A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial.

We compared the effect of an inhaled corticosteroid, budesonide, and an inhaled beta 2-agonist, terbutaline, on clinical symptoms, lung function, and airway inflammation in 14 adult patients with newly diagnosed asthma. The study was conducted as a randomized, double-blind, parallel-group trial. Seven patients inhaled 600 micrograms, twice daily, of budesonide, the other seven patients inhaled 375 micrograms, twice daily, of terbutaline via identical metered-dose inhalers with a spacer. Bronchial biopsy specimens, obtained before randomization and after 3 months of treatment, were analyzed by electron microscopy. Both groups improved clinically budesonide was more effective than terbutaline in improving morning and evening peak expiratory flow rates, as well as bronchial responsiveness to inhaled histamine. Treatment with budesonide was accompanied by increased numbers of ciliated airway cells and intraepithelial nerves and fewer inflammatory cells, including eosinophils, especially in the epithelium, these changes were not observed in specimens from terbutaline-treated patients. We conclude that, in contrast to inhaled terbutaline, inhaled budesonide improved lung function and bronchial hyperreactivity in adult subjects with asthma treated for 3 months and that this corticosteroid was more effective in ameliorating abnormalities of the bronchial epithelium and decreasing inflammation in the airways.     

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.     

Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma

BACKGROUND. The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy. We compared the effect of an inhaled corticosteroid, budesonide, with that of an inhaled beta 2-agonist, terbutaline, in the long-term treatment of newly detected asthma. METHODS. We studied 103 patients (29 male and 74 female patients 15 to 64 years old) in whom asthma had appeared within the previous year. The patients were randomly assigned in blinded fashion to two treatment groups: one to receive 600 micrograms of inhaled budesonide twice a day, and the other to receive 375 micrograms of inhaled terbutaline twice a day. The study period was two years. RESULTS. After six weeks of treatment, the patients treated with budesonide tolerated inhaled histamine better than the patients treated with terbutaline (a difference of one doubling dose step, P less than 0.001), and the difference was sustained. Patients' diaries kept during the first three months of the study and during the last month of the first and second years showed budesonide to be more effective than terbutaline in improving peak expiratory flow in the morning (average increase from the pretreatment value, 32.8 liters per minute for budesonide vs. 4.8 liters per minute for terbutaline; P less than 0.001) and in the evening (P less than 0.01). Budesonide was also more effective in reducing the symptoms of asthma (P less than 0.01) and the use of supplemental beta 2-agonist medication (P less than 0.01). Ten patients were withdrawn from the terbutaline group because treatment was insufficiently effective, whereas only one dropped out of the budesonide group. The adverse reactions to both treatments were few and mild. CONCLUSIONS. Antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected, mild asthma, and it is superior to the use of terbutaline in such patients.     

Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma

Airway inflammation is assumed to be an important determinant in increased bronchial responsiveness (BR). We tested the hypothesis that treatment with an inhaled anti-inflammatory drug (i.e., budesonide) but not with an inhaled beta-agonist (i.e., terbutaline) would reduce BR in children with asthma and with minimal or no bronchoconstriction. Twelve patients were treated with budesonide and seven with terbutaline for 6 months. BR decreased in 11 patients receiving budesonide and was significant in seven patients. BR decreased in none of the patients receiving terbutaline. FEV1 demonstrated a small increase with budesonide but remained unchanged with terbutaline. Except in one patient who received terbutaline, the clinical effect was good. We conclude that inhaled corticosteroids but not inhaled beta-agonists will decrease persistent BR in most children with asthma.     

Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure

Background:  The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2–60 months) after cessation of exposure by following up lung function and bronchial inflammation.
Methods:  Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 μg a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects.
Results:  Nonspecific bronchial hyperreactivity diminished significantly ( P  = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased ( P  = 0.012) and that of macrophages increased ( P  = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up.
Conclusion:  Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.     

Long-term effects of asthma medications in children

PURPOSE OF REVIEW: This review describes recent studies in children that evaluated long-term outcomes of controller asthma medications. RECENT FINDINGS: The literature is replete with studies demonstrating the immediate profound effects of inhaled corticosteroids on symptom control, reduction in morbidity and mortality rates, improvement in lung function, bronchial hyperresponsiveness, and inflammatory markers. Recent evidence supports that even this most effective class of medication does not alter the progression of recurrent wheeze to asthma, and that its effects on decline in lung function are limited. The lack of evidence supporting the superiority of lower dose inhaled corticosteroids combined with a long-acting beta-agonist over a full dose inhaled corticosteroid with respect to long-term efficacy measures and growth effects suggests that monotherapy with acceptable inhaled corticosteroid dose is the preferred treatment in children with mild to moderate persistent asthma. Montelukast has been shown to significantly reduce asthma exacerbations and lower use of supplemental inhaled corticosteroids compared with placebo. SUMMARY: There is mounting evidence that the currently available medications for childhood asthma have a substantial impact on multiple dimensions of asthma control. No drug in our current armamentarium, however, has been found to alter the natural progression of childhood asthma nor halt progressive airway damage in the more susceptible children.     

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.     

Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma

The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P<0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.     

Effects of immunotherapy on symptoms, PEFR, spirometry, and airway responsiveness in patients with allergic asthma to house-dust mites (D. pteronyssinus) on inhaled steroid therapy

The present study was designed to investigate the effects of immunotherapy (IT) with an extract of Dermatophagoides pteronyssinus (Alergo-Merck Depot®) during a 27-month period in patients with allergic asthma to house-dust mites. We included 11 patients (mean age 18 years) treated with a combination of IT and inhaled beclomethasone dipropionate (BDP) in comparison to another 11 (mean age 22 years) treated with BDP alone. We evaluated symptom scores, salbutamol use, peak expiratory flow rates (PEFR), spirometry, and bronchial hyperresponsiveness (BHR) during 18 months of therapy with BDP and in the 9 months after BDP interruption. The two kinds of treatment were efficient and comparable in relation to symptom score, salbutamol use, morning PEFR, FVC, and FEV_l but patients treated with IT and BDP had a faster improvement of BHR and PEFR variability. The interruption of BDP after 18 months of therapy was linked to an impairment of all end points, which were more pronounced in patients previously treated only with BDP. These findings suggest that in selected asthmatic patients allergic to house-dust mites, the association of IT and BDP is more effective than therapy with this inhaled steroid alone due to a faster and more striking improvement during the first months of treatment and to a lower rate of relapse after the interruption of therapy with BDP.     

Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma

Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen-induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects.     

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler®

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients

Background: The purpose of this study was to determine if house dust mite immunotherapy with Alutard SQ is effective in improving symptom control and reducing rescue medication use in Chinese patients with mild to moderate allergic asthma. Methods: This is a double‐blind, placebo‐controlled study involving 132 asthmatic subjects aged 6–45 years recruited from three different regions of Mainland China. Subjects were given a 52‐week course of immunotherapy with Dermatophagoides pteronyssinus extract (Alutard Der p, ALK‐Abelló, Hørsholm, Denmark) or placebo while their dose of inhaled corticosteroids (ICS) was maintained. Results: 129 subjects (64 in active group) completed the study. The symptom scores began to diverge at week 29 with the immunotherapy group showing a significantly lower score until week 48 (P = 0.018). Immunotherapy resulted in a significant decline in symptom (P = 0.002) and medication (P = 0.007) scores during the second half of the treatment period. Both groups showed significant improvement in peak flow rate and bronchial hyperresponsiveness. Serum eosinophil cationic protein (ECP) also decreased in both groups of subjects, but peripheral blood eosinophil count remained unchanged. Skin test response decreased in actively treated subjects only, but Der p‐specific immunoglobulin E (IgE) remained unchanged. Immunotherapy resulted in a significantly greater improvement in self‐evaluation scores (P < 0.01). Conclusions: One year treatment with Alutard SQ house dust mite immunotherapy significantly reduced symptoms and medication use in asthmatic subjects. This was associated with a greater subjective improvement in asthma control.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

A double-blind comparison of inhaled budesonide, long-acting theophylline, and their combination in treatment of nocturnal asthma

In 61 patients with nocturnal asthma, the effects of budesonide, an inhaled steroid (Pulmicort®; 200 μg twice daily), long-acting theophylline (Theodur®; 200 mg twice daily), and their combination were compared. After a 2-week placebo run-in period, the patients were entered into double-blind, crossover periods of 3 weeks. Patients were allowed to use inhaled β²-agonists as required throughout the study. Morning and evening peak expiratory flow rate (PEFR) (percentage of predicted normal ± SEM) was significantly higher during the budesonide (morning 77 ± 1%; evening 80 ± 1%) and combination therapy (morning 79 ± 1%; evening 81 ± 1%) than the theophylline treatment (morning 74 ± 1%; evening 76 ± 1; P ≤0.01, respectively). Significantly fewer sleep disturbances and fewer nighttime inhalations of β₂-agonists were required during budesonide and combination therapy than theophylline treatment. No statistically significant differences were seen between combined therapy and budesonide alone. Budesonide, an inhaled steroid, was significantly better than the bronchodilator, theophylline, in controlling nocturnal asthma, but no additional improvement in efficacy was seen when the drugs were used in combination.     

Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite

BACKGROUND: Although several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown. OBJECTIVE: A double-blind, placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite (HDM; Dermatophagoides species) was conducted to assess the effects of specific immunotherapy added to guideline-adjusted pharmacologic treatment and allergen avoidance. METHODS: After 1 observational year of pharmacologic treatment and standard measures of HDM avoidance, 2 groups of asthmatic subjects were randomly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine (n=41) or placebo (n=31) for 3 years. Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines. RESULTS: The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects. The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators, an increase in morning and evening peak expiratory flow, and a reduced skin sensitivity to HDM extracts. The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids, asthma symptoms, lung volumes, or bronchial responsiveness to methacholine. CONCLUSION: These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits, possibly by reducing the allergic response of asthmatic patients sensitized to HDM.     

Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?

BACKGROUND: Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success. AIM: To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids. DESIGN OF STUDY: Randomised, parallel group, open-label trial. SETTING: Forty-four general practices in Nottinghamshire. METHOD: Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose. RESULTS: Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified. CONCLUSION: Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.     

Circulating ICAM-1 levels in bronchial asthma and the effect of inhaled corticosteroids.

BACKGROUND: Even mild asthma has an inflammatory component. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in inflammation. Higher levels of circulating ICAM-1 (cICAM-1) in sera may reflect the upregulation of ICAM-1 expression in allergic inflammation. OBJECTIVE: The aim of this study was to assess cICAM-1 levels in children with atopic bronchial asthma and to determine the effects of inhaled glucocorticoids on cICAM-1 levels. METHODS: The study group consisted of 25 children with moderate atopic bronchial asthma with a mean age of 9.9 +/- 4.2 years, and the control group consisted of 18 healthy children with a mean age of 9.6 +/- 2.6 years. Serum cICAM-1 levels and pulmonary function tests were measured. The patients were treated 2 months with inhaled budesonide 400 to 800 microg (mean 440 microg) per day. After this treatment, cICAM-1 levels and pulmonary function tests were compared with pretreatment levels. The pretreatment cICAM-1 values were compared with healthy control group. RESULTS: The initial cICAM-1 levels of the patient group were significantly higher than the cICAM-1 levels of the control group (P = .001). The post-treatment cICAM-1 levels of the patient group were significantly lower than the pretreatment values (P = .007). Pulmonary function test results (FEV1, FEF25-75, and PEFR) rose significantly with the treatment in patients (P < .05). CONCLUSION: This study revealed the presence of inflammation in children with even moderate atopic asthma as reflected with elevated levels of cICAM-1 levels, which decreased following corticosteroid treatment as a result of decreased inflammation.     

Slight steroid-sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma

Jakobsson T, Croner S, Kjellman N-IM, Pettersson A, Vassella C, Björkstén B. Slight steroid-sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma. Twenty subjects (aged 6-20 years) with moderately severe bronchial asthma participated in an open controlled trial with intravenous immunoglobulin (IVIG) given as five monthly infusions with a mean dose of 0.8 g/kg body weight. A follow-up was performed 4 and 14 months after the treatment period. Nine of 14 children in the treatment group completed the trial. Two children experienced severe headache after the first infusion, another two patients were taken off the study for reasons unrelated to the IVIG therapy, and one patient dropped out from lack of motivation. In six of the IVIG-treated children, there was a reduction in the daily intake of inhaled steroids at an unchanged or reduced histamine reactivity. Of the remaining three children, two showed a reduction in bronchial hyperreactivity, but their steroid dose was not reduced. Six patients participated in a reference group to determine seasonal variations of symptoms. One of them improved during the study period, and the condition of the other five deteriorated, as indicated by increased medication without reduced histamine reactivity. After 14 months, there were no significant differences in clinical symptoms, nor in sensitivity to histamine between the treated patients and the controls, as the condition had improved also in the latter. We have thus been able to confirm, in a group larger than those in previously published reports, some clinical improvement of asthma by IVIG therapy at a lower dose than previously used and in children with only moderately severe disease. The effect was still present 4 months after the termination of IVIG therapy but not after 14 months. As the effects were small and temporary and the treatment is complicated and expensive, IVIG therapy cannot at present be recommended for general use. A double-blind, placebo-controlled study of the effect of IVIG in asthma is needed.     

Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)

BACKGROUND: Children with allergic rhinitis are likely to develop asthma. OBJECTIVE: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis. METHODS: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter. RESULTS: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P <.05). Methacholine bronchial provocation test results improved significant in the active group (P <.05). CONCLUSION: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.     

Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation

BACKGROUND: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out. OBJECTIVES: We compared changes in AHR to inhaled methacholine and adenosine 5'-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment. METHODS: In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV(1) (PC(20)). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC(20) methacholine, PC(20) AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks. RESULTS: Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 +/- 0.3 doubling doses for methacholine and by 2.6 +/- 0.5 doubling doses for AMP. These changes were significantly different from each other (P =.003). Significant variation in PC(20) methacholine (P <.05) value, PC(20) AMP (P <.001) value, percentage of sputum eosinophils (P <.001), and percentage of sputum epithelial cells (P <.001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC(20) AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 +/- 0.3, 2.2 +/- 0.3, and 2.8 +/- 0.3 doubling doses of PC(20) AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment. CONCLUSIONS: The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.