Factors influencing the occurrence of late bronchial reactions after allergen challenge

Forty-seven patients with allergic bronchial asthma were challenged with the relevant allergen. Forty-eight per cent of the provocations resulted in a positive immediate reaction followed by a late bronchial response. Late bronchial obstruction was more common among patients with a high than with a low RAST score. Ten patients were challenged with different allergens on two different occasions, but the same type of bronchial response was observed in only six of them. Nine patients with an isolated immediate response were rechallenged with higher allergen doses, the early bronchial response being partially counteracted by terbutaline inhalations in clinically appropriate doses before and during the inhalation of allergen. The treatment alleviated the early reaction in six of the patients. A late reaction occurred in all patients with an immediate response. The non-specific bronchial reactivity to methacholine was assessed in 24 patients before allergen challenge. No relation was found between this reactivity and the observed patterns of reactions to allergen. It was concluded that the occurrence of a late bronchial response probably depends on the dose of allergen administered but is independent of the degree of unspecific bronchial responsiveness to methacholine prior to the challenge.     

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.     

Local immunotherapy with Dermatophagoides extract in asthma

Local immunotherapy (LIT) with Dermatophagoides extract or placebo were administered to two groups of 11 patients with allergic asthma in a double-blind fashion. All patients received cromolyn sodium (20 mg four times a day) during treatments. Bronchial provocation tests with allergen and methacholine were performed before, 1 week, and 4 weeks after the end of treatments. Symptom score, drug consumption, and peak expiratory flow were monitored daily from 2 weeks before to 4 weeks after treatments. Compared to baseline, early bronchial sensitivity to allergen was significantly reduced both 1 week (p less than 0.0005) and 4 weeks (p less than 0.01) after LIT but not after placebo administration. Late bronchial reaction to allergen occurred similarly after placebo administration and LIT. However, in the group with LIT, the severity of late reaction was unchanged after treatment in spite of the significantly larger doses of allergen administered to provoke the early asthmatic reaction. Neither symptom score, nor drug consumption, nor peak expiratory flow were significantly different in the two groups before and during the treatment period even though both symptom score and drug consumption tended to be reduced after LIT. We conclude that LIT may be an effective and safe alternative to traditional immunotherapy.     

Green tea-induced asthma: relationship between immunological reactivity, specific and non-specific bronchial responsiveness

BACKGROUND: The relationships between immunological reactivity and bronchial responsiveness to allergen and non-specific bronchial responsiveness are unclear in occupational asthma caused by low molecular weight substances. OBJECTIVE: We assessed the above relationships in green tea-induced asthma, an occupational asthma of green tea factory workers, in which epigallocatechin gallate (EGCg), a low molecular weight component of green tea leaves, is the causative agent. METHODS: Subjects consisted of 21 patients suspected of having green tea-induced asthma, on whom skin test and inhalation challenge with EGCg were performed. The skin sensitivity or end-point titration to EGCg as a measure of immunological reactivity, together with the provocative concentrations causing a 20% or greater fall in forced expiratory volume in 1 s (PC20) of EGCg and methacholine, were determined. RESULTS: We found that 11 patients had green tea-induced asthma, with immediate asthmatic reactions in eight and dual asthmatic reactions in three. We also found that 11 of 13 patients (85%) with immunological reactivity and bronchial hyper-responsiveness to methacholine experienced an asthmatic reaction and that no subject without immunological reactivity reacted. There were significant correlations among skin sensitivity, EGCg PC20 and methacholine PC20. Multiple linear regression analysis showed the relationship: log (EGCg PC20)=0.42 log (skin sensitivity)+1.17 log (methacholine PC20)+0.93 (r=0.796, P<0.05). CONCLUSION: It is concluded that bronchial responsiveness to EGCg can be highly satisfactorily predicted by skin sensitivity to EGCg and bronchial responsiveness to methacholine.     

Decrease of complement hemolytic activity after an allergen-house dust-bronchial provocation test

Twenty-two children with bronchial asthma and positive skin tests to house-dust allergen were subjected to a bronchial provocation test with the allergen, and both bronchial reactions and serum complement hemolytic activity were measured at different intervals after the challenge. Changes in complement hemolytic activity did not correspond either with early or late bronchial reaction to the allergen. A reproducible drop in complement hemolytic activity after allergen challenge was observed in eight patients and could be prevented in four out of seven patients by sodium cromoglycate. The duration of early bronchial obstructive reaction was longer in tests where parallel complement changes were observed.     

Late asthmatic reactions and bronchial variability after challenge with low doses of allergen

Late allergic inflammatory reactions are probably of major importance for the development of asthma. In order to study the occurrence of early and late asthmatic reactions after challenge with different doses of allergen, inhalation provocation tests were performed in 13 patients with mild or moderate symptoms of allergic asthma. The provocation series was started with a low allergen dose (0.1–10 BU), which was then increased in successive ten-fold increments at intervals of 1 week until a pronounced bronchial reaction developed. Three different reaction patterns were observed. Six patients showed an isolated late reaction to relatively low doses of allergen. In four patients an immediate reaction was followed by a late reaction—a so-called dual response, and in three patients only an immediate reaction occurred. In four of the six patients who showed only a late reaction a higher allergen dose was given and this resulted in dual reactions in all four. One patient was challenged with an even higher dose, to which she reacted with an immediate response alone. After a late reaction, bronchial variability with low PEF values was observed over a period of several days. It is thus possible for an isolated late asthmatic reaction to be provoked by a low dose of inhaled allergen. This can be of clinical importance, repeated small doses of allergen may be unnoticed but still give bronchial inflammation and asthmatic symptoms.     

Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma.

Two groups of six asthmatic patients with biphasic bronchospastic response to inhaled Dermatophagoides pteronyssinus allergen extract were studied in a double-blind fashion. Early and late asthmatic reactions to allergen inhalation challenge were determined before and at the end of a 2-week treatment period with nimesulide (100 mg bid orally), a sulfonanilide with antioxidant properties, or placebo. Bronchial responsiveness to methacholine was evaluated 24 hours before and after allergen inhalation challenges. The dose of allergen causing EAR (15% decrease in FEV1) and the severity of LAR (maximum FEV1 fall) were similar before and at the end of the treatment period in both groups. In patients treated with nimesulide, bronchial responsiveness to methacholine was significantly increased after allergen inhalation challenge both before and at the end of the treatment period. These results do not support the hypothesis that the production of oxygen-free radicals plays a significant role in the development of bronchial hyperresponsiveness and late phase reaction to allergen in asthma.     

Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and asthma

Although H1 antihistamine compounds (H1) are highly effective in the treatment of allergic rhinitis (AR), their role in the treatment of asthma is still controversial. Because a strong association between AR and bronchial hyperresponsiveness (BHR) has been reported, this study was designed to assess the effect of a new H1 anti histamine, cetirizine (C), on nonspecific BHR in patients with AR. Twelve patients were included in a double-blind, crossover, placebo-controlled trial. All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge. After a washout period of 1 week to ensure the stability of the BHR, the patients received, by crossover randomization, C 10 mg daily or placebo (P) for 2 weeks. After each treatment period, BHR and nasal blocking index (NBI) were measured 1 and 6 h after nasal challenge. Bronchial responsiveness was expressed as methacholine PD20, the provocation dose of methacholine causing a 20% decrease in FEV1. Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 (median) measured before challenge showed no difference after cetirizine or after placebo (1.36 mg). Results 1 h after allergen did not show significant differences between C (methacholine PD20=0.522 mg) and placebo (methacholine PD20=0.455 mg). By contrast, 6 h after challenge, methacholine PD20 was 0.918 mg for C and 0.483 mg for P (P=0.042). Similarly, NBI showed no change between C and P 1 h after challenge, whereas the difference was significant 6 h after challenge (P=0.011 ). These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR. They suggest that C may be useful in patients with asthma associated with AR.     

Bronchial responsiveness to adenosine-5''-monophosphate and methacholine as predictors for nasal symptoms due to newly introduced allergens. A follow-up study among laboratory animal workers and bakery apprentices

BACKGROUND: In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine-5'-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to methacholine. In this follow-up study we studied bronchial responsiveness to both stimuli as predictors of new-onset airway symptoms. METHODS: We included 118 laboratory animal workers and bakery apprentices with a work experience of maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests (SPTs) to common and work allergens, blood eosinophil counting, and bronchial challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work allergens were repeated. Airway symptoms to common allergens and work allergens were defined as nasal symptoms, chest tightness or asthma attack during or after contact with either common or work allergen. Bronchial challenge tests were analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1), and by dose-response-slope (DRS). RESULTS: Fourteen subjects (12%) developed airway symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work allergens occurred in 64%, and was the strongest predictor of airway symptoms [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0-28.6]. Other predictors were airway symptoms to common allergens (RR 4.3, 95% CI 1.4-12.8), blood hypereosinophilia (RR 4.4, 95% CI 1.2-15.4) and BHR, with a slightly higher risk estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1-12.5 and RRmeth 2.8, 95% CI 1.0-8.5). The difference was more distinct analysing airway responsiveness by DRS, for which AMP predicted symptoms better than methacholine (P < 0.05). CONCLUSIONS: Pre-existent bronchial inflammation or a preinflammatory state marked by AMP (hyper)responsiveness increases the vulnerability to develop nasal symptoms.     

The effect of H1-receptor blockade on the development of early- and late-phase bronchoconstriction and increased bronchial responsiveness in allergen-induced asthma

Background: Allergen challenge of subjects with asthma produces an early asthmatic response, late asthmatic response, and increases bronchial responsiveness. Histamine partly mediates the early asthmatic response, and may play a role in late-phase responses. Azelastine has antiallergic properties and has been proposed as a treatment for asthma. We therefore investigated the contribution of histamine to late-phase responses with the use of the potent H₁-receptor antagonist azelastine.Methods: Ten subjects with atopic asthma were studied in a double-blind, randomized, placebo-controlled trial. Azelastine was administered over 4 days before allergen challenge. Changes in airway caliber were followed with measurements of forced expiratory volume in 1 second, and changes in bronchial responsiveness were followed by methacholine and prostaglandin D₂ bronchial provocation tests.Results: Azelastine significantly inhibited the development of the early asthmatic response. Azelastine had no effect on the late asthmatic response or on the development of allergen-induced increases in bronchial responsiveness. The power of the study was sufficient to have had a high probability of detecting any important differences between placebo and azelastine during the late phase.Conclusions: Azelastine had no significant effect on the late-phase response model of asthma. This study does not support the hypothesis that histamine is an important mediator of the late asthmatic response or allergen-induced increases in bronchial responsiveness.     

Bronchial allergen challenge: dose versus concentration

This study was designed to investigate if two equivalent doses of allergen administered by different dosing regimes--two breaths and 10 breaths of each concentration--would result in the same magnitude of the early and late asthmatic response. Fifteen patients with extrinsic allergic asthma were challenged twice with either two or 10 breaths of twofold increasing allergen concentrations. The challenge was continued until a 20% decrease in FEV1 had been achieved. A non-cumulative PC20FEV1 allergen was derived, and the cumulative dose of allergen given was similarly derived. In order to assess the reproducibility of the challenge, seven patients were challenged twice with two-breath regime. The mean value of allergen PC20 obtained by the two-breath regime was 4.1 fold (95% CI: 2.3-7.1 fold) greater than those obtained by the 10-breath regime (P less than 0.05), whereas the difference was 1.4 fold (95% CI: -3.3-0.5 fold) for the cumulative dose (P greater than 0.05). A statistically significant larger magnitude of the early asthmatic response, as determined by the maximum per cent fall in FEV1, and late asthmatic response determined by the maximum per cent fall in peak expiratory flow domiciliary recorded during the following 24 hr after challenge, was observed in favour of the 10-breath regime compared to the two-breath regime (mean difference 6%, 95% CI: 0.6-11%). The reproducibility of the provocation test was acceptable (+/- 1.8 two-fold concentration difference). These results confirm the 'equivalent dose hypothesis', and demonstrates that dosage rather than concentration appears to determine the early and late asthmatic response after bronchial allergen challenge.     

Changes in bronchial responsiveness following nasal provocation with allergen.

The relationship between upper airway inflammation and asthma is controversial. In the current study, we sought to investigate the relationship between allergic rhinitis and lower airway dysfunction by performing double-blind, randomized nasal challenges with allergen or placebo. Subjects were selected for a prior history of asthma exacerbations after the onset of seasonal allergic rhinitis symptoms. After the induction of a marked nasal-allergic reaction (with a technique of nasal provocation that limited allergen delivery to the nose), there were no changes in FEV1, specific conductance, or lung volumes either 30 minutes or 4 1/2 hours after nasal allergen challenge, nor any changes in peak flow rates followed hourly until the next day. However, nasal provocation with allergen resulted in a relative increase in bronchial responsiveness to methacholine compared with that to placebo (p = 0.011 at 30 minutes and p = 0.0009 at 4 1/2 hours after challenge). Our study suggests that, although a nasal-allergic response does not induce airflow limitation of the lower airways, it can alter bronchial responsiveness.     

Late bronchial response and increase in methacholine hyperresponsiveness after exercise and distilled water challenge in atopic subjects with asthma with dual asthmatic response to allergen inhalation

We investigated the occurrence of late asthmatic response and increased methacholine responsiveness after exercise and ultrasonically nebulized distilled water (UNDW) inhalation in 12 subjects with asthma with dual asthmatic response and increased responsiveness after allergen challenge. On 3 separate days, allergen, exercise, and UNDW challenges were performed 2 hours after methacholine. FEV1 was measured for 8 hours to detect any delayed change in airway caliber. If there were a further significant reduction in FEV1 after the recovery from the immediate bronchoconstriction, methacholine challenge was performed again when FEV1 had returned to baseline. Reproducibility of any observed late response to exercise and UNDW was also investigated by repeating these challenges on 2 subsequent days. After allergen inhalation only nine subjects had an early asthmatic response, whereas all the tested subjects demonstrated a late reaction and increased methacholine responsiveness. Ten subjects had an immediate response to exercise, and this was followed by a late response in only four patients. Nine subjects demonstrated early response to UNDW inhalation, and five subjects also had a late reaction. These late responses were associated with an increase in methacholine responsiveness in a subset of the tested subjects. Late-phase reactions to exercise and UNDW were not reproducible.     

The effect of an inhaled leukotriene antagonist, L-648,051, on early and late asthmatic reactions and subsequent increase in airway responsiveness in man

We have investigated the protective effects of the inhaled cysteinyl leukotriene antagonist, L-648,051, on allergen-induced early asthmatic response (EAR) and late asthmatic response (LAR) and the subsequent changes in bronchial responsiveness to methacholine. Ten atopic men with asthma participated in a double-blind, crossover, placebo-controlled trial. All subjects had documented EAR and LAR to house dust-mite extract. Responsiveness to methacholine was measured the day before and the day after a standardized allergen-challenge test. L-648,051 was inhaled in two doses of 12 mg 20 minutes before and 3 hours after the allergen challenge. The response was obtained from FEV1 and flows from maximal (V40m) and partial (V40p) expiratory flow-volume curves. All subjects had an EAR and LAR during placebo therapy, but only a minority demonstrated an increase in methacholine responsiveness of more than one doubling dose. The ratio of V40m to V40p during methacholine challenge was higher than during both EAR and LAR (p less than 0.05). There was no difference between drug- and placebo-therapy periods in baseline function, EAR, LAR, ratio of V40m to V40p, and the allergen-induced hyperresponsiveness (p greater than 0.1). These results indicate that an effective aerosolized leukotriene antagonist in man does not protect against allergen-induced airflow obstruction, despite the evidence of an inflammatory response to allergen challenge. This suggests that either the potency or duration of activity of L-648,051 is limited or that leukotrienes C4 and D4 do not play a causative role in human allergic 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.     

Lower respiratory tract complications during nasal provocation: nonspecific stimulant or specific allergen?

BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease in which allergen exposure leads to the appearance of symptoms in sensitized individuals because of histamine liberation from nasal mucosal mast cells. Comorbidity of this disease with allergic asthma is common. Therefore, the one airway one disease theory has been put forward. Lower respiratory tract provocation tests with both nonspecific (methacholine) and specific stimulants (allergen) have yielded positive results in nonasthmatic patients with AR. However, not enough research is available to demonstrate whether there is a response in the lower respiratory tract during nasal provocation tests (NPTs) performed to evaluate only nasal airway in these patients. OBJECTIVES: To determine if the lower respiratory tract was affected as a result of NPTs with nonspecific and specific stimulants in nonasthmatic patients with AR and to determine the frequency of lower respiratory tract obstruction due to NPT with nonspecific and specific stimulants. METHODS: Thirty-six participants were enrolled in the study between November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). Patients underwent 2 sessions of NPT. The first session was performed with nasal methacholine as a nonspecific stimulant, and the second session was performed with nasal Olea europaea extract as a specific stimulant. The control group underwent only nonspecific nasal provocation with methacholine. Basal nasal opening and nasal pressures were evaluated spirometrically by rhinomanometric measurements and basal respiratory function tests in both groups before methacholine nasal provocation. Whether or not nasal provocation was achieved, spirometric measurements were performed in all patients and controls after NPTs. RESULTS: NPTs with methacholine resulted in a similar frequency of nasal provocation in the patient and control groups (P = .63). However, the mean methacholine dose was lower in patients with AR (P = .049). There was a decrease in parameters of asthma, including the ratio of forced expiratory volume in 1 second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with methacholine in the patient group. However, NPTs with allergen did not cause a change in lower respiratory tract obstruction criteria. CONCLUSIONS: Lower respiratory tract obstruction can occur after NPTs with nonspecific stimulants; therefore, tests performed with specific allergens can be regarded as safer.     

Do diagnostic procedures other than inhalation challenge predict immediate bronchial responses to inhaled allergen?

To investigate the relationships between allergen inhalation challenge and other diagnostic procedures, inhalation challenge with house dust (HD) allergen, intradermal skin tests with HD allergen, inhalation challenge with methacholine and circulating HD allergen-specific IgE levels were examined in 104 patients with bronchial asthma. Using the single exposure method, allergen inhalation challenge was performed. Forty-three patients had positive bronchial responses to allergen and 61 patients had negative bronchial responses. With serially diluted HD allergen (10(-3) to 10(-6), w/v), skin-test sensitivity was expressed as the highest dilution required to produce a weal of more than 9 x 9 mm. With the continuous exposure method, bronchial responsiveness to methacholine was evaluated as the number of units of inhaled methacholine (PD35-Grs) from the start to the point at which Grs had decreased by 35% from its baseline value. The level of circulating HD allergen-specific IgE was measured with the Phadebas RAST system and the results were assessed as a RAST score. Using discriminant analysis, in which the independent variables were skin-test sensitivity, PD35-Grs and the RAST score, only in 30% of all patients was bronchial responsiveness to inhaled HD allergen predictable. Therefore, we suggest that inhalation challenge with allergen is an essential test for determining the role of a specific allergen in airways at present.     

Increase in non-specific bronchial responsiveness after repeated inhalation of low doses of allergen

The development of bronchial hyperresponsiveness (BHR) in asthma is considered to be caused by inflammation of the airway. In IgE-mediated allergy BHR is related to the occurrence of late phase reactions. We have previously shown that exposure to low doses of allergen can cause isolated late reactions. These findings are potentially of clinical importance, since exposure to low, subclinical allergen doses may lead to bronchial inflammation and increasing bronchial responsiveness without necessarily causing immediate bronchoconstriction. This study was performed to investigate whether repeated exposure to low doses of allergen could induce a change in BHR. The trial comprised two groups of five and eight patients with a history of allergic asthma. They were submitted to a series of allergen inhalations for 5–7 days. They were given the same low allergen dose (1–10 biological units) each day. Before and after the allergen exposure period histamine challenges were performed. After the week of allergen inhalation the bronchial responsiveness was increased in 11 of 13 patients.     

Exercise-induced biphasic responses and methacholine reactivity in asthma

Biphasic (early and late) asthmatic responses to exercise occurred in seven of 43 children with reproducible exercise-induced asthma. As biphasic allergen-induced asthma is associated with a prolonged increase in nonspecific bronchial hyperreactivity, this effect was not sought in the 43 asthmatic children. There was no significant change in methacholine PD20 FEV1 before and after exercise challenge, either in children who had early, or early and late, exercise responses. Late reactions after allergen exposure are likely to be of considerable clinical significance in relation to the enhancement of bronchial responsiveness. It is reassuring that this is not the case for exercise challenge, as it would have major implications in relation to the recommendations that asthmatics should participate in normal activities and even in training programs. Furthermore, it suggests that there are differences between the pathophysiology of asthma induced by exercise and that produced by allergens.     

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.