Der p 1 and Der p 2 induce less severe late asthmatic responses than native Dermatophagoides pteronyssinus extract after a similar early asthmatic response

Background The models for exposure to house dust in research and clinical practice are selected with respect to their role in IgE‐mediated immediate hypersensitivity. The use of isolated major allergens instead of complex allergen extracts is becoming increasingly popular as it offers some important advantages for quantitative measures in diagnosis and research. Objective To compare house dust mite extract and isolated mite major allergens with respect to their ability to induce early and late asthmatic responses and bronchial hyperreactivity. Methods Bronchial responses to house dust mite (HDM, Dermatophagoides pteronyssinus) extract and isolated major allergens from HDM (Der p 1 and Der p 2) were compared in a double‐blind, randomized, cross‐over study in 20 patients with mild to moderate asthma who were allergic to HDM. Allergen was titrated to a standardized early asthmatic response. Bronchial hyper‐responsiveness to histamine (PC₂₀histamine) was determined before and after allergen inhalation to assess allergen‐induced bronchial hyper‐responsiveness and IL‐5 was measured in serum. In addition, the allergens were applied in intracutaneous skin tests and activation of basophil leucocytes and proliferation of peripheral blood mononuclear cells was tested in vitro. Results After a similar early asthmatic response (mean Δforced expiratory volume in 1 s (FEV₁)_,max?29.4 (SD 7.2) vs. ?33.1 (8.6) %; mean difference 3.6 (95% CI ?0.9 to 8.2) %), the late asthmatic response (mean ΔFEV_1,max?45.9 (21.9) vs. ?32.7 (22.3) %; mean difference 13.2 (3.8–22.3) %), the degree of allergen‐induced bronchial hyper‐responsiveness (mean ΔPC₂₀histamine, 1.8 (1.0) vs. 1.2 (0.9) doubling dose; mean difference 0.6 (0.2–1.1) doubling dose) and serum IL‐5 at 6 h were found to be significantly higher after bronchial challenge with HDM extract than after challenge with an isolated HDM major allergen. Likewise, there was an increased late skin reaction with HDM compared with isolated major allergen after a similar early skin reaction. Conclusion Constituents of HDM extract, other than Der p 1 or Der p 2, with no significant influence on the IgE‐mediated early asthmatic response contribute significantly to the allergen‐induced late asthmatic response and bronchial hyper‐reactivity.     

Bronchial and cutaneous responses in atopic dermatitis patients after allergen inhalation challenge

Background Atopic dermatitis (AD) is often associated with allergic asthma (AA). Inhalation of allergens influences the activity of AA but the effect on the skin in AD is unclear. Objectives We evaluated the degree of bronchial hyperresponsiveness to methacholine in eight AD patients with AA (AD⁺) and eight AD patients without AA (AD^–) and studied bronchial and cutaneous responses after allergen inhalation challenge. Methods All patients were treated in hospital for their eczema with tar ointment (pix liquida) and orally administered antihistamines (mean hospital stay 37 days). After clearing of the skin lesions allergen inhalation challenge was performed. Cutaneous responses were studied by measuring the‘Costa’ score before and 24 h after allergen inhalation challenge. Results The median value of the provocative concentration of methacholine causing a 20% fall (PC₂₀ Mch) in forced expiratory volume in 1 second (FEV₁) was significantly higher in the AD^– group compared to the AD⁺ group with median values of 10.70 and 0.60mg/mL, respectively. These values did not change significantly in both groups during hospital stay. After challenge all AD⁺ patients showed early and late asthmatic responses whereas only four AD^– patients showed early asthmatic responses (mean values of the maximal fall in FEV_l during the EAR 37%/16% and in PEF during the LAR 27%/4% for AD⁺ and AD^–patients, respectively). The‘Costa’ score increased in both groups (mean score before 19.1/ 24.4 and after challenge 26.8/26.9 for AD⁺ and AD⁺ patients, respectively). The increase in the AD^– group was significantly higher compared with the AD^– group (P= 0.016). Conclusion We conclude that allergen inhalation challenge causes a flare up of the skin lesions in atopic dermatitis patients. This was more prominent in atopic dermatitis patients who already suffered from an IgE-mediated allergic inflammation in the lung.     

Effect of Sch1000 in allergen-induced asthma

Carefully controlled allergen inhalation tests were carried out in twelve subjects to provoke early asthmatic responses with a mean maximum FEV₁ fall of 30·7 ± 5·2% (mean ± s.d.). Four subjects had additional late asthmatic responses with a maximum mean FEV₁ fall of 21·0 ± 5·9%. The tests were repeated at intervals of 7 days in an identical way, following inhalation of Sch1000 (80 μg) and placebo, each given 45 min before the onset of the early asthmatic response. This dose of Sch1000 produced a marked and uniform inhibition of methacholine-induced bronchoconstriction in the same subjects. The allergen-induced responses were reproducible in eleven out of the twelve subjects; the coefficient of variation for the decrease in FEV₁ in the early responses being ±7% and in the late response ±43%. Sch1000 produced a slight and variable inhibition of early asthmatic responses (P<0·02) and no inhibition of late asthmatic responses. We examined the relationship between the degree of inhibition of the early asthmatic response by Sch1000 and: (a) the degree of inhibition produced by Sch1000 on histamine- and methacholine-induced bronchoconstriction; (b) the level of non-specific bronchial reactivity measured by inhaled histamine and methacholine; and (c) the degree of bronchodilatation produced by Sch1000. No relationship was found.     

Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber

Allergen-induced late asthmatic responses are associated with an increase in bronchial responsiveness to histamine. We have examined the relationship between the magnitude of the late asthmatic response and the magnitude and duration of increased histamine responsiveness. Allergen inhalation tests were carried out in 12 asthmatic subjects to induce a mild early asthmatic response (16% to 40% reduction in FEV₁ in the first hour after allergen inhalation); the response was followed over 8 hr to identify the occurrence and magnitude of any late asthmatic response (maximum fall in FEV₁ from baseline between 3 and 8 hr). The provocation concentration of histamine causing a decrease in FEV₁ of 20% (PC₂₀) was measured before and after inhalation of allergen. The magnitude of decrease in PC₂₀ correlated with the magnitude of the late asthmatic response as measured by the percent fall in FEV₁ (r = 0.8, p < 0.002). The duration of decrease in PC₂₀ was from 2 to 74 days and this also correlated with the magnitude of the late response (r = 0.53, p < 0.05). Total lung capacity (TLC), residual volume (RV), FEV₁, maximal expiratory flow-volume curves (on air and He-O₂), and histamine responsiveness were also measured before and at intervals after allergen inhalation. Four of seven subjects still had a reduction in PC₂₀ when the TLC, RV, FEV₁, maximal expiratory flow-volume rates on air (V?₅₀air) and He-O₂ (V?₅₀He-O₂) (measured at an absolute volume corresponding plus 50% of control vital capacity) and ratio of V?₅₀He-O₂ to V?₅₀air were back t preallergen inhalation levels. In two of these subjects volume of isoflow was also back to ±10% of preallergen inhalation levels when the PC₂₀ was still significantly reduced. The results suggest that allergen-induced late asthmatic responses can be associated with an increase in bronchial responsiveness to histamine by mechanisms other than a reduction in baseline airway caliber alone.     

Factors in allergen-induced asthma: relevance of the intensity of the airways allergic reaction and non-specific bronchial reactivity

Early asthmatic responses (EAR) of similar severity were produced by allergen inhalation challenges in nine asthmatic subjects. The severity of the airways allergic reaction was estimated by measuring the skin test weal size produced by the same dilution of allergen which caused the EAR. The non-specific bronchial reactivity was assessed by inhalation of increasing concentrations of histamine acid phosphate. Possible relationships between the severity of the airways allergic reaction, the level of non-specific bronchial hyper-reactivity and the pattern of asthmatic response were examined. There was a marked inverse correlation between the required severity of the airways allergic reaction and the non-specific bronchial reactivity (log₁₀) of the individual (r =?0·96, P < 0·001). The EAR was followed by a late asthmatic response (LAR) in five subjects. There was no evident correlation between the magnitude of the EAR and that of the LAR. In addition, no correlation was obtained between the pattern of response in terms of EAR or LAR and the severity of the allergic reaction, or the level of non-specific bronchial reactivity. These results indicate that the allergic reaction and the non-specific bronchial reactivity are interrelated in the production of allergen-induced asthma. Thus a mild allergic reaction will induce an EAR in patients with markedly increased non-specific bronchial reactivity, whereas a severe allergic reaction is required to produce an EAR in those with only slightly increased non-specific reactivity. The lack of correlation between the occurrence of the LAR and the intensity of the airways allergic reaction, the non-specific bronchial reactivity and the intensity of the EAR indicates that other factors are involved in the development of LAR.     

Recurrent nocturnal asthma after bronchoprovocation with Western Red Cedar sawdust: association with acute increase in non-allergic bronchial responsiveness

Recurrent nocturnal asthma following a single exposure to Western Red Cedar sawdust was documented by measurements of peak flow rates in two sensitized subjects. The nocturnal asthma followed a dual asthmatic response in the first subject and a late (non-immediate) asthmatic response in the second. Both subjects developed a 10-fold reduction in the dose of histamine required to decrease the FEV₁ by 20%. This cedar-induced increase in non-specific bronchial reactivity was maximal at the time of the recurrent nocturnal asthma, and persisted after nocturnal asthma had ceased and after FEV₁ had returned to normal. We hypothesize that the enhanced non-specific bronchial reactivity which occurs following late asthmatic responses to bronchial challenge is the cause of recurrent nocturnal asthma following single exposure to a sensitizing agent.     

Bronchial responsiveness to bakery-derived allergens is strongly dependent on specific skin sensitivity

BACKGROUND: Quantitative relationships between immunological reactivity, non-specific bronchial responsiveness and bronchial responsiveness to allergens have scarcely been investigated in occupational asthma. METHODS: We assessed the above relationships in 24 subjects with baker's asthma. The skin endpoint titration to bakery allergens as a measure of immunological reactivity, together with the methacholine PC20 and allergen PC20 during early asthmatic reaction were determined. RESULTS: All patients had positive skin tests to some bakery allergens (wheat and rye flour, soybean flour, fungal enzymes and egg white proteins) and bronchial hyperresponsiveness to methacholine. Specific inhalation challenge (SIC) tests were performed with aqueous allergen extracts of cereal flour (n = 14), soybean (n = 8), baking enzymes (n = 12), and egg white proteins (n = 8) in sensitized workers. A positive asthmatic reaction was observed in 84% of the inhalation challenges. SIC elicited isolated early asthmatic reactions in 62%, dual reactions in 32% and isolated late reactions in 5%. Multiple linear regression analysis showed allergen PC20 as a function of skin sensitivity to allergen and methacholine PC20, yielding the following highly significant regression formula: log-allergen PC20 = 0.18 + 0.99 log(skin sensitivity) + 0.343 log(methacholine PC20) (r = 0.89, P < 0.001). This formula predicted allergen PC20 to within one double concentration in 67%, to within two double concentrations in 85% and within three double concentrations in 97%. CONCLUSION: The main determinant of bronchial responsiveness to allergen in patients with baker's asthma is the degree of sensitization to occupational allergens as determined by skin reactivity, modulated to a lesser extent by non-specific bronchial hyperresponsiveness.     

Allergen inhalation challenge in smoking compared with non‐smoking asthmatic subjects

Background Smoking asthmatics experience more severe symptoms, require more rescue medication and have more asthma‐related hospitalizations than non‐smoking asthmatics. However, studies in mice suggest that mainstream cigarette smoke may reduce airway inflammation and may attenuate airway hyperresponsiveness. A comparison of allergen‐induced airway inflammatory responses of smoking and non‐smoking atopic asthmatics has not been examined previously. Objectives To determine whether allergen‐induced airway responses and inflammatory profiles are attenuated in smoking when compared with non‐smoking mild allergic asthmatic subjects. Methods Allergen inhalation challenges were performed in 13 smoking and 19 non‐smoking mild allergic asthmatic subjects. The forced expired volume in 1 s (FEV₁) was measured up to 7 h after allergen inhalation. Methacholine airway responsiveness was measured before and at 24 h after allergen and sputum was induced before and at 7 and 24 h after allergen. Results Both the smoking and non‐smoking groups developed similar allergen‐induced falls in FEV₁ during the early and late asthmatic responses and similar increases in allergen‐induced airway eosinophils. The mean maximum fall in FEV₁ during the late response was 16.3±4.3% in non‐smokers and 12.9±7.2% in smokers. The smoking asthmatics, however, did not develop allergen‐induced methacholine airway hyperresponsiveness, whereas the non‐smoking controls developed a 1.18 doubling dose shift in methacholine PC₂₀ (P<0.05). Conclusions and Clinical Relevance Mild allergic asthmatic subjects, who were current smokers with a mean 6‐year pack history, develop allergen‐induced eosinophilic airway inflammation and late responses, similar in magnitude to non‐smoking asthmatics, but do not develop methacholine airway hyperresponsiveness associated with the allergen‐induced airway eosinophilia. Cite this as: Z. Meghji, B. Dua, R. M. Watson, G. M. Gauvreau and P. M. O'Byrne, Clinical & Experimental Allergy, 2011 (41) 1084–1090.     

A comparison of the protective effect of fenoterol and Sch 1000 on allergen-induced asthma.

The protective effects of inhaled Sch1000 (80 μg), inhaled fenoterol (800 μg), and placebo on the early asthmatic response induced by inhaled allergen were compared in 10 subjects in a single-blind investigation. Allergen inhalation produced early asthmatic responses in all 10 subjects, with a mean 1-sec forced expiratory volume (FEV₁) fall of 31.1% (range, 23% to 40%). The similarity of the responses to allergen inhalation following no pretreatment and following placebo showed that the allergen-induced response was highly reproducible, with coefficients of variation for the maximum percentage FEV₁ fall of ± 7.2%. Sch1000 produced a slight nonsignificant reduction in the magnitude of the early asthmatic response of 20.7% ± 39.7% (p > 0.10) for the maximum FEV₁ fall. Fenoterol, however, produced a highly significant reduction in the magnitude of the early of 76.4% ± 23.5% (p < 0.001) for the maximum FEV₁ fall, which was significantly greater than that produced by Sch1000 (p < 0.001). These results show that β-adrenergic agonists, such as fenoterol, are more effective than cholinergic antagonists, such as Sch1000, in preventing the early asthmatic response induced by inhaled allergen. Reflex parasympathetic bronchoconstriction is involved to a variable and minor extent in the production of allergen-induced early asthmatic responses.     

Inhibition of allergen-induced asthma by three forms of sodium cromoglycate

The effect of three forms of sodium cromoglycate (SCG), 20 mg, on allergen-induced early asthmatic responses was examined in ten stable asthmatics. Dose response allergen inhalation tests were performed on five occasions at intervals of from 1 to 2 weeks to determine the provocation concentration producing a 20% reduction (PC20 allergen) in FEV₁. Placebo was given before the first and the last tests to determine the reproducibility of responses to allergen over the study period; reduced responsiveness was observed in eight of the ten subjects. Major changes in levels-of specific serum antibodies of the IgE and IgG classes did not serve to explain the changes in bronchial responses although there was a trend which suggested IgG-related desensitization. The observed changes in bronchial responses and antibody levels illustrate the requirement for tests of reproducibility of responses by the use of placebo controls at the beginning and end of a series of allergen inhalation challenges. SCG as (i) a micronized powder with lactose, (ii) micropellets without lactose, or (iii) an aerosol, were inhaled double-blind, in random order, 5 min before the additional three allergen inhalation tests. PC₂₀ allergen was reduced following SCG in seven subjects; the differences were statistically significant for the group. There was no observed difference in efficacy between the different forms of SCG. In this study, the efficacy of SCG could not be related to age, atopic status, the initial level of allergen-specific IgE antibody, baseline FEV₁, level of bronchial responsiveness to inhaled histamine or an effect of SCG on responsiveness to histamine.     

Airways of allergic rhinitics are 'primed' to repeated allergen inhalation challenge

The hypothesis that repeated exposure to a specific allergen will further increase bronchial responsiveness to that allergen is supported by indirect evidence. However, it has not been tested as intensely in the laboratory setting, and in some cases, conflicting results are presented. In order to test the hypothesis in the atopic subjects, allergen inhalation challenge tests were performed in 29 house dust mite (Dermatophagoides pternyssinus) sensitive subjects with allergic rhinitis. Nine subjects displayed early asthmatic responses (EARs) to the first challenge (Group 1). Twenty subjects with no significant airway response were submitted to the second challenge 24 h later. Thirteen subjects showed EARs (Group FI) and two of these showed late asthmatic responses (LARs)aswell. In Group II, there were significant changes between the first and second challenge in post-allergen early phase FEV₁, (88.1 ± 4.2 vs 71.7 ± 4.2%, baseline, P < 0.05) and in post-allergen late phase FEV₁, (93.1 ± 3.4 vs 86.6 ± 7.8. P < 0.05). After the second challenge. PD20 (provocative dose of methacholine required to produce a 20% fall in FEV¹) decreased significantly from the baseline values. When challenged separately with twofold dose of allergen, only three and one of the Group II showed EAR and LAR respectively. PD20 did not change significantly after this challenge. These results indicated that two repeated exposure to allergen dose, which is not enough to cause significant airway responses at a time, may provoke asthmatic airway responses in the subjects with allergic rhinitis and that this effect of priming is not attributed to the cumulative dose but to the consequent effect of repeated allergen exposure.     

A comparison of spirometric measurements in allergen bronchial challenge testing

We compared the usefulness of several spirometric measurements in detecting asthmatic reactions after allergen bronchial challenge in fourteen asthmatic children. All of the children had a history suggesting mite-induced asthma and eleven had a 3 mm or larger diameter weal on prick testing with Dermatophagoides farinae extract. On bronchial challenge testing with dilutions of this extract twelve children had an early asthmatic reaction and nine had a late asthmatic reaction. In decreasing order of sensitivity for detecting the early asthmatic reaction the tests ranked as follows: FEV₁, FEF_50%, FEF_25-75%, PEFR and FVC. For the late asthmatic reaction the order was FEF_50% FEV₁, FEF_25-75%, PEFR and FVC. No single test identified all the early or all the late reactions but the FEV₁, a test useful for indicating large airways obstruction, when combined with the FEF_25-75%, a test influenced by small airways obstruction, detected all early and late asthmatic reactions. The FEF_50%, was a sensitive test but was the only one to become falsely positive. It became falsely positive in four patients. Although the FEV₁, was the most useful single test the results suggest that it is, by itself, an inadequate indicator of the asthmatic reaction and that it should be used with the FEF_25-75%, to ensure the detection of all asthmatic reactions induced by allergen bronchial challenge testing.     

The effect of verapamil on histamine and methacholine-induced bronchoconstriction

Calcium antagonist, verapamil given by inhalation did not alter histamine bronchial hyper-reactivity in ten patients with extrinsic bronchial asthma and similarly did not modify methacholine-induced bronchoconstriction in further five patients. In eight non-asthmatic subjects verapamil reduced histamine sensitivity with increase in PC_20H from 8.07(±2.33) to 12.10(±2.71, P < 0.05) but failed to have an effect on methacholine sensitivity in five controls. The failure of inhaled verapamil to modify histamine and methacholine bronchial hyper-reactivity in asthmatic patients and the beneficial effect of calcium antagonists in exercise asthma suggests that these agents may act predominantly on the mast cell degranulation rather than the bronchial smooth muscle.     

Comparison of responses to pollen extract in subjects with allergic asthma and nonasthmatic subjects with allergic rhinitis

We compared pulmonary responses with inhaled pollen-antigen extract in eight subjects with allergic asthma and eight nonasthmatic subjects with allergic rhinitis. Lower respiratory tract sensitivity to antigen was determined from dose-response curves using SGaw and FEV₁ measurements to quantitate responses. We found no difference in antigen sensitivity in terms of SGaw between the two groups (p > 0.05). Hay fever subjects required almost eight times more antigen to produce a 20% fall in FEV₁, although there was considerable overlap between the two groups. After antigen challenge there were significant increases in lung volumes in asthmatic subjects (RV, +78.6%; FRC, +33.6%; TLC, +12.6%) which were not significantly different from rhinitis subjects (RV, +98.3%; FRC, +39.1%; TLC, +10.3%). Six rhinitis and five asthmatic subjects were rechallenged after pretreatment with atropine (2.5 mg aerosol). Atropine caused an initial increase in SGaw and FEV₁ but failed to alter sensitivity or volume responses in both groups. The effects of a maximum inspiration on physiologic responses to antigen were different in the two groups. Deep inspiration transiently improved SGaw and FRC toward prechallenge values in rhinitis subjects but the same maneuver had little effect in asthma subjects. Although only asthma subjects experience lower respiratory tract symptoms during periods of environmental pollen exposure, these two groups of subjects were indistinguishable on the basis of their immediate responses to inhaled antigen. This suggests that asthmatic symptoms during the pollen season are unrelated to the immediate effects of allergic reactions to pollen. This also suggests that these bronchial challenge responses represent a localized anaphylactic reaction, whereas naturally occurring asthma during the pollen season may represent a syndrome of increased airways reactivity which is perhaps related to antigen exposure.     

Atopy and bronchial reactivity in Australian and Melanesian populations

In order to compare the prevalence of atopy and bronchial hyperreactivity among Papua New Guinian (P.N.G.) and Australian populations, skin prick tests and methacholine bronchial challenge tests were performed. A civilian and an army population from each country were examined and those with past or present asthma, recent respiratory tract infection and chronic lung disease were excluded. No statistical difference in the prevalence of atopy was found between the four populations. In the P.N.G. population 40 and 49%, and in the Australian population 27 and 39%, were found to be atopic, without symptoms of past or present allergic disease. The house dust mites were the commonest allergens in all populations. In response to methacholine (0·3 mg), only 6% of subjects had falls in 1 sec forced expiratory volume (FEV₁) of more than 12% (upper limit of normal range) and only two were in the asthmatic range. There was no correlation between the degree of bronchial hyper-reactivity and atopic status; however, the degree of bronchial hyperreactivity was slightly greater in the New Guinea civilian than in the Australian civilian population. In the absence of asthma, atopic status does not appear to cause increased bronchial reactivity, suggesting that some factor other than atopy must be present for the development of bronchial hyperreactivity characteristic of asthma.     

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.     

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,     

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)     

Effects of nedocromil sodium on bronchospasm and HS-NCA release induced by allergen inhalation in asthmatic patients

The aim of this study was to assess the ability of nedocromil sodium (NS) to prevent the immediate asthmatic reaction and the increase in the scrum level of heal stable neutrophil chemotactie activity (HS-NCA) induced by antigen inhalation. In a double-blind, cross-over study. 13 atopic subjects affected with seasonal asthma underwent a bronchial provocation lest with a preselected dose of grass pollen allergen (enough to cause a decrease of ≥ 20% in FEV₁:FEV₁ PD20) after pre-treatment with 4 mg NS or placebo. Serum samples were withdrawn from 11 subjects for HS-NCA determination. After NS administration the decrease in FEV₁ was significantly less than after placebo administration at all lime points after challenge (2 min P= 0.0004; 7 min, P= 0.0005; 17 min P= 0.0002 and 27 min P= 0.0005). The percentage increase in HS-NCA was significantly higher after placebo than after NS inhalation, both 10 (P= 0.0048) and 2d (P= 0.0068) min after challenge. Our study confirms previous investigations, showing that NS inhibits the immediate asthmatic response to allergen inhalation in atopic, asthmatic subjects and moreover it shows that this drug prevents in vivo the increase of the serum HS-NCA. This last finding has not been previously reported.     

Basophil histamine release and airway response to mite allergen in atopic dermatitis.

Twelve patients with atopic dermatitis (AD) were subjected to in vitro histamine release from peripheral blood leukocytes (basophils) and in vivo bronchial inhalation challenge using house dust mite (Dermatophagoides farinae) allergen. Not only seven patients with asthmatic history but also five patients without asthma responded to both the in vitro and the in vivo challenges. A significant correlation was observed between HR30 (a mite concentration producing a 30% release of total cellular histamine) and PC20 allergen (a mite concentration producing a 20% fall in FEV1). There was also a significant correlation between MHR (maximal histamine release) and the maximal fall in FEV1. The relationship held for both AD patients with asthma and without asthma. These results suggest that histamine release induced by the house dust mite allergen is a good in vitro test for predicting the bronchial response to this allergen. They also suggest that these tests are not disease specific, but are valuable in evaluating the degree of atopic state in a subject.