Dual Asthmatic Response Research Articles

Occupational asthma caused by soybean flour in bakers--differences with soybean-induced epidemic asthma.

Soybean dust has been identified as the causative agent of occupational asthma and asthma epidemics. Two main soybean hull allergens responsible for asthma outbreaks, Gly m 1 and Gly m 2, have been identified and purified. The soybean allergens causing occupational asthma in exposed bakers were investigated and compared with those involved in epidemic asthma. We report four bakers or confectioners with work-related respiratory symptoms who were exposed to soybean flour used as a baking additive. The causative role of soybean flour was investigated by immunological tests and specific inhalation challenge tests. Soybean flour allergens causing occupational asthma were characterized by immunoblotting. Immunoglobulin (Ig) E-reactivity to Gly m 1 and Gly m 2 was assessed using enzyme-linked immunosorbent assay. Sensitization to soybean flour was demonstrated by skin and serological tests and was confirmed by positive inhalation tests. Bronchial challenge test to soybean flour extract elicited immediate or dual asthmatic responses. Immunoblotting with soybean flour and soybean hull extracts showed IgE-binding mainly to high molecular weight (MW) allergens. There was an important individually different allergic response to inhalant soybean components. None of the patients showed IgE-reactivity against Gly m 1 and only one patient showed IgE-reactivity to the soybean hull allergen Gly m 2. These bakery workers had developed IgE-mediated occupational asthma to soybean flour. The allergens involved in occupational asthma caused by soybean flour are predominantly high MW proteins that are present both in soybean hull and flour, and they are different from the allergens causing asthma outbreaks, which are mainly low MW proteins concentrated in the hull.

O-82 - Effect of a peptide-leukotriene (p-LT) antagonist, pranlukast, on antigen-induced dual asthmatic response, and blood and lung eosinophilia in guinea pigs

O-82 - Effect of a peptide-leukotriene (p-LT) antagonist, pranlukast, on antigen-induced dual asthmatic response, and blood and lung eosinophilia in guinea pigs

Effect of cyclosporin A on the allergen-induced late asthmatic reaction.

BACKGROUND: The allergen-induced late asthmatic reaction (LAR) is associated with mucosal inflammation involving several cell types including activated T lymphocytes and eosinophils. In contrast, the early asthmatic reaction (EAR) is...

Influence of salmeterol on chronic and allergen-induced airway inflammation in mild allergic asthma: a pilot study

Salmeterol xinafoate, a potent, long-acting, selective beta 2-agonist, inhibits allergen-induced asthmatic responses. To evaluate if this bronchoprotection was also associated with anti-inflammatory effects, mild asthmatic patients presenting a dual asthmatic response to allergens were randomized in a double-masked, placebo-controlled, parallel-group study to take either salmeterol 50 μg twice daily (n = 7) or placebo (n = 6) for 2 months. At the end of the treatment period, airway inflammation was assessed by bronchoalveolar lavage and bronchial biopsies, both before and after allergen challenge. After treatment, allergen-induced responses were decreased in the salmeterol group and, to a lesser degree, in the placebo group. Postallergen and preallergen challenge, lavage total, and differential cell counts were similar in the two groups. Before allergen challenge, bronchial biopsies of both groups indicated extensive airway inflammation with similar total inflammatory cell counts but with a higher percentage of epithelial desquamation in the salmeterol group. The allergen challenge did not modify the inflammatory variables measured except for an increase in eosinophil counts in connective tissue. Comparison of the postchallenge data of the two groups showed that counts of AA1-, HLA-DR-, and CD45ro-positive cells were reduced in the salmeterol group. When prechallenge and postchallenge data were pooled to compare the two treatments, the salmeterol group had lower numbers of CD3-, CD25-, HLA-DR-, AA1-, CD45-, and CD45ro-positive cells. In conclusion, these results confirmed the bronchodilator and bronchoprotective effects of salmeterol. They also suggested that even though salmeterol did not modify lavage and overall bronchial biopsy cellular infiltrate, the drug apparently reduced expression of some bronchial mucosa activation cell markers. This study, however, was mainly exploratory, and the reproducibility and clinical significance of these observations require further clarification

Occupational asthma and rhinitis caused by ash (Fraxinus excelsior) wood dust

An 18-year-old man who worked in a furniture factory reported rhinitis and asthma when he was exposed to ash wood dust. Monitoring of the patient's peak expiratory flow rate (PEFR) when off work and at work showed increased variations of PEFR at work. Basal PC20 methacholine was 1.41 mg/ml. A bronchial provocation test (BPT) with a 1:1000 w/v ash wood dust extract induced a dual asthmatic response with a 7.5-fold increase of nonspecific bronchial responsiveness. Intradermal testing with ash wood extract elicited a positive immediate response. IgE antibodies against ash wood were found in the patient's serum with a RAST value of 0.57 PRU/ ml. Similar skin tests, BPT, and RAST with ash wood dust performed in control patients were all negative. All the studies performed suggest that our patient had occupational rhinitis and asthma caused by exposure to ash wood dust in which a type I immunologic mechanism was implicated.

Circulating intracellular adhesion molecule-1 concentrations following bronchial provocation in atopic asthma.

A house dust bronchial provocation test (BPT) was used to investigate the effect of allergen-induced airway inflammation and airway hyperresponsiveness (AHR) on the level of circulating intracellular adhesion molecule-1 (c-ICAM-1). The concentration of c-ICAM-1 was measured by the sandwich ELISA while the level of eosinophil cationic protein (ECP) in the sputum was determined by RIA. The parameter used for quantification of AHR was the minimum dose of methacholine (Mch) required to produce a fall in respiratory resistance and was expressed as log Dmin. Fourteen subjects with mild atopic asthma participated in this study. Ten patients (dual asthmatic response group; DAR group) developed a late asthmatic response (LAR) following an immediate asthmatic response (IAR). Four subjects (IAR alone group) exhibited only IAR following BPT. In both groups, the mean baseline concentration of c-ICAM-1 did not change 6 h after BPT (from 195.3+/-20.3 to 220.9+/-27.6 and from 215.5+/-23.5 to 231.3+/-30.5 ng/ml, respectively). However, BPT produced a significant increase in the mean concentration of c-ICAM-1 24 h later in the DAR group (257.3+/-41.14 ng/ml, p < 0.05), but not in the IAR alone group (225.5+/-18.1 ng/ml). BPT also increased ECP levels in the sputum from a baseline value 24 h after BPT in the DAR group (from 30.2+/-10.1 to 68.8+/-19.8 ng/ml; p<0.05), but not in the IAR alone group (from 28.1+/-8.3 to 43.3+/-23.7 ng/ml). There was a significant (p<0.05) correlation between c-ICAM-1-concentrations and sputum ECP levels 24 h after BPT in each group. Furthermore an inverse and significant (p<0.05) correlation was found between c-ICAM-1 concentrations and percent changes in log Dmin 24 h after BPT in each group. Our results suggest that increased concentrations of c-ICAM-1 after BPT may reflect the upregulated expression of airway ICAM-1 during allergen-induced airway inflammation. We propose that c-ICAM-1 is a useful marker for allergic inflammation, particularly that of eosinophilic infiltration into the airway, an essential feature of asthma.

The effect of inhaled thiorphan on allergen‐induced airway responses in asthmatic subjects

Neuropeptides are likely to be implicated in the pathophysiology of allergen-induced airway responses. However, upon release in the airways, neuropeptides are potentially inactivated by neutral endopeptidase (NEP). We hypothesized that NEP-inhibition by inhaled thiorphan (TH) would increase allergen-induced early (EAR) and late (LAR) asthmatic responses, and allergen-induced airway hyperresponsiveness to histamine in asthmatic subjects in vivo. The dose and dosing intervals of TH were derived from previous pharmacokinetic and dose-finding studies. Nine non-smoking, atopic, asthmatic men with dual asthmatic responses to inhaled house-dust mite extract participated in a double-blind, placebo-controlled, cross-over study. During each study period PC20 histamine was measured 24 h before, and 3 and 24 h post-allergen. TH (1.25 mg/mL, 0.5 mL) or placebo (P) were aerosolized pre-allergen, and three times at 2 h intervals post-allergen (total dose of TH: 2.5 mg). Forced expiratory volume in one second (FEV1) was recorded and expressed as percentage fall from baseline. The EAR (0-3 h) and the LAR (3-8 h) were defined as maximum percentage fall from the pre-allergen baseline and as corresponding areas under the time-response curves (AUC). As compared with P, TH failed to induce an acute effect on FEV1 at any of the timepoints (P > 0.08). There was no significant difference between P and TH in the EAR and the LAR: neither in terms of maximum percentage fall from baseline (mean +/- SEM: EAR: 22.3 +/- 4.7% (P) and 20.4 +/- 4.1% (TH), P = 0.75; LAR: 25.2 +/- 4.7% (P) and 26.4 +/- 5.8% (TH), P = 0.77) nor in terms of AUC (P = 0.76). Correspondingly, the changes in PC20 histamine were not different between the two treatments (P > 0.40). We conclude that four adequate doses of the inhaled NEP-inhibitor, thiorphan, failed to potentiate allergen-induced airway responses in asthma. These results suggest that either neuropeptides do not play a predominant role in allergen-induced airway responses, or that allergen challenge induces NEP-dysfunction in humans in vivo.

Effect of Saiboku-to (chai-pu-tang), a traditional herbal medicine, on the expression of tumor necrosis factor during late asthmatic response in guinea-pigs

Saiboku-to (TJ-96) has been used orally for the prophylactic treatment of bronchial asthma including chronic, severe and steroid-dependent types. In this experiment we examined the effect of this remedy on the late asthmatic response (LAR) and the expression of TNF-α in a guinea-pig asthmatic model. Approximately 3-weekold male Hartley strain guinea-pigs were immunized with a mixture of ascaris suum extract and silica gel and challenged with inhalation of the antigen, by which a dual asthmatic response was developed. TJ-96 was administered 500 mg/kg/day (corresponding to the maximum clinical dose) for 14 days before the challenge using a gastric tube. Lung tissues were fixed in periodate-lysine-paraformaldehyde. The enzyme linked indirect imunoperoxidase method was applied on 3 μm thick sections. The antibodies used were anti-human TNF-α polyclonal rabbit IgG. TJ-96 significantly suppressed the LAR and the infiltration of eosinophils and mast cells in the lung. The immunohistochemistry revealed that this cytokine was strongly expressed in mast cells, macrophages and bronchial epithelial cells of the lung tissues from asthmatic guinea-pigs with LAR, while its expression was reduced in the TJ-96 treatment group in which LAR was suppressed.

Early and late onset asthmatic responses following lysine-aspirin inhalation in aspirin-sensitive asthmatic patients.

Inhalation of aerosolized lysine-aspirin (L-ASA) has been described as an alternative diagnostic method in aspirin-sensitive asthma. To further understand the pathogenetic mechanism of aspirin-sensitive asthma, we performed L-ASA (Inyesprin) bronchoprovocation test (BPT) in 51 asthmatic patients (45 non-atopic and six atopic asthma). Twenty-six patients showed significant bronchoconstriction after the inhalation of L-ASA. Bronchoprovocation test produced immediate asthmatic responses in 13 cases as well as dual asthmatic responses in four cases, whose late onset asthmatic response was noted at 4-7 h after L-ASA inhalation. We conclude that L-ASA bronchoprovocation might be a useful method for the diagnosis and investigation of aspirin-sensitive asthma. However, L-ASA inhalation can also induce late onset asthmatic responses.

Aluminium potroom asthma confirmed by monitoring of forced expiratory volume in one second.

Chronic airflow obstruction has long been seen among aluminium potroom workers. Currently referred to as "potroom asthma," it is debatable as to whether it is occupational asthma or nonspecific airway obstruction. A 35-yr-old male lifelong nonsmoker, with no history of asthma or atopy, was hired by an aluminium plant that had begun its operation in 1986. Preemployment screening, consisting of spirometry and a chest radiograph, was normal. During his 12-h shifts, he replaced 10 to 20 anodes (prebake type), spending 5 min each time close to open pots releasing hot fumes. The patient experienced episodes of cough and dyspnea, which were resolved during withdrawal from work in January and December 1991. He resumed work in the potrooms in March 1992, his dyspnea recurred at work and at night with 25% drops in peak expiratory flow rates (PEFR), associated with mild-to-moderate bronchial hyperresponsiveness (PC20 histamine, 1.0 mg/ml). After a chest physician's assessment, he was withdrawn from the potroom department. Assessment of the bronchial response to the occupational exposure in potrooms carried out in November 1992 revealed a pattern of dual asthmatic response, paralleled by a drop in PC20 methacholine from 5.1 to 0.7 mg/ml. A similar pattern was seen again during repeat workplace challenges 3 wk later. Spirometry obtained on control days was stable. We conclude that asthmatic reactions can exist among workers in aluminium smelters.

Occupational asthma caused by two herb materials, Dioscorea batatas and Pinellia ternata

There have been very few cases of occupational allergies caused by herb materials. In this paper, we report a case of occupational asthma and rhinitis caused by two herb materials, Dioscorea batatas and Pinellia ternata, which are known as Sanyak and Banha respectively. The patient had strong positive responses to grass pollens and cat fur, as well as to Sanyak and Banha extracts on skin-prick tests. Bronchoprovocation tests showed a dual asthmatic response to Sanyak whereas only an early asthmatic response to Banha. Serum specific IgE and IgG4 antibodies to Sanyak were detected by enzyme-linked immunosorbent assay (ELISA) but there was no specific IgE antibody binding to Banha. In order to further characterize the allergenic component of these extracts, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting studies were also performed. Three IgE binding components (29,000, 57,000, 63,000 Da) were detected within the Sanyak extracts, but no IgE-binding component was noted within the Banha extracts. It is suggested that Sanyak can induce IgE-mediated bronchoconstriction in an exposed worker. Further studies are needed to investigate the pathogenetic mechanism triggered by Banha.

Allergen-induced Recruitment of Inflammatory Cells in Lavage 3 and 24 h After Challenge in Allergic Asthmatic Lungs

To determine whether a link exists between the recruitment of inflammatory cells in the airways on a bronchial and bronchoalveolar level and the development of allergen-induced increase in bronchial hyperresponsiveness after allergen challenge, we used bronchial lavage and bronchoalveolar lavage to assess the airway responses to allergen. Twelve symptomatic atopic asthmatics were studied. In all patients bronchial and bronchoalveolar lavage was performed before, 3 h, and 24 h after allergen challenge. Monoclonal antibodies were used directed against T cells (CD3, CD4, CD8) and the eosinophil cationic protein (EG2). Eight patients showed a dual asthmatic response; four patients showed only an early asthmatic reaction after allergen challenge. Clear differences were found between bronchial and bronchoalveolar lavage. Activated eosinophils (EG2) were significantly increased both at 3 h (p = 0.01) and 24 h (p = 0.005). The number of activated eosinophils was significantly higher in the dual responders. A correlation was observed between the severity of the late asthmatic reaction (LAR) and the number of epithelial cells in the bronchial recovery at 3 h, but not at 24 h, in patients who clinically developed a LAR. No significant changes in the number of CD3, CD4, and CD8 cells 3 and 24 h after the challenge both in the bronchial and bronchoalveolar recovery were observed. We conclude that the number of activated eosinophils in bronchial lavage is associated with the development of the LAR and allergen-induced increase in bronchial hyperresponsiveness.

Bronchial lavage and bronchoalveolar lavage in allergen-induced single early and dual asthmatic responders.

The phenotypic cellular profile of bronchial lavage (BL) and bronchoalveolar lavage (BAL) was studied in 7 single early (SR) and 10 dual asthmatic responders (DR). Lavage was performed, after previously having determined bronchial hyperresponsiveness to histamine and the response to house dust mite (HDM) challenge. The recovered lavage fluid was separated in two fractions, BL and BAL. Total fluid recovery and cell number from the BL and BAL were comparable in both patient groups. Differential cell counting and immunocytochemistry were performed. DR had a significantly higher number of eosinophils and EG2+ cells in BL but not in their BAL. No differences could be found in CD4+, CD8+, and HLA-DR+ cells. A strong correlation was found between eosinophils in the BL+ and EG2+ cells in the BL (r = 0.79, p < 0.001) and between eosinophils in the BL and peripheral blood eosinophils (r = 0.70, p < 0.0025). The number of EG2+ cells and the number of epithelial cells in both BL and BAL showed a correlation (r = 0.55, p < 0.05). Dual responders had a higher total IgE (p < 0.01), and total serum IgE correlated well with the eosinophils in the BL (r = 0.85, p < 0.0001). Our observations demonstrate cellular differences in the lung on mainly a bronchial level between single early and dual asthmatic responders. A bronchial lavage eosinophil and EG2+ cell count and higher blood total IgE level are associated with the tendency to develop a dual asthmatic response.

Increase in airway responsiveness and effect of deep inhalation on airway caliber in allergen-induced asthma. Relationship to the late-phase response.

The airway responsiveness to methacholine (MCh) and the effect of deep inhalation (DI) on airway caliber were determined in 18 asthmatic patients at baseline and 3 and 24 h after an allergen inhalation challenge. The dose of MCh causing a 20% fall of FEV1 (PD20) was used as an index of airway responsiveness; the ratio of forced expiratory flow at 40% of FVC from maximal and partial flow/volume curves (MEF40M/P) was used to assess the effect of DI on airway caliber. Thirteen patients showed a dual asthmatic response (DAR) to allergen, 5 patients an isolated early-phase asthmatic response (EAR). In the DAR patients, 3 h after allergen challenge, when the early-phase response had resolved and the late-phase response had yet to develop, MChPD20 (geometric mean) was reduced from 202 to 71 micrograms (P less than 0.001) whereas MEF40M/P at the MCh end point was unchanged (p greater than 0.4). Twenty-four hours after allergen challenge, when late-phase response had developed, MChPD20 was further reduced to 51 micrograms (p less than 0.02), and this reduction was accompanied by a decrease of MEF40M/P at the MCh end point (p less than 0.01). In the EAR patients, neither MChPD20 nor MEF40M/P was significantly changed at any time during the study. We conclude that most of the increase in airway responsiveness that follows acute exposure to allergen precedes the late-phase response and is not determined by the same mechanisms that impair the ability of the lung to dilate airways with a DI.(ABSTRACT TRUNCATED AT 250 WORDS)

Nedocromil sodium inhibits the early and late asthmatic response to exercise

A double-blind, crossover study was carried out to investigate the effect of nedocromil sodium on the dual asthmatic response to exercise challenge. Nineteen patients with a late response to bicycle exercise were randomly treated on two study days with 4 mg nedocromil sodium or a matched placebo aerosol, 30 min before commencing exercise. Peak flow was measured before exercise, at intervals up to 60 min after exercise, then hourly for up to 13 h. In 12 of the 19 patients an early reaction to exercise occurred. In 8 of these 12 patients the early reaction could be inhibited by nedocromil sodium (p less than 0.01) although in half of these patients placebo was also shown to be protective. In the case of the late reaction after exercise challenge, 4-13 h after exercise challenge, nine patients were clearly protected by pretreatment with nedocromil sodium (p less than 0.01) when the fall in peak expiratory flow rate was related to the pre-exercise baseline, four patients showed an equal protective effect of placebo and nedocromil sodium, whilst the others were not protected. When the late asthmatic response (fall in peak expiratory flow rate) after exercise challenge was related to control diurnal peak flow values, the number of responses was reduced; the protective effect of nedocromil sodium remained.

The role of bronchial responsiveness to leukotrienes in antigen-induced immediate and late asthmatic response

In order to clarify the role of leukotriene in the antigen-induced asthmatic response, we carried out mite-antigen, leukotriene D4 (LTD4) and histamine inhalation tests in 21 mite-sensitive atopic asthma patients, and investigated the relationship between the bronchial responsiveness to mite (PD20-Mite) and that to LTD4 and histamine (PD20-LTD4, PD20-Hist). We then compared PD20-LTD4 and PD20-Hist between the groups with and without late asthmatic response (LAR), and investigated the relationship between the peak percentage fall of FEV1.0 in LAR (magnitude of LAR) and PD20-LTD4 and PD20-Hist. There were significant correlations between PD20-LTD4 and PD20-Mite (r = 0.590, p < 0.01), and between PD20-Hist and PD20-Mite (r = 0.669, p < 0.001). The bronchial responsiveness to LTD4 and histamine was significantly higher in the group with LAR. In addition, PD20-LTD4 showed a significant negative correlation with the magnitude of LAR (r = 0.724, p < 0.001). Furthermore we analyzed the relationship between PD20-LTD and the ratio of the magnitude of LAR to that of IAR (immediate asthmatic response), because there was a significant correlation between the magnitude of IAR and that of LAR (r = 0.842, p < 0.001) in 16 asthmatic patients with dual asthmatic response, and found that the correlation coefficient was also very high (r = -0.836, p < 0.001). These results suggest an important role of leukotriene in the antigen-induced asthmatic response.

Effect of the selective PAF antagonist SM‐10661 on an asthmatic model. 2. Effect on antigen‐induced dual asthmatic response and infiltration of leukocytes into airways in actively sensitized conscious guinea pigs

The effect of a selective platelet-activating factor (PAF) receptor antagonist, SM-10661, on antigen-induced dual asthmatic response and leukocyte infiltration into the airways of actively sensitized conscious guinea pigs was investigated. The animals were pretreated with mepyramine maleate (10 mg/kg i.p.) and then challenged with ovalbumin. The inhalation of ovalbumin caused an immediate decline in specific airway conductance (sGaw) which peaked at 5 min after the challenge. sGaw gradually returned to the baseline 6 hr after the challenge. After the early asthmatic response (EAR), a second phase change, a late asthmatic response (LAR) in sGaw peaking at 17-20 hr was observed. When 1% w/v disodium cromoglycate was inhaled for 2 min on two occasions, EAR was not affected, but LAR was significantly inhibited. Oral administration of 50 mg/kg fenoterol (30 min before challenge) significantly inhibited EAR, but had no significant effect on LAR. SM-10661 administered orally 1 hr before the challenge inhibited EAR dose-dependently (50% inhibitory dose (ID50); 59 mg/kg, but was even more effective against the LAR (ID50); 13-16 mg/kg). When 30 mg/kg of SM-10661 was administered orally 6 hr after ovalbumin challenge, LAR was completely inhibited. The number of total cells, macrophages and eosinophils in bronchoalveolar lavage fluids rose significantly 17 hr after antigen challenge compared to that observed after saline challenge. The number of neutrophils and lymphocytes also increased in response to the ovalbumin challenge, but not significantly. SM-10661 (30 mg/kg) administered orally 1 hr before the challenge significantly inhibited the increase in total cells, macrophages and eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Olive pollen induces asthmatic response

We provide evidence that olive pollen extract can induce asthmatic response. The pattern of airway response to olive pollen is investigated. Nineteen patients with seasonal allergic rhinitis and asthma, suspected to be due to olive pollen, all of whom had positive skin-prick test, were investigated. Bronchial challenge with olive pollen extract were performed and the peak flow rate was followed for 20 hr. Eight patients developed dual asthmatic response (DAR), six patients developed early asthmatic response (EAR) and five patients had no asthmatic response. The early maximal fall in FEV1 and the PD15 were not different between the group with DAR and the group with EAR only. We conclude that olive pollen can induce dual asthmatic response.

Occupational asthma due to styrene.

In a patient with asthma who was exposed to styrene serial self recorded measurements of peak expiratory flow showed the asthma to be work related, and inhalation tests with styrene reproducibly provoked a dual asthmatic response and increased responsiveness to inhaled histamine.

The effect of nedocromil sodium on the early and late reaction and allergen-induced bronchial hyperresponsiveness

Bronchial hyperresponsiveness (BHR) to methacholine was studied in 14 patients with asthma and five healthy control subjects, with and without pretreatment with nedocromil sodium, 3 and 24 hours after allergen challenge. Eleven patients demonstrated a dual asthmatic response. A significant decrease in the provocative concentration causing a 20% fall in FEV 1 was found from a geometric mean starting value of 1.18 mg/ml on the control day to 0.24 mg/ml ( p < 0.001) and to 0.17 mg/ml ( p < 0.007) 3 and 24 hours after allergen challenge. A significant correlation was observed between the increased BHR at 3 hours and the magnitude of the late response ( r = −0.57; p < 0.05). Nedocromil sodium (6 mg) significantly inhibited the increase in BHR, 1 mg/ml ( p < 0.001) at 3 hours and 0.50 mg/ml ( p < 0.001) at 24 hours. Nedocromil sodium shifted the severity of the early allergic reaction (EAR) from mean −34.8% to −6.9% and inhibited the later allergic reaction (LAR)from −30.5% to +0.4% ( p < 0.005). From the study can be concluded that nedocromil sodium inhibits the EAR and LAR and the allergen-induced increase in BHR. The inhibitory effect of nedocromil sodium on the LAR may be related to its ability to inhibit the increased BHR before the development of the LAR.