Persistent Asthma In Children Research Articles

Neutrophilic Cells in Sputum of Allergic Asthmatic Children

Airway inflammation is regarded as a central feature of asthma and is mostly sustained by eosinophilic infiltrate. Recent studies have shown that a co-activation of eosinophil- and neutrophil-dependent inflammatory mechanisms might explain why some asthmatics do not respond to conventional asthma therapy. The aim of our study is to determine whether neutrophilic inflammation was involved in 55 allergic children with mild-moderate persistent asthma and the relationship with the response to steroid treatment. Before the sputum analysis, all children underwent spirometry with the reversibility test, and were divided into two groups on the basis of the response (such as >12% of baseline FEV1): group 1 positive and group 2 negative. Eosinophil cationic protein concentrations were measured by radioimmunoassay and neutrophyl myeloperoxidase (MPO) concentrations were measured by an MPO-EIA. Ten healthy children of comparable ages served as control group. Total IgE, FEV1 and FEV/FVC values were similar in both groups. The sputum macrophage count was higher in controls than in allergic asthmatics, but there was no difference between groups 1 and 2 (59.6% vs 18.3% and 17%; p≤ 0.005). Sputum neutrophils were significantly higher in group 2 both vs controls (62% vs 34%; p≤ 0.005) and vs group 1 (62% vs 37%; p≤ 0.005). Our data suggest that neutrophils are involved in airway allergic inflammation in mild-moderate persistent childhood asthma and a high neutrophil count in sputum may be related to a lower responsiveness to inhaled corticosteroids.

Rapid improvement of respiratory quality in asthmatic children after "assisted drainage" therapy

Background Whilst current asthma management is well-developed, there are still 5-10% uncontrolled asthma patients with unknown etiologies. However, its connection with oral focal infection is still uncertain. Therefore, a collaborated research for asthma management was conducted by pediatricians and dental practitioners. Within minutes after the "assisted drainage" therapy, a modification of healing root planning procedure, there is rapid improvement of respiratory function, ie., forced expiratory-volume one second (FEV1) in asthmatic children. This quick response usually achieved by oral inhalation.Objective To investigate the effectiveness of the assisted drainage therapy in the improvement of respiratory quality.Methods Fifteen asthmatic children were subjected to a longitudinal study for two weeks. In tbe first week they were instructed for al lergen avoidance only and the fOllowing one week was combined with tbe assisted drainage therapy, followed by mental health education and dental plaque control therapy. Each s'ubject was af'sef'sed for respiratory quality with a computerized spirometer and blood sampling test. Paired t-test analysis was used for statistical analysis.Results Assisted drainage therapy was performed, within minutes FEV1 increased significantly (P= 0.001). Additionally, there were significant differences serum histamine (P= 0,001) pre and post treatment.Conclusions The assisted drainage therapy is effective as an adjuvant therapy for mild persistent asthma in children.

Lung Function Impairment Evidenced by Sequential Specific Airway Resistance in Childhood Persistent Asthma: A Longitudinal Study

Background. Specific airway resistance (sRaw) is virtually independent of lung growth, height, and gender, thus facilitating longitudinal follow-up. Objective. To assess whether a specific phenotype of asthmatic children with a decline in lung function can be evidenced using sRaw. Methods. The authors hypothesized that sequential sRaw measurements over a long period would detect subtle trends. Clinical and functional data of children with persistent asthma under inhaled corticosteroids, evaluated at least three times per year for at least 4 years, were retrieved from a database. Results. One hundred fourteen children (30 girls) were followed for (median [interquartile range]) 6.9 years [5.6–7.9]. Data from 1699 measurements of sRaw (median 14/child) allowed the calculation of individual slopes of sRaw plotted against time demonstrating stable values in the group as a whole between 4 and 18 years. A positive correlation between individual slopes and the degree of intraindividual variation of sRaw was observed (R2 = .16; p < .0001). Children with more than one positive skin test showed larger intrasubject variation of sRaw (p = .011). In 19/114 children (17%), a significant increase in sRaw of 12.3% per year (median) was observed. As compared to children without, those with a significant increase in sRaw were boys (p < .0001), had a lower initial (p = .008) and a higher final resistance (p = .025) but did not differ in terms of inhaled corticosteroid dose. Conclusion. This retrospective study identifies a specific phenotype of asthmatic children that develops an impairment of lung function, confirming the results of a post hoc analysis of the Childhood Asthma Management Program study.

Corticoïdes inhalés dans l’asthme : quelle tolérance en 2009 ?

Asthmatic syndrome, better definition of asthma, is an inflammatory chronic disease, probably the most frequent in pediatrics. An important characteristic of asthma is the bronchial inflammation with a complex network of cells and inflammatory mediators of pivotal importance in the pathogenesis. The long term control and treatment of this disease are cardinal points of the management of asthmatic syndrome. Inhaled corticosteroids (ICS) are the first-line treatment for persistent asthma in children of any age. The adverse events of the inhaled steroids on growth, bone mineralization, and hypothalamic-pituitary adrenal (HPA) axis function are the main concerns for the pediatricians. The long-term effects on growth and bone mineralization are actually reassuring. Good tolerance is achieved on hypothalamic-pituitary adrenal axis function with low to moderate doses in children. Scientific and clinical researches are pointed to find out molecules able to improve clinical efficacy of ICS with better tolerance and higher reduction of adverse events.

Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma

Eosinophilic inflammation has a central role in the pathogenesis of asthma. We aimed to elucidate whether elevated blood eosinophil count (B-EOS), eosinophil cationic protein in serum (S-ECP) or in nasopharyngeal aspirate (NPA-ECP) predict later asthma after hospitalization for wheezing in infancy. In 1992-1993, 100 infants aged <24 months were hospitalized for wheezing associated with respiratory infection. B-EOS, S-ECP and NPA-ECP were measured on admission. Asthma status was evaluated at the follow-up visits at the median ages of 4.0, 7.2 and 12.3 yr. Twenty (25%) of 81 children had asthma at all three visits and were considered to have persistent childhood asthma (PCA). Children with B-EOS >or= 0.450 x 10(9) cells/l had a 2.9-fold PCA risk compared with other children. The risk was 6.1-fold when S-ECP was >or=20.0 microg/l and 6.7-fold when NPA-ECP was >or=815.0 ng/g. By these cut-off limits, all these markers were specific (75-93%), but not very sensitive (30-58%) in predicting PCA. At least one marker was elevated in 75% of the children with PCA. The respective figure for NPA-ECP alone was 58%. In adjusted analyses, only elevated NPA-ECP was an independent risk factor for PCA (OR 4.09). In conclusion, eosinophil activity in early life predicts the development of childhood asthma after hospitalization for wheezing in infancy. The results highlight NPA-ECP as an independent predictor of the persistence of asthma at school age.

Childhood Persistent Asthma after In Utero Tobacco Exposure in Mexican, Puerto Rican, and African Americans

RATIONALE: Fetal tobacco exposure on childhood respiratory health has been investigated with inconsistent outcomes. The goal of this study was to determine if fetal tobacco exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and African American children.

Predictors of remitting, periodic, and persistent childhood asthma

The course of mild to moderate persistent asthma in children is not clearly established. To determine the rate and predictors for remitting, periodic, and persistent asthma in adolescence. The Childhood Asthma Management Program (CAMP) was a 4.3-year randomized, double-masked, multicenter trial in children with mild to moderate persistent asthma that compared continuous therapy with either budesonide or nedocromil, each to placebo, followed by a 4-year observational follow-up period. Asthma activity during the observation period included remitting (no asthma activity in the last year), persistent (asthma activity in every quarter), and periodic asthma (neither remitting nor persistent). Asthma was identified as remitting in 6%, periodic in 39%, and persistent in 55% of the 909 participants, with no effect noted from earlier anti-inflammatory treatment during the CAMP trial. Within all 3 asthma activity categories, improvements in airway hyperresponsiveness, eosinophilia, and asthma morbidity were observed over time. Features at entry into CAMP associated with remitting versus persistent asthma were lack of allergen sensitization and exposure to indoor allergens (odds ratio [OR], 3.23; P < .001), milder asthma (OR, 2.01; P = .03), older age (OR, 1.23; P = .01), less airway hyperresponsiveness (higher log methacholine FEV(1) PC(20) (OR, 1.39; P = .03), higher prebronchodilator FEV(1) percent predicted (OR, 1.05; P = .02), and lower forced vital capacity percent predicted (OR, 0.96; P = .04). Remission of asthma in adolescence is infrequent and not affected by 4 years of anti-inflammatory controller therapy. Factors such as sensitization and exposure, low lung function, and airway greater hyperresponsiveness decrease the likelihood of remitting asthma.

Early Exposure and Sensitization to Cat and Dog: Different Effects on Asthma Risk After Wheezing in Infancy

Korppi M, Hyvärinen M, Kotaniemi-Syrjänen A, Piippo-Savolainen E, Reijonen T. Pediatr Allergy Immunol. 2008;19(8):696–701PURPOSE OF THE STUDY. Birth cohort studies have suggested that early exposure to furred pets protects from later asthma and allergy. The aim of this study was to evaluate the association between exposure or sensitization to cat or dog in infancy and later asthma and allergy assessed at the median ages of 4.0, 7.2, and 12.3 years.STUDY POPULATION. Children 1 to 23 months of age who had wheezing and respiratory distress that required hospital care during an acute respiratory tract infection were enrolled.METHODS. Exposure to cat and dog in infancy was assessed by interviewing the parents. The child was considered to be sensitized if the allergen-specific immunoglobulin E level to cat or dog was ≥0.35 kU/L or if there was a positive skin-test response.RESULTS. When the 20 children with persistent childhood asthma (doctor-diagnosed asthma at all 3 control visits) were compared with the other 61 children, early exposure to dog (odds ratio [OR]: 0.14; P = .034) decreased the asthma risk, and early sensitization to cat (OR: 5.92; P = .008) and dog (OR: 9.33; P = .001) increased the asthma risk. There was less cat- and dog-keeping in atopic families, and the effect of sensitization was, but the effect of exposure was not, robust to adjustments in multivariate analyses.CONCLUSIONS. This study demonstrates that, in long-term follow-up evaluation after early wheezing, early sensitization to cat and dog increases the risk of later asthma but early exposure to cat or dog has no such effect. Dog-keeping was less frequent in atopic families, which may explain why the protective effect of early exposure to dog was lost in multivariate analyses.REVIEWER COMMENTS. Studies have shown that early high-dose exposure to allergens may be protective for the development of allergy, and children who do not develop early allergic sensitization to environmental allergens are at lower risk for having persistent wheezing symptoms. This study's results are consistent with those of previous studies; although early sensitization to cat and dog increases the risk for later asthma in children at high risk, early high-dose exposure to furred animals does not seem to be a risk factor. It should be noted that atopic families tended to have pets less frequently, which might have introduced confounding effects.

Recommendations for treatment of intermittent mild persistent asthma in children and adolescents

Many parents and caretakers of children and adolescents with mild persistent asthma (MPA) do not follow proposed guidelines, namely the daily and continuous administration of inhaled corticosteroids (ICS). Instead, parents and caretakers tend to use ICS and bronchodilators intermittently for short periods and restart such therapy only when symptoms reappear. It is our opinion that intermittent treatment of MPA in children and adolescents might achieve the same level of asthma control as has been achieved in adults. We propose, therefore, that after an initial period of stabilization with age-appropriate doses of oral glucocorticoids or high-dose ICS and short-acting beta-2 agonists (SABA), caretakers can stop treatment once there are no longer signs or symptoms of asthma. When asthmatic symptoms recur, treatment should be restarted with ICS and SABA, or oral corticosteroids if the exacerbation is severe. The perception of developing asthma symptoms remains an unsolved problem. Based on our clinical experience in children and adolescents with asthma, we list a number of signs and symptoms that precede an exacerbation of asthma, allowing for an early re-introduction of treatment to prevent an exacerbation.

The effect of inhaled corticosteroids on Chlamydophila pneumoniae and Mycoplasma pneumoniae infection in children with bronchial asthma

The purpose of this study was to clarify whether inhaled corticosteroids (ICSs) increased the infectious load of Chlamydophila pneumoniae and/or Mycoplasma pneumoniae in the respiratory tracts of asthmatic children. We studied a total of 310 outpatients with chronic stable asthma. Real-time polymerase chain reaction (PCR)-positive results for C. pneumoniae were obtained in 21 of 310 (6.8%) throat samples and 21 of 293 (7.2%) nasopharyngeal samples. There was no significant difference in the rate of detection or in the quantity of detection for C. pneumoniae between the ICS group and the non-ICS group, nor were there differences among groups classified by Japanese pediatric guidelines (JPGL) severity criteria. Real-time PCR-positive results for M. pneumoniae were obtained in 60 of 310 (19.4%) throat samples and 49 of 293 (16.7%) nasopharyngeal samples. There was no significant difference in the rate of detection or the quantity of detection between the ICS group and the non-ICS group, nor were there differences among age groups. The results of this research do not support the hypothesis that ICSs influence the infectious load of C. pneumoniae and M. pneumoniae. ICSs did not increase C. pneumoniae or M. pneumoniae infection in the upper respiratory tract, in contrast to the effect of ICSs in causing oral candidiasis. Our data exclude the concern that there is an increase in C. pneumoniae and M. pneumoniae infections due to ICS use, the use of ICSs being the gold standard in the long-term anti-inflammatory treatment of persistent asthma in children and adults.

Early exposure and sensitization to cat and dog: Different effects on asthma risk after wheezing in infancy

Birth cohort studies have suggested that early exposure to furred pets protects from later asthma and allergy. The aim of the present study was to evaluate the association between exposure or sensitization to cat or dog in infancy, and later asthma and allergy assessed at the median ages of 4.0, 7.2 and 12.3 yr, in children who have wheezed at <24 months of age. Exposure to cat and dog in infancy was assessed by interviewing the parents. The child was considered as sensitized, if the allergen-specific IgE to cat or to dog was >or=0.35 kU/l, or if there was a positive skin test response. When the 20 children with persistent childhood asthma (doctor-diagnosed asthma at all three control visits) were compared with the other 61 children, an early exposure to dog (OR = 0.14, p = 0.034)) decreased the asthma risk and an early sensitization to cat (OR = 5.92, p = 0.008) and dog (OR = 9.33, p = 0.001) increased the asthma risk. There were less cat and dog keeping in atopic families and the effect of sensitization was, but the effect of exposure was not, robust to adjustments in multivariate analyses. The present study demonstrates, in a long-term follow-up after early wheezing, that early sensitization to cat and dog increases the risk of later asthma but early exposure to cat or dog has no such effect. Dog keeping was less frequent in atopic families, which may explain that the protective effect of early exposure to dog was lost in multivariate analyses.

Clues to Improving Management of Persistent Asthma in Children

Poor control of asthma is associated with underuse of controller medication. In a cross-sectional study, investigators in Boston examined whether poor

Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast in childhood asthma: A prospective, randomized, double-blind, double-dummy, parallel-group study

Background: Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma. Objective: This study, the PEdiatric Asthma Control Evaluation (PEACE), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children. Methods: Children with asthma (forced expiratory volume in 1 second [FEV 1] 55%–80% predicted; reversibility ≥12%) aged 6 to 14 years who were receiving only short-acting β 2-agonists entered a 2-week run-in period. Symptomatic patients (rescue use or symptoms during 4 of the last 7 days) were randomized to double-blind, double-dummy treatment with SFC 50/100 µg BID via multidose dry powder inhaler or MON 5-mg tablet QD for 12 weeks. The primary end point was change from baseline in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations. Results: Of 607 patients screened, 548 were randomized to treatment. The SFC group contained 281 patients and the MON group included 267. Demographic characteristics and baseline data were similar for both groups (mean age, 9.3 years for both groups; mean [SD] FEV 1, 1.49 [0.43] L in the SFC group and 1.48 [0.43] L in the MON group). There were more males in the MON group (179 [67%]) than in the SFC group (156 [56%]). The adjusted mean (SE) changes from baseline in morning PEF were 45.88 (2.82) L/min with SFC and 28.7 (2.86) L/min with MON (treatment difference, 17.16 L/min; 95% CI, 9.23–25.08; P < 0.001). Compared with MON, the SFC group had significantly more asthma symptom-free days (odds ratio [OR], 1.74; 95% CI, 1.07–2.82; P = 0.025), more rescue-free days (OR, 3.24; 95% CI, 2.09–5.02; P < 0.001), and more asthma-controlled weeks (difference in treatment medians over weeks 1–12, 16.77%; 95% CI, 8.3–16.77; P < 0.001). Both treatments were well tolerated, with a similar number of patients reporting AEs (SFC group, 155/281 [55%]; MON group, 153/267 [57%]); the most common AE in both groups was headache (SFC group, 66 [23%]; MON group, 72 [27%]). The mean exacerbation rates over 12 weeks (post hoc analysis) were 0.12 in the SFC group and 0.30 in the MON group (SFC/MON ratio, 0.40; 95% CI, 0.29–0.57; P < 0.001). Conclusions: In these children with uncontrolled asthma previously on short-acting β 2-agonist monotherapy (% predicted FEV 1 <80%, frequent asthma symptoms and rescue medication use), treatment with SFC was significantly more effective in improving morning PEF and other measures of asthma control and in decreasing exacerbation rates (in a post hoc analysis) than treatment with MON. The 2 drugs were both well tolerated, with similar numbers and types of AEs reported.

Safety of Inhaled Corticosteroids. Why the Variation in Systemic Adverse Effects?

Inhaled corticosteroids (ICS) are currently the mainstay of therapy in persistent childhood asthma. However, systemic adverse effects of various available agents - particularly on growth, bone metabolism, and the hypothalamicpituitary- adrenal (HPA) axis - continue to concern the families of asthmatic children, and are debated within the medical community. Although there is short- and medium-term suppressive effect of usual doses of ICS on linear growth, the findings of long term studies are reassuring, suggesting attainment of the full potential of adult height. ICS do not appear to exert significant untoward effects on bone mineral density. Measurable systemic effect of ICS by sensitive measurements of function of the HPA axis does not necessarily translate into clinically significant side effects. However, use of higher than recommended doses of ICS may on occasion lead to symptomatic adrenal insufficiency and should be of concern; there may be important differences among available compounds regarding such potential. Variation in adverse effects of ICS is explained by differences in their pharmacokinetic and pharmacodynamic properties, formulation and delivery devices, and patient factors such as degree of airway obstruction, suppressive effect of airway inflammation per se on the HPA axis, genetic factors, patient training in the use of delivery devices, and compliance.

Clinical research: Protection of the “vulnerable”?

In this age of evidence-based medicine, clinical research is critical for developing new therapeutics and determining the best way to use these therapies. To perform appropriate clinical research, researchers must adhere to ethical standards. These standards have developed in large part as a response to egregious violations of ethically appropriate behavior. In this respect certain populations have been identified as at risk of being treated inappropriately in medical research. Current ethical guidelines prohibit or severely limit what types of research can be performed involving these "vulnerable" populations. Although this might protect these populations, the lack of research on them might actually do harm in limiting their access to life-saving therapies. We explore the historical underpinnings of protecting the vulnerable populations and whether a newer ethical paradigm that would allow for protected research on these populations should be adopted by society.

Natural history of asthma: Persistence versus progression—does the beginning predict the end?

Environmental exposures during the early years and airway obstruction that develops during this time, in conjunction with genetic susceptibility, are important factors in the development of persistent asthma in childhood. Established risk factors for childhood asthma include frequent wheezing during the first 3 years, a parental history of asthma, a history of eczema, allergic rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well as allergic sensitization to aeroallergens and certain foods. Risk factors for the development of asthma in adulthood remain ill defined. Moreover, reasons for variability in the clinical course of asthma--persistence in some individuals and progression in others--remain an enigma. The distinction between disease persistence and disease progression suggests that these are different entities or phenotypes. There is currently no consensus on whether disease progression requires either airway inflammation or airway remodeling or the combination of the two. For patients with irreversible airway obstruction, inflammation might, in part, be necessary but perhaps not entirely sufficient to induce the irreversible component, some of which could be attributed to alterations in the structure of the bronchial wall. Intervening with intermittent or daily inhaled corticosteroids in high-risk infants and children does not prevent disease progression or impaired lung growth. These findings, however, might not apply to adults, and further study in adults is needed to determine the effect of inhaled corticosteroid therapy on disease progression.

Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for pediatric asthma?

According to current guidelines, inhaled corticosteroids (ICS) are the preferred primary long-term treatment for asthmatic children of all age groups, but leukotriene receptor antagonists can be considered to be an alternative treatment for mild persistent asthma. In this article, all randomized double-blind efficacy studies comparing the long-term (>4-week) treatment using a leukotriene receptor antagonist with an inhaled corticosteroid in asthmatic children were critically reviewed. In school-aged children, five reports with an adequate study design were available. All of these studies compared montelukast with inhaled fluticasone. The meta-analysis of the two main outcome measures, forced expiratory volume in 1 s (weighted mean difference, 4.6% predicted, 95% confidence interval: 3.5-5.5) and asthma control days (respectively, 5.6%, 4.3-6.9) demonstrated the superiority of fluticasone over montelukast. Many other clinical and pulmonary outcomes also consistently showed that low-dose inhaled fluticasone was more effective than montelukast in the long-term management of mild to moderate persistent asthma. A more favorable response to fluticasone over montelukast was associated with more severe disease or markers of allergic inflammation. About a quarter of patients benefited more from montelukast than fluticasone. In children under school age, no comparative studies were available. However, long-term montelukast treatment was found to be effective in placebo-controlled studies in asthmatic children aged >2 years. These findings support the present international recommendations for ICS as the preferred first-line controller therapy for mild to moderate persistent childhood asthma. If montelukast is selected as a monotherapy and asthma is not adequately controlled within 4-6 weeks, the treatment should be discontinued and the preferred medication initiated.

IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study

BackgroundTobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.MethodsIn the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.ResultsMaternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).ConclusionThis is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.

Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial

Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial

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

Chen YZ, Busse WW, Pedersen S, Tan W, Lamm CJ, O’Byrne PM. Pediatr Allergy Immunol. 2006;17:7–13 PURPOSE OF THE STUDY. To determine the long-term efficacy of regular inhaled low-dose budesonide in children aged &amp;lt;11 years with recent-onset mild-persistent asthma. STUDY POPULATION. Children aged 5 to 10 years with current symptoms of mild-persistent asthma during the 3 months preceding trial entry. Patients had no symptoms for &amp;gt;2 years before study entry and had received neither inhaled corticosteroids (ICSs) for ≥30 days nor depot corticosteroid injection in the previous year. METHODS. Patients were randomly assigned to receive once-daily budesonide 200 μg (1000 children) or placebo (974 children). Patients were followed at weeks 6 and 12 and then subsequently every 3 months for a 3-year period. Patients and their caregivers kept a record of asthma symptoms between visits. At each visit, spirometry was performed, and data were collected on medication compliance and asthma control. The primary end point was the time to the first severe asthma-related event (SARE) or introduction of corticosteroid treatment other than the study medication. RESULTS. There was a 40% relative-risk reduction of SAREs in the treatment group over the 3-year study visit. Fewer children in the budesonide group required treatment with other corticosteroids as compared with those in the placebo group (12.3% vs 22.7%). There was a trend toward decreased β2-agonist use, decreased systemic corticosteroid use, and improved lung function in the children in the treatment arm. CONCLUSIONS. The early addition of once-daily budesonide treatment in young children with mild-persistent asthma improves asthma control and lung function and decreases the risk of SAREs. REVIEWER COMMENTS. Early asthma intervention in children is a topic of much debate, particularly in the very young with mild symptoms. Oftentimes, caregivers are faced with the difficult task of deciding on the right time to initiate an ICS, and the decision may be delayed until a serious event such as hospitalization occurs. This study demonstrates the benefits of using an ICS as early intervention in children &amp;lt;11 years of age to improve lung function and decrease the risks of serious and potentially life-threatening asthma exacerbations. Unlike previous studies in pediatric populations with mild asthma, researchers with this study enrolled patients with relatively newly diagnosed asthma, perhaps before the onset of chronic irreversible inflammatory changes such as basement-membrane thickening. These findings support early intervention to improve lung function and to potentially prevent loss of lung function in hopes of improving long-term outcomes.