Frequency and intensity of late asthmatic reactions after bronchial allergen challenge in asthma and rhinitis

The occurrence of late asthmatic reactions after bronchial allergen challenge was studied in 50 house dust mite allergic patients subdivided in three groups: one group had asthma without nasal symptoms, another group had rhinitis without pulmonary symptoms and a third group had a combination of both asthma and rhinitis. Late asthmatic reactions were present in 80% of asthmatic patients and in 18.7% of rhinitis patients. The degree of non-specific bronchial reactivity to histamine (provocative dose 15 or PD15 histamine) and the degree of immediate reactivity to allergen (PD15 house dust mite) did not differ significantly between patients with and without late asthmatic reactions. These findings suggest that an important difference between asthma and rhinitis is the lack of late asthmatic reactions in rhinitis patients, whereas the degree of immediate bronchial reactivity to the allergen is similar in asthma and rhinitis.     

Effect of cetirizine, a new H1 antihistamine, on the early and late allergic reactions in a bronchial provocation test with allergen

Background: Cetirizine is a highly sensitive H₁ antihistamine with particular antiallergic properties, which has been shown to be effective in the treatment of allergic rhinitis, urticaria, and hay-fever-associated asthma.Methods: To assess the effect of cetirizine on the late allergic reaction to a specific bronchial provocation test (BPT) with allergen, we selected 25 patients with allergic asthma as determined by history, skin tests, and specific IgE levels. They were challenged with increasing doses of a cat or mite extract until a 20% drop in forced expiratory volume in 1 second (FEV₁) was recorded. Sixteen patients (11 men and 5 women with a mean age of 22 years; range, 18 to 48 years) exhibited a dual response (early and late allergic reactions). These 16 patients underwent a second BPT 2 weeks later, and each again showed a dual response. They were then randomized to receive either a placebo (8 patients) or cetirizine, 15 mg twice daily (8 patients) in a double-blind fashion. After 7 days of treatment, they underwent a third BPT with the same allergen dose as given in the second BPT.Results: The intensity and duration of early allergic reaction were not affected by cetirizine, whereas all parameters of late allergic reaction were statistically significantly improved in the cetirizine group when compared with those of the placebo group (maximum FEV₁ decrease, p = 0.046; FEV₁ [area above the curve], p = 0.027; maximum airway resistance increase, p = 0.021; airway resistance [area under the curve], p = 0.036).Conclusions: Cetirizine produced a significant protective effect against an allergen-induced late allergic reaction in a BPT. Cetirizine might therefore be effective in the treatment of asthma.     

Rhinoconjunctivitis,bronchial responsiveness,and atopy as determinants for incident non-work-related asthma symptoms in apprentices exposed to high-molecular-weight allergens

OBJECTIVE: The aim of this study was to explore the role of rhinoconjunctivitis (RC), taking into account atopy and the level of bronchial responsiveness to methacholine, on the incidence of respiratory symptoms and in the development and/or worsening of asthma. METHODS: We examined data from a prospective study in 769 students starting exposure to high-molecular-weight occupational allergens and who were serially followed for up to 44 months. RESULTS: The presence of RC symptoms at baseline was significantly associated with an increased risk of developing shortness of breath and wheezing in atopic subjects regardless of PC20 level and in subjects with a PC20 相似文献   

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge

BACKGROUND: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. METHODS: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. RESULTS: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P < 0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). CONCLUSION: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhinitis.     

Increased Bronchial Hypersensitivity after Early and Late Bronchial Reactions Provoked by Allergen Inhalation

The non-specific bronchial reactivity following bronchial allergen challenge was studied in 40 patients with allergic bronchial asthma, particularly in subjects without definite late reactions 6 h after the provocations (reduction in peak expiratory flow or forced expiratory volume in 1 s of less than 15% of the control value at this time). Among a group of 21 patients submitted to bronchial provocation tests, 13 carried out maximal exercise tests 6 and 1 week after the allergen challenge. In another group of 19 patients, the bronchial hyperreactivity to methacholine was assessed before and 6 h and 1 week after challenge. Two patients with a dual response (early & late) reacted with bronchial obstruction to the exercise. Exercise tests performed after 1 week did not provoke asthma in any patient. In the methacholine group a marked increase in responsiveness to methacholine 6 h after the provocation was observed in those patients with a dual response who were tested and in those with equivocal late reactions and even in three patients with an isolated immediate reaction. The increases responsiveness was still present in many patients 1 week after challenge. The airway caliber did not influence the degree of responsiveness to methacholine. Nor did the degree of responsiveness have any influence on the patterns of reactions observed after allergen exposure. It was concluded that in some individuals exposure to the relevant allergen predisposes them to exercise-inducible bronchial obstruction. Further, it was confirmed that non-specific bronchial reactivity can be increased not only in patients with late responses - both definite and equivocal--but also in some patients with immediate reactions alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early and late nasal symptom response to allergen challenge

We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 μg twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P <0.01), a moderate effect on discharge (37% reduction; P <0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P <0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes 76% reduction of nose-blowings, 96% reduction of blockage; P <0.01). In conclusion, we found it difficult in the individual subject to identify a well-defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response.     

Late airway response increases at repeat allergen challenge

The relationship between the immediate and late responses to repeated inhalations of allergen was studied. Sixteen male atopic asthmatics were challenged twice with an interval of 2 weeks. Forced expiratory volume in 1 s (FEV1) was measured serially over an 8-hour period after challenge. The method of provocation used implied that only slight differences between the immediate responses on the two provocation days were observed. However, differences in the late responses were demonstrated. Thus, the maximum percent change in FEV1 at the first and second provocation differed significantly in the late (P less than 0.01), but not in the immediate phase. The increase in maximal late response was greater than the small change in maximal immediate response (P less than 0.05). Further, the FEV1 values from 4 to 8 h post-challenge were in each recording significantly lower on the second day suggesting a more pronounced late bronchial response to repeat challenge. The results suggest that after one challenge specific airway reactivity, i.e., reactivity to allergen, at a subsequent rechallenge is increased in the late phase. This late phase hyperreactivity seems to persist for at least 2 weeks after allergen provocation.     

Effect of multiple doses of nedocromil sodium given after allergen inhalation in asthma

Aim: Twelve subjects with asthma took part in a placebo-controlled crossover study designed to investigate whether nedocromil sodium given after the occurrence of the early phase asthmatic reaction to allergen has an effect on the late-phase response and the associated increase in airway responsiveness.Methods: The treatments were administered four times at 4-hour intervals at a dose of 4 mg, with the first dose given 1 hour after the last allergen challenge. Changes in airway caliber were monitored for 15 hours after allergen exposure by measuring forced expiratory volume in 1 second hourly. Airway responsiveness to methacholine was determined 24 hours before and 24 hours after allergen challenge.Results: Nedocromil sodium failed to reduce significantly the maximum late fall in forced expiratory volume in 1 second as compared with placebo but delayed its occurrence by 1.5 hours (p = 0.05). Nonspecific airway responsiveness to methacholine was similarly increased after allergen challenge when patients received nedocromil sodium and placebo. No unusual events were reported during the study period by any patient. These results indicate that nedocromil sodium is not able to interrupt the ongoing cascade of inflammatory events leading to the late-phase reaction and the associated increase in airway responsiveness.Conclusion: In allergic asthma, nedocromil can be used only as a preventive treatment.     

Nasal conditioning in perennial allergic rhinitis after nasal allergen challenge

BACKGROUND: Antigen challenge in seasonal allergic rhinitis is considered to be associated with an increased ability of the nose to condition inspired air. In contrast, little is known about air conditioning after antigen challenge in perennial allergic rhinitis (PAR). OBJECTIVE: The aims of this study were to investigate whether antigen challenge in PAR changes nasal air conditioning and to assess the relationship between nasal conditioning and nasal patency and geometry. METHODS: Nineteen subjects with PAR were enrolled into this study. Measurement of nasal conditioning, active anterior rhinomanometry (AAR), acoustic rhinometry (AR), and clinical symptom evaluation were performed before and after nasal allergen challenge with allergen extracts from house dust mites. RESULTS: Ten and 20 min after nasal allergen challenge, the total water content of the air measured in the nasopharynx and the water gradient across the nose were significantly higher in the nasal cavity in which the allergen extract was sprayed. The temperature on both sides of the nose increased non-significantly after nasal allergen challenge. No correlation to data obtained by AAR, AR, and clinical symptom evaluation after nasal allergen challenge was found. CONCLUSION: We suggest that an increase in mucosal humidity due to the allergic provocation might be responsible for the increase in nasal conditioning capacity because no correlation to changes in nasal perimeter and patency was found.     

Predictors of early- and late-phase reactions to bronchial allergen challenge

The influence of inhaled steroids and predictive factors on the response to bronchial allergen challenge (BCA) was evaluated in. 80 asthmatics allergic to Dermatophagoides pteronyssinus (Der p). All underwent BCA with Der p and measurement of early (EAR) and late asthmatic reaction (LAR). The cumulative dose of allergen producing 20% fall in FEV₁, in the EAR (PD₂₀) was calculated. Bronchial histamine provocation, conjunctival provocation test (CPT), and skin prick test with Der p extract were performed. Specific IgE to Der p in serum (RAST), blood eosinophil (EOS) count, serum eosinophil cationic protein, and eosinophil protein X were measured. Thirty patients (38%) were treated with inhaled steroids. All patients had at least a 20% fall in FEV₁ in EAR. Some 42% of nonsteroid- and 33% of steroid-treated patients had LAR with fall in peak flow of at least 20%. For patients not treated with steroid, 35% of variation in PD₂₀ was explained by RAST and histamine reactivity, and 53% of variation of observed PD₂₀ could be predicted. The baseline FEV₁, EOS, and EAR explained 28% of variation in LAR, and 28% of variation in observed LAR could be predicted. For patients treated with steroids, 38% of variation in PD₂₀ was explained by EOS and histamine reactivity, and only 18% of variation of observed PD₂₀ could be predicted. For patients treated with steroids, it was impossible to predict LAR. We conclude that to achieve a quantitative estimation of allergen-specific EAR and LAR, BCA cannot be replaced by the tests used in this study. Treatment with inhaled steroids modifies the response to BCA, making quantitative prediction of EAR less accurate and prediction of the magnitude of LAR impossible.     

Factors influencing the occurrence of a late reaction to allergen challenge in atopic asthmatics

Thirty extrinsic asthmatics were challenged by inhalation with Dermatophagoides pteronyssinus extract. In twenty-four an immediate reaction was observed and in sixteen this was followed by a late reaction. Those with late reactions tended to have more severe asthma but did not report greater sensitivity to housedust mite. The occurrence of a late reaction was not related to the degree of airways obstruction before challenge or to the intensity of the immediate reaction. Patients in whom the early reaction was induced by a low dose of inhaled antigen were those most likely to develop a late response. Results of histamine challenge testing suggested that this greater sensitivity of the airway might in part be due to greater non-specific bronchial reactivity.     

Sustained eosinophil cationic protein release into tears after a single high-dose conjunctival allergen challenge

Background The appearance of eosinophils is a hallmark sign of the allergic late-phase response (LPR). Eosinophil cationic protein (ECP), a readily measurable product released from activated eosinophils, has so far not been evaluated in the ocular LPR. Objective Two sets of trials were performed in order to investigate changes of local and systemic eosinophil activity and their possible link with symptoms and hyper-reactivity in the allergic LPR in the eye. Methods In the first experiment, ECP was analysed in tears and serum and the clinical reaction was evaluated during a 72-h time–course after a single, high-dose allergen challenge out of season in one eye of 15 pollen-sensitized volunteers. In a second experiment, the hypothesis of an increased clinical response to an allergen challenge in an eye that had been provoked with allergen 48h previously was tested in nine sensitized individuals. Results In the first experiment, symptoms at 10 min and 2, 4, 6, 8 and 24 h significantly exceeded base line scores of the challenged eyes. Tear ECP was significantly elevated in challenged eyes compared to contralateral eyes at 6, 8 and 24 h. In addition, symptoms and ECP release correlated significantly at the 24-h evaluation. Serum ECP remained unchanged throughout the study period. In the second experiment, conjunctival hyperreactivity 48h after an allergen challenge was not confirmed. Conclusion ECP secretion occurs in the experimental ocular LPR and is in part associated with the magnitude of the clinical reaction, which suggests a truly pathogenic role of the activated eosinophil in pollen-induced allergic conjunctivitis.     

Changes in serum haptoglobin level after allergen challenge test in asthmatic children

Bronchial asthma is characterized by airway inflammation, which underlies the phenomenon of bronchial hyperresponsiveness. Previous studies have shown that this correlates with the serum concentration of haptoglobin. The occurrence of the late asthmatic response (LAR) after an allergen challenge test is associated with airway inflammation. The objectives of this study were to examine serum levels of haptoglobin during the 24 h after allergen challenge and to compare changes between the subjects with and without LAR. We studied two groups of children with perennial asthma who developed the early asthmatic response (EAR) only (group 1: n = 14), and EAR but also LAR (group II: n = 14) after an allergen (Dermatophagoides pteronyssinus) challenge test. Serum concentrations of haptoglobin were measured at baseline, at EAR, and at 2 h (recovery), 8 h (LAR), and 24 h after the challenge. Baseline levels were similar in the two groups (group I: 128±57 mg/dl: group II: 129±50 mg/dl). In group I, there was no significant change in the level at any time point; in contrast, the subjects in group II showed a relative fall (92±40 mg/dl) at 8 h, and an increase (161±79 mg/dl) at 24 h after the challenge. Our results indicate that the serum concentration of haptoglobin decreases at the time of LAR and is subsequently replenished during the ensuing time. Although further studies are needed, we think that haptoglobin may be inflused into the airways during the inflammatory process associated with LAR, and that this may be followed by "overshooting" production.     

Immediate and late phase allergic cutaneous reactions are not inducers of unspecific or specific local hyperreactivity

The present study evaluates the possibility of allergen-induced unspecific and specific dermal hyperreactivity with special reference to the presence of late cutaneous reactions and allergen-induced nasal hyperreactivity. Twenty-six patients with strictly seasonal allergic rhinitis participated. All had a positive skin prick test for birch (Betula verrucosa) and/or timothy (Phleum pratense). Ten patients had previously displayed an allergen-induced nasal hyperreactivity and six patients a late cutaneous reaction. An initial skin prick test with a relevant pollen allergen was done in triplicate. The immediate skin reactions were recorded after 15 min and any late-phase reaction after 6 h. Twenty-four hours later the patients were retested. The same pollen allergen was sited in the first flare reaction from the previous day. A histamine prick test was sited in the weal as well as in the third reaction from day 1. A histamine control was also performed in a previously unaffected area. The allergen-induced weal reactions decreased significantly at rechallenge compared with the results from the previous day (P less than 0.05). The histamine tests resulted in similar skin reactions regardless of whether or not they were done on a previous allergen test site. This was true for both specific and unspecific reactions when the subgroups of patients with previously demonstrated allergen-induced nasal hyperreactivity or late-phase skin reactions were evaluated separately. These results indicate that allergen-induced hyperreactivity is not a general feature of allergic inflammation but is a phenomenon restricted to specific sites, such as the airway mucosa.     

Inter-Relation of Immediate and Late Asthmatic Reactions in Childhood

Following bronchial provocation tests with inhalent allergens, late asthmatic reactions (LAR) frequently follow immediate asthma reactions (IAR). This study of atopic asthmatic children demonstrated that patients could show IARs to one allergen, ryegrass extract, but isolated LARs without any preceding immediate response when challenged with an unrelated allergen extract of D. pteronyssinus. The patients' degree of skirt sensitivity to the concentration of extract inhaled appeared one factor which determined whether an isolated LAR or IAR followed allergen inhalation,     

The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge

BACKGROUND: Late phase reactions after allergen challenge can be understood as a correlate of the inflammatory reaction in allergic rhinitis. METHODS: To investigate which cytokines are involved in it and to dissect direct and indirect effects of nasal allergen challenge, we performed unilateral nasal allergen provocation with the disc method in 12 seasonal allergic volunteers. Symptom scores, nasal secretions and nasal airflow were quantified. In the secretions that were collected in the early phase and for 8 h after provocation, we measured histamine, and the cytokines interleukin (IL)-1beta, IL-8, IL-4, and the natural antagonist of IL-1beta, IL-1 receptor type 1 (IL-1Ra) using enzyme-linked immunosorbent (ELISA)-assays. Control challenges with diluent instead of allergen were performed in all subjects. RESULTS: We demonstrated a bilateral increase in nasal secretion weights in the early and late phase. Histamine was significantly increased in the early and late phase in nasal secretions from both nostrils. IL-1beta increased in the late phase only, where it was also found on the unchallenged, contralateral side. Its antagonist IL-1Ra was found in very high quantities (1000-fold higher than IL-1beta) but demonstrated only marginal changes after provocation. IL-8 was increased in both nostrils early and late after challenge, whereas IL-4 was significantly elevated in the late phase. CONCLUSIONS: We described the time course of mediator and cytokine release into nasal secretions after allergen challenge. We hypothesize that the observed indirect effects on the unchallenged, contralateral side can be at least partially attributed to neuronal reflexes.     

Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity

Background:  Remarkable relationship exists between upper and lower airways. Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be considered a strong risk factor for the onset of asthma in patients with allergic rhinitis.
Objective:  This study is aimed at evaluating the presence of BHR in a large group of patients with moderate-severe persistent allergic rhinitis alone, and at investigating possible risk factors related to severe BHR.
Methods:  Three hundred and forty-two patients with moderate-severe persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test, spirometry and bronchial methacholine (MCH) test were performed in all patients.
Results:  Twenty-two (6.4%) patients had severe BHR, 74 (21.6%) patients had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a negative MCH test. The logistic regression analysis evidenced that trees and house dust mites sensitization (OR_Adj: 8.1), rhinitis duration > 5 years (OR_Adj: 5.4) and FEV₁ ≤ 86% of predicted (OR_Adj: 4.0) were significantly associated with severe BHR. The discriminative ability of this model is appreciably satisfactory, being the AUC = 0.90.
Conclusion:  This study highlights the close link between upper and lower airways and the role of some risk factors, such as tree and mite sensitization, > 5-year duration, and ≤ 86% FEV₁ values, as risk factors for severe BHR in patients with moderate-severe persistent allergic rhinitis alone. Therefore, BHR is frequently present in patients with chronic rhinitis and should be suspected in the presence of defined risk factors.     

Long-term intense exposure to grass pollen can mask positive effects of allergenic immunotherapy on non-specific bronchial hyperresponsiveness

Introduction

There are many potential factors that can modulate bronchial reactivity, including exposure to allergens, viral infections, and medications. The aim of this study was to analyze the effect of grass pollination intensity on the bronchial reactivity in seasonal allergic rhinitis (SAR) patients subjected to subcutaneous allergenic immunotherapy (SCIT).

Material and methods

This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of SAR, randomly assigned to desensitization by pre-seasonal or maintenance SCIT. Bronchial provocation challenge with histamine was performed before the onset of immunotherapy, and repeated three times after each pollen season covered by this study. Bronchial reactivity was analyzed with regard to grass pollination intensity in 2005–2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 20 or 50 grains per 1 m³).

Results

After 3 years of SCIT, a significant decrease in bronchial responsiveness was observed in the analyzed group as confirmed by an increase in PC₂₀ FEV₁ histamine values (p = 0.001). An inverse tendency was observed after 2 years of SCIT, however. This second year of SCIT corresponded to the 2007 season, when a significantly higher number of days with at least 50 grains of pollen per 1 m³ of air was recorded.

Conclusions

Fluctuations in pollination intensity observed during consecutive years of immunotherapy can influence bronchial reactivity in patients subjected to SCIT (ISRCTN Register: ISRCTN 86562422).