Natural allergen exposure does not diminish the sensitivity of cytokine production to glucocorticosteroids in blood cells of seasonal allergic asthma and rhinitis patients

Glucocorticosteroid (GCS) inhibition of cytokine production is a major anti-inflammatory mechanism. However, increased production of pro-inflammatory cytokines during allergic airway inflammation has been proposed to reduce GCS effects. This study aimed to investigate whether allergic airway inflammation due to natural allergen exposure might decrease the sensitivity of granulocyte-macrophage colony-stimulating factor (GM-CSF) production to GCS in blood cells. Blood samples were collected from patients with seasonal allergic asthma (n = 10) and rhinitis (n = 8) and healthy subjects (n = 9), before, during, and after the birch pollen season. Whole blood cultures were stimulated with LPS (10 ng/ml) and treated with budesonide (10(-11)-10(-7) M) for 20 h. GM-CSF levels were analysed using immunoassay. Birch pollen exposure did not alter LPS-stimulated GM-CSF production, although disease symptoms and blood eosinophils increased in the patients. There were no significant differences in budesonide inhibition of GM-CSF production by blood cells of asthma and rhinitis patients compared with cells of healthy subjects before, during or after the birch pollen season and no change in response to allergen exposure. A concentration of 1 nM budesonide inhibited GM-CSF production by more than 50% at all time points. In conclusion, natural allergen exposure did not reduce the sensitivity of GM-CSF production to GCS inhibition in blood cells of seasonal allergic asthma and rhinitis patients.     

Bronchial hyperreactivity and spirometric impairment in patients with seasonal allergic rhinitis

We previously demonstrated in a group of patients with perennial allergic rhinitis alone, impairment of spirometric parameters and high percentage of bronchial hyperreactivity (BHR). Thus, the present study aimed at evaluating a group of subjects suffering from seasonal allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. METHODS: One-hundred rhinitics sensitized to pollen allergens only were evaluated during and outside the pollen season. Spirometry and methacholine bronchial challenge were performed. RESULTS: Four rhinitics showed impaired values of FEV1 without referred symptoms of asthma during the pollen season. FEF 25-75 values were impaired in 17 rhinitics during the pollen season and in 11 rhinitics outside the pollen season (P<0.05). Fifty-four patients showed positive methacholine bronchial challenge both during and outside the pollen season. PD20/FEV1 methacholine was lower during the pollen season than outside (P<0.05). In BHR positive patients, reduced values of FVC (P<0.05), FEV1 (P<0.05), and FEF 25-75 (P<0.01) were significantly demonstrated in comparison with BHR negative rhinitics. There was a relationship between BHR degree and FEF 25-75 values only during the pollen season (P<0.001). CONCLUSIONS: This study evidences that an impairment of spirometric parameters may be observed also in patients with seasonal allergic rhinitis alone during the pollen season. A high percentage of these patients had BHR. A close relationship between upper and lower airways is confirmed also in the model of pollen allergy. Thus, a careful evaluation of lower airways should be performed also in those patients with seasonal allergic rhinitis alone.     

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.     

Objective monitoring of the allergic inflammatory response of the nasal mucosa in patients with hay fever during natural allergen exposure

A method is presented for the objective monitoring of the inflammatory response of the nasal mucosa to natural allergen exposure through measurements of biochemical markers such as TAME-esterase activity in a daily nasal lavage. Nine patients with strictly seasonal allergic rhinitis caused by birch pollen and five healthy nonatopic control subjects participated in the present study, which started 1 wk before the birch pollen season and continued throughout the entire pollen season. A diary card was used to assess daily nasal symptoms, and a daily nasal lavage was performed once every afternoon. The degree of pollen exposure was assessed by daily pollen counts. The TAME-esterase activity in the lavage fluid from the allergic patients, but not in that from the nonallergic control subjects, increased significantly during pollen exposure despite low pollen counts and was found to correlate with daily nasal symptoms (r = 0.36; p less than 0.05) and the degree of pollen exposure (r = 0.45; p less than 0.01). The area under the curve for the daily TAME-esterase measurements thus differed significantly (p less than 0.02) between allergic patients (158 +/- 28) and control subjects (74 +/- 9). This approach for the monitoring of patients with hay fever during natural allergen exposure will make further objective studies on the pathophysiology and pharmacology of hay fever possible. We also provide support for the validity of previous findings obtained in allergen challenge situations utilizing the lavage approach.     

Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness.

Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma.     

Seasonal Changes in Platelet Activity in Pollen-Induced Seasonal Allergic Rhinitis and Asthma

Background. Previously we reported that patients sensitized to pollen-allergens who had seasonal allergic rhinitis and seasonal asthma may show increased plasma levels of platelet activation markers during grass pollen season. Objective. To find out whether the pattern of platelet activity measured by plasma PF-4 level in the same group of patients changed off-season compared with the pollen season as well as in comparison with healthy control subjects. Methods. Off-pollen season, plasma PF-4 level was determined by enzyme-linked immunosorbent assay (ELISA) in 16 grass pollen allergic patients who had seasonal allergic rhinitis and seasonal asthmatic symptoms (none of them had any history of allergic diseases outside the season) and in 29 healthy nonatopic subjects. Results. Plasma PF-4 level in the patients off–pollen season was significantly lower as compared with the season and did not differ significantly as compared to the healthy subjects. Conclusions. This observation taken along with our previous results indicates that patients with seasonal allergic rhinitis and asthma symptoms may have an increased circulating platelet activation, yet this phenomenon disappears in the asymptomatic period of the disease. This might indicate that platelet activation within the systemic circulation is an important factor in the development of seasonal allergic airway inflammation.     

Early bronchial airflow impairment in patients with persistent allergic rhinitis and bronchial hyperreactivity

BACKGROUND: Allergic rhinitis and its impact on asthma (ARIA) document underlines the link between upper and lower airways. Patients suffering from allergic rhinitis frequently (up to 80%) show bronchial hyperreactivity (BHR). OBJECTIVES: This study aimed at evaluating a group of subjects suffering from persistent allergic rhinitis, with BHR but with nasal symptoms only, to investigate the type and intensity of nasal symptoms, nasal and bronchial airflow, and BHR grade during the pollen season. METHODS: One hundred and twenty one polysensitized rhinitics were investigated. Total symptom score (TSS) was assessed in all patients. Rhinomanometry, spirometry and methacholine bronchial challenge were performed in all patients. RESULTS: 65 (53.7%) patients had impaired FEF 25-75 values. TSS correlated with nasal airflow (P<0.001) and BHR grade (P<0.001). Nasal airflow correlated with FEF 25-75 values (P<0.05) and BHR (P<0.001). FEF 25-75 values correlated with FEV(1) levels (P<0.003), BHR grade (P<0.001), and nasal obstruction symptom (P<0.05). Severe BHR correlated with FEV(1) (P<0.05) and FEF 25-75 (P<0.03) values, nasal airflow (P<0.05) and nasal symptoms (P<0.001). CONCLUSIONS: This study evidences that early bronchial impairment is frequently detectable in patients with persistent allergic rhinitis and BHR. Moreover, nasal function is strictly related with bronchial calibre and BHR grade. Therefore, careful evaluation of lower airways should be investigated in all rhinitics as suggested by the ARIA document.     

Airway Hyperresponsiveness: A Comparative Study of Methacholine and Exercise Challenges in Seasonal Allergic Rhinitis with or without Asthma

Background. Asymptomatic airway hyperreactivity in allergic rhinitis is a risk factor for later development of asthma. Although non-specific bronchial hyperresponsiveness (BHR) has been measured by several stimuli, the most appropriate measurement technique still remains unclear. Objective. To investigate whether an exercise challenge can be used to predict BHR in seasonal allergic rhinitis patients with or without asthma and to compare this bronchial reactivity with a methacholine challenge technique. Methods. Forty-six consecutive patients with seasonal allergic rhinitis only (n = 31) and with both seasonal allergic rhinitis and asthma (n = 15) were included in the study during the pollination period. Subjects underwent first methacholine (mch) and then exercise challenge testing (ECT). There was a 1-week interval between the tests. ECT was performed on a bicycle ergometer. Positive result was defined as a 15% decrease in forced expiratory volume in 1 second (FEV₁) post-exercise. A patient's bronchial reactivity to methacholine was considered as hyperresponsive if PC₂₀ was less than 8 mg/mL. Results. Mch PC₂₀ values were significantly lower in patients with both rhinitis and asthma (p < 0.062). Among the 46 patients, mch PC₂₀ values were significantly different between patients who had positive and negative exercise challenge tests (p = 0.007). All patients with rhinitis alone had a negative ECT and 10 had a positive mch challenge. Change in FEV₁ values after ECT was significantly higher in patients with both rhinitis and asthma compared to those with rhinitis alone (p = 0.009). There was a significant relation between positivity of mch and exercise challenges (p = 0.025). ECT positivity was found to be a significant confounding factor in the diagnosis of asthma (p = 0.001). Specificity and sensitivity values were 100% and 24% for ECT and 68% and 100% for mch, respectively. Conclusion. Exercise challenge presents poor diagnostic value for detecting bronchial responsiveness in individuals with allergic rhinitis alone during the pollen season.     

Exhaled nitric oxide, bronchial hyperresponsiveness and spirometric parameters in patients with allergic rhinitis during pollen season

Allergic rhinitis and asthma share common epidemiological features and inflammatory processes. The aim of the present study was to document the influence of natural allergen exposure in exhaled NO (eNO) and in spirometric parameters of patients with seasonal allergic rhinitis(SAR) and to investigate the differences among subjects with positive versus negative bronchial provocation to metacholine(BPMch).Twenty-six non-smoking patients (13F/13M; mean age 28.4ys) with a documented history of SAR, 15 healthy, non-atopic(6F/9M; mean age 37.1ys) and 6 non-symptomatic atopic subjects (3F/3M; mean age 36.5ys) were studied. At the first visit during pollen season each subject filled symptom-score card, underwent eNO and nasal NO (nNO) measurements and spirometry. BPMch was performed within the next 10 days. At the second visit out of pollen season, all measurements but BPMch were repeated. Control subjects underwent eNO and nNO measurements.eNO was significantly increased during pollen season in BPMch positive vs BPMch negative(46.22±32.60 vs 17.81±12.67, p=0.014) and vs non-atopic controls(11.40±5.84, p<0.001) as well as atopic controls(13.56±5.34, p=0.001). No difference was detected out of pollen season in both patients' groups. nNO values were increased only in BPMch(+) group compared to both control groups in pollen season (vs non-atopics p=0.002, vs atopics p=0.002) and only vs non-atopics out of season, p=0.004. Regression analysis has shown that the difference in FEF25-75 values (off season-in season) is a predictor of positive BPMch .eNO is markedly increased in BPMch patients with allergic rhinitis while mid-expiratory flow may represent an early marker of lower airway involvement in respiratory allergy.     

Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis.

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma which is often associated with airways inflammation. However, some patients with allergic rhinitis and no clinical evidence of asthma also exhibit BHR. This study therefore investigated whether inflammatory cell infiltrate is present in the induced sputum of nonasthmatic subjects with allergic rhinitis during the pollen season and examined its relationship with airway hyperresponsiveness to inhaled methacholine and adenosine 5'-monophosphate (AMP). Twenty subjects (12 allergic rhinitis, eight nonallergic controls) underwent methacholine and AMP challenge and sputum induction with hypertonic saline on separate days. Cell differentials were calculated from whole sputum samples. A significantly greater number of eosinophils was found in the sputum of nonasthmatic subjects with allergic rhinitis compared to that of nonallergic controls, their median (range) percentages being 17.5 (4-47) and 1.5 (0-5) (p<0.001) respectively. Although sputum eosinophilia failed to be significantly associated with methacholine responsiveness (r(s)=-0.50; p=0.095), the provocative concentration of AMP causing a 20% fall in forced expiratory volume in one second correlated strongly and significantly with the absolute number of eosinophils (r(s)= -0.73; p=0.007). Eosinophil cationic protein levels in the sputum of rhinitic subjects were significantly elevated compared to controls and correlated with eosinophil number (r(s)=0.67; p=0.017). These findings support the view that bronchial eosinophilia alone is insufficient to cause asthmatic symptoms. Diverse agonists for assessing bronchial hyperresponsiveness are selectively associated with airway inflammation in allergic rhinitis.     

Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis.

As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p<0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p<0.01-0.05) and were found to be well correlated (p<0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p<0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases.     

Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics.

Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.     

Association of serum specific IgE levels with asthma in autumn pollen-induced allergic rhinitis: A retrospective analysis

Background: Artemisia and Humulus pollen are the two most important aeroallergens of autumn allergies in North China. Cross-sectional data in 2001 have shown that allergic rhinitis often preceded or occurred at the same time as asthma in patients with autumn pollinosis in North China. Objective: We used this cross-sectional data to investigate the association of serum specific IgE (sIgE) levels to Humulus and/or Artemisia pollen with the onset of asthma in patients with autumn pollen-induced allergic rhinitis. Methods: 1096 patients with autumn pollinosis were face-to-face interviewed and underwent sIgE tests to Artemisia and Humulus. The temporal sequence of allergic rhinitis and asthma was documented. 1013 patients were positive to Artemisia and/or Humulus by sIgE. Multinomial logistic regression and survival analysis were used to examine the potential implication of sIgE levels for the progression of asthma in autumn pollen-induced allergic rhinitis. Results: Of the 1013 participants with a positive sIgE test to Artemisia and/or Humulus, 563 (55.6%) had a history of allergic rhinitis which preceded or occurred at the same time as asthma. 450 (44.4%) had allergic rhinitis alone. After controlling of sex, age at onset of allergic rhinitis, and parental asthma, the risk of developing asthma increased with the levels of sIgE to both Artemisia and Humulus (p < 0.05). In Kaplan–Meier analysis, IgE classes 5–6 to Humulus or Artemisia increased the risk of asthma development (p < 0.05). Conclusion: Autumn pollen-induced allergic rhinitis often coexists with seasonal asthma. The incidence of asthma is more pronounced when the sIgE level was higher.     

Nitric oxide metabolites in allergic rhinitis: The effect of pollen allergen exposure

BackgroundSeasonal allergic rhinitis (SAR) is characterised by an inflammation consequent to allergen exposure. Nitric oxide may be involved in allergic inflammation.ObjectiveThis study evaluated the serum nitrite concentrations in SAR patients during and outside pollen exposure in order to estimate activity of nitric oxide synthases.MethodsOne hundred and two (56 females, 46 males, median age: 28.7 years) were included in this study: 56 with SAR evaluated outside the pollen season and so without allergic inflammation and symptoms, and 46 with SAR evaluated during the pollen season with symptoms. Serum concentrations of nitrite were measured and in those patients exposed to pollens, results were compared to scores of the Visual Analogue Scale for nasal obstruction perception.ResultsSerum nitrite concentrations were higher in SAR patients evaluated outside the pollen season (U = ?6.78; p < 0.0001), moreover, there was a significant relationship between nasal obstruction perception and nitrite in patients evaluated during the pollen season.ConclusionThis preliminary study demonstrates that serum nitric oxide metabolism depends on allergen exposure.     

Incorrect Application Technique of Metered Dose Inhalers by Internal Medicine Residents: Impact of Exposure to a Practical Situation

Background. Several well-controlled studies have proven the clinical benefit of specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However, whether subcutaneous SIT injection could cause a transient increase in bronchial reactivity (BR) remains unknown. Objective. To investigate whether subcutaneous SIT injection, either during or outside the pollen season, could cause an increase in BR in children with pollen allergy. Methods. Twenty-two children (mean age 13.6 ± 0.7 years) with AR who were receiving maintenance SIT for 15 months were included in the study. Pre-injection BR of the patients was evaluated with methacholine provocation test immediately before maintenance dose of SIT during the peak pollen season and outside the season. The post-injection test was administered 24 hours after SIT injection. Results. There was no difference in FEV₁ measures recorded during [98(93–109)%] and outside [102(96–111)%] the pollen season. There was no significant difference between pre- [64(7–64)mg/mL] and post-allergen injection [32(7.5–64) mg/mL] BR outside the pollen season (p = 0.9). A trend towards improvement following allergen injection [64(5.4–64)] as compared to pre-allergen injection [14.6(3.5–64)] was shown during the pollen season (p = 0.053). Although PC20 measures in the pollen season were lower than outside the season, the difference was not significant. The percentage of the patients with bronchial hyperreactivity was 62% during and 43% outside the season. Conclusion. SIT injections both during and outside the pollen season cause no increase in BR in children with AR. This calls into question the necessity of empirical dose reduction during the pollen season.     

Allergy in marathon runners and effect of Lactobacillus GG supplementation on allergic inflammatory markers

OBJECTIVE: We studied the prevalence of asthma and allergy in non-elite marathon runners and investigated the effects of probiotic supplementation on allergic inflammatory markers. METHODS: Asthma and allergies were surveyed by questionnaire, and blood eosinophils, serum eosinophil cationic protein (ECP), total IgE, and Phadiatop were measured in 141 Finnish marathon runners who took part in the Helsinki City Marathon. They were also randomized to receive either Lactobacillus GG (LGG) or placebo during the 3 months of the pollen season prior to the marathon. RESULTS: Lifetime prevalence of physician-diagnosed asthma was 4.3% (six out of 139 athletes), of allergic rhinitis 17.3% (24/139), of food allergy 5.0% (7/139), and of atopic eczema 4.3% (6/139). Prevalence of atopy was 31% (35/112), and 21% (24/112) of the athletes were sensitized to birch pollen. Asthma or allergy medication was used by 20% (28/139) of the athletes. During pollen season, serum ECP increased significantly in all athletes, and total IgE and Phadiatop in atopics. The marathon induced a significant eosinopenia but had no effect on serum ECP or total IgE. No differences in changes were seen between groups receiving LGG or placebo. CONCLUSION: Non-elite marathon runners have asthma and allergies similar to Finnish general population. LGG supplementation did not prevent the increase of allergic markers during the pollen season, or the eosinopenia induced by the marathon.     

Natural exposure to pollen reduces the threshold but does not change the pattern of response to the allergen in allergic subjects

It is known that exposure to seasonal allergen in sensitized asthmatics increases non-specific bronchial responsiveness, but it is controversial if exposure to seasonal allergen influences the presence and the severity of the late asthmatic response (LAR) to allergen. Fifteen asthmatic subjects sensitized to grass pollen performed a specific bronchial provocative test (sBPT) with Phleum pratensis extract before and during the pollen season. Changes of methacholine were also assessed. Allergen PD20FEV1 significantly decreased during the pollen season with respect to outside (allergen PD20FEV1, geometric mean: 0.10 vs. 0.23 biological units; P < 0.05), but the pattern of specific airway response did not change. Particularly, a consistent LAR was observed in three subjects outside the pollen season and in two subjects during the pollen season. Seven subjects with isolated early asthmatic response (EAR) outside the season did not show LAR after allergen inhalation during the pollen season. However, four of five subjects with slight LAR outside the pollen season (deltaFEV1% between 15 and 20%) lost LAR during season. Methacholine sensitivity increased slightly but significantly from outside to during the pollen season. This increase was greater in subjects with LAR outside the pollen season. The natural exposure to pollen induces an increase in bronchial sensitivity to allergen in sensitized subjects, but it does not induce LAR in subjects without LAR outside the pollen season.     

Vaccination with genetically engineered allergens prevents progression of allergic disease

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.     

Discriminant analysis in allergic rhinitis and asthma: methacholine dose-response slope allows a good differentiation between mild asthma and rhinitis

Asthma and rhinitis frequently coexist in allergic patients, but nasal symptoms may predominate, leading to asthma underdiagnosis and undertreatment. Discriminant analysis obtains the best differentiation between groups using one or one set of variables. Our aim was to identify the laboratory test [allergen exposure, total and specific serum IgE, lung function, blood eosinophils and, bronchial response and sensitivity to methacholine (Mth) and allergen] or combination of them that allowed the best differentiation between mild asthma and allergic rhinitis. A cross-sectional analysis was performed in 86 Dermatophogoides pteronyssinus allergic rhinitis patients, who were classified according to clinical data as rhinitis plus mild asthma (n = 62) or "pure" rhinitis (n = 24). Bronchial symptoms had been exhaustively evaluated during a 2-years pre-inclusion period. Patients underwent skin tests and bronchial challenge with Mth and allergen. The exposure to D. pteronyssinus allergen (Der pl) was quantified in dust samples. Dose-response curves with Mth [until the FEV1 fell by 40% or the maximal dose (200 mg/ml) was inhaled] were attained. We developed multiple models of discriminant analysis in order to evaluate the capacity of the above variables to differentiate groups. Asthma patients had higher total and specific IgE levels and a greater sensitivity (PD20 values) and response [dose-response slope (DRS)] to both Mth and allergen. The model entering these variables was the one that correctly classified more patients (79.2%). The discriminative power of the model that only included Mth-DRS values was similar to the above (78.8%). Bronchial response to Mth is quantitatively different in allergic rhinitis patients who display mild asthma symptoms when compared to those that only report rhinitis, suggesting a distinct bronchial intrinsic behavior. The utilization of complete dose-response curves with Mth allows a good separation between mild asthma and "pure" rhinitis patients and might be useful in the diagnosis of mild asthma. Whether the early detection and treatment of these patients prevents the development of symptomatic asthma needs further evaluation.     

Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis

BACKGROUND: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. While available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. OBJECTIVE: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. METHODS: Patients were examined in a pollen season model. Budesonide 64 microg, alone and in combination with formoterol 9 microg, as well as formoterol 9 microg alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobulin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. RESULTS: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobulin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. CONCLUSION: The present dose of formoterol does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.