Use of a pocket‐sized turbine spirometer in monitoring exercise‐induced bronchospasm and bronchodilator responses in children

For field studies of asthma, portable hand‐held pulmonary function testing devices are required. Other than for peak flow measurements, little has been done to validate their use in children. Fifty children aged 5–15 years having asthma symptoms were examined using an exercise challenge (8 min free running outdoors) and a bronchodilation test (salbutamol inhalation at a dose of 0.15 mg/kg). Pulmonary function was measured with a turbine spirometer, with a Wright peak flow meter (WPEF) and with a flow–volume spirometer (FVS). A fall of 15% or more in WPEF associated with wheezing or cough was considered diagnostic for bronchial hyper‐responsiveness to exercise (BHRE). A rise of 15% or more from baseline in WPEF after salbutamol inhalation was considered as a positive bronchodilator response (BDR). BHRE was present in 16 children (32%). Using the limit of a 15% or greater fall in FEV₁, turbine spirometry identified 12 as BHRE‐positive and no additional cases, giving a sensitivity of 75% and a specificity of 100%. The turbine spirometer showed lower FEV₁ values than the FVS, the difference increasing with airway obstruction. BDR was positive in eight children (16%). Using the limit of a 10% or greater rise in FEV₁, turbine spirometry was positive in six cases. FEV₁ measured by turbine spirometry could not be used interchangeably with conventional FVS. However, the turbine spirometer offers the possibility to measure FEV₁ repeatedly in field conditions, such as during exercise challenges outdoors.     

Evaluation of clinical and immunological effects of inactivated influenza vaccine in children with asthma

Although annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic children because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study, the effect of split influenza vaccine on clinical symptoms, airway responsiveness and its influence on T lymphocytes was evaluated. Twenty-one asthmatic children with stable asthma were recruited and divided into two groups. Eleven patients who received the influenza vaccine formed the vaccination group and 10 patients who received a placebo formed the placebo group. Forced expiratory volume in 1 s ( FEV ₁), airway response (PC₂₀ methacholine, PC₂₀ = provocation concentration causing a 20% fall in FEV ₁) and the T lymphocyte subset ratio (Th1/Th2) were recorded on day 1 pre-vaccination and day 14 post-vaccination. Patients were also asked to record their peak expiratory flow (PEF) every morning and evening and to complete daily symptom scores over the period of 2 weeks. There were no significant changes in PC₂₀, FEV ₁, PEF variability, symptom scores and the Th1/Th2 ratio between the vaccination and placebo groups between day 1 pre-vaccination and day 14 post-vaccination. Similar results of PEF variability and asthma symptom score were obtained when the analysis was restricted to the day 1 pre-vaccination and day 3 post-vaccination. Immunization with split influenza vaccine does not exacerbate asthma in children either with a clinical or immunological effect. These results suggest that children with stable asthma can safely be immunized with a split influenza vaccine.     

Wheezing in school children is not always asthma

Our objective was to study whether children with reported asthma differed from children with wheeze but without asthma, and from children with neither asthma nor wheeze, regarding lung function, bronchial hyper‐responsiveness (BHR) using methacholine inhalation, exercise‐induced bronchoconstriction (EIB), and skin prick test (SPT) reactivity. School children (n=2188), enrolled in a survey of asthma, were classified into three mutually exclusive groups by parental report of: asthma, wheeze, and no asthma/no wheeze. A random sample of 80 children in each group was tested (n=240). Among asthmatics, 68% (95% confidence interval (CI), 57–79) had a BHR (measured as PD₂₀ forced expiratory volume in 1 s (FEV₁) ≤ 8.16 μmol using methacholine) compared to 31% (CI 20–42%) and 30% (CI 19–40%) in the wheeze and no asthma/no wheeze groups. The dose–response slope (DRS) confirmed the PD₂₀ data and distinguished equally between groups. EIB (≥10% fall in FEV₁) was more frequent (40%, CI 29–52%) among asthmatics than among children with wheeze (12%, CI 4–19%) and no asthma/no wheeze (7%, CI 1–13%). The prevalence of at least one positive SPT was twice as high in the asthma group (58%, 47–69%) than in the wheeze (27%, CI 16–37%) and the no asthma/no wheeze (25%, 15–35%) groups. These results indicate that children with asthma differ from children with wheeze and children with no asthma/no wheeze regarding lung function, BHR, EIB, and SPT reactivity. Children with wheeze are more similar to children with no asthma/no wheeze with respect to these parameters.     

Early intervention of recent onset mild persistent asthma in children aged under 11 yrs: the Steroid Treatment As Regular Therapy in early asthma (START) trial

Inhaled corticosteroids are known to be effective in persistent asthma, but their long-term effect in mild persistent disease of recent onset, which is particularly relevant in children, requires clarification. The objective of this study was to determine the long-term efficacy of regular inhaled low-dose budesonide in children aged <11 yrs with mild persistent asthma with onset within 2 yrs of enrollment. Children aged 5–10 yrs formed part of the population of the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study, and they were randomized in a double-blind manner to treatment with once daily budesonide 200  μ g or placebo via Turbuhaler^TM in addition to usual clinical care and other asthma medication. The double-blind treatment phase continued for 3 yrs. Of the 1974 children, 1000 in the budesonide group and 974 in the placebo group, were analyzed for efficacy. Addition of once-daily budesonide to usual care was associated with a significant increase in the time to first severe asthma-related event (SARE) and significantly reduced risk of SARE over 3 yrs. The hazard ratio relative to usual care (placebo) was 0.60 (95% confidence interval: 0.40–0.90; p = 0.012), with a relative risk reduction of 40%. Children receiving budesonide also needed significantly less intervention with other inhaled corticosteroids (12.3% vs. 22.5% over 3 yrs; p < 0.01), with trends towards decreased usage of oral/systemic corticosteroids and inhaled short-acting β ₂-agonists. Budesonide treatment also had a significant beneficial effect on lung function relative to placebo. In conclusion, early intervention adding once-daily budesonide to usual care in children with mild, persistent asthma of recent onset reduces the long-term risk and frequency of SAREs and improves lung function compared with usual care alone.     

Leukocyte‐reduction to prevent transfusion‐transmitted cytomegalovirus infections

Abstract: Certain infectious organisms, including cytomegalovirus, are associated 'exclusively' with blood leukocytes (WBC), and their transmission by transfusion is strikingly diminished by marked WBC‐reduction of cellular blood components. Based on several reports of WBC‐reduction, it is clear that the risk of CMV is nearly eliminated by consistently removing WBC to a level < 1–5 × 10⁶ WBCs/unit (≤ 1 × 10⁶ preferred in Europe; ≤ 5 × 10⁶ in the United States). Alternatively, the rate of CMV infections is reduced by transfusing blood components collected from donors negative for CMV antibody. However, neither technique is perfect, with a failure rate of 1–4%. Although WBC‐reduction is favored by many experts, practitioners must choose the method that they believe to be most efficacious – being mindful that data do not exist to establish additive protection by combining WBC‐reduction and transfusion of blood components collected from antibody negative donors.     

Application and efficacy of the multi‐dose powder inhaler, Easyhaler®, in children with asthma

With powder inhalers, optimal performance is dependent on the inspiratory flow produced by the patient through the devices. The objective of this open, non‐randomized study was to evaluate the suitability of a new, multi‐dose, dry powder inhaler, the Easyhaler^®, for children with asthma. The peak inspiratory flow (PIF) through the Easyhaler (PIF_EH) was measured with a pneumotachograph in 120 asthmatic children aged 4–16 yr. The bronchodilatory effect of 0.2 mg salbutamol through the Easyhaler was compared with that of 0.2 mg salbutamol through a metered dose inhaler (MDI) with a spacer, in 15 children with obstruction. The mean PIF_EH was 56 l/min (range 22–83 l/min). The PIF_EH correlated significantly with age, height, and absolute peak expiratory flow (PEF), but not with the level of obstruction (PEF percentage of predicted, range 45–146%). Only four children (aged 5, 6, 10, and 16 yr) had PIF_EH values below 28 l/min, which has been shown in in vitro studies to be the threshold for effective use of the Easyhaler. In 15 children with PEF, < 85% of predicted bronchodilatory effects of 0.2 mg salbutamol through the Easyhaler and from an MDI‐cum‐spacer were equal. Most children aged 6–16 yr produce PIF values sufficient for the use of the Easyhaler. The gain of 0.2 mg salbutamol from the Easyhaler was equal to that from a new, unprimed, MDI with a spacer in children with asthma.     

Short-term effects of budesonide, nedocromil sodium and salmeterol on bronchial hyperresponsiveness in childhood asthma

Abstract Background: The effects of budesonide, nedocromil sodium and salmeterol on bronchial hyperresponsiveness were determined over a period of 3 weeks.
Methods: Forty-three asymptomatic children (22 male, 21 female, aged7–17 years) with mild-to-moderate asthma were evaluated. The study was placebo-controlled and double-blind. At the beginning the forced expiratory volume in 1 second (FEV₁) was measured and a methacholine challenge was performed to determine PC₂₀ (provocative concentration of inhaled methacholine required to reduce FEV_t by 20%). The patients in group I (n = 12), group II (n = 10), group III (n = 11), and group IV ( n = 10) inhaled 200 μg of budesonide, 2 mg of nedocromil sodium, 25 μg of salmeterol and a placebo, respectively, twice a day over the period of 3 weeks. Then the methacholine PC₂₀ values of all patients were measured again and the results were compared statistically with their previous values.
Results: The statistical data revealed that the methacholine doses in PC₂₀ before and after treatment were different in group I (P < 0.01). However, these differences were not statistically significant in the other groups (P > 0.05).
Conclusions: The short term usage of budesonide decreases bronchial hyperresponsiveness, but nedocromil sodium and salmeterol in the given doses do not affect bronchial hyperresponsiveness.     

Clinical pharmacology of the H1‐receptor antagonists cetirizine and loratadine in children

H₁‐receptor antagonists are widely used in children but are not as well‐studied in children as they are in adults. Our objective was to determine the onset and duration of action and the relative potency of the H₁‐receptor antagonists cetirizine and loratadine in children. We performed a prospective, randomized, placebo‐controlled, double‐blind, crossover, single‐dose study of cetirizine and loratadine using suppression of the histamine‐induced wheal and flare as the primary outcome. In 15 allergic children, mean age 9 years, compared with baseline, cetirizine (10 mg) suppressed the wheals and flares significantly from 0.25 to 24 h, achieving nearly 100% of flare suppression from 2 to 24 h, inclusive, and loratadine (10 mg) suppressed the wheals and flares significantly from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares significantly more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2, 3, 5, 6, 7, and 24 h, respectively. Placebo also suppressed the wheal and flare significantly at some assessment times. Cetirizine and loratadine both have excellent antihistaminic activity in children, with a rapid onset of action and a 24‐h duration of action in this population.     

Asthma severity and inflammation markers in children

The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any method. Neither did any marker of airway inflammation relate to recent symptoms, unlike PC₂₀, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s ( FEV ₁) and both NO and sputum ECP ( r =−0.46, p=<0.001; r =−0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV ₁ (PC₂₀) ( r =−0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.     

Exhaled nitric oxide and exercise-induced bronchoconstriction in young wheezy children – interactions with atopy

The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FE_NO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FE_NO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FE_NO by standard online technique. Although FE_NO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FE_NO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FE_NO and the severity of EIB was found ( r  = 0.44, p = 0.0004), and FE_NO was significantly predictive of EIB. No clear association between FE_NO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FE_NO levels. However, the association between the severity of EIB and FE_NO is present and FE_NO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze.     

Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before ( t ₀) and immediately after ( t ₁) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t ₀ and t ₁, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.     

Cutaneous lymphocyte‐associated antigen expression in children with atopic dermatitis and non‐atopic healthy children

Cutaneous lymphocyte‐associated antigen (CLA) is a cell surface glycoprotein which has been implicated in the homing of lymphocytes to cutaneous sites. It is postulated to play an important role in T‐cell migration to skin in atopic dermatitis; however, the expression of CLA in both normal children and children with atopic dermatitis has not been extensively studied. If CLA expression on T cells were important in the traffic of lymphocytes to atopic dermatitis skin lesions, it might be expected that the proportion of CLA⁺ T cells in unstimulated peripheral blood from children with atopic dermatitis would be elevated. We have examined the proportion of CLA⁺ T cells in children with atopic dermatitis and non‐atopic age‐matched controls. The proportion of CLA⁺ T cells in non‐atopic children was highly associated with and increased with increasing age ( r  = 0.88, p < 0.001). There was no difference between the proportion of T cells expressing CLA in the unstimulated PBMC from children with severe or mild/moderate atopic dermatitis and age‐matched non‐atopic controls (p = 0.18, p = 0.3, respectively). Despite this, children with atopic dermatitis did show evidence of perturbation of CLA expression, as unlike the non‐atopic children the proportion of CLA⁺ T cells in the atopic children did not correlate with age. These findings suggest that while CLA expression may play a role in atopic dermatitis, other as yet undefined surface markers are likely to principally determine the migration of T cells to skin in atopic dermatitis.     

Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study

OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.     

Time efficacy of a single dose of montelukast on exercise-induced asthma in children

The aim of this study was to evaluate the timing of onset and the duration of action of a single oral-dose treatment with montelukast in comparison to placebo on exercise-induced asthma (EIA) in asthmatic children. Nineteen children (7–13 years) with stable asthma were evaluated. Patients undertook three consecutive treadmill exercise tests, respectively, 2, 12 and 24 h after a single-dose administration. A double-blind randomized, single-dose, placebo-controlled, crossover design was used. To assess bronchoconstriction after the exercise challenge, the maximal percentage fall in FEV₁ (ΔFEV₁) from the baseline value was considered. Two hours after dosing, ΔFEV₁ was −15.33  ±  2.93 for placebo and −13.33  ±  2.03 for montelukast. At 12 h, ΔFEV₁ was −18.69  ±  2.83 for placebo, −9.78  ±  1.85 for montelukast (p < 0.005). No difference was observed between placebo (ΔFEV₁−10.21  ±  2.07) and montelukast (ΔFEV₁−9.10  ±  2.02) at 24 h. Analysis of the degree of protection showed a significant efficacy of montelukast (p = 0.02) in comparison with placebo only at 12 h. Montelukast showed a significant protective effect 12 h after dosing, but no effect after 2 and 24 h. In mild asthmatics, the timing of administration of single dosage before exercise should be strictly considered in order to obtain the drug protective effects.     

β2-MICROGLOBULIN IN CEREBROSPINAL FLUID FROM CHILDREN WITH DIFFERENT DISEASES

Abstract. Kaas Ibsen, K. (The University Clinic of Paediatrics, Children's Hospital Fuglebakken, Copenhagen, Denmark). β₂-microglobulin in cerebrospinal fluid from children with different diseases. Acta Paediatr Scand, 69: 633, 1980.—β₂-microglobulin concentrations in cerebrospinal fluid (CSF) were measured in a prospective study on 56 children 0–12 years old. In all the patients with virus meningitis values of β₂-microglobulin exceeded 3000 µg/l (=10.825 µg/l). The highest value (48.096 µg/l) of β₂-microglobulin in CSF was found in a 13-day-old infant with serious herpes simplex meningitis. The value was 50 times the values found in normal children. None of the patients with fever of other origin had values exceeding 3500 µg/l, except for one patient with facial nerve paresis and 3 patients with sepsis. Some correlation between the concentrations of β₂-microglobulin and albumin was found in the diagnostic groups as a whole, while this correlation disappeared when considering each patient individually. The significance of β₂-microglobulin as a guide in serious infections is discussed.     

Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitis

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and α₂-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of α₂-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in α₂-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.     

A 3-year longitudinal analysis of changes in fitness, physical activity, fatness and screen time

Aim:  To analyse whether changes in physical activity index (PAI), screen time (ST: television, computer) and body mass index (BMI) made a contribution to longitudinal changes in fitness of children and adolescents. Additionally, we analysed the interaction between baseline fitness level and changes in fitness.
Methods:  This is a 3-year longitudinal study of 345 high school students aged 11–19 years. Students performed curl-ups, push-ups and 20-m shuttle run tests from Fitnessgram. PA and ST were evaluated using a standard questionnaire. Standardized scores of fitness tests were summed. Changes over time were calculated as Δ₁ (2007 minus 2006), Δ₂ (2008 minus 2007) and Δ₃ (2008 minus 2006).
Results:  Changes in PAI were positively and independently associated with changes in fitness in Δ₁, Δ₂ and Δ₃. Changes in BMI were negatively associated with changes in fitness in Δ₃. Participants highly fit at baseline were those who showed positive changes in PAI over Δ₃, decreased changes in ST and had the lowest increase in BMI over 3 years compared with those low-fit at baseline.
Conclusions:  Changes in BMI were associated with changes in fitness over 3 years. However, changes in PAI were the best predictor for changes in fitness in each year and over the 3 years of evaluation in youth.     

Transforming growth factor-β1 is elevated in unpasteurized cow's milk

Unpasteurized milk consumption was associated with less atopy prevalence. Not only microbial load but also fatty acids and cytokines such as transforming growth factor-β₁ (TGF-β₁) may play a role on the effect of unpasteurized milk. Levels of TGF-β₁ in different cow's milk samples were evaluated: we consider raw unpasteurized milk before and after boiling, commercial pasteurized and micro-filtrated cow's milk and different commercially available cow's milk formulas. TGF-β₁ concentration in raw unpasteurized cow's milk was 642.0 ± 52.9 pg/ml before boiling and decreased significantly after boiling (302.7 ± 50.59 pg/ml) (p < 0.05). TGF-β₁ concentrations were also significantly lower in commercial pasteurized milk (246.2 ± 43.15 pg/ml) and in commercial micro-filtrated milk (213.0 ± 31.6 pg/ml) in comparison to unpasteurized unboiled milk (p = 0.002). The levels of TGF-β₁ in all formula samples were below the threshold of detectability for the assays. As TGF-β₁ in the milk may contribute to the development of the immature gastrointestinal tract by influencing IgA production and oral tolerance induction, we suggest to consider not only the microbial compounds but also the cytokine patterns to explain the protective effect of unpasteurized cow's milk on allergic disorders.     

Inhaled corticosteroids during and after respiratory syncytial virus-bronchiolitis may decrease subsequent asthma

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper-reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 µg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 µg twice per day for two months. Follow-up consisted of out-patient check-ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.     

Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma.

We aimed to compare the efficacy and safety of budesonide/formoterol (Symbicort) with budesonide alone (Pulmicort) or budesonide (Pulmicort) and formoterol (Oxis) administered via separate inhalers in children with asthma. In a 12 wk, double-blind study, a total of 630 children with asthma (mean age 8 yr [4-11 yr]; mean forced expiratory volume in 1 s (FEV(1)) 92% predicted; mean inhaled corticosteroid dose 454 microg/day) were randomized to: budesonide/formoterol (80/4.5 microg, two inhalations twice daily); a corresponding dose of budesonide alone (100 microg, two inhalations twice daily); or a corresponding dose of budesonide (100 microg, two inhalations twice daily) and formoterol (4.5 microg, two inhalations twice daily) (budesonide + formoterol in separate inhalers). The primary efficacy variable was the change from baseline to treatment (average of the 12-wk treatment period) in morning peak expiratory flow (PEF). Other changes in lung function and asthma symptoms were assessed, as was safety. Budesonide/formoterol significantly improved morning PEF, evening PEF and FEV(1) compared with budesonide (all p < 0.001); there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables. All other diary card variables improved from baseline in all treatment groups; there were no significant between-group differences. Adverse-event profiles were similar in all groups; there were no serious asthma-related adverse events in any treatment group. Conclusion: budesonide/formoterol significantly improved lung function in children (aged 4-11 yr) with asthma compared with budesonide alone. Budesonide/formoterol is a safe and effective treatment option for children with asthma.