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Background Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement in cancer research. The aim of this prospective study was to evaluate minimal residual disease (MRD) using ddPCR in patients with chronic myeloid leukemia (CML). We also evaluated treatment outcome depending on BCR/ABL1 transcript level using ddPCR. Methods Between May 2013 and November 2014, CML patients treated with nilotinib as the first-line therapy were enrolled. BCR/ABL1 transcripts levels were evaluated using ddPCR at the first time of complete molecular response (CMR). CMR was verified by quantitative real-time polymerase chain reaction. Results We enrolled 15 patients from 7 institutions. The treatment period and median follow-up period were 45 months (range, 37–55 months) and 47 months (range, 39–61 months), respectively. The median value of BCR/ABL1 measured by ddPCR was 3.6 copies/20 μl (range, 1.2–6.8 copies/20 μl). Patients with a high level of BCR/ABL1 transcript had a greater tendency to lose the CMR during the follow-up period (0/10 (0%) for low levels vs. 2/5 (40%) for high levels, P = 0.095). In addition, patients with a low level of BCR/ABL1 transcript showed a longer duration of CMR than those with a high level (rate of sustained CMR at 2 years: 100% for low levels vs. 37.5% for high levels, P = 0.032). Conclusions We found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response. Legal entity responsible for the study The authors. Funding Novartis Pharmaceuticals Corporation. Disclosure All authors have declared no conflicts of interest.

Background Test for Respiratory and Asthma Control in Kids (TRACK) questionnaires were developed and validated in various languages to monitor respiratory control in preschool-aged children. We aimed to assess the reliability and validity of the Korean version of the TRACK questionnaire. Methods We administered the linguistically validated TRACK questionnaires to caregivers of asthmatic preschool children on two separate visits 4–6 weeks apart. Each physician graded the level of the guideline-based asthma control, assessed the timing of symptoms, and adjusted the therapeutic level at each visit. Results A total of 137 children were enrolled in the study. Cronbach's alpha was 0.65 for a questionnaire as a whole. The test-retest reliability was 0.72. The median TRACK scores were significantly different between asthma control status categories, with the lowest scores in children classified as poorly controlled and the highest in the well-controlled group (P < 0.001). They were different among groups classified according to the physician adjusted therapeutic levels, with the lowest values in children prescribed step-up therapy (P < 0.001), and according to the recency of respiratory symptoms (P < 0.001). Finally, the changes in TRACK scores between visits were highest in subjects showing improved control, followed by unchanged, and worsened control. When we applied the traditional cut-off of 80 for a well-controlled condition, a sensitivity of 75.6% and a specificity of 70.9% were calculated. Conclusion The Korean translated version of the TRACK questionnaire is valid and reliable to assess respiratory and asthma control in Korean preschool children with asthma symptoms., Graphical Abstract

Purpose Prenatal maternal stress affects offspring's atopic dermatitis (AD) development, which is thought to be mediated by the oxidative stress. We aimed to evaluate the difference in leukocyte telomere length (LTL), a marker for exposure to oxidative stress, according to the prenatal stress exposure and the later AD development. Methods From a birth cohort (the COhort for Childhood Origin of Asthma and allergic diseases) that had displayed a good epidemiologic association between the exposure to prenatal stress and AD development in the offspring, we selected 68 pairs of samples from 4 subject groups based on the level of prenatal maternal stress and later AD development. The LTL was measured from both cord blood and 1-year peripheral blood, and their LTLs were compared between subject groups. Finally, the proportion of AD development was examined in the subject groups that are reclassified based on subjects' exposure to prenatal stress and there LTL. Results Cord-blood LTL was shorter in prenatally stressed infants than in unstressed ones (P = 0.026), which difference was still significant when subjects became 1 year old (P = 0.008). LTL of cord blood, as well as one of the 1-year peripheral blood, was not different according to later AD development at 1 year (P = 0.915 and 0.174, respectively). Shorter LTL made no increase in the proportion of later AD development in either prenatally high-stressed or low-stressed groups (P = 1.000 and 0.473, respectively). Conclusions Cord-blood LTL may reflect subjects' exposure to maternal prenatal stress. However, the LTL shortening is not a risk factor of increasing AD development until the age of 1, and a longer investigation may be necessary for validation. Currently, the results doubt the role of LTL shortening as a marker for risk assessment tool for the prenatal stress associated with AD development in the offspring.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis (CRS) is a commonly diagnosed disease that has a significant impact on a child's quality of life. However, no useful biomarker is available to identify antibiotic-responsive CRS. We determined the significance of eosinophil-related markers and total IgE levels in childhood CRS with regard to antibiotic response. DESIGN AND SETTING: This was a case-control study of patients admitted to Uijeongbu St. Mary's Hospital between November 2010 and November 2011 and diagnosed with CRS. PATIENTS AND METHODS: In this analytical cross-sectional study, we identified children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotics (non-responder CRS group), children whose symptoms and radiologic abnormalities resolved after 12 weeks with appropriate antibiotics (responder CRS group), and healthy controls selected from clinic patients. Skin prick tests were performed along with serum total IgE, total eosinophil count (TEC), serum eosinophil cationic protein (ECP) level, and ImmunoCAP analysis for common allergens. RESULTS: This study included 36 responders, 22 nonresponders and 22 healthy controls. The prevalence of allergic diseases, atopy, and a family history of allergic diseases were significantly higher in the non-responder group than in the responder and control groups. TEC, ECP, and total IgE levels were significantly higher in the non-responder group than in the responder and control groups (all P

Purpose Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. Methods Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. Results A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered “taking as prescribed” was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was “Easy” or “Very easy” to use (P < 0.001). “Method of administration” was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., “Frequency of administration”). Conclusions Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.

Background The aim of this study was to investigate the safety and efficacy of dexibuprofen compared to ibuprofen. Methods This double-blind, double-dummy study enrolled patients from January 2008 to May 2009 presenting at one of five tertiary care centers in Seoul, Korea with febrile illness who were then given one of three active treatments: one dose of dexibuprofen 2.5 or 5 mg/kg (DEX 1); dexibuprofen 3.5 or 7 mg/kg (DEX 2); or ibuprofen 5 or 10 mg/kg (control) syrup. Those with a temperature

The coagulation cascade and inflammatory process are known to be associated with the pathophysiology of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We retrospectively investigated laboratory values indicating coagulopathy obtained within 24 hr from diagnosis of ALI/ARDS in 79 children who received mechanical ventilation between 2008 and 2009 and their final outcomes. Prothrombin time (PT) (P = 0.001) and activated partial thromboplastin time PTT (APTT) (P = 0.001) were more prolonged in non-survivors than survivors (mean; 1.57 vs 1.33; 63 vs 57). In multivariate analysis with stratification by oxygenation-index (< 14.5, ≥ 14.5), prolonged PT (≥ 1.46 international normalized ratio, [INR]) (hazard ratio; 2.043, 1.027-4.064) was associated with lower non-pulmonary-organ-failure-free survival rate (FFS), and prolonged APTT (≥ 50 seconds) (2.062, 1.031-4.121; 2.422, 1.227-4.781) was associated with lower overall survival rate (OS) and lower FFS. In stratification by ventilation-index (< 40, ≥ 40), prolonged PT (2.232, 1.095-4.540; 2.177, 1.092-4.342) and prolonged APTT (2.574, 1.230-5.386; 3.089, 1.500-6.360) were associated with lower OS and lower FFS. Prolonged PT and APTT are associated with mortality in mechanically ventilated children with ALI/ARDS. We suggest PT and APTT as prognostic factors of ALI/ARDS in children.

Chronic rhinosinusitis (CRS) is a commonly diagnosed disease that has a significant impact on a child's quality of life. However, no useful biomarker is available to identify antibiotic-responsive CRS. We determined the significance of eosinophil-related markers and total IgE levels in childhood CRS with regard to antibiotic response.This was a case-control study of patients admitted to Uijeongbu St. Mary's Hospital between November 2010 and November 2011 and diagnosed with CRS.In this analytical cross-sectional study, we identified children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotics (non-responder CRS group), children whose symptoms and radiologic abnormalities resolved after 12 weeks with appropriate antibiotics (responder CRS group), and healthy controls selected from clinic patients. Skin prick tests were performed along with serum total IgE, total eosinophil count (TEC), serum eosinophil cationic protein (ECP) level, and ImmunoCAP analysis for common allergens.This study included 36 responders, 22 nonresponders and 22 healthy controls. The prevalence of allergic diseases, atopy, and a family history of allergic diseases were significantly higher in the non-responder group than in the responder and control groups. TEC, ECP, and total IgE levels were significantly higher in the non-responder group than in the responder and control groups (all P.05). Multiple linear regression analysis showed that no response to appropriate antibiotics and TEC was positively associated with ECP concentration.These findings suggest that there is a high prevalence of allergic diseases in the non-responder group, that the TEC and ECP levels in the non-responder group are significantly higher than those in the responder group and controls, and that no response to antibiotics may be due to eosinophilic inflammation. The measurement of serum ECP may be useful in monitoring the progress of childhood CRS with regard to antibiotic response.

This study was designed to investigate the possible role of IFN-γ in eosinophil degranulation that occurs during respiratory syncytial virus (RSV) bronchiolitis.Sixty-seven infants, 2-24 months old and hospitalized with their first episode of acute RSV bronchiolitis, were selected for this study. Eosinophil-active cytokine and chemokine profiles in nasal lavage supernatants taken within the first 48 h of admission were determined by a multiplex bead array system (Luminex). Comparisons were made with control (Control group) subjects (n = 20).Nasal IFN-γ levels were significantly higher (P0.0001) in RSV bronchiolitis (median = 4.4 pg/ml) infants compared to controls (0.0 pg/ml). IFN-γ levels correlated significantly with the levels of nasal eotaxin (r = 0.566, P0.0001), RANTES (r = 0.627, P0.0001), GM-CSF (r = 0.849, P0.0001), and EDN (r = 0.693, P0.001). Nasal interleukin (IL)-4, IL-5, and IL-13 were below sensitivity levels in most RSV bronchiolitis and control subjects.These results suggest that IFN-γ may play an important role in eosinophilic inflammation in RSV bronchiolitis.

Background Nonasthmatic subjects with allergic rhinitis often have bronchial hyperresponsiveness (BHR), characteristic of asthma. The presence and degree of atopy is suggested to be important for BHR in patients with asthma. We aimed to assess BHR to methacholine (direct stimulus) and to adenosine 5′-monophosphate (AMP; indirect stimulus) in preschool children with allergic rhinitis and to investigate their relationship with the degree of atopy. Methods Methacholine and AMP bronchial challenges were performed in preschool children with allergic rhinitis (n = 96), using a modified auscultation method. The end point concentration, resulting in audible wheezing and/or oxygen desaturation, was determined for each challenge. The degree of atopy was assessed using serum total IgE levels, the number of positive skin-prick tests, and atopic scores (sum of graded wheal size). Results BHR to methacholine (end point concentration, ≤ 8 mg/mL) and to AMP (end point concentration, ≤ 200 mg/mL) was observed in 32 (33.3%) and 26 (27.1%) subjects, respectively. No significant relationship was observed between BHR to methacholine and any atopy parameter. In contrast, the atopic scores were higher in the AMP–BHR+ group compared with the AMP–BHR− group, and a significant association was found between the degree of atopic scores and the frequency of BHR to AMP (score for trend, p = 0.006). Such a relationship was not observed for serum total IgE levels and the number of positive SPTs. Conclusion BHR to methacholine and BHR to AMP were detected in a significant proportion of preschool children with allergic rhinitis. The degree of atopy in terms of atopic scores seems to be an important factor for BHR to AMP but not for BHR to methacholine.

Exercise and inhaled mannitol are thought to cause bronchoconstriction through a similar mechanism in asthma. The response to exercise becomes refractory with repeated challenges. This study aimed to investigate whether repeated challenge with mannitol induces refractoriness, as with exercise. Forty-one children with asthma underwent two consecutive dose–response mannitol challenges (Phase 1); the second challenge proceeded after recovery (FEV1: 95% or more of baseline value) from the first. The response to mannitol was expressed as a provocative dose causing a 15% fall in FEV1 (PD15) and the response–dose ratio (RDR) (% fall in FEV1/cumulative dose). In 18 subjects who were deemed to have mannitol refractoriness in Phase 1, a mannitol challenge was performed before and after a methacholine challenge (Phase 2). In Phase 1, the time taken for the FEV1 to recover after the first mannitol challenge ranged from 20 to 100 min with a median of 50 min. In the 23 subjects with a measurable mannitol PD15 in both challenges, the geometric mean (95%CI) PD15 in the second challenge (163 mg [114–232]) was significantly higher than that in the first challenge (66 mg [50–88], P

Background. Airway remodeling has been assumed to cause bronchial hyperresponsiveness (BHR). A low postbronchodilator FEV1/FVC ratio has been suggested to be a functional surrogate marker of airway remodeling in asthma. BHR is commonly assessed by bronchial challenges using direct or indirect stimuli. Objective. The aim of this study was to compare BHR to methacholine and adenosine 5′-monophosphate (AMP) with regard to their relationship with a marker of airway remodeling in children with asthma. Methods. Methacholine and AMP challenge tests were performed in 129 children with asthma, aged 12 years, and a provocative concentration causing a 20% fall in FEV1 (PC20) was calculated for each challenge. All subjects also underwent pre- and postbronchodilator spirometry. A postbronchodilator FEV1/FVC ratio below the lower limits of normal was used as a marker of airway remodeling. Results. A low postbronchodilator FEV1/FVC ratio was found in 17 subjects (13.2%). These subjects had a significantly lower methacho...

To cite this article: Suh DI, Lee JK, Kim CK, Koh YY. Methacholine and adenosine 5′-monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma. Pediatr Allergy Immunol 2011; 22: e101–e106. Abstract The relationship between atopy and bronchial hyperresponsiveness (BHR), both key features of asthma, remains to be clarified. BHR is commonly evaluated by bronchial challenges using direct and indirect stimuli. The aim of this study was to investigate the degree of BHR to methacholine (direct stimulus) and adenosine 5′-monophosphate (AMP) (indirect stimulus) according to the presence and degree of atopy in children with asthma. We performed a retrospective analysis of data from 120 children presenting with a diagnosis of asthma. These children were characterized by skin-prick tests (SPTs), spirometry and bronchial challenges with methacholine and AMP. Atopy was defined by at least one positive reaction to SPTs, and its degree was measured using serum total IgE levels, number of positive SPTs and atopic scores (sum of graded wheal size). A provocative concentration causing a 20% decline in FEV1 (PC20) was determined for each challenge. Patients with atopy(n = 94) had a significantly lower AMP PC20 than non-atopic patients (n = 26), whereas methacholine PC20 was not different between the two groups. Among the patients with atopy, there was no association between methacholine PC20 and any atopy parameter. In contrast, a significant association was found between AMP PC20 and the degree of atopy reflected in serum total IgE, number of positive SPTs and atopic scores (anova trend test, p = 0.002, 0.001, 0.003, respectively). AMP responsiveness was associated with the presence and degree of atopy, whereas such a relationship was not observed for methacholine responsiveness. These findings suggest that atopic status may be better reflected by bronchial responsiveness assessed by AMP than by methacholine.

nonasthmatic patients with allergic rhinitis often have bronchial hyperresponsiveness (BHR). Not only the presence but also the degree of atopy are important factors in BHR of patients with asthma. BHR is commonly evaluated by bronchial challenges using direct or indirect stimuli.to assess BHR to methacholine (direct) and to adenosine monophosphate (AMP) (indirect) in children with allergic rhinitis and to compare their relationships with the degree of atopy.methacholine and AMP challenges were performed in 88 children with allergic rhinitis, and a provocative concentration causing a 20% decrease in forced expiratory volume in 1 second (PC(20)) was calculated for each challenge. The degree of atopy was measured using serum total IgE levels, number of positive skin prick test results, and atopic scores (sum of graded wheal size).BHR to methacholine (PC(20)8 mg/mL) and to AMP (PC(20)200 mg/mL) was observed in 22 (25%) and 30 (34%) patients, respectively. No association was found between BHR to methacholine and any atopy parameter. In contrast, serum total IgE levels and atopic scores were higher in the group with BHR to AMP than in the group without BHR to AMP. Furthermore, a significant association was found between the degree of these 2 parameters and BHR to AMP (score for trend, P.001 and P = .03, respectively).both BHR to methacholine and BHR to AMP were detected in a significant proportion of children with allergic rhinitis. The degree of atopy seems to be an important factor in BHR to AMP but not in BHR to methacholine.

Bronchodilator response (BDR) is assessed to estimate the reversibility of airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma and is usually measured by means of bronchial challenges using direct or indirect stimuli. The aim of the present study was to compare BHR to methacholine (direct) and that to adenosine 5'-monophosphate (AMP) (indirect) with regard to their relationships to BDR in asthmatic children. Methacholine and AMP challenge tests were performed on 138 children with mild-to-moderate asthma, and the provocative concentration causing a 20% decline in forced expiratory volume in 1 s (FEV₁) (PC₂₀) was determined for each challenge. BDR was calculated as the change in FEV(1), expressed as a percentage of the initial value, after inhalation of 400 μg salbutamol. Methacholine PC₂₀ correlated significantly but weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and strong correlation between AMP PC₂₀ and BDR (r = -0.489; p = 0.000). For AMP PC₂₀, the relationship was closer than for methacholine PC₂₀ (p = 0.024 for comparison between correlation coefficients). The same figures were observed when BDR was expressed as a percentage of the predicted value. A stronger correlation of BDR with AMP PC₂₀ than with methacholine PC₂₀ suggests that BDR may be better reflected by BHR as assessed by AMP challenge than by methacholine challenge.

Eosinophil numbers and eosinophil cationic protein (ECP) levels have been proposed as markers of disease activity; however, the usefulness of eosinophil-derived neurotoxin (EDN)--another eosinophil granular protein--as a marker in pediatric asthma has not been established.The authors compared the concentrations of blood eosinophil counts (TECs), serum ECP, and serum EDN to asthma symptom severity in young children.Forty-three young children with asthma (Asthma group: mean age, 2.9 years; range, 1.4-5.0 years) were evaluated during both the acute and stable phases of disease. Asthma severity was measured using a symptom-scoring technique, and serum eosinophil indices (EDN and ECP levels and TECs) were determined. Nineteen age-matched controls (Control group: mean age, 2.7 years; range, 1.0-5.0 years) were used for comparison.Levels of serum EDN, serum ECP, and TECs were significantly higher in children with acute asthma compared with Controls (p.0001). However, in stable asthma only EDN and ECP levels differed significantly when compared to Controls (p.0001 and p.001, respectively). When comparing acute and stable phases, EDN and TECs differed significantly (p.0001), whereas ECP did not. Symptom scores correlated significantly with EDN (r = 0.850, p0.0001), ECP (r = 0.374, p0.01) and TECs (r = 0.457, p0.01) in acute asthma patients. When symptom scores were divided into three subgroups based on severity, only EDN levels showed significant differences amongst the three groups.These findings suggest that serum EDN is a useful marker for identifying disease activity in children with asthma. EDN levels may better reflect disease severity than ECP levels or total eosinophil counts.

Eosinophils play a central role in the inflammatory response associated with bronchial asthma (1). The recruitment of eosinophils into sites of airway inflammation is a complex process that potentially is regulated by various cytokines, including interleukin (IL)-3, IL-5, and granulocyte macrophage colony stimulating factor (GM-CSF), and by various chemokines, including eotaxin, regulated on activation, normal T-cell expressed and secreted (RANTES), and monocyte chemoattractant protein-3 (MCP-3) (2). Cooperation of the eosinophilic cytokines and chemokines seems to be necessary for eosinophil recruitment in the airways (3). The striking feature of the eosinophilic inflammatory reaction is the marked deposition of eosinophil degranulation products, such as eosinophil-derived neurotoxin (EDN) and eosinophil-cationic protein (ECP), and has been documented in asthma (4). However, the precise mechanisms of eosinophil degranulation in vivo are still poorly understood. An increase in Th2 cytokine production has been found in asthma. The cytokine IL-5, a key Th2 cytokine in eosinophil biology, is involved in eosinophil differentiation, maturation, and migration. IL-5 has been shown to be chemotactic for eosinophils in vitro (5). Indeed, an increase in IL-5 production in the airways has been found in acute exacerbation of asthma (6). However, the role of IL-5 in human asthma is not as strong as previously suspected and is currently being reevaluated. Flood-Page et al. (7) observed in an allergen-challenged asthma model that anti-IL-5 treatment produced a weak reduction in airway eosinophils and no change in the level of eosinophilic degranulation. The results from the allergen-challenged asthma model and acute asthma exacerbation do not necessarily reflect events in the natural course of asthma (high dose vs. low dose of allergen exposure). Furthermore, in pediatric asthma, the role of IL-5 in eosinophilic airway inflammation is not fully understood. Several CC chemokines, such as eotaxin, RANTES, and MCP-3, have been implicated in eosinophil recruitment and degranulation. Eotaxin seems specific for eosinophil chemoattraction (8); however, RANTES and MCP-3 are active on eosinophils as well as other leukocytes (2). CC chemokines bind to a CCR3 receptor, a chemokine receptor highly expressed on eosinophils, suggesting their key role in eosinophilic inflammation (9). The aim of this study was to evaluate the production of IL-5, the predominant eosinophil-active Th2 cytokine (10), and eotaxin, the most important eosinophil chemoattractive CC chemokine (5), in airways of children with stable asthma (SA). We also examined correlations of IL-5 and eotaxin with eosinophil indices (percentage eosinophils and EDN and ECP levels).

There are a number of useful direct airway sampling procedures to help diagnose and monitor asthma in patients. However, non-invasive techniques are the ideal, especially in children, given the necessity of safe and repeatable measurements to monitor treatment efficacy and disease progression. Bronchoalveolar lavage (BAL) may be too invasive for clinical use in children, while questions still surround the utility of induced sputum (IS). More novel techniques, such as fractional exhaled nitric oxide (FE(NO)) and exhaled breath condensate (EBC), are still unproven. Eosinophilic airway inflammation is a major feature of childhood asthma, and it has been revealed as a major treatment target with inhaled corticosteroids. Moreover, treatment protocols governed by sputum eosinophil counts may be more efficacious - by reducing the frequency and severity of exacerbations - than treatment based on clinical symptoms and other traditional objective measures of lung function. The selection of an appropriate airway inflammation monitoring technique must take everything into consideration, including safety, reproducibility, repeatability, sensitivity to treatment, and the overall clinical/research goals.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain. WHAT THIS STUDY ADDS • Dexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children. AIM To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI). METHODS The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group. RESULTS In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05). CONCLUSIONS Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children.

Summary Background Both bronchial responsiveness (BR) and peak expiratory flow (PEF) variability are increased in asthma. PEF variability is presumed to reflect the degree of BR in asthma. BR is commonly assessed by bronchial challenges using direct or indirect stimuli. Objective The aim of this study was to compare methacholine and adenosine 5′-monophosphate (AMP) responsiveness with regard to their relationships with PEF variability in children with asthma. Methods Methacholine and AMP challenge tests were performed in 79 children with mild to moderate asthma, and a provocative concentration causing a 20% decline in forced expiratory volume in 1 s (PC20) was calculated for each challenge. Subjects recorded PEF each morning and each evening for 14 consecutive days. PEF variability was expressed as amplitude percentage mean (amp%mean; high PEF minus low PEF on each day, expressed as a percentage of their mean, averaged over 14 days), and as the lowest percentage highest (low%high; the lowest PEF expressed as a percentage of the highest PEF recorded over the period). Results Methacholine PC20 correlated significantly but weakly with both indices of PEF variability (amp%mean: r=−0.285, P=0.011; low%high: r=0.238, P=0.034). However, there was a significant and strong correlation between AMP PC20 and both amp%mean (r=−0.583, P=0.000) and low%high (r=0.496, P=0.000). For AMP PC20, the correlations were stronger than for methacholine PC20 (comparison of correlation coefficients with amp%mean: P=0.021; with low%high: P=0.063). Conclusion Both methacholine PC20 and AMP PC20 correlated significantly with PEF variability. However, the stronger correlations for AMP PC20 than for methacholine PC20 suggest that PEF variability may be better reflected by BR assessed by AMP than by methacholine.

A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC.Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20)16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups.There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%).Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.

Aim: To investigate aspiration risks associated with bronchiolitis in infants using the lipid-laden macrophage index (LLMI) from laryngeal lavages. Methods: Laryngeal lavages from 29 infants with acute bronchiolitis caused by respiratory syncytial virus were evaluated (acute stage). Repeated studies were then performed at 3–4 weeks after the initial study (remission stage). Lavage cell counts and differentials were determined. The amount of lipid per single macrophage was evaluated and the LLMI was determined by evaluating 100 cells. In addition, 24-h pH monitoring (pHm) was performed in 16 patients. Results: The LLMIs in the acute stage were significantly higher than those in the remission stage (p < 0.05). The neutrophil percentage of the laryngeal lavage correlated significantly with the LLMI (r = 0.707, p < 0.0001) during the acute stage of bronchiolitis. When patients were divided into pHm-positive (n = 5) and pHm-negative (n = 11) subgroups, a significant decrease in LLMI between acute and remission stages was noted among the pHm-positive (p < 0.01) subgroup, but not in the pHm-negative subgroup. Conclusion: These findings suggest that there is a transient increased LLMI in patients with bronchiolitis, which could be caused by gastroesophageal reflux.

Background: Cysteinyl leukotrienes (CysLTs), including LTC4, LTD4 and LTE4, are pivotal mediators in the pathophysiology of asthma. Aim: To determine whether CysLT levels are increased in the lower airways of children with respiratory syncytial virus (RSV) bronchiolitis, as they are in asthmatic children, and to investigate a possible heterogeneity in CysLT levels in children with RSV bronchiolitis. Methods: Bronchoalveolar lavage (BAL) fluids were obtained from children with acute RSV bronchiolitis (n = 20), from children with acute asthma who had no identifiable virus infection (n = 16) and from control subjects (n = 14). BAL cell counts and differentials were determined, and the concentrations of CysLTs were measured by ELISA. Results: CysLT levels in the asthma (70.6 ± 52.7 pg/ml, p < 0.001) and bronchiolitis groups (21.9 ± 23.3 pg/ml, p < 0.05) were significantly higher than in the control group (8.7±5.2 pg/ml). Among bronchiolitis subjects, the eosinophil-positive subgroup (n = 6) showed significantly higher CysLT levels (49.0±26.7 pg/ml, p = 0.001) than the control group, but this was not observed in the eosinophil-negative subgroup (n = 14, 10.3±6.3 pg/ml, p = 0.47). Conclusion: CysLT levels are increased in the lower airways during RSV bronchiolitis, although their intensities are lower than those in acute asthma. Among bronchiolitis subjects, high CysLT producers could be distinguished from low CysLT producers by the presence of eosinophilia in BAL fluids, suggesting a pathophysiological heterogeneity in RSV bronchiolitis.

The percentage decrease in forced vital capacity (FVC) at the methacholine PC(20) (Delta FVC) has been proposed as a surrogate marker of maximal airway response. The aim of this study was to compare the Delta FVC between patients with cough-variant asthma (CVA) and those with classic asthma (CA). We performed a retrospective analysis of methacholine challenge test data from 47 children who were diagnosed as having CVA and from 75 children who had CA of mild severity. The mean (+/- SD) Delta FVC was significantly (p = 0.001) lower in the CVA group (14.7 +/- 3.4%) compared with the CA group (17.1 +/- 4.4%), whereas PC(20) was not different between the two groups. Our results suggest that CVA is associated with a lower level of maximal airway response than CA.

BACKGROUND Cysteinyl leukotrienes (CysLTs), including LTC4, LTD4 and LTE4, are pivotal mediators in the pathophysiology of asthma. AIM To determine whether CysLT levels are increased in the lower airways of children with respiratory syncytial virus (RSV) bronchiolitis, as they are in asthmatic children, and to investigate a possible heterogeneity in CysLT levels in children with RSV bronchiolitis. METHODS Bronchoalveolar lavage (BAL) fluids were obtained from children with acute RSV bronchiolitis (n = 20), from children with acute asthma who had no identifiable virus infection (n = 16) and from control subjects (n = 14). BAL cell counts and differentials were determined, and the concentrations of CysLTs were measured by ELISA. RESULTS CysLT levels in the asthma (70.6 +/- 52.7 pg/ml, p < 0.001) and bronchiolitis groups (21.9 +/- 23.3 pg/ml, p < 0.05) were significantly higher than in the control group (8.7 +/- 5.2 pg/ml). Among bronchiolitis subjects, the eosinophil-positive subgroup (n = 6) showed significantly higher CysLT levels (49.0 +/- 26.7 pg/ml, p = 0.001) than the control group, but this was not observed in the eosinophil-negative subgroup (n = 14, 10.3 +/- 6.3 pg/ml, p = 0.47). CONCLUSION CysLT levels are increased in the lower airways during RSV bronchiolitis, although their intensities are lower than those in acute asthma. Among bronchiolitis subjects, high CysLT producers could be distinguished from low CysLT producers by the presence of eosinophilia in BAL fluids, suggesting a pathophysiological heterogeneity in RSV bronchiolitis.

AIM: Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it is also frequently demonstrated by children and adults with chronic obstructive lung diseases. BHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in young children with post-infectious bronchiolitis obliterans (BO). METHODS: Methacholine and adenosine 5'-monophosphate (AMP) bronchial challenges were performed on preschool children with post-infectious BO (n=18), those with asthma (n=23) and in controls (n=20), using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. RESULTS: A positive response to methacholine (an endpoint concentration < or = 8 mg/ml) was observed in 88.9% (16/18) of the patients with post-infectious BO, but a positive response to AMP (an endpoint concentration < or = 200 mg/ml) was observed in only 22.2% (4/18). All patients with asthma responded positively to methacholine, and most (21/23, 91.3%) of them also responded positively to AMP. The majority of the controls were insensitive to both challenges. CONCLUSION: BHR to methacholine is a frequent, but by no means universal, finding in young children with post-infectious BO, but is usually not accompanied by BHR to AMP.

The toxicity of formulations of oil of cassia, Cinnamomum cassia Blume, (20 and 50 g L(-1) sprays and 100% oil-based fumigant) to adult Dermatophagoides farinae Hughes and D. pteronyssinus Trouessart was examined using contact and vapour-phase toxicity bioassays. Results were compared with the lethal activity of three commercial acaricides: benzyl benzoate, dibutyl phthalate and diethyl-m-toluamide (deet). The contact toxicity of cassia oil to both dust mite species was comparable with that of benzyl benzoate but was higher than that of the other two acaricides. Sprays containing 20 and 50 g L(-1) cassia oil were effective against both mite species when applied to fabric, glass, paper, plastic, tin or wood substrates. Applications of the 50 g L(-1) spray to different space volumes and surface areas determined that 50-60 mg of cassia oil was needed to control dust mites in 3.4 m(3) or in 1 m(2). In tests with fumigant devices, toxicity varied according to the thickness of non-woven fabric covering the device, the exposure time, the number of fumigant devices used and the volume of the space sprayed. Fumigant toxicity to adult D. pteronyssinus was more pronounced with devices enclosed in thinner (40 microm) versus thicker (45 or 50 microm) non-woven fabric covers. A single fumigant device with a 40 microm thick non-woven fabric cover resulted in substantial control in a space of 0.05 m(3) but exhibited only moderate to weak control in spaces >or= 0.097 m(3) at 4 days after application. Two fumigant devices gave 88% mortality in a space of 1.73 m(3). Cassia oil applied as sprays or in fumigant devices appears to provide effective protection of humans from house dust mites.

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it is also frequently present in children and adults with chronic obstructive lung diseases. Bronchopulmonary dysplasia (BPD) is a chronic lung disease, most commonly developing after mechanical ventilation and oxygen therapy in premature infants. BHR is usually measured by bronchial challenges, using direct or indirect stimuli. The aim of this study was to evaluate BHR to direct and indirect stimuli in young children with BPD. Methacholine and adenosine 5′-monophosphate (AMP) bronchial challenges were performed on preschool children with BPD (n = 19), using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. The results obtained were then compared with those of asthmatic (n = 25) and control (n = 23) preschool children. A positive response to methacholine (endpoint concentration, ≤8 mg/ml) was observed in 89.5% (17/19) of patients with BPD, but a positive response to AMP (endpoint concentration, ≤200 mg/ml) was observed only in 21.1% (4/19). All patients with asthma responded positively to methacholine, and most (23/25, 92.0%) of them also responded positively to AMP. The majority of controls were unresponsive to both challenges. BHR to methacholine is a frequent finding in preschool-age survivors of BPD, but is usually not accompanied by BHR to AMP. This suggests that most patients with BPD do not have the inflammatory airway response which is characteristic of asthmatic patients. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc.

Background: In asthmatic subjects, not only airway sensitivity but maximal airway response are increased on the dose-response curve to methacholine, and peak expiratory flow (PEF) variability is closely related to airway hypersensitivity and maximal airway response. Objective: The aims of this study were to compare the prevalence and the level of maximal response plateau between patients with cough-variant asthma (CVA) and those with classic asthma (CA), and to examine the relationship between airway hypersensitivity or maximal airway response and PEF variability in patients with CVA. Methods: A high-dose methacholine inhalation test was performed on 83 patients with CVA and on 83 patients with CA matched for provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 ). PEF was recorded in the morning and evening for 14 consecutive days in 78 CVA patients, and the amplitude percentage mean was used to express the diurnal PEF variation. Results: Fifty-two CVA subjects (62.7%) but only 33 CA subjects (39.8%) showed a maximal response plateau. This difference was significant after correction by the Bonferroni method (corrected p = 0.024). Subjects in the CVA and CA groups showing a plateau had significantly different plateau levels (38.0 ± 5.9% vs 42.9 ± 3.9%, corrected p = 1.0 × 10 -4 ). In patients with CVA, no significant relationship was found between PC 20 and PEF variability. However, the absence of a maximal response plateau and a higher plateau level were associated with increased PEF variability. Conclusions: Maximal airway response may be an important confounder in the relationship between airway hypersensitivity and the clinical expression of asthma. The identification of a maximal response plateau and the level of this plateau in patients with CVA provide information relevant to PEF variability.

Background Results of epidemiologic studies have shown that childhood atopy is probably a hereditary disorder. In the atopic population, some individuals are sensitized to only 1 class of allergens (monosensitized), whereas others are sensitized to more than 1 class of allergens (polysensitized). Objective To investigate whether atopy and its profile (monosensitization/polysensitization) tend to coincide in sibling pairs. Methods We evaluated sensitization to 5 classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) using skin prick testing in 564 children with symptoms suggestive of allergic diseases (index children) and their paired siblings. Results The frequency of sibling atopy was highest (56.8%) for polysensitized index children (n = 222), intermediate (45.4%) for monosensitized index children (n = 196), and lowest (30.8%) for nonsensitized index children (n = 146). The proportion of polysensitization among atopic siblings was significantly higher for polysensitized (47.6%) than for monosensitized (32.6%) index children. Polysensitized index children were found to more frequently have polysensitized siblings (27.0%) than were monosensitized index children (14.8%), with an odds ratio of 2.13 (95% confidence interval, 1.30-3.49), whereas the likelihood of having a monosensitized sibling was similar for monosensitized and polysensitized index children. Conclusion These data suggest a coincidence of atopy and its profile in terms of monosensitization and polysensitization in sibling pairs, although the relative importance of genetic and environmental influences requires further study.

Background: Early exposure to high quantities of allergen has an important role in the incidence of atopic sensitization. In fact, subjects sensitized to house dust mites (HDMs) have a significantly higher proportion of births in the season when HDMs are most abundant. Objective: The aim of this study was to investigate whether birth month patterns differ for asthmatic patients sensitized only to HDMs and for those sensitized to HDMs and other allergen(s). Methods: Among 2225 patients with asthma, aged 10–16 years, 1642 sensitized to HDMs were identified by skin prick testing. This group was composed of patients sensitized only to HDMs (n = 715) and patients sensitized to HDMs and other allergen(s) (n = 927). The birth month distributions of the group of HDM-sensitive asthmatics or its subgroups were compared with that of a reference population (total live births in the same years as the studied subjects). The risk ratio of a given birth month in relation to all the other months was calculated as an odds ratio (OR) with the corresponding 95% confidence interval (CI). Results: A significant difference in birth month distribution was observed for HDM-sensitive asthmatics (χ2 = 23.6, P = 0.015), with higher rates of birth in August (OR: 1.23, 95% CI: 1.04–1.46) and September (1.24, 1.04–1.46). When the two subgroups were analyzed separately, significantly more births were noted in August (1.34, 1.06–1.71) and September (1.34, 1.05–1.70) for those sensitized only to HDMs, whereas no such birth month preference was observed for those sensitized to HDMs and other allergen(s). Conclusions: The HDM-positive asthmatics showed a greater proportion of births in August and September, which correspond to high HDM exposure. However, this birth month pattern was evident in asthmatic-sensitive only to HDMs, but was not observed in those sensitive to HDMs and other allergen(s).

Summary Objective In this study, we measured the levels of eosinophil cationic protein (ECP) and interleukin (IL)-8 in bronchoalveolar lavage (BAL) fluid from patients with acute asthma and acute bronchiolitis, to determine any similarities or dissimilarities in the profiles of these biochemical markers in the two diseases. Methods BAL fluids were obtained from children with acute asthma (n=16), infants with acute bronchiolitis caused by respiratory syncytial virus (n=18), and control subjects (n=14). Children with asthma were selected to be free of viral infection. BAL cell counts and differentials were determined, and ECP and IL-8 levels were measured by radioimmunoassay and ELISA, respectively. Results ECP levels in BAL fluids were significantly higher in the asthma group than in the bronchiolitis (P

Background: Recently, the incidence of atypical presentation of chronic lung disease (CLD) that develops in infants without a history of preceding respiratory distress syndrome (RDS) is increasing. Therefore, the clinical characteristics of CLD without RDS in comparison with CLD with RDS were assessed. Methods: Prospective cohort analysis was done from 117 very low-birthweight infants who were born in Seoul National University Hospital and survived more than 36 weeks postmenstrual age (PMA). Results: Of the 117 infants analyzed, CLD developed in 44 infants (38%). Among these 44 infants, CLD with RDS developed in 27 infants (23%) and CLD without RDS developed in 17 infants (15%). Each type of CLD was subgrouped according to the presence of chorioamnionitis (CA): RDS+CA+ CLD (n = 8) and RDS+CA– CLD (n = 19); and RDS–CA+ CLD (n = 12) and RDS–CA– CLD (n = 5). There were no significant differences in the demographic characteristics between CLD with RDS and CLD without RDS. Chorioamnionitis was significantly more common in CLD without RDS, while patent ductus arteriosus was more common in CLD with RDS. Although the severity of initial respiratory failure was not greater than that of CLD with RDS, CLD without RDS showed a gradually increasing chronic oxygen requirement pattern. Chronic oxygen requirement pattern showed that infants with RDS+CA+CLD required the highest concentrations of oxygen not only initially but also thereafter until the 28th day of life and 36 weeks PMA. Conclusions: Although CLD without RDS was still less common than CLD with RDS, it comprised over a third of all cases of CLD in our study. Clinical characteristics and chronic oxygen requirement pattern of CLD without RDS seems to be less severe than those of CLD with RDS. Our data suggest that CLD without RDS may be developed by causes other than initial acute lung injury. Chorioamnionitis may be one of antecedents of CLD without RDS.

The aim of this study was to investigate whether bronchial hyperresponsiveness in adolescents with long-term asthma remission is associated with increased peak expiratory flow (PEF) variability and/or increased bronchial response to exercise (BRE). Twenty-nine adolescents with asthma remission (neither symptoms nor any medication used during the previous two years), but with persistent methacholine hyperresponsiveness (PC2018 mg/mL; remission group), 29 methacholine PC20-matched adolescents with symptomatic asthma (symptomatic group), and 20 healthy subjects (control group) were studied. Subjects recorded PEF twice daily for 14 days and PEF variability, expressed as amplitude % mean, was calculated. Subjects also underwent a standardized exercise challenge; BRE was defined as a maximal % fall in FEV1 within 30 min after exercise. The mean (+/- SD) PEF variations in the symptomatic group and in the remission group were 12.10 +/- 6.35% and 10.02 +/- 4.73%, respectively, which were significantly higher than that (5.94 +/- 2.44%) of the control group. On the other hand, the degree of BRE (7.36 +/- 3.85%) in the remission group was significantly lower than that (22.31 +/- 10.50%) of the symptomatic group, and similar to that (5.98 +/- 2.70%) of the control group. Methacholine hyperresponsiveness in asthma remission during adolescence is associated with increased PEF variability but not with increased BRE.

The mechanisms responsible for persistent bronchial hyperresponsiveness (BHR) in adolescents with long-term asthma remission are poorly understood.To determine whether BHR in adolescents with asthma remission is associated with peripheral blood eosinophilia, increased serum levels of eosinophil cationic protein (ECP), or both findings.We classified 51 adolescents with long-term asthma remission (neither asthma-related symptoms nor medication during the previous 2 years) into 28 BHR-positive patients (methacholine PC20 [provocative concentration causing a 20% decrease in forced expiratory volume in 1 second]18 mg/mL) and 23 BHR-negative patients. The peripheral blood eosinophil counts and serum ECP concentrations were compared between these 2 groups. Twenty-eight patients with symptomatic asthma (symptomatic group), matched for methacholine PC20 level with study subjects in the BHR-positive remission group, and 28 healthy adolescents (control group) were also studied.No significant differences in the peripheral blood eosinophil counts (262.1 +/- 117.0/microL vs 253.9 +/- 165.0/microL) and the serum ECP levels (15.6 +/- 10.0 microg/L vs 15.8 +/- 11.9 microg/L) were found between the BHR-positive and BHR-negative remission groups, respectively. The BHR-positive remission group differed from the symptomatic group (372.9 +/- 190.3/microL, P0.05; 26.6 +/- 11.3 microg/L, P0.01) in both blood indices but resembled the control group (214.6 +/- 118.6/microL and 12.1 +/- 4.8 microg/L; both, no significant difference).BHR in adolescents with long-term asthma remission is not associated with peripheral blood eosinophilia or an increase in serum ECP concentration. This finding suggests that the mechanism underlying BHR in this clinical setting may differ from that in symptomatic asthma.

Background: The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma. Objective: The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence. Methods: One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 ) and the bronchial responsiveness (BR) index were calculated for each individual. Results: Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC 20 Conclusion: Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.

Background Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these subjects. BHR in asthma is characterized by an increase in sensitivity and in maximal airway response to bronchoconstrictor stimuli. Objective The aims of this study were to compare the profiles of maximal airway response between adolescents with asthma remission and adolescents with symptomatic asthma to a similar degree of airway hypersensitivity, and to determine whether maximal airway response in adolescents with asthma remission is reduced by prolonged treatment with inhaled corticosteroids. Methods A high-dose methacholine inhalation test was performed in 46 adolescents with long-term asthma remission (remission group) and 44 adolescents with symptomatic asthma (symptomatic group). Subjects exhibiting a maximal response plateau in the remission group were administered inhaled budesonide (400 μg bid, budesonide/remission group, n = 15) or identical placebo (placebo/remission group, n = 15) for 6 months, and the subjects in the symptomatic group were administered the same regimen of budesonide (budesonide/symptomatic group, n = 17). The plateau level was measured after 3 months and 6 months of treatment. Results Thirty-four subjects (73.9%) in the remission group featured a maximal response plateau on the dose-response curve to methacholine, whereas 19 subjects (43.2%) in the symptomatic group had a plateau (p = 0.003). In neither the placebo/remission group nor the budesonide/remission group did the plateau level change significantly over the 6-month period, whereas budesonide markedly decreased the level in the budesonide/symptomatic group. Conclusion The difference in frequency of detection of a plateau between the remission group and the symptomatic group, as well as the difference in its response to treatment with budesonide between the two groups, suggests that inflammatory changes impact the maximal airway response in symptomatic asthmatic adolescents but not in adolescents with asthma remission.

The extent of improvement in bronchial hyperresponsiveness (BHR) with corticosteroids varies considerably among patients with asthma, although predictive factors for improvement are largely unknown. We tested the hypothesis that the improvement may vary according to family history of BHR. Children with atopic asthma (n = 121) received inhaled budesonide (800 micro g per day) regularly for 6 months. Methacholine provocative concentration causing a 20% fall in FEV(1) was measured before treatment and again after 3 and 6 months of treatment. A methacholine challenge test was also performed in each patient's parents, and the results were analyzed with regard to their children's response to corticosteroid therapy. When the children were classified into large (n = 40) and small (n = 40) improvement groups after 6 months of treatment, the prevalence of BHR and the bronchial responsiveness index were higher in parents of the small improvement group (28.8%, 1.145 +/- 0.104) than in parents of the large improvement group (6.3%, 1.095 +/- 0.064; both, p0.01). The magnitude of improvement in BHR at 6 months was lower in children with at least one parent with BHR (n = 45; 1.666 +/- 1.244 doubling doses) than in children with non-BHR parents (n = 76; 2.531 +/- 1.726, p0.01). Our results suggest that a family history of BHR may be an important factor in the sensitivity of BHR of individuals with asthma to inhaled corticosteroids.

Summary Background Our previous work on linkage analysis showed that histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11q13, where the β chain of the high-affinity receptor for IgE (FceRI-β) is located. Objective To evaluate the association between FceRI-mediated histamine release from basophils and four bi-allelic single nucleotide polymorphisms of the FceRI-β gene. Methods Phenotypes of asthma, such as maximal histamine release from basophils and atopy, were measured from 80 randomly recruited asthmatic children. Polymorphisms of the FceRI-β gene were determined by PCR-based methods. Results The polymorphism in exon 7, resulting in Glu to Gly substitution, was significantly associated with histamine release from basophils to anti-IgE stimuli, but not with total IgE levels and skin test responses to aeroallergens. Conclusion This study supports a role for the FceRI-β gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.

The aim of this study was to examine the relationship of wheezing to airflow obstruction during acute episodes of asthma in patients who had CVA (cough variant asthma). Two groups of asthmatic children, one group with a past history of CVA (n = 13) and the other group without such a history (n = 14), were followed longitudinally for 12 months. During that time, they were evaluated for the presence of wheezing and the severity of airflow obstruction during acute episodes of asthma. Significant airflow obstruction occurred free of wheezing more frequently, and the presence of clinical wheezing was associated with more severe airflow limitation, in asthmatic patients with a past history of CVA than in those without such a history. We conclude that asthmatic patients who have experienced CVA develop the wheezing symptom at a higher level of airflow obstruction.

Purpose: Dyspnea is the cardinal symptom of asthma, but it is difficult to quantify clinically. Although modified Borg (mBorg) scale has been successfully used in adult, but there has been some difficulties to apply in children. Recently, Pediatric Dyspnea Scale (PDS) was adequately designed and has been widely used. The aim of this study is to compare 2 evaluating scales of dyspnea provoked by induced-bronchoconstriction in childhood asthma. Methods: Seventy-three clinically suspected children with asthma were enrolled in this study. Each ‘fractional exhaled nitric oxide (FeNO)’ was documented. Forced expiratory volume in 1 second (FEV1), mBorg score and PDS score were recorded during metha-choline provocation test. Results: Mapping using canonical plot demonstrated global similarity between 2 scales with some distinctive features. Whereas mBorg score showed more diverse categories in low level of dyspnea, PDS score did in medium level of it. A distribution of dyspnea perception score at a 20% decrease in FEV1 relative to baseline (PS20), a perception score of dyspnea at 20% fall in FEV1 of 2 scales represented similar wide, biphasic feature. Statistical relevance was verified with spearman correlation (Rs=0.903, P

Study objective Many children with asthma go into long-term clinical remission at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these subjects. The regular use of inhaled corticosteroids improves BHR in patients with symptomatic asthma. The aim of this study was to determine whether BHR in adolescents with asthma remission could be reduced by prolonged treatment with inhaled corticosteroids. Design A randomized, double-blind, placebo-controlled, parallel study. Patients Thirty-seven adolescents with BHR and long-term remission of their asthma (neither symptoms nor any medication use during the previous 2 years). Intervention Subjects received inhaled budesonide (two 200-μg puffs bid; budesonide group, n=19) or identical placebo (placebo group, n=18) for 9 months. A separate group of patients with symptomatic asthma (symptomatic group, n=19), using the same regimen of budesonide, was also studied. Measurements and results The provocative concentration of methacholine producing a 20% fall in FEV 1 (PC 20 ) was measured before and every 3 months during treatment. There was no significant difference among the three groups for the baseline PC 20 . In neither the placebo nor the budesonide group did the geometric mean of PC 20 change significantly over the 9-month period. In contrast, a significant increase in PC 20 was noted in the symptomatic group as a result of the budesonide treatment. Conclusion Our data have shown that budesonide inhaled regularly for 9 months did not cause a significant improvement in the BHR of adolescents with long-term asthma remission. This suggests that the mechanism underlying BHR in this clinical setting may be different from that in symptomatic asthma.

Study objectives Our current knowledge of pediatric bronchiolitis obliterans (BO) is based largely on a few small series of patients that were reported in the older literature. In these older cases, the mortality rate was high. This study was conducted to investigate the characteristics of pediatric BO cases in two different countries. Design We extracted specific information regarding predisposing factors, symptoms and signs, diagnostic studies, treatment, and outcome from the medical records of 31 children who received diagnoses of BO at four university medical centers in Korea and the United States in the 1990s. Results The large number of Asian children reflects a clustering of cases in Korea due to adenovirus and Mycoplasma pneumoniae epidemics. The characteristic diagnostic features of BO were present in 29 of 30 high-resolution CT (HRCT) studies. Seven of nine children who underwent biopsies had histologic confirmations of BO. In two patients whose biopsy results were nondiagnostic, the diagnosis was established by HRCT together with pulmonary function testing results that were consistent with nonreversible small airways obstruction. Fifteen children (48.4%) had evidence of hypoxemia. At present, all but one are alive. Patients with elevated severity-of-illness scores were observed to have increased likelihoods of lung transplantation or death. Conclusions We conclude that BO has a good overall prognosis and that the mortality rate has declined over the past decade. This could be related primarily to the use of HRCT for accurate diagnosis and the availability of pediatric lung transplantation. BO cases in Korea were associated with infectious epidemics, whereas those in United States had variable predisposing factors.

On occasion, outbreaks of infection with adenovirus types 3, 7, and 21 cause severe lower respiratory tract infections (LRTIs) in children. From 1990 to 1998, all cases of LRTI due to adenovirus at the Seoul National University Children's Hospital, Seoul, Korea, were reviewed. Adenoviruses were recovered from nasal aspirate specimens of 87 (5.9%) of 1472 children with LRTI. The principal adenovirus serotypes were type 2 (13 [15%] of 87 strains), type 3 (13 [15%]), and type 7 (36 [41%]). Of the 87 infections, 62 (71%) occurred in children