The effect of zafirlukast on repetitive exercise–induced bronchoconstriction: The possible role of leukotrienes in exercise-induced refractoriness

Background: Single doses of zafirlukast attenuate exercise-induced bronchoconstriction (EIB), but previous studies have not measured zafirlukast’s effects after regular dosing or its duration of effect beyond 4 hours. Objective: The purpose of this study was to assess the effects of zafirlukast 20 mg and 80 mg twice daily compared with placebo on exercise challenges performed at 2 and 8 hours after the last dose of regular administration. Methods: Twenty-four adult patients with stable asthma taking β₂-agonists, inhaled corticosteroids, or both received treatment with zafirlukast (20 mg and 80 mg) and placebo. The patients were treated twice daily for 14 days in a randomized, double-blind, 3-way cross-over fashion, with a 7-day washout period between each treatment. Exercise challenges were performed at 2 and 8 hours after the morning dose on day 14. FEV₁ was measured before exercise and at set intervals after exercise until it returned to within 7% of its baseline value. Results: Both zafirlukast treatments significantly reduced EIB, as measured by the area under the FEV₁ time curve after the 2-hour (P < .001) and 8-hour (P < .001) exercise challenges and maximum fall in FEV₁ at the 2-hour challenge (P < .001). The comparison at 8 hours between treatments was affected by the unexpected finding that EIB was less in the placebo group after the 8-hour challenge than after the 2-hour challenge, as measured by the within-group change in the maximum fall in FEV₁ (P < .001) and the area under the FEV₁ time curve (P = .0023). Conclusion: Regular zafirlukast treatment protects against EIB for at least 8 hours after regular dosing. A refractory period, which may be caused by exercise-induced leukotriene release, may last for up to 6 hours after the initial response to exercise. (J Allergy Clin Immunol 1999;1155-61.)     

Assessing nonresponse bias at follow-up in a large prospective cohort of relatively young and mobile military service members

Background

Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES - Paediatric Asthma Gene Environment Study).

Methods

Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database.

Results

To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV₁ 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV₁ between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part.

Conclusions

It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.     

Effect of cetirizine, a new H1 antihistamine, on the early and late allergic reactions in a bronchial provocation test with allergen

Background: Cetirizine is a highly sensitive H₁ antihistamine with particular antiallergic properties, which has been shown to be effective in the treatment of allergic rhinitis, urticaria, and hay-fever-associated asthma.Methods: To assess the effect of cetirizine on the late allergic reaction to a specific bronchial provocation test (BPT) with allergen, we selected 25 patients with allergic asthma as determined by history, skin tests, and specific IgE levels. They were challenged with increasing doses of a cat or mite extract until a 20% drop in forced expiratory volume in 1 second (FEV₁) was recorded. Sixteen patients (11 men and 5 women with a mean age of 22 years; range, 18 to 48 years) exhibited a dual response (early and late allergic reactions). These 16 patients underwent a second BPT 2 weeks later, and each again showed a dual response. They were then randomized to receive either a placebo (8 patients) or cetirizine, 15 mg twice daily (8 patients) in a double-blind fashion. After 7 days of treatment, they underwent a third BPT with the same allergen dose as given in the second BPT.Results: The intensity and duration of early allergic reaction were not affected by cetirizine, whereas all parameters of late allergic reaction were statistically significantly improved in the cetirizine group when compared with those of the placebo group (maximum FEV₁ decrease, p = 0.046; FEV₁ [area above the curve], p = 0.027; maximum airway resistance increase, p = 0.021; airway resistance [area under the curve], p = 0.036).Conclusions: Cetirizine produced a significant protective effect against an allergen-induced late allergic reaction in a BPT. Cetirizine might therefore be effective in the treatment of asthma.     

Normal diurnal variation in serum cortisol concentration in asthmatic children treated with inhaled budesonide

Background: Twenty-four-hour serum cortisol secretion is a sensitive parameter for the assessment of the pituitary-adrenal function of asthmatic children treated with inhaled corticosteroids. This study was undertaken to determine the effect of the long-term administration of inhaled budesonide on 24-hour cortisol production in young children with asthma. Methods: We studied 11 children, aged 7 to 12 years, with severe perennial asthma. All had been receiving 100 μg of inhaled budesonide twice daily, administered with a spacer device, for 3 to 5 years. Serum cortisol concentration was measured at 8:00 AM, 60 minutes after intravenous administration of 0.25 mg of corticotropin, and every 30 minutes for 24 hours in an open-design study. Urinary cortisol secretion was measured by 24-hour urine collection. All determinations were made with a radioimmunoassay kit. Results: The individual morning serum cortisol concentration and the serum cortisol concentration at 60 minutes after corticotropin stimulation were within normal limits in all children. The 24-hour urinary cortisol excretion was also normal. The individual 24-hour serum cortisol concentration showed a normal pattern in all children, with no evidence of nocturnal suppression of serum cortisol concentration. Conclusion: Prolonged (3 to 5 years) administration of 200 μg/day of inhaled budesonide in young children with severe asthma does not impair pituitary-adrenal function, even according to the sensitive test for 24-hour serum cortisol secretion. (J ALLERGY CLIN IMMUNOL 1995;96:874-8.)     

Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids

Background: Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma. Objective: We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma. Methods: We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (≥1500 μg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4. Results: Data were available from 34 patients. After the reduction of BDP doses, FEV₁, peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P = .003). Conclusion: Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma. (J Allergy Clin Immunol 2000;105:1134-9.)     

An evaluation of the efficacy and safety of azelastine in patients with chronic asthma

BACKGROUND: Azelastine, an oral nonsteroidal, antiinflammatory drug with a good safety profile, has demonstrated relief of symptoms in patients with asthma. OBJECTIVE: The study was designed to evaluate the efficacy and safety of azelastine, a novel antiallergy compound, in patients with asthma who required maintenance therapy. METHODS: During this 16-week, double-blind, randomized, parallel-group study, patients received orally administered azelastine (4 mg twice daily), albuterol sulfate (4 mg twice daily), or placebo. RESULTS: Overall, patients in the azelastine group used 2.5 times less backup medication (p = 0.024) for relief of their asthma symptoms than patients in the placebo group. Reductions in asthma symptoms in the azelastine group were also noted throughout the double-blind treatment period. Moreover, the azelastine group had statistically significant improvements in FEV₁ after the first dose of medication. The only notable adverse experiences in the azelastine group were alterations in taste perception and a small mean increase in body weight. CONCLUSION: Oral administration of azelastine to patients with asthma resulted in overall improvement in airway function while reducing the requirement for adjunctive antiasthma medications. (J ALLERGY CLIN IMMUNOL 1996;97:1218-24.)     

Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma

Background: Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma. Objective: Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting β₂-agonists alone. Methods: A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting β₂-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 μg twice daily or zafirlukast 20 mg twice daily. Results: Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV₁ (by 0.42 L vs 0.20 L over baseline, P < .001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P < .001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P < .001). Statistically significant differences between the two treatments in FEV₁ were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P < .001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast (P < .001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day (P < .001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast (P < .001). Conclusion: The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on β₂-agonists alone is superior to that of zafirlukast. (J Allergy Clin Immunol 2000;105:1123-9.)     

Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma

Background: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV₁ after 4 weeks. Results: The change in peak FEV₁ response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV₁ was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV₁ was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV₁ value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)     

The effect of an experimental rhinovirus 16 infection on bronchial lavage neutrophils

Background: Viral respiratory tract infections are the most frequent cause of asthma exacerbations. Of the respiratory viruses associated with these exacerbations, rhinovirus (RV) is the most common. It is proposed that these RV infections may enhance airway inflammation and thus provoke asthma. Objective: It is our hypothesis that RV infections generate nasal proinflammatory mediators that are associated with an initial increase in circulating leukocytes and may contribute to later development of neutrophilic airway inflammation. Methods: To evaluate this hypothesis, subjects with a history of allergic asthma were experimentally inoculated with strain 16 RV (RV16). The effect of this experimental infection was evaluated on circulating leukocytes, nasal-derived mediators, and markers of bronchial inflammation that were obtained by bronchoscopy and lavage. Results: RV16 inoculation was associated with an initial increase in circulating neutrophils. Paralleling these acute changes in circulating neutrophils was an increase in nasal concentrations of IL-8 and granulocyte–colony-stimulating factor (G-CSF). The RV16-associated changes in circulating and nasal G-CSF correlated with increases in peripheral blood neutrophils (r_s = 0.874, P < .001 and r_s = 0.898, P < .001, respectively). Bronchial lavage samples showed no increase in neutrophils 48 hours after RV16 inoculation; however, 96 hours after RV inoculation there was a significant increase in bronchial neutrophils compared with preinoculation values. Conclusions: These results suggest that the production of nasal mediators associated with the RV infection, particularly G-CSF, may be important to the eventual development of neutrophilic bronchial inflammation and thus contribute to asthma exacerbations. (J Allergy Clin Immunol 2000;105:1169-77.)     

Add‐on montelukast to inhaled corticosteroids protects against excessive airway narrowing

Rationale Excessive airway narrowing in response to broncho‐active stimuli is a predictor for severe exacerbations in asthma. Leukotriene receptor antagonists (LTRAs) have complementary properties to inhaled corticosteroids (ICS) on asthma control. Objectives The LTRA montelukast may provide an additional protection against excessive airway narrowing. We tested the add‐on effects of montelukast on the maximal response plateau and PD₂₀ to inhaled methacholine in asthmatics on a stable dose of ICS. Methods Thirty‐one patients with allergic asthma [14M/17F, 19–50 years, forced expiratory volume in 1 s (FEV₁) >70% pred., PD₂₀ <3.9 μmol methacholine], with a twice documented response plateau to methacholine, were randomized in a double‐blind (montelukast 10 mg or matching placebo once daily), 12‐week parallel study. Bronchoprovocation tests with methacholine (0.03–256 μmol or 40% decline in FEV₁) were repeated every 4 weeks and after wash‐out. The main study objectives were changes from baseline in maximal FEV₁ decline at the response plateau (i.e. >2 post‐dose FEV₁ values within 5%) and PD₂₀ to methacholine after 12 weeks' treatment. Results Neither treatment affected baseline FEV₁ (P=0.62). Compared with placebo, montelukast significantly decreased the maximal response plateau to methacholine (mean difference 9.4%; 95% confidence interval 3.9–15.7; P<0.005), improved the FEV₁ decline (mean change in FEV₁ decline was 2.1% [montelukast] and ?0.8% [placebo], respectively, P<0.05), and increased PD₂₀ methacholine (mean change in PD₂₀ of 5.3 [montelukast] and 1.4 [placebo] doubling doses, respectively, P<0.001). Conclusion Add‐on montelukast to ICS has disease‐modifying effects in adults with persistent asthma, and hence reduces the risk of excessive airway narrowing (NCT 00913328). Cite this as: C. S. Ulrik and Z. Diamant, Clinical & Experimental Allergy, 2010 (40) 576–581.     

Acute asthma intervention: insights from the STAY study

In some patients, asthma control is improved by combining inhaled corticosteroids with long-acting beta(2)-agonists. However, fluctuating asthma control and exacerbations can still occur. The STAY study evaluated whether, in patients with moderate to severe asthma, replacing a short-acting beta(2)-agonist reliever with the combination of budesonide/formoterol as reliever would both provide rapid symptom relief and reduce asthma exacerbations. The study evaluated 2760 patients with asthma (4-80 years) randomized to budesonide 400 microg twice daily (bid) and terbutaline as reliever, budesonide/formoterol 100/6 microg bid and terbutaline as reliever, or budesonide/formoterol 100/6 microg bid both as maintenance and reliever. Children (age 4-11 years) used a once-daily maintenance dose. Budesonide/formoterol as maintenance and reliever significantly reduced severe exacerbation risk by 45% to 47% compared with the other 2 treatments and improved symptoms, awakenings, and lung function. The benefit was seen in patients of all ages. Subsequent studies have revealed that this beneficial effect of budesonide/formoterol as maintenance and reliever requires both components of the combination.     

Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate

BACKGROUND: There are few controlled studies on the effects of anti-inflammatory treatment on airway inflammation in newly diagnosed childhood asthma. METHODS: Sixty children with newly diagnosed mild persistent asthma, 5-10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 microg twice daily for 1 month, 200 microg twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three-times daily for 6 months. All exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study. RESULTS: Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 x 10(9)/l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness (R = -0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma (P < 0.0001), and in children with a history wheezing than in children without wheezing (P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function (P = 0.007), decreased symptoms (P = 0.007) and sputum eosinophils (P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (>3%). CONCLUSION: Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement.     

Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma

The Global Initiative for Asthma (GINA) guidelines aim at improving asthma control and preventing future risk. For patients with moderate to severe asthma an inhaled corticosteroid (ICS) or an ICS/long‐acting β₂‐agonist (LABA) combination with a short‐acting β₂‐agonist (SABA) as reliever is recommended. Despite the availability of effective maintenance therapies, a large proportion of patients still fail to achieve guideline‐defined asthma control, and overuse of SABA reliever medication at the expense of ICS is commonly observed. New simplified treatment approaches may offer a solution and assist physicians to achieve overall asthma control. One such treatment approach, which is recommended in the GINA guidelines, is budesonide/formoterol for both maintenance and reliever therapy. This treatment strategy significantly reduces the rate of severe asthma exacerbations compared with ICS/LABA plus SABA and achieves equivalent daily symptom control compared with higher doses of ICS/LABA plus separate SABA for relief. These benefits are achieved at a lower overall steroid load, and budesonide/formoterol maintenance and reliever therapy is well tolerated in patients with moderate to severe asthma. This review discusses current asthma management in patients with moderate to severe disease and examines the evidence for alternative asthma management approaches.     

Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by Diskus device in patients with asthma treated with or without inhaled corticosteroids

Background: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. Objective: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 μg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). Methods: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 μg twice daily (FP100BID) or 200 μg once daily (FP200QD) or placebo. Results: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV₁ from baseline to end point of 0.49 L, 0.37 L, and 0.21 L, respectively (P < .001, FP100BID vs placebo; P = .05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV₁ of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV₁ of –0.08 L with placebo (P < .001, FP100BID vs placebo; P = .023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of –3 L/min and –12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. Conclusion: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability. (J Allergy Clin Immunol 2000;105:1153-61.)     

Does body mass index influence responsiveness to inhaled corticosteroids in persistent asthma?

BackgroundAlthough the relationship between asthma and obesity has been extensively explored, the effect of body mass index (BMI) on the dose–response relationship to inhaled corticosteroids (ICS) has received little attention.ObjectiveTo assess the dose–response of inhaled budesonide on outcome measures of asthma between overweight and normal weight patients with persistent asthma.MethodsSeventy-two patients with mild to moderate persistent asthma from a post hoc analysis of previously reported trial data were divided into 2 groups: overweight, BMI 25 kg/m² or higher; normal weight, BMI less than 25 kg/m². Each group received 4 weeks' treatment with inhaled (hydrofluoroalkane) budesonide 200 μg/day then 800 μg/day with ICS washout pretreatment. Outcome measures forced expiratory volume in 1 second (FEV₁), fractional exhaled nitric oxide (FeNO), methacholine PC20, total daily asthma symptom score, and overnight urinary cortisol/creatinine ratio were performed at baseline and after each dose.ResultsSignificantly greater improvements were seen in the normal weight group for both FeNO and symptom responses at 0 to 200 μg and 0 to 800 μg ICS doses (as change from baseline), compared with the overweight group: FeNO 0 to 200 μg, P = .002; 0 to 800 μg, P = .045; symptoms 0 to 200 μg, P = .002; 0 to 800 μg, P = .013. A trend also was seen toward attenuated cortisol suppression in overweight subjects at 0 to 800 μg (P = .06), but no significant difference was seen at either dose in FEV₁ and methacholine PC20 between weight groups.ConclusionOverweight patients with persistent asthma may have attenuated symptom and FeNO dose responses to inhaled budesonide compared with normal weight patients with asthma, with no differences in FEV₁ or methacholine PC20 between groups. Attenuated cortisol suppression in the overweight group may be the clue to this difference, alluding to reduced peripheral lung deposition or absorption in overweight patients with asthma.     

Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis

Background: Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis. Objective: The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray. Methods: This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment). Results: Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P = .03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P = .009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P = .01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient. Conclusions: Once daily budesonide aqueous nasal spray, 256 μg, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 μg, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone. (J Allergy Clin Immunol 1998;102:902-8.)     

The effects of monosodium glutamate in adults with asthma who perceive themselves to be monosodium glutamate–intolerant

Background: Many previous clinical studies of food-induced asthma suffer from inadequate baseline or control data. A statistically valid, randomized, double-blind, placebo-controlled, monosodium glutamate (MSG)–challenge protocol was developed for identifying early and late asthmatic reactions in an individual. Objective: We sought to determine whether MSG would induce bronchoconstriction in a group of adults with asthma who perceived that they were MSG sensitive. Methods: Twelve subjects (seven women, mean age 35.3 years) with clinically documented asthma and a perception of MSG-induced asthma were recruited. FEV₁ and peak expiratory flow data were obtained for 3 whole control days, as well as time-matched data for 3 separate challenge days (1 gm MSG, 5 gm MSG, and 5 gm lactose [placebo]). Opaque capsule challenges were given as a single dose in the morning after an overnight fast. Subjects complied with an elimination diet throughout the study. Nonspecific bronchial hyperresponsiveness was measured at baseline, after the control days, and at the conclusion of the challenges. Venous blood samples were taken at baseline and on each challenge day to determine soluble inflammatory marker (eosinophil cationic protein and tryptase) activity. Results: No immediate or definite late asthmatic reactions occurred. One subject's FEV₁ declined more than 15% on MSG challenge, but 95% confidence limits for the control-day spirometry showed that this decline was within her daily variation, hence the challenge was deemed to be negative. No significant changes in bronchial hyperresponsiveness or soluble inflammatory markers were found. Conclusions: MSG-induced asthma was not demonstrated in this study. This study highlighted the importance of adequate baseline and control data and indicated that such a rigorous protocol for individual assessment is feasible. (J Allergy Clin Immunol 1998;101:762-71.)     

Inhaled budesonide aerosols in treatment of childhood asthma

Twenty-six children with chronic bronchial asthma, 19 boys and 7 girls, aged between 6 and 16 years with duration of asthma ranging from 1-12 years, were studied by a control, oral prednisolone 5 mg twice a day and inhaled budesonide 200 micrograms twice daily, each for 3 weeks. The clinical efficacy assessed daily by day and night symptom scores of cough, wheeze, sleep disturbance, limitation of activity, symptomatic inhaled terbutaline usage, daily morning and afternoon Peak Expiratory Flow Rate (PEFR), and weekly PEFR and Forced Expiratory Volume in 1 second (FEV1) in percent of predict, showed statistically significant improvement during the inhaled budesonide aerosol and oral prednisolone treatment periods in comparison with the control. No side effect was observed during any study periods.     

Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods

In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results

In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion

Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

     

Serum-Soluble HLA-G Is Associated with Specific IgE in Patients with Allergic Rhinitis and Asthma

Allergic rhinitis (AR) and allergic asthma (AA) are characterized by T helper (Th)2-polarized immune response. Soluble human leukocyte antigen G (sHLA-G) molecule plays an immunomodulatory activity. Previously, it has been reported that children with AR or AA had higher sHLA-G levels in comparison with normal subjects. Thus, the present study aimed at confirming these data in adults and investigating whether there was a relationship between serum sHLA-G levels and serum IgE levels, in patients with AR or AA. One hundred twenty symptomatic patients, suffering from respiratory symptoms, were enrolled: 45 non-allergic and 75 allergic. A group of 44 healthy subjects was considered as control. Serum sHLA-G levels and serum allergen-specific IgE were determined by immunoenzymatic methods. Allergic patients had significantly higher levels of sHLA-G molecules than non-allergic patients and normal controls (p?IgE both in AR (r?=?0.468) and AA patients (r?=?0.479). The present study confirms that serum sHLA-G molecules are significantly increased in allergic disease and demonstrates that sHLA-G levels are related with allergen-specific IgE levels.