Effects of allergen inhalation and oral glucocorticoid on concentrations of serum-soluble CD86 in allergic asthmatics

The aim of the present study was to investigate effects of allergen inhalation and oral glucocorticoid on concentration of serum soluble CD86 in patients with allergic asthma. Our results showed that the serum soluble CD86 concentrations in the dual responder group increased from 491.8 +/- 15.4 IU/ml before allergen inhalation to 603.8 +/- 19.3 IU/ml 24 h after allergen inhalation. In the isolated early responders, there was no significant increase in serum soluble CD86 concentrations after allergen inhalation compared with baseline levels. There was a significant decrease in serum soluble CD86 concentrations after 2 weeks of glucocorticoid therapy (448.3 +/- 15.1 IU/ml) compared with baseline values (532.7 +/- 12.3 IU/ml), whereas there was no significant difference in the placebo group. This study has demonstrated that serum soluble CD86 concentrations increased after allergen inhalation in sensitized asthmatic subjects, and that serum sCD86 concentrations were downregulated by prednisolone therapy.     

Repeated inhalation of low doses of cat allergen that do not induce clinical symptoms increases bronchial hyperresponsiveness and eosinophil cationic protein levels.

The aim of this study was to investigate whether repeated exposure to subclinical doses of cat allergens, not inducing asthma symptoms, could affect eosinophil cationic protein (ECP) levels in bronchoalveolar lavage (BAL) or in peripheral blood, without the appearance of clinical symptoms. Twelve patients with mild asthma, all sensitized to cats and not exposed to cat allergen at home, underwent a series of inhalations of cat allergen or placebo for 8 days over 2 weeks. A methacholine challenge was performed before and after the allergen and saline exposures, and BAL and blood were sampled for ECP measurements and eosinophil counts. No patients experienced asthma symptoms. However, PD20 methacholine (geometric mean) decreased significantly from 263 microg before to 126 microg after inhalation of allergen. Inhalation of saline did not induce any significant change in PD20. The change in log PD20 before and after cat allergen exposure was statistically different from the change in log PD20 before and after saline. Median ECP levels in BAL and serum increased significantly after allergen exposure, from 0.8 to 3.1 microg/l (p<0.02) and from 15.9 to 31.4 microg/l (p<0.05), respectively. No change was observed after saline inhalations. The change in BAL and serum ECP levels was statistically significant compared to that in the control group. The number of eosinophils did not change, however, nor did IL-5 and RANTES levels in BAL and serum. In conclusion, our results show that (1) exposure of asthma patients to repeated low doses of allergen, which did not provoke any clinical symptoms, is capable of inducing a local eosinophil activation associated with an increase in nonspecific bronchial hyperresponsiveness and (2) the increase in serum ECP levels due to eosinophil activation precedes the occurrence of asthma symptoms and may thus be a marker of allergen exposure in allergic asthma.     

Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis

BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc. RESULTS: Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.     

A randomized controlled trial of mite allergen-impermeable bed covers in adult mite-sensitized asthmatics

BACKGROUND: Mite-allergic patients with allergic disease should benefit from avoiding mite allergens. Many physicians, however, are yet to be convinced that allergen avoidance can make a significant contribution to asthma management in these patients. Many allergen-avoidance regimes include multiple measures of allergen reduction, but as mite exposure in the home is most likely to be greatest in bed dust, bedding is usually the first target for intervention. OBJECTIVE: This study selected adult patients considered to be most likely to benefit from avoiding mite allergens, namely diagnosed asthmatics, sensitized to house dust mites and exposed to mite allergen in their mattresses. Patients were randomized into a placebo-controlled trial of the use of allergen-impermeable bed covers for 12 months, without any other form of mite-reduction measures. METHODS: Adults with asthma were selected from general practices and asthma clinics in south-east London. Their serum IgE to mite allergens and allergen content of mattress dust samples were measured. Those with >0.70 kU/L mite-specific IgE and >2 microg/g Der p 1 were randomized into active or placebo treatments. Information was collected on allergic symptoms and medication use and quarterly peak flow diaries were kept throughout the trial. Dog or cat allergic patients were excluded if they had a pet at home to which they were sensitized. RESULTS: The mean decrease in microg/g Der p 1 was 25.7 (95% CI 8.9, 74.1) in the active group and 4.5 (95% CI 1.8, 11.5) in the placebo group. Der p 1 concentrations in the active and placebo groups at the end of the trial were not significantly different. There was no effect on peak flow or asthma symptoms in a simple comparison of the treatment and placebo groups. CONCLUSION: In this group of patients, mite allergen avoidance in the bed by the use of allergen-impermeable bedding alone cannot be recommended as an effective way of relieving asthma symptoms.     

Glucocorticosteroids rapidly inhibit allergen-induced expression of E-selectin in vitro in a mucosal model of allergic rhinitis

BACKGROUND: Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E-selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30-min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic rhinitis. METHODS: Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml. The expression of E-selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation. RESULTS: In this model, E-selectin expression was significantly upregulated by allergen and rhIL- 1beta within 1 and 2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by > or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l, respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid upregulation of E-selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l. CONCLUSIONS: Allergen-induced E-selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen-induced cytokine release.     

The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis

BACKGROUND: The beneficial effects of phosphodiesterase 4 (PDE4) inhibitors in allergic asthma have been shown in previous preclinical and clinical studies. Because allergic rhinitis and asthma share several epidemiologic and pathophysiologic factors, PDE4 inhibitors might also be effective in allergic rhinitis. OBJECTIVE: The main objective of this study was to investigate the efficacy of oral roflumilast (500 microg/day) in allergic rhinitis. METHODS: In a randomized, placebo-controlled, double-blinded, crossover study, 25 subjects (16 male, 9 female; median age, 28 years) with histories of allergic rhinitis but asymptomatic at screening received roflumilast (500 microg once daily) and placebo for 9 days each with a washout period of at least 14 days in between treatment periods. In each of the treatment periods, controlled intranasal allergen provocation with pollen extracts was performed daily beginning the third day of treatment, each time approximately 2 hours after study drug administration. Five and 30 minutes after each allergen provocation, rhinal airflow was measured by means of anterior rhinomanometry and the subjective symptoms obstruction, itching, and rhinorrhea were assessed by means of a standardized visual analog scale. RESULTS: Rhinal airflow improved almost consistently during the 9 days of roflumilast treatment, and it was significantly higher at study day 9 on roflumilast in comparison with placebo, a result also found for itching and rhinorrhea. With respect to the subjective obstruction score, a significant difference in comparison with placebo could be demonstrated within 4 days. CONCLUSION: This study shows that a PDE4 inhibitor, roflumilast, effectively controls symptoms of allergic rhinitis. Thus PDE4 inhibitors might be a future treatment option not only in allergic asthma but also in allergic rhinitis or the combination of the 2 diseases.     

Cord blood mononuclear cell cytokine responses in relation to maternal house dust mite allergen exposure

BACKGROUND: Cord blood mononuclear cells have demonstrated specific immune responses to environmental allergens. OBJECTIVE: To establish whether the nature of this response is related to the level of maternal antenatal exposure to house dust mite (HDM) allergen and, hence, whether antenatal allergen avoidance may have a role in the prevention of allergic sensitization in children. METHODS: Children with a family history of asthma were recruited antenatally as subjects in a randomised controlled trial: the Childhood Asthma Prevention Study. HDM allergen (Der p 1) concentrations were measured in dust collected from the maternal bed at 36 weeks gestation. Cord blood mononuclear cells were stimulated in culture, separately, with phytohaemaglutinin (PHA) and HDM extract. Cytokine IL-4, IL-5, IL-10 and IFN-gamma concentrations in supernatant were measured by ELISA. mRNA signals for these cytokines were measured using RT-PCR. RESULTS: The median concentration of HDM allergen was 18.4 microg/g (interquartile range 7.3-35.3 microg/g). Median concentrations of IL-4, IL-5, IL-10 and IFN-gamma, after PHA stimulation were 4, 19, 401 and 1781 pg/mL, respectively. After HDM allergen stimulation the median concentrations were 0, 0, 20 and 14 pg/mL, respectively. The distribution of mRNA cytokine signals was similar. Neither cytokine protein concentrations nor cytokine mRNA signal levels were correlated with the concentration of HDM allergen in the mothers' beds at 36 weeks gestation. CONCLUSION: These findings do not support the view that the prevention of allergic disease in children requires the institution of HDM avoidance interventions during pregnancy.     

Effects of allergic inflammation of the nasal mucosa on the severity of rhinovirus 16 cold

BACKGROUND: Despite the strong association of asthma exacerbations with rhinovirus (RV) infection, inoculation of asthmatic subjects with RV only causes small changes in lower airway function, suggesting that RV infection is not itself sufficient to provoke asthma exacerbations. OBJECTIVE: Our purpose was to test whether allergic inflammation increases the airway response to RV infection. METHODS: We compared the severity of RV type 16-induced colds in 2 groups of 10 subjects with allergic rhinitis. One group received 3 nasal challenges with allergen and the other received challenges with placebo over the week before nasal inoculation with RV type 16 (4000 tissue culture infective dose 50% per subject). Subjects kept symptom diaries and were assessed with spirometry, methacholine challenge, nasal lavage, and sputum induction on days 2, 4, 7, 10, 15, and 30 after inoculation. RESULTS: The 2 groups developed equal rates of infection (90%), similar cold symptoms (Jackson score median [interquartile range], 11 [6-33] vs 20.5 [6-42] for allergen and placebo groups respectively, P =.54), and similar changes in cellular profile and in IL-6 and IL-8 concentrations in nasal lavage fluid and induced sputum after RV inoculation. The incubation period was significantly longer in the allergen group (2.5 [1-5.5] vs 1 [1-1] day, P =.03) and the duration of cold symptoms was shorter (5 [4-7] vs 8.5 [6-10] days, P =.008). We also found an inverse correlation between the percent of eosinophils in nasal lavage fluid before inoculation and the severity of cold symptoms (r = -0.58, P =. 008). CONCLUSION: In subjects with allergic rhinitis, augmented nasal allergic inflammation before inoculation with RV type 16 does not worsen the severity of cold symptoms but delays their onset and shortens their duration.     

Progenitor egress from the bone marrow after allergen challenge: role of stromal cell-derived factor 1alpha and eotaxin

BACKGROUND: CCR3 expression on CD34+ cells mediates migration to eotaxin in vitro. CXCR4 and stromal cell-derived factor (SDF)-1alpha are important for stem cell homing to hemopoietic compartments. OBJECTIVE: To study chemokine-mediated progenitor cell traffic in allergic inflammation. METHODS: Bone marrow (BM) aspirates were obtained at baseline from normal subjects; atopic subjects without asthma; and subjects with asthma before, 5 hours after, and 24 hours after allergen inhalation (dual and early responders). Changes in chemokine receptor expression and migration were assessed. RESULTS: Expression of CXCR4, but not CCR3, on BM CD34+ cells was greater in normal subjects compared with atopic subjects with asthma. Likewise, SDF-1alpha, but not eotaxin, stimulated a greater migrational response by BM CD34+ cells from normal subjects compared with subjects with asthma. For all subjects, a positive correlation was found between intensity of CXCR4 expression and magnitude of CD34+ cell response to SDF-1alpha. Allergen inhalation attenuated both intensity of CXCR4 expression and SDF-1alpha levels in marrow from dual compared with early responders 24 hours postallergen. In contrast, the intensity of CCR3 expression on BM CD34+ cells increased in dual compared with early responders at 24 hours postallergen. In addition, an increase in migrational responsiveness of BM CD34+ cells to eotaxin and a decrease to SDF-1alpha 24 hours postallergen was found in dual responder subjects with asthma. CONCLUSION: After allergen inhalation in subjects with asthma, a downregulation in CXCR4 intensity on BM CD34+ cells and a reduction in BM SDF-1alpha levels may reduce progenitor retention to marrow stroma promoting peripheral egress, possibly mediated by the CCR3/eotaxin axis.     

Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma

The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.     

Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils

BACKGROUND: Adding a long-acting beta(2)-agonist to inhaled corticosteroids results in better symptomatic asthma control than increasing the dose of inhaled corticosteroids. OBJECTIVE: Investigating whether adding the long-acting beta(2)-agonist salmeterol to the inhaled corticosteroid fluticasone propionate has an effect on allergen-induced allergic inflammation in asthma. METHODS: Bronchial allergen challenges were performed in 26 patients with allergic asthma, pretreating them with a single dose of either fluticasone/salmeterol (100/50 microg) or fluticasone alone (100 microg), in a double-blind, randomized, cross-over design. Sputum and serum markers of bronchial inflammation were measured after allergen challenge, as well as lung function parameters. Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein. RESULTS: Asthmatic responses after allergen challenge were significantly reduced after pretreatment with fluticasone/salmeterol relative to fluticasone alone. Sputum inflammatory markers after allergen challenge were not significantly affected by fluticasone/salmeterol pretreatment. By contrast, serum IL-5 was significantly reduced (geometric mean serum IL-5 [SEM]: 0.5 [0.3] vs 1.1 [0.3] pg/mL 1 hour and 0.6 [0.3] vs 1.1 [0.3] pg/mL 6 hours after challenge with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P values < .05). Also, peripheral blood eosinophils were significantly reduced (geometric mean number x 10(6)/L [SEM]: 172 [0.1] vs 237 [0.1] at 6 hours and 271 [0.1] vs 351 [0.1] at 24 hours with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P < .05). CONCLUSION: Adding salmeterol to fluticasone reduces allergen-induced serum IL-5 and peripheral blood eosinophils. This phenomenon may contribute to the improved clinical outcomes that result from adding a long-acting beta(2)-agonist to inhaled corticosteroids.     

House dust mite allergen in US beds: results from the First National Survey of Lead and Allergens in Housing

BACKGROUND: Although exposure to house dust mite allergen is a major risk factor for allergic sensitization and asthma, nationwide estimates of dust mite allergen levels in US homes have not been reported. OBJECTIVE: The purpose of this study was to estimate the prevalence of dust mite allergen in beds of US homes and to identify predictors of dust mite allergen concentration. METHODS: Data were obtained from the first National Survey of Lead and Allergens in Housing, a cross-sectional survey of 831 permanently occupied noninstitutional housing units that permitted resident children. Dust mite allergen concentration (Der f 1 plus Der p 1) was determined from a dust sample collected from a bed. The percentages of homes with concentrations at or greater than detection, 2.0 microg/g bed dust, and 10.0 microg/g bed dust were estimated. Independent predictors of allergen concentration were assessed with multivariable linear regression. RESULTS: The percentages of US homes with dust mite allergen concentrations at or greater than detection, 2.0 microg/g, and 10.0 microg/g were 84.2% (SE, 1.73), 46.2% (SE, 2.0), and 24.2% (SE, 2.1), respectively. Independent predictors of higher levels were older homes, non-West census regions, single-family homes, no resident children, lower household income, heating sources other than forced air, musty or mildew odor, and higher bedroom humidity. CONCLUSION: Most US homes have detectable levels of dust mite allergen in a bed. Levels previously associated with allergic sensitization and asthma are common in US bedrooms. Predictors can be used to identify conditions under which homes are more likely to have increased dust mite allergen levels.     

Protective effect of inhaled furosemide on allergen-induced early and late asthmatic reactions

The movement of ions and water across the membranes of bronchial cells is part of the control of the bronchial obstructive response to physical stimuli. In a double-blind, randomized, crossover study, we compared the effect of an aerosol of the loop diuretic furosemide with that of a placebo on the early (within 60 minutes) and late (4 to 12 hours) asthmatic responses to a specific inhaled allergen. We studied 11 subjects with mild allergic asthma, who had both early and late asthmatic responses to a specific inhaled allergen in a preliminary challenge. After placebo administration, the maximal changes (mean +/- SE) from base line in the forced expiratory volume in one second (FEV1) and specific airway resistance were, respectively, a decrease of 35 +/- 4 percent and an increase of 288 +/- 56 percent between 0 and 60 minutes after inhalation of the allergen (early response) and a decrease of 35 +/- 5 percent and an increase of 301 +/- 40 percent between 4 and 12 hours (late response). After furosemide administration (4 ml; 10 mg per milliliter), the early response to inhaled allergen was markedly attenuated in all the subjects, and the late response in all but one. The maximal changes in the FEV1 and specific airway resistance were, respectively, a decrease of 11 +/- 2 percent and an increase of 61 +/- 2 percent between 0 and 60 minutes and a decrease of 20 +/- 4 percent and an increase of 178 +/- 25 percent between 4 and 12 hours (P less than 0.05 for all comparisons). No significant differences were seen in the bronchoconstrictor response to inhaled methacholine after furosemide or placebo administration. We conclude that a furosemide-sensitive mechanism in the airways is involved in the pathogenesis of the reactions of patients with allergic asthma. Whether inhaled furosemide might be useful in the treatment of allergic asthma is uncertain and will require further study.     

Effect of fluticasone propionate aqueous nasal spray on allergen-induced inflammatory changes in the nasal airways of allergic rhinitics following exposure to nitrogen dioxide

BACKGROUND: The authors have recently demonstrated that prior exposure for 6 h to 400 p.p.b. nitrogen dioxide significantly enhances the early phase response of eosinophils in the nasal airways of allergic rhinitics to subsequent allergen provocation. OBJECTIVE: To investigate whether treatment with fluticasone propionate aqueous nasal spray (FP) can alter the inflammatory response in the nasal airways under these conditions. METHODS: Sixteen allergic, rhinitic patients were recruited for this double-blind, randomized, cross-over study and received either topical FP 200 microg once daily or matched placebo for 4 weeks. At the end of treatment, all underwent nasal lavage followed by a 6 h exposure to 400 p.p.b. NO2. Following exposure to NO2, nasal allergen challenge was performed and nasal lavage repeated. After a 4 week washout period, patients were given alternate treatment and tested as above. RESULTS: Analysis of eosinophil cationic protein (ECP) in lavage samples from patients treated with placebo, demonstrated that this was significantly increased from a median value of 2.3 ng/mL (range: 1.0-7.1) to 15.1 ng/mL (range: 1.5-40.0; P = 0.001) following exposure to NO2 and allergen challenge. However, in patients treated with FP, ECP concentrations only increased from 3.3 ng/mL (range: 0.2-9.2) to 5.1 ng/mL (range: 0.3-20.0; P = 0.034) following exposure to NO2 and allergen challenge. The difference of the changes in ECP concentration between the placebo and the FP-treated group was significant (P = 0.003). Similarly, there was a significant increase in the number of eosinophils in nasal lavage after exposure to NO2 and allergen challenge in the placebo group, and this increase was inhibited in FP group (P = 0.002). CONCLUSION: These results suggest that FP influences NO2- and allergen-induced changes in eosinophil function, as well as eosinophil number in the nasal airway of allergic rhinitics.     

Theophylline inhibits early and late asthmatic reactions induced by allergens in asthmatic subjects

To determine whether oral slow-release theophylline inhibits asthmatic reactions and the associated increase of airway responsiveness to methacholine induced by allergens, we examined six asthmatic subjects who developed a dual asthmatic reactions after allergen bronchoprovocation with Dermatophagoides pteronyssinus or with grass pollen. We gave oral slow-release theophylline and placebo to each subject for seven days in two series of experiments in a double-blind, randomized, crossover study. The individual daily dose of theophylline (4.7 to 16.6 mg/kg/day, divided into two doses) was calculated for each subject by measuring individual theophylline clearance and optimal daily dosage. During treatment with placebo, the subjects developed dual asthmatic reactions, ie, FEV1 decreased from 4.1 +/- 0.17 L before bronchoprovocation to 3.2 +/- 0.14 L at 15 minutes and to 3.2 +/- 0.19 L at seven hours after allergen bronchoprovocation. By contrast, during active treatment FEV1 decreased from 4.2 +/- 0.28 L to 3.9 +/- 0.26 L at 15 minutes, and to 3.8 +/- 0.13 L at seven hours (both cases, P less than .03 compared with placebo). Mean serum theophylline concentration was 13.2 +/- 0.6 mg/L. Although 1 week's treatment with slow-release theophylline did not modify significantly either prechallenge airway responsiveness to methacholine or its increase after allergen inhalation challenge, in five out of six subjects theophylline significantly inhibited the increase of airway responsiveness to methacholine induced by allergens compared to placebo and control day (P less than .05). These results suggest that slow-release theophylline may inhibit allergen-induced asthmatic reactions and the associated increase of airway responsiveness, suggesting some antiinflammatory effects for this drug.     

Mouse allergen-specific antibody responses in inner-city children with asthma

BACKGROUND: Although mouse allergen exposure is common in inner-city homes, little is known about the relationships between exposure and humoral immune responses to mouse allergen in this population. OBJECTIVE: To examine relationships between mouse allergen exposure and allergen-specific IgE and IgG responses in inner-city children with asthma. METHODS: Inner-city children with asthma underwent skin testing and venipuncture for determination of mouse allergen-specific IgE and IgG levels. Settled dust samples were collected from their homes for allergen analysis. RESULTS: The study population (n = 112) was predominantly African American (92%) with a mean age of 4.4 years. The prevalence rate of mouse sensitization was 25% and did not consistently increase with increasing Mus m 1 levels. Instead, the prevalence rate was lowest among those exposed to <2 microg/g, increased among those exposed to 2-7.9 microg/g and 8-29.9 microg/g, and then decreased among participants exposed to >29.9 microg/g (14%, 20%, 40%, and 28%, respectively). Similarly, the prevalence rates of mouse allergen-specific IgG and IgG(4) did not increase across increasing exposure categories. Mouse allergen-specific IgG and IgG(4) were strongly associated with IgE sensitization (odds ratios [95% CI], 82.8 [20.5-334.4] and 50.4 [14.0-181.7], respectively). CONCLUSION: High-level exposure to mouse allergen in children may be associated with attenuated humoral responses of all isotypes rather than selective attenuation of IgE. CLINICAL IMPLICATIONS: Protection against allergic sensitization by high-dose allergen exposure may not be mediated by preferential production of IgG over IgE.     

Effect of mattress and pillow encasings on children with asthma and house dust mite allergy

BACKGROUND: House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients. OBJECTIVE: Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy. METHODS: In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for 1 year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria. RESULTS: Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 microg/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01). CONCLUSION: Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.     

Inhaled formaldehyde exposure: effect on bronchial response to mite allergen in sensitized asthma patients

BACKGROUND: Formaldehyde, an indoor air pollutant, is known to be an irritant and an etiologic factor in occupational asthma. An epidemiologic study suggests that it may also increase the risk of childhood asthma for concentrations above 60 microg/m(3). AIM: To evaluate the influence of pre-exposure to low-dose formaldehyde (100 microg/m(3) in 30 min according to the World Health Organization's recommended maximum value for indoor environments) on bronchial response to Dermatophagoides pteronyssinus. METHOD: Nineteen asthmatic subjects were included. Each subject underwent a mite allergen bronchial challenge test immediately after a standardized exposure in a chamber to formaldehyde or air (random order). Induced sputum were collected 24 h before and after mite challenge. RESULTS: After formaldehyde inhalation, patients developed an immediate bronchial response at a significantly lower dose of mite allergen than after air exposure (the geometric mean PD(20) for Der p 1 was 34.3 ng after formaldehyde and 45.4 ng after placebo, P = 0.05). The late-phase reaction, expressed as the maximum fall in forced expiratory volume in 1 s (FEV(1)) from baseline, was significantly higher after formaldehyde (15%vs 11%, P = 0.046). CONCLUSION: Our study demonstrated that exposure to low levels of formaldehyde significantly enhanced bronchial responsiveness to mite allergen in mite-sensitized subjects with asthma.     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

Effects of azelastine on allergen- and exercise-induced asthma

The effects of the new anti-allergic drug, azelastine, on allergen- and exercise-induced asthma were studied. In six allergen inhalation tests for five asymptomatic asthmatic patients, the maximum percentage fall in FEV1.0 immediately after inhalation of allergen extract was 37.2 +/- 6.4 per cent (mean +/- SEM). As compared with a placebo, the maximum percentage fall in FEV1.0 with azelastine after inhalation of allergen extract in the same manner as with the placebo was 17.3 +/- 6.9 per cent. The difference was statistically significant (p less than 0.05). The percentage fall in FEV1.0 with placebo and azelastine in late asthmatic response (n = 4) was 36.0 +/- 5.3 per cent and 10.0 +/- 5.2 per cent, respectively. The difference was also statistically significant (p less than 0.01). An exercise test was carried out on seven asymptomatic asthmatic patients using an inclined treadmill. The maximum percentage fall in FEV1.0 without drugs, with diphenhydramine and azelastine was 38.9 +/- 5.0 per cent, 20.1 +/- 3.8 per cent and 11.3 +/- 3.1 per cent, respectively. Significant differences were found among each group (p less than 0.05). Azelastine was regarded as having sufficient potency to inhibit exercise-induced asthma; however, placebo effects cannot be ruled out with regard to the effects of diphenhydramine. These results suggests that chemical mediator release is involved not only in allergen-induced asthma but also in exercise-induced asthma, suggesting the clinical utility of azelastine.