Bronchial allergen challenge: comparison between two different methods of provocation

Bronchial allergen challenge was performed twice in ten well-defined stable asthmatic patients. On each provocation day the allergen was administered either by a standard method at tidal volume breathing or by a dosimeter method. Ten-fold increasing concentrations of allergen were administered with an interval of 10 min. Total amount of allergen of 9, 90, 900, 9000 and 90000 SQ units using the standard method, whereas the corresponding amount by the dosimeter method was 0.5, 5, 50, 500, and 5000 SQ units. The bronchial response was determined by forced expiratory volume in the first second (FEV₁) and by total resistance to breathing (R_t) measured by an opening interrupter method. The provocation was stopped when a decrease of at least 20% of the post-saline FEV₁ and a 4O% increase in post-saline R_t, was observed. A PC₂₀-FEV₁ and a PC₄₀-R_t was calculated by interpolation on the log dose-response curve. The late reaction was recorded and defined as a 20% reduction in peak expiratory flow (PEF) occurring during the 24-hr period after challenge. The comparability of PC₂₀-FEV₁ and PC₄₀-R_t obtained with the standard method and with the dosimeter was high. r= 0.89 and r= 0.88. Furthermore, no significant difference was found by comparing Δ FEV₁ and Δ R_t during provocation by either method as well as the occurrence and magnitude of the late reaction. We conclude that there exists a high comparability of the bronchial response to an allergen challenge performed either by a standard method at tidal volume breathing by continuous inhalation of the allergen aerosol or by a dosimeter method of inhalation despite the difference in the total allergen doses inhaled.     

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.     

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.     

Effect of calcium antagonists on allergen-induced asthma

The protective effect of inhaled verapamil (estimated dose 2-4 mg) and sub-lingual nifedipine (20 mg) against allergen-induced asthma were each assessed by the administration of calcium antagonists 30 min before bronchial provocation tests using Dermatophagoides pteronyssinus extracts on eight young perennial asthmatics. Neither drug changed the basal forced expiratory volume in one second (FEV₁) or the provocation dose of allergen required to cause a 20% fall in FEV₁ (PD₂₀ FEV₁). That calcium antagonists are ineffective in preventing allergen-induced asthma suggest indirectly that mechanism other than mediator release from mast cells may also be involved.     

Sodium cromoglycate in histamine and methacholine reactivity in asthma

The effect of increasing concentrations of inhaled sodium cromoglycate (SCG) (2, 10, 20 and 40 g/l) on histamine and methacholine bronchial reactivity was studied in nine patients with extrinsic bronchial asthma. The responses to histamine and methacholine were expressed in terms of provocative concentrations producing 20% fall in the FEV₁ (PC₂₀)- The PC₂₀ for histamine and methacholine was unaffected by all the concentrations of SCG used in the study. These results suggest that the effect of SCG on the bronchial smooth muscle or on the muscarinic receptors is minimal.     

Methacholine challenge testing: improved patient comfort with a 2-tiered protocol

BackgroundThe methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV₁) decreases 20% (PC₂₀). The requirement for a 20% or greater decrease in FEV₁ results in precipitous decreases in FEV₁ in some patients.ObjectiveTo improve MCT safety without compromising accuracy.MethodsWe performed a retrospective analysis of 879 consecutive MCTs (derivation cohort). A novel protocol for MCT was developed and validated in a cohort of 564 MCTs performed in a second institution.ResultsIn comparison with a PC₂₀ cutoff of less than 8 mg/mL, a provocation concentration at which the FEV₁ decreases 10% (PC₁₀) cutoff of 1 mg/mL or less has a sensitivity of 86%, a specificity of 98%, a positive predictive value (PPV) of 97%, and a negative predictive value (NPV) of 91%. We propose a novel 2-tiered protocol for MCT. If the PC₁₀ is 1 mg/mL or less, bronchial hyperreactivity is present; if the PC₁₀ is greater than 1 mg/mL, the test is continued until the provocative concentration is 8 mg/mL or a 20% decrease in FEV₁ is achieved. Compared with the standard protocol, the proposed protocol has a sensitivity, specificity, PPV, NPV, and overall accuracy of 100%, 98%, 97.6%, 100%, and 99%, respectively. The modified protocol would have enabled us to avoid 26 of 42 cases (62%) in which a 40% or greater decrease in FEV₁ occurred and would save 0.65 dose for every MCT performed. The 2-tiered protocol performed well in the validation cohort; sensitivity, specificity, PPV, NPV, and overall accuracy were 100%, 98%, 87%, 100%, and 98%, respectively.ConclusionThe proposed 2-tiered protocol is accurate, saves time, and avoids precipitous decreases in FEV₁.     

Lack of tachyphylaxis to histamine in both moderate and mild asthmatic subjects

While some studies have clearly shown that tachyphylaxis occurs in asthmatic subjects when challenged consecutively with inhaled histamine, others were unable to demonstrate this phenomenon. There is reason to believe that these conflicting findings may be related to the different degrees of bronchial reactivity in the subjects studied. We selected 2 groups of 10 asthmatics on the basis of their degree of bronchial reactivity: a group with PC₂₀<1 mg/ml (moderate asthmatics); and a group with PC₂₀>2.5 mg/ml (mild asthmatics). Each subject underwent 3 successive histamine challenges, allowing recovery of FEV₁ after each to within 5% of the baseline value prior to the first challenge. Test results were recorded as the provoking concentration of histamine needed to produce a 20% fall in FEV₁ (PC₂₀). No significant change in histamine reactivity occurred in either group. However, one moderate and two mild asthmatics appeared to develop some tachyphylaxis. We conclude that tachyphylaxis to histamine is not a general phenomenon in asthma.     

Allergen-induced increase in non-allergic bronchial reactivity

Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV₁ fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV₁ fall) in four, and equivocal late asthmatic responses (5–11% FEV₁ fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.     

Reversibility of the allergen-provoked late asthmatic response by an inhaled β2-adrenoceptor agonist

There is uncertainly about the relative contributions of bronchial smooth muscle contract ion. mucosal oedema and mucus plugging lo airflow obstruct ion in the allergen induced late asthmatic response (LAR). We systematically studied the ability of the inhaled β₂-agonist salbutamol to reverse the LAR in eight subjects after allergen bronchoprovocation. Salbutamol reversed the LAR by restoring FEV₁, to a level similar to the initial value measured at the same time of day (18.00 h)on the previous evening. For the eight subjects studied, this initial FEV₁ value, measured after abstaining from β-agonists for 8 h, was a mean ±SEM 90.7 ± 5.6% of predicted, which suggests further bronchodilation may have been possible at this time. We then studied six of the eight subjects in an identical protocol with saline challenge substituted for allergen bronchoprovocation to answer the question whether further bronchodilation was possible at that time after salbutamol in the absence of an LAR. After salbutamol on the allergen challenge day the FEV₁ for the six subjects was 84.1 ± 7.0% of predicted, compared with 94.0 ± 3.7% of predicted at the same point on the saline challenge day (p < 0.05). We conclude that, although the LAR may be effectively reversed by β₂-agonists, there is evidence for some residual airway narrowing, presumably related lo mucosal oedema, exudate and mucus plugging.     

Effect of nedocromil sodium on histamine airway responsiveness in grass-pollen sensitive asthmatics during the pollen season

We examined the effect of nedocromil sodium on histamine airway responsiveness in twelve grass-pollen sensitive patients during the 1984 pollen season. The study was a randomized double-blind crossover comparison of nedocromil sodium administered by a pressurized aerosol (4 mg b.d.) with placebo. Crossovers were made at 14-day intervals throughout 8 weeks of the grass pollen season. Histamine airway responsiveness was assessed twice before the pollen season and at the end of each 14-day treatment period. Results were expressed as the provocation concentration (PC) producing a 10% fall in FEV₁ (PC₁₀ FEV₁) and a 40% fall in flow at 30% of the vital capacity (PC₄₀V?_30(P)). During the pollen season all patients developed hay fever and seven had symptoms of asthma. The observed lowest values of PC₁₀ FEV₁ and PC₄₀V?_30(P) during the placebo treatment periods were significantly lower than mean preseasonal values although not significantly lower than theoretical expected values. Geometric means PC₁₀ FEV₁ and PC₄₀V?_30(P) were significantly higher during nedocromil sodium treatment compared with placebo. These results indicate that nedocromil sodium has a small but statistically significant effect reducing histamine airway responsiveness in grass-pollen sensitive patients during the pollen season.     

Standardization of inhalation provocation tests: Influence of nebulizer output,particle size,and method of inhalation

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 μm aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 μm AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV₁) by 20% (PC₂₀). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC₂₀. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.     

Influence of β2-adrenergic receptor polymorphism on methacholine hyperresponsiveness in asthmatic patients

BackgroundWe previously reported that the β₂-adrenergic receptor (ADRB2) polymorphism had no effect on bronchial hyperresponsiveness (BHR) to methacholine in asthmatic patients. We have now replicated this analysis in a different and larger cohort of patients.ObjectiveTo assess the effect of the ADRB2 polymorphism in methacholine-responsive patients with asthma.MethodsWe conducted a retrospective analysis of the effects of ADRB2 haplotypes at position 16 (Gly/Arg) and 27(Gln/Glu) in 449 patients with a physician diagnosis of asthma who were responsive to methacholine (ie, provocation concentration that caused a decrease in forced expiratory volume in 1 second [FEV₁] of 20% [PC₂₀], <8 mg/mL).ResultsNo differences were found in age, FEV₁, or inhaled corticosteroid dose among the genotypes or haplotypes. No significant differences were found in methacholine PC₂₀ (ie, <8 mg/mL) between the separate genotypes at position 16 or 27 or between the haplotypes at positions 16/27 combined. In addition, no significant differences were found among individual genotypes when stratified according to severity of BHR using different doubling dilution cutoff points for methacholine PC₂₀ (ie, <4 mg/mL, <2 mg/mL, and <1 mg/mL).ConclusionWe have confirmed in this replication study that common ADRB2 genotypes or haplotypes at positions 16/27 do not influence BHR in methacholine-responsive patients with asthma.     

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.     

Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment

Background: Anti‐IgE, omalizumab, inhibits the allergen response in patients with asthma. This has not been directly related to changes in inflammatory conditions. We hypothesized that anti‐IgE exerts its effects by reducing airway inflammation. To that end, the effect of anti‐IgE on allergen‐induced inflammation in bronchial biopsies in 25 patients with asthma was investigated in a randomized, double‐blind, placebo‐controlled study. Methods: Allergen challenge followed by a bronchoscopy at 24 h was performed at baseline and after 12 weeks of treatment with anti‐IgE or placebo. Provocative concentration that causes a 20% fall in forced expiratory volume in 1 s (PC₂₀) methacholine and induced sputum was performed at baseline, 8 and 12 weeks of treatment. Changes in the early and late responses to allergen, PC₂₀, inflammatory cells in biopsies and sputum were assessed. Results: Both the early and late asthmatic responses were suppressed to 15.3% and 4.7% following anti‐IgE treatment as compared with placebo (P < 0.002). This was paralleled by a decrease in eosinophil counts in sputum (4–0.5%) and postallergen biopsies (15–2 cells/0.1 mm²) (P < 0.03). Furthermore, biopsy IgE+ cells were significantly reduced between both the groups, whereas high‐affinity IgE receptor and CD4+ cells were decreased within the anti‐IgE group. There were no significant differences for PC₂₀ methacholine. Conclusion: The response to inhaled allergen in asthma is diminished by anti‐IgE, which in bronchial mucosa is paralleled by a reduction in eosinophils and a decline in IgE‐bearing cells postallergen without changing PC₂₀ methacholine. This suggests that the benefits of anti‐IgE in asthma may be explained by a decrease in eosinophilic inflammation and IgE‐bearing cells.     

Effect of one hour of passive cigarette smoking on lung function and airway responsiveness in adults and children with asthma

Summary We exposed 18 adults with bronchial asthma, 16 healthy controls and 11 children with asthma for 1 h either to ambient air (AA) or to environmental tobacco smoke (ETS). Exposure was performed at rest in an exposure chamber. Before and after exposure symptom scores and lung function were determined. After exposure bronchoprovocation tests with methacholine (adults) or histamine (children) were performed to determine the concentrations causing a 100% increase in SRaw (PC₁₀₀SRaw), and a 20% fall in FEV₁ (PC_2OFEV₁). In adult asthmatics mean (SD) SRaw before and after Sham was 8.8 (3.6) and 8.4 (3.6) cmH₂O · s, and mean FEV₁ (SD) was 3.18 (0.97) and 3.14 (0.9) 1, respectively. Before and after passive smoking mean SRaw (SD) was 7.5 (3.0) and 7.2 (2.7) cmH₂O · s, and mean FEV₁ (SD) was 3.31 (1.0) and 3.21 (0.88) 1, respectively. Geometric mean (SD) PC₁₀₀SRaw and PC_2OFEV₁ after Sham were 0.38 (4.5) and 0.29 (4.1) mg/ml, after passive smoking 0.39 (5.1) and 0.36 (4.7) mg/ ml, respectively. In healthy controls there was no consistent effect on the respective parameters during exposure. In children mean (SD) SRaw before and after Sham was 8.7 (3.6) and 9.0 (3.2) cmH₂O · s, and mean FEV₁ (SD) was 1.97 (0.32) and 1.98 (0.40) 1, respectively. Before and after passive smoking mean SRaw (SD) was 10.4 (5.3) and 9.4 (3.3) cmH₂O · s, and mean FEV₁ (SD) was 1.95 (0.37) and 1.94 (0.35) 1, respectively. Geometric mean (SD) PC₁₀₀SRaw and PC₂₀FEV₁ after Sham were 1.39 (3.0) and 0.70 (2.7) mg/ml, and after passive smoking 1.65 (2.5) and 0.96 (2.3) mg/ml, respectively. There were no significant differences in lung function and airway responsiveness between exposure to ambient air or ETS. The main symptoms during passive smoking were eye and nasopharyngeal irritation. Our observations suggest that in children and adults with mild to moderate bronchial asthma, 1 h of passive cigarette smoking does not cause airway obstruction or con sistent changes in bronchial responsiveness.Abbreviations AA ambient air (Sham) - ETS environmental tobacco smoke - SRaw specific airway resistance - FEV₁a one-second forced expiratory volume - PC₂₀FEV₁a provocative concentrations of histamine/methacholine to decrease FEV₁ by 20% - PC₁₀₀SRaw provocative concentrations of histamine/methacholine to increase SRaw by 100% Supported by Forschungsrat Rauchen und Gesundheit, Hamburg, Federal Republic of Germany     

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.     

Relation between bronchial responsiveness to methacholine and levels of IgE antibody against Dermatophagoides farinae and serum IgE in asthmatic children

The relation between non-specific bronchial responsiveness and allergic sensitivity was evaluated in children with asthma. Bronchial responsiveness was determined by methacholine inhalation challenge test, and was expressed as a provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀). RAST titre for Dermatophagoides farinae and serum IgE level were evaluated as parameters of allergic sensitivity. When the PC₂₀ vaiues, RAST titres for D. farinae. and serum IgE levels of 47 asthmatic children and 16 normal controls were compared. the asthmatic children had significantly lower PC₂₀ values and higher D. farinae-RAST titres and serum IgE levels than the normal controls. The correlation analyses in 47 asthmatic children have shown that there is no significant correlation between PC₂₀ values and RAST titres for D. farinae (r= 0.04. P > 0.1) or between PC₂₀ values and serum IgE levels (r= < 0.03 P > 0.1). These results suggest thaty although both bronchial hyperresponsiveness and allergic sensitizalion may be in some way related to one another in children with asthma, the magnitude of allergie sensilization does not influence the degree of the non-specific bronchial responsiveness.     

Bronchial provocation with cat allergen: correlation between the individual IgE-CRIE pattern and the occurrence of a late allergic reaction

Twenty-one mild asthmatic patients allergic to cat dander underwent a bronchial provocation test (BPT) with a cat extract. An early allergic response (EAR) was observed in all 21 patients and a late allergic response (LAR) in 8/21 patients. In the EAR, the patients with subsequent LAR had a greater full in FEV₁, Their baseline FEV₁, and total dose of inhaled allergen were not significantly different from patients who did not develop a LAR, but their serum specific IgE level was higher. Crossed immunoelectrophoresis (CIE) of the same cal extract showed that it contained eight different proteins. An IgE-CRIE was obtained from all 21 patients, using radiolabelled anti-lgE and autoradiography. Radiolabelled standards allowed a semiquantitative scoring of the radiosiaining. The CRIE pattern of the eight patients with LAR showed a higher score of radiostaining and a greater number of proteins hound to IgE. The two major allergen cal albumin and Fel d I bound equally to IgE of patients with and without LAR whereas another protein (antigen No. 7) bound to IgE of 100% of patients with LAR but of only 38% of patients without LAR. These data suggest that the pattern of the IgE response to specific proteins of a cat extract may be related to the occurrence of LAR after BPT with this allergen.     

Tolerance to the bronchoprotective effect of β2 -agonists: Comparison of the enantiomers of salbutamol with racemic salbutamol and placebo

Background: Regular use of racemic salbutamol results in the partial loss of its bronchoprotective effect. The 2 enantiomers of salbutamol, the bronchodilator R-salbutamol and nonbronchodilator S-salbutamol, are now available. Objective: We sought to compare the effect of regular use of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the bronchoprotective effect of a single dose of racemic salbutamol against methacholine-induced bronchoconstriction. Methods: Eleven of 13 well-controlled β₂ -agonist–free asthmatic subjects completed a double-blind, randomized study comparing racemic salbutamol 2.5 mg, S-salbutamol 1.25 mg, R-salbutamol 1.25 mg, and diluent placebo nebulized and inhaled 3 times daily for 6 days (≥6-day washout period). Ten to 12 hours after the last dose, the subjects performed measurement of FEV₁ , methacholine PC₂₀ , and a repeat methacholine PC₂₀ done 1 hour after the first methacholine test and 10 minutes after 2 puffs (200 μg) of racemic salbutamol administered from a metered-dose inhaler. The primary endpoint was the methacholine PC₂₀ dose shift (Δlog PC₂₀ ÷ log 2) from before to after administration of 200 μg of racemic salbutamol. Results: The methacholine dose shift was 3.2 doubling doses (9-fold increase in methacholine PC₂₀ after 200 μg of racemic salbutamol) during the placebo treatment and was unaltered (3.2) after administration of S-salbutamol. The dose shift was significantly lower after both the R-salbutamol and racemic salbutamol treatments (2.2 and 2.6 doubling doses, respectively); there was no significant difference between R-salbutamol and racemic salbutamol. There was no treatment effect on baseline FEV₁ , baseline methacholine PC₂₀ , or bronchodilation. Conclusion: Regular treatment with racemic salbutamol or R-salbutamol, but not S-salbutamol, results in a partial loss of bronchoprotection, without loss of bronchodilation, compared with placebo. (J Allergy Clin Immunol 1999;103:1049-53.)     

Effect of levocetirizine on nasal provocation testing with adenosine monophosphate compared with allergen challenge in allergic rhinitis

Background End‐organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT). Objective We compared the effect of levocetirizine on nasal adenosine 5′‐monophosphate (AMP) with specific allergen challenge in patients with intermittent and persistent allergic rhinitis (AR). Methods Patients with AR were randomized in double‐blind cross‐over fashion to receive single doses of levocetirizine 5 mg or identical placebo, with nasal challenge performed 12 h after dosing. Sixteen participants completed per protocol. Nasal AMP or allergen challenge was conducted on separate days with 1‐ and 2‐week washout periods in between, respectively. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after each challenge. The primary end‐point was the provocative concentration of AMP or allergen causing a 20% drop in the PNIF (PC₂₀). Results The time‐profile for PNIF recovery [area under the 60 min time–response curve as % PNIF change (min)] were significantly attenuated for AMP challenge, as mean difference [95% confidence interval (CI)]: 11.57 (3.87, 19.25), P=0.005 and for allergen challenge: 17.82 (0.11, 35.53), P=0.04. A highly significant correlation was shown between methods for the area under the curve: (R=0.86, P<0.001). A statistically significant correlation was also seen for the PC₂₀: (R=0.94, P<0.001). PC₂₀ improvement amounted to a 1.26 (95% CI 0.16, 2.35) and 0.16 (95% CI ?0.41, 0.73) doubling‐dilution shifts for allergen and AMP challenges, respectively. Bland–Altman plots confirmed good agreement between methods. Conclusion A high correlation and statistical agreement has been demonstrated between AMP and allergen challenge for all outcome measures. In particular, the recovery profile after NPT is a sensitive and discriminatory measure of anti‐allergic treatment.