Duiverman, E.J.

Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma (Article)

2010-11-15T00:00:00Z

Rationale: For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids. Objective: To evaluate whether salmeterol/fluticasone propionate (SFP), 50/100 μg twice a day, is noninferior regarding symptom control compared with fluticasone propionate (FP), 200 μg twice a day Diskus in children with symptomatic asthma. Methods: A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function. Measurements and Main Results: A total of 158 children, 6-16 years old, still symptomatic on FP, 100 μg twice a day, during a 4-week runin period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV1, FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth. Conclusions: In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid. Clinical trial registered with www.clinicaltrials.gov (NCT 00197106).

Health-related quality of life of food allergic patients: Comparison with the general population and other diseases (Article)

2010-02-01T00:00:00Z

Background: To date no studies have compared generic health-related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. Methods: Generic HRQL questionnaires (CHQ-CF87 and RAND-36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). Results: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems (P ≤ 0.013), but food allergic adolescents and adults reported more pain (P = 0.020), poorer overall health (P < 0.001), more limitations in social activities (P < 0.001) and less vitality (P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. Conclusion: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy.

Inhaled corticosteroids for recurrent respiratory symptoms in preschool children in general practice: Randomized controlled trial (Article)

2008-02-01T00:00:00Z

Background: Therapy with inhaled corticosteroids (ICS) is beneficial in patients with asthma. However, in preschool children with symptoms like cough, wheeze, or shortness of breath diagnosing asthma is difficult. Therefore, the role of ICS in the management of preschool children with recurrent respiratory symptoms is unclear. We assessed the effectiveness of ICS in preschool children with recurrent respiratory symptoms in general practice. Methods: In this multicenter, randomized, double blind, placebo controlled trial, 96 children aged 1-5 years consulting their general practitioners for recurrent respiratory symptoms and in whom treatment with ICS was considered by the general practitioner were randomly allocated to receive ICS (fluticasone propionate 200 mcg/day by metered dose inhaler/spacer combination) or placebo for 6 months. Outcome assessments were carried out 1, 3, and 6 months after randomization. The primary outcome measure was the symptom score (cough, shortness of breath and wheeze during day and night) as measured by a symptom diary card. Secondary endpoints were symptom-free days, use of rescue medication, adverse events, and lung function variables as measured by the interrupter technique and forced oscillation technique. Results: During the 6 months treatment period, symptoms improved in both groups, with no differences between ICS and placebo. In addition, none of the secondary outcome parameters showed differences between both treatment groups. Conclusion: ICS treatment has no beneficial effect in preschool children with recurrent respiratory symptoms in general practice. We therefore recommend a watchful waiting policy with only symptomatic treatment in these children. General practitioners and pediatricians should be aware of the high probability of overtreatment when prescribing ICS in these children.

Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: An international study (Article)

2008-01-01T00:00:00Z

Background: Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE-FS) that are commonly associated with IgE food allergy. Objectives: To explore the relationship between high levels of IgE-FS and AE in a large cohort of young children with eczema participating in a multi-centre, international study. Methods: Two thousand one hundred and eighty-four subjects (mean age 17.6 months, range 11.8-25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP-FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP-FEIA levels exceeded previously reported age-specific cut-off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high-risk IgE-FS (HR-IgE-FS). Results: Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR-IgE-FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR-IgE-FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset-age <3 months had HR-IgE-FS. Conclusion: Early-onset severe eczema in infancy was associated with HR-IgE-FS. Clinical implications: Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary: In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE-FS.

Inhaled corticosteroids and growth of airway function in asthmatic children (Article)

2004-01-01T00:00:00Z

Airway inflammation and remodelling play an important role in the pathophysiology of asthma. Remodelling may affect childhood lung function, and this process may be reversed by anti-inflammatory treatment. The current study assessed longitudinally whether asthma affects growth of airway function relative to airspaces, and if so whether this is redressed by inhaled corticosteroids (ICS). Every 4 months for up to 3 yrs, lung function was assessed in 54 asthmatic children (initial age 7-16 yrs), who inhaled 0.2 mg salbutamol t.i.d. and 0.2 mg budesonide t.i.d. (beta2-agonist (BA)+ICS), or placebo (PL) t.i.d. (BA+PL) in a randomised, double-blind design. Measurements were carried out before and after maximal bronchodilation. Airway growth was assessed from the change of forced expiratory volume in one second and of maximal expiratory flows (at 60% and 40% of total lung capacity (TLC) remaining in the lung) relative to TLC, as measures of more central, intermediate and more peripheral airways. Growth patterns were compared with the longitudinal findings in 376 healthy children. Airway patency after maximal bronchodilation in patients on BA+PL remained reduced compared to healthy subjects, whereas in patients on BA+ICS a marked improvement was observed to subnormal. No differences between patients and controls could be demonstrated for growth patterns of central and intermediate airway function. Compliance with BA+ICS was 75% of the prescribed dose, resulting in significant, sustained improvement of symptoms and postbronchodilator calibre of central and intermediate airways to subnormal within 2 months, but postbronchodilator small airway patency remained reduced, though improved compared to patients on BA+PL. Anti-inflammatory treatment of asthmatic children is associated with normal functional development of central and intermediate airways. The persistently reduced postbronchodilator patency of peripheral airways may reflect remodelling, or insufficient anti-inflammatory treatment.

Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group (Article)

1998-01-01T00:00:00Z

Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid resulted in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid. The aim of this three group study was to compare the effects of a moderate dose of beclomethasone, the same dose of beclomethasone with salmeterol, and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma. A total of 177 children already treated with inhaled corticosteroids, were randomized in a double-blind parallel study either to salmeterol 50 microg twice daily (BDP400+salm), beclomethasone 200 microg twice daily (BDP800), or placebo (BDP400) in addition to beclomethasone 200 microg twice daily. No significant differences between groups were found in FEV1, PD20 methacholine, symptom scores, and exacerbation rates after 1 yr. Salmeterol resulted in slightly better PEF in the first months of treatment. FEV1, and PD20 methacholine significantly improved in all groups. After 1 yr mean changes in FEV1, percent predicted were 4.3% (95% CI 1.3; 7.2), 5.8% (95% CI 2.9; 8.7), and 4.3% (95% CI 2.1; 6.5) for BDP400+salm, BDP800, and BDP400, respectively. Changes in airway responsiveness were 0.60 (95% CI 0.05; 1.14), 1.30 (95% CI 0.73; 1. 87), and 0.80 (95% CI 0.33; 1.27) doubling doses. Growth was significantly slower in the BDP800 group. We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication.

Lung function and bronchial responsiveness in preschool children (Doctoral Thesis)

1985-10-23T00:00:00Z

It is hypothesized that childhood asthma, especially when not well controlled, may constitute a risk factor for the development of COLD in adulthood (Cropp, 1985), It is unknown whether lung injury during early life is a risk factor for the development of COLD in adulthood, Asthma often starts before schoolage (Cropp, 1985), Except for the disturbing symptoms, a reason for paying attention to asthma in preschool children is the hypothesis that adequate intervention may reduce the risk of COLD in adult life (Kerrebijn, 1982). To detect lung function abnormalities at as young as possible ages suitable methods should be available. Most lung function methods can only be performed in children over 6 years of age. Lung function was measured with the forced pseudo-random noise oscillation technique (FOT) (Uindser et al., 1976a) because only passive cooperation is needed. Resistance (R,) and reactance (X,) of the respiratory system are simultaneously measured over a frequency spectrum of 2 to 26 Hz. R, is mainly determined by the patency of the upper and large airways. X, is influenced by mass-inertial and elastic properties of the respiratory system. The applicability ofFOT in preschool children was investigated. The method is now suitable for use in clinical practice to measure lung function and BR in children from about 2lfz years of age. We measured airway patency, bronchial smooth muscle tone and BR in preschool asthmatic children. Secondly, we investigated whether lung injury during early influences the development of lung function and bronchial responsiveness in children who do not have a genetic predisposition of asthma. This was investigated in children who had infant bronchiolitis, in subjects who survived infant bronchopulmonary dysplasia after neonatal respiratory distress syndrome and in individuals who experienced a near-drowning accident. The results are compared to data found in healthy controls.