT3 and phosphorylated STAT3 in both NALF and lung. Futher, SSA could also significantly inhibit the expressions of NF-κB p65 and phosphorylated NF-κB p65 in NALF and lung. These present results suggested that SSA may attenuate OVA-induced allergic rhinitis through regulating the expression of IL-6/ROR-γt/STAT3/IL-17/NF-κB signaling. The results indicate that SSA may be used as a therapeutic candidate for allergic rhinitis disease.

Effector cell signature in peripheral blood following nasal allergen challenge in grass pollen allergic individuals.

Several studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge. Twelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay). Robust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1h) response and modest significant changes during the late (1-24h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3h, CD63 at 6h, and CD203c(bright) at 24h). T effector/memory cells (CD4(+) CD25(lo) ) were increased at 6h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+) CD4(+) T cells were significantly increased at 6h after NAC when compared to the control day. Basophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+) CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation.

Work-related airway symptoms, nasal reactivity and health-related quality of life in female hairdressers: a follow-up study during exposure

ObjectivesHairdressers often complain of work-related rhinitis (WR). They are infrequently sensitized to persulphates. The cause and mechanism of the symptoms and the effects on their health-related quality of life (HRQoL) remains unclear. The objectives were to follow female hairdressers with WR mainly from bleaching powder regarding nasal reactivity to persulphate and to evaluate symptoms, HRQoL and inflammatory markers in nasal lavage during a working period after vacation and compared with hairdressers without symptoms and pollen allergic women.MethodsSkin prick tests to persulphate were performed in the hairdressers. Participants kept a diary of symptoms and of work tasks (hairdressers only). They completed HRQoL questionnaires. Eosinophil cationic protein (ECP) in nasal lavage fluid was examined. The symptomatic hairdressers performed nasal challenges with persulphate before and after the exposure.ResultsSkin prick tests were negative. Although the nasal reactivity to persulphate did not change a steady increase in nasal symptoms, especially blockage, and in ECP was noticed in the symptomatic hairdressers. The HRQoL deteriorated in the symptomatic hairdressers indicating an effect on their working situation and daily life. The atopics had more, but varying symptoms (itching, sneezing and secretion).ConclusionsThe difference in the clinical picture between the symptomatic hairdressers and the pollen allergic women, the increase in symptoms and ECP in the nasal lavage support the view that a sensitization to hairdresser chemicals by a mechanism not yet understood is operating. The deterioration of the HRQoL in the symptomatic hairdressers indicates a considerable effect on their life.

Physical morbidity by surgical approach and tumor location in skull base surgery

Skull base tumors are associated with physical symptoms that vary depending on location and surgical approach. Skull base surgery patients (n = 138) were retrospectively reviewed and physical symptoms were quantified. Patients were divided into 4 groups by surgical approach (open, endoscopic) and tumor location (anterior, central). Multivariate analyses determined odds for symptom development. Patients with anterior lesions presented with more nasal symptoms compared to those with central lesions (63% vs 6.8%; p < .001). Those with central lesions presented with more neurologic (41.1% vs 12.3%; p < .001) and endocrine symptoms (19.2% vs 0%; p < .001). Three of 4 groups experienced a reduction in neurologic and visual symptoms after surgery. One group (endoscopic/central) experienced a reduction in endocrine and an increase in nasal symptoms. Anterior tumors (p = .02) and endoscopic approaches (p = .002) predicted increased nasal morbidity. Physical morbidity from skull base tumors may vary based on tumor location and surgical approach.

Effect of intense swimming training on rhinitis in high‐level competitive swimmers

Rhinitis is commonly reported by swimmers. Seasonal allergic rhinitis may impair athletes' performance and quality of life (QOL). No data are currently available on the changes of nasal symptoms during and after a swimming season. We aimed to determine in competitive swimmers: (1) the prevalence of rhinitis and its impact on their QOL during an intense training programme, (2) the changes in nasal symptoms and QOL after a resting period and (3) the relationship between rhinitis and airway hyperresponsiveness (AHR). Thirty-nine swimmers and 30 healthy controls answered the Rhinitis Quality of Life Questionnaire (RQLQ) and scored nasal symptoms on a seven-point Likert scale during the week preceding their visit. Subjects had allergy skin prick tests and a methacholine challenge. Peak nasal inspiratory flows were also measured. The athletes performed these tests during an intense training period (V1), outside the pollen season and after at least 2 weeks without swimming (V2). At V1, rhinitis symptoms were reported by 74% of swimmers and 40% of controls (P<0.01). Eighty-four percent of swimmers and 72% of controls were atopic (NS). RQLQ score was higher in swimmers compared with controls at V1 (27.3+/-28.5 vs. 9.5+/-12.7, respectively, P<0.005). The presence of AHR during training did not correlate with the presence of rhinitis symptoms. At V2, the nasal symptoms and RQLQ scores were similar in swimmers and controls. Intense swimming training is associated with an increase in nasal symptoms and impairment in QOL in most competitive swimmers. Such an increase is not related to seasonal allergen exposure in atopic athletes and probably results from chlorine derivative exposure.

Persulphate challenge in female hairdressers with nasal hyperreactivity suggests immune cell, but no IgE reaction

The aim of this study was to examine the effects of persulphate on the nasal mucosa and on the immune cells in hairdressers suffering from bleaching powder associated rhinitis (BAR) versus subjects with rhinitis not previously exposed to bleaching powder. Fifteen hairdressers (S) with BAR, 14 without symptoms (WS) and 12 atopics (A) with rhinitis but without exposure to bleaching powder were studied. Each performed a nasal challenge with persulphates. Effect parameters were symptom score, acoustic rhinometry, albumin in nasal lavage, subpopulations of lymphocytes in blood and specific serum antibodies. The S group had a post-challenge increase in nasal symptoms and nasal lavage albumin. The A group reacted to a lesser intent. The S and A groups showed an increase in Th1 cells. An HLA class II cell expression was noticed in both groups of hairdressers. No evidence of a type 1 reaction (immediate type) to persulphate was noticed. Persulphate challenge affects hairdressers with BAR, but also atopics. The reaction may be driven by a Th1 cell activation.

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).

Effects of beta-endorphin on nasal allergic inflammation.

Beta-endorphin is a derivative of pro-opiomelanocortin. Cells of the immune system can also synthesize and secrete beta-endorphin. Its concentration is increased during the allergic reaction and during stress. Increased reactivity during psychological stress of allergic subjects is also well known. Is beta-endorphin one physiological link between stress and an exacerbation of the allergic reaction? First, intranasal beta-endorphin challenges with subsequent lavages to determine histamine and albumin levels and measurements of nasal flow and resistance in dose-response and time course experiments were performed. Secondly, we examined whether beta-endorphin pre-treatment increased the antigen-induced release of histamine and albumin in nasal lavages and the clinical symptoms. Exogenous beta-endorphin (100 pM-10 microM/mL) induced a dose-dependent increase in nasal symptoms in asymptomatic allergic subjects with rhinitis (n = 14) as well as in non-allergic controls (n = 10), but did not release any mediators into nasal secretion. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a beta-endorphin pre-treated antigen challenge we could note a significant enhancement of human serum albumin influx (P < 0.05) and histamine liberation (P < 0.05) 10 min after antigen challenge compared with the allergen challenge alone, with also a correlation with the more pronounced decrease in nasal flow (P < 0.05). These results suggest that beta-endorphin-induced increase in nasal congestion is mediated through direct neuroendocrine receptor activation independent of mast cell activation and that during the allergic reaction there is a beta-endorphin/mast cell interaction that enhances the mediator response to nasal allergen challenge.

A case-control study of the role of cold symptoms and other historical triggering factors in asthma exacerbations.

Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study. To assess the relative importance of colds and other nonclimatic historical triggers of asthma exacerbations. One hundred and nineteen adults and children with asthma in two Canadian cities participated in a one-year study of the role of exacerbating factors in asthma. Among these, 36 pairs (21 adult, 15 children) completed the case-control study. Patients were considered cases if they developed an acute asthma exacerbation and notified the centre within 24 h to allow the completion of a questionnaire and viral studies (cultures of nasopharyngeal swabs and serology). Control people with asthma were matched for sex, age and area of residence, had no exacerbation during the preceding four weeks and participated within 48 h of the case patients. Case patients versus control patients had a mean age of 22 years versus 20 years, 50% versus 55% were male, and 92% versus 86% had at least one positive aeroallergen skin test. Cases were more likely to have taken regular inhaled steroids (63% versus 33%, P<0.002). Cases were more likely to report the following within the previous week: fever (P<0.001), sore throat (P<0.001), increase in nasal symptoms (P<0.01), increased dust exposure (P<0. 05), exposure to others with a cold (P<0.001) and, over the previous year, increased passive smoke exposure (P<0.05). Viral cultures and paired serology were negative. Symptomatic colds were the most common trigger of asthma exacerbations in the winter and spring, while a transient increase in dust exposure was also identified as a significant trigger. The association with chronic, passive smoke exposure and the use of inhaled costicosteroid medications likely reflected less stable pre-study asthma in those with exacerbations.

Lower airway responses to influenza A virus in healthy allergic and nonallergic subjects.

Acute asthma is considered a complication of respiratory viral infections. This investigation assessed the effects of influenza A virus infection on both the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 21) and without AR (non-AR; n = 25) were intranasally inoculated with influenza A virus and monitored for 8 d in a cloistered environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected after inoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on Days 3 and 4. Cough was a relatively minor symptom, and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No effects on allergy status were observed. Under these experimental conditions, influenza A virus infection did not produce detectable alterations in lower airway function in health AR and non-AR subjects.

Substance P enhances antigen-evoked mediator release from human nasal mucosa.

Exogenous substance P (10-80 nmol/ml) induced a dose-dependent increase in nasal symptoms in asymptomatic allergics with rhinitis (n = 15) and controls (n = 8), but did not release any mediators. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a substance P-pretreated antigen challenge, we found a significant enhancement of kinins, TAME esterase activity (p < 0.05-0.01), and histamine (p < 0.001, NS) 10-20 min after antigen challenge. These results suggest 1) that substance P-induced increase in nasal congestion is mediated through direct neurokinin receptor activation independently of mast cell activation, and 2) that during the allergic reaction there is a substance P-mast cell interaction that enhances the mediator response to nasal allergen challenge.

Maintenance of stellite and tungsten carbide saw tips: respiratory health and exposure-response evaluations.

To study exposure to cobalt and chromium in saw maintenance rooms and test respiratory health among saw filers at lumber mills. Hard-metal lung disease is associated with cobalt in the manufacture of tungsten carbide tools; recently it has also been reported among tool maintenance workers. Lumber mills often use saws tipped with tungsten carbide or with a newer alloy, stellite (containing more cobalt, as well as chromium). A cross sectional study of 118 saw filers at eight lumber mills was carried out that included a standardised questionnaire, spirometry, personal air sampling, and examination of tasks every 10 minutes (by observation). Comparison data were from a study of bus mechanics tested with similar methods. Cobalt exposure was associated with tungsten carbide grinding but not with stellite grinding. Chromium exposure was associated mainly with stellite welding. Saw filers had a twofold increase in phlegm and wheeze (P < 0.01) and a threefold increase in cough, phlegm, and wheeze related to work (P < 0.001), but no increase in breathlessness. Stellite welding was associated with a significant increase in nasal symptoms and cough related to work and a small decrease in airflow (forced expiratory volume in one second/forced vital capacity (FEV1/FVC%), P < 0.05). Saw filers wet grinding with tungsten carbide had significant reductions in forced expiratory lung volumes (FEV1 and FVC, P < 0.05) and were significantly more likely to have FEV1 and FVC values in the abnormal range. Cobalt exposure (in wet grinding) and duration of work that involved tungsten carbide grinding were both associated with significant reductions in FEV1 and FVC. Average cobalt exposures in this study were about 5 micrograms/m3, well below the currently accepted permissible concentration, which suggests that the current workplace limit for cobalt may be too high.

Direct evidence for a role of the mast cell in the nasal response to aspirin in aspirin-sensitive asthma

Background: A subset of patients with asthma experience adverse nasoocular reactions after ingestion of aspirin or agents that inhibit cyclooxygenase. Recent evidence has implicated the leukotrienes in the nasoocular reaction, but the cellular sources and mechanism of activation are unknown. We used nasal lavage with and without a 5-lipoxygenase inhibitor; zileuton, to define the role of leukotrienes and to profile nasal cellular activation during this reaction. Methods: A group of eight patients with asthma shown to have adverse reactions to aspirin documented by a 15% or greater decrease in forced expiratory volume in 1 second, accompanied by an elevation in urinary leukotriene E4 after ingestion of aspirin, received aspirin or placebo in a study with a crossover design. Nasal symptoms and nasal tryptase, histamine, leukotriene, and eosinophil cationic protein levels were evaluated. Serum tryptase and urinary histamine levels were also assessed. Subjects were then randomized to receive a week of treatment with zileuton or placebo, according to a double-blind, crossover design followed by aspirin challenge and measurement of the same mediators. Results: Aspirin ingestion produced a marked increase in nasal symptoms from a baseline symptom score of 2.1 ± 0.7 to a maximum of 8.4 ± 1.2 (p < 0.0007). Aspirin ingestion produced a mean maximal increase in nasal tryptase of 3.5 ± 2.6 ng/ml whereas placebo ingestion produced a mean maximal increase of 0.1 ± 0.2 ng/ml (p < 0.05, aspirin vs placebo). Mean maximal nasal histamine increased 1.73 ± 1.16 ng/ml versus 0.08 ± 0.08 ng/ml from baseline (p < 0.05, aspirin vs placebo). Aspirin produced a mean maximal increase in nasal leukotriene value of 152 pg/ml versus a 16 pg/ml decrease after placebo ingestion (p < 0.05). Zileuton treatment blocked the increase in nasal symptoms after aspirin ingestion (maximum nasal symptom score of 1.6 ± 0.6 with zileuton vs 5.5 ± 0.9 with placebo [p < 0.0053]). It also blocked the rise in nasal tryptase (p = 0.011) and nasal leukotriene (p < 0.05) levels after aspirin ingestion. Zileuton treatment had no significant effect on the recovery of nasal histamine. Conclusion: The increase in nasal symptoms in aspirin-sensitive patients with asthma after aspirin ingestion is associated with increases in nasal tryptase, histamine, and cysteinyl leukotriene levels. This mediator profile is consistent with mast cell activation during the nasal response to aspirin and suggests that 5-lipoxygenase products are essential for the nasal response to aspirin. (J ALLERGY CLIN IMMUNOL 1994;94:1046-56.)

Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride

Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems. A high fraction of HHPA-exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE-sensitized against HHPA (positive in RAST and in skin-prick test against the HHPA-HSA conjugate), and who reported work-related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work-related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE-mediated mast cell degranulation, followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.

Nasal mucosal response to repeated challenges with pollen allergen.

In order to explore the dynamics of the cellular response of the airway mucosa to allergen exposure, controlled daily allergen challenges were performed for 7 days during the pollen-free winter months in nine patients with strictly seasonal allergic rhinitis caused by birch pollen allergen. Symptoms obtained after the challenge were related to morphologic changes within and on the surface of the nasal mucosa. Cell samples were obtained daily prior to challenge from the nasal mucosa using mucosal imprints on plastic strips, brush samplings from the nasal mucosa, and nasal lavage. For light microscopy, the cellular material obtained by brushing and nasal lavage were cytocentrifuged onto object slides. Histamine was measured in the cell pellets that were obtained using the lavage and brush procedures as well as in the lavage supernatant fluid. Four symptoms (sneezes, itching, secretion, and blockage) were recorded and expressed individually as well as in the form of a composite symptom score. Nasal blockage was measured using a nasal peak flow meter. The patients displayed an increase in nasal symptoms after the allergen challenge, which was further increased between Days 2 to 7 (p less than 0.05). The light microscopic evaluation of the lavage revealed an immediate increase in eosinophils from 2.3 to 13.1% and was maintained on the same level throughout the period of challenges. A similar increase was noted in the brush specimens, and a strong correlation was obtained between these two methods of sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Topical glucocorticosteroids and allergen-induced increase in nasal reactivity: Relationship between treatment time and inhibitory effect

The effect of topical glucocorticosteroids on the allergen-induced nasal hyperresponsiveness, with special reference to treatment time, was studied in a double-blind, randomized, placebo-controlled crossover study. Ten patients who previously had shown allergen-induced nasal hyperresponsiveness participated. After pretreatment with either placebo or various periods with topical glucocorticosteroids, they were subjected to an initial challenge with three increasing doses of allergen and were rechallenged after 24 hours with the lowest allergen dose from the previous day. The nasal responses were monitored by means of symptom scores and measurements of Nα-p-tosyl- l-arginine methyl esterase (TAME) activity in nasal lavages. Five different treatment schedules were used. In the active treatment alternatives, the glucocorticosteroid treatment was started 48, 12 or 2 hours before or 2 hours after the initial allergen challenge. All treatments were continued up to rechallenge on the second day. As the active treatment we used budesonide, 100 μg in each nasal cavity every 12 hours. After placebo pretreatment, as expected, there was an increase in nasal symptoms at rechallenge as compared with the initial allergen challenge with the same allergen dose. The mean (±SEM) number of sneezes increased from 5.1 ± 1.7 to 9.5 ± 2.0 ( p < 0.05), a composite nasal symptoms score increased from 3.3 ± 0.66 to 4.4 ± 0.7 (NS), and TAME activity increased from 14.9 ± 2.83 to 25.3 ± 0.5 cpm · 10 3 ( p < 0.05). Topical glucocorticosteroid treatment abolished this increase in nasal symptoms and TAME activity ( p < 0.05 for all treatment alternatives). This was true even if the active treatment was applied merely between the 2 challenge days. The longest active pretreatment, 48 hours, had a tendency to reduce both symptoms ( p < 0.05 for the lowest allergen dose) and TAME activity on the initial challenge day as well. These findings indicate that there is a varied response of the allergic reaction to glucocorticosteroids depending on treatment duration. Furthermore, these data give some experimental support to the observation that the clinical effect in hay fever treatment can start to appear early after the start of topical glucocorticoid treatment.

Sulfur Dioxide Does Not Acutely Increase Nasal Symptoms or Nasal Resistance in Subjects with Rhinitis or in Subjects with Bronchial Responsiveness to Sulfur Dioxide

We examined whether brief exposures to moderately high concentrations of sulfur dioxide (SO2) causes acute increases in nasal symptoms and nasal resistance in subjects with chronic rhinitis. We studied 19 subjects with allergic rhinitis and 3 subjects with chronic intermittent rhinorrhea, nasal congestion, and sneezing without any other manifestation of allergy. We found that the change in nasal resistance and symptoms caused by nasal inhalation of 4 ppm of SO2 for 10 min was no greater than the changes caused by nasal inhalation of conditioned room air. In a second set of experiments, we examined whether allergic subjects with demonstrable bronchomotor responsiveness to SO2 also had nasal responsiveness to the gas. We studied 8 subjects with a history of both asthma and allergic rhinitis. Each subject developed symptoms of dyspnea or wheezing and an increase in specific airway resistance of at least 8 L x cm H2O/L/s after breathing 1 or 2 ppm of SO2 by mouthpiece at 20 L/min, and did not develop these changes after breathing room air under the same conditions. No subject, however, developed more nasal symptoms or a greater increase in nasal airway resistance after tidally breathing SO2 through the nose than after breathing room air, even when the concentration of SO2 delivered to the nose was double the concentration delivered through the mouthpiece to the lower airways. We conclude that brief exposure to SO2 at a concentration of 4 ppm or less is unlikely to cause significant nasal dysfunction in most subjects with chronic rhinitis, and that in subjects with both allergic rhinitis and asthma, responsiveness to SO2 is not uniform throughout the respiratory tract.