Development and validation of a new asthma questionnaire to help achieve a high level of control in school-age children and adolescents.

BACKGROUND: Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents. METHODS: A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6-15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires. RESULTS: A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year. CONCLUSIONS: The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR CHILDREN WITH FOOD ALLERGY REPORTED BY PARENTS].

OBJECTIVE: No questionnaire aimed at evaluating the quality of life (QOL) of children with food allergies has been developed in Japan. Therefore, this study was aimed at developing a Japanese version of a QOL questionnaire for children with food allergies to be responded to by their parents. METHODS: A 59-question primary questionnaire was developed for parents of children aged 0 to 15 years who had food allergies. Responses to the primary questionnaire were collected, and question items were reduced using factor analysis. Then, a secondary questionnaire consisting of nine questions was developed. The secondary questionnaire, the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF), and the parent-reported questionnaire on health-related quality of life in children and adolescents (KINDL) were administered to parents of children aged 3 to 15 years who had food allergies. RESULTS: Overall, 342 parents completed all questionnaires. The QOL scores of the secondary questionnaire were significantly correlated to those of the FAQLQ-PF (r=0.765) and weakly correlated to those of the KINDL (r=-0.358). In addition, QOL scores were significantly worse in patients with a history of anaphylaxis, who were prescribed an adrenaline auto-injector, and who were allergic to hen's eggs, cow milk, or wheat. CONCLUSION: We were able to develop a parent-reported validated Japanese version of the QOL questionnaire for children with food allergies.

[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR PARENT BURDEN OF CHILDREN WITH FOOD ALLERGY].

OBJECTIVE: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan. METHODS: We collected QOL-related questions from parents of children with food allergies aged 0-15 years, and created a primary questionnaire. Responses to the primary questionnaire were obtained from the parents again, and question items were reduced using factor analysis to create a secondary questionnaire comprising eight items. In addition to the secondary questionnaire, responses to the Food Allergy QOL Questionnaire-Parent Form (FAQLQ-PF) Japanese version, Parent reported Health-Related QOL in children and adolescents (KINDL) and Health-related QOL (SF-8) were obtained from parents to assess the validity of the secondary questionnaire. RESULTS: A total of 407 parents completed all questionnaires. The secondary questionnaire scores were positively correlated with those of FAQLQ-PF and weakly negatively correlated with the KINDL and SF-8 mental component summary scores. Parents of children with food allergies with ≥3 culprit foods or severe reactions to daily foods, a history of anaphylaxis, and those carrying adrenaline autoinjectors scored higher and had lower QOL. CONCLUSION: The developed original questionnaire is a valid QOL questionnaire for Parents of children with food allergies.

Nocturnal Scratching and Quality of Sleep in Children with Atopic Dermatitis.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

Effect of age on exercise-induced bronchoconstriction in children and adolescents with asthma.

OBJECTIVE: The relationship between exercise-induced bronchoconstriction (EIB) and exertional dyspnea in children and adolescents is yet to be fully established. This study examined whether indicators of fractional exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV1) percent predicted at baseline, and dyspnea are useful for predicting children and adolescents with EIB. METHODS: We enrolled 184 children and adolescents diagnosed with asthma (mean age 11.2 years); participants were divided into two groups according to age (12 years) and were subjected to a 6-min exercise challenge test. Lung function tests and modified Borg scale scores were used to examine perceptions of dyspnea at 0, 5 and 15 min after exercise. RESULTS: Among children, the maximum percentage drop in FEV1 after exercise correlated significantly with FeNO (adjusted ß = 2.3, P < 0.001) and with the perception of dyspnea at 5 min after exercise (adjusted ß = 1.9, P < 0.001). Among adolescents, the maximum percentage drop in FEV1 correlated with FeNO (adjusted ß = 2.7, P = 0.007) and with lung function (FEV1, percent predicted; adjusted ß = -0.28, P = 0.006). Children with EIB had significantly stronger dyspnea after exercise than did children without EIB. Adolescents even without EIB may experience more exertional dyspnea than children without EIB. CONCLUSIONS: Overall, our findings indicated that EIB was associated with FeNO and exertional dyspnea in asthmatic children. By contrast, EIB was associated with FEV1 percent predicted at baseline and FeNO but not with exertional dyspnea in asthmatic adolescents.

Impact of omalizumab on medical cost of childhood asthma in Japan.

Omalizumab is effective in children with severe asthma, but its impact on medical cost in Japan is not clear. We evaluated the impact of omalizumab on medical cost by comparing the pre- vs post-omalizumab-initiation medical costs of 12 children with severe asthma who received omalizumab for 2 years, and calculating incremental cost-effectiveness ratio for omalizumab therapy. Health outcome was measured as hospital-free days (HFD). The median total medical costs and medication fee per patient increased significantly after omalizumab initiation because of the high cost of omalizumab. The median hospitalization fee per patient, however, decreased significantly after omalizumab initiation due to reduction in hospitalization. Omalizumab led to an estimated increase of 40.8 HFD per omalizumab responder patient per 2 years. The cost was JPY 20 868 per additional HFD. Omalizumab can therefore reduce hospitalization cost in children with severe asthma in Japan.

[A case of food-dependent exercise-induced anaphylaxis caused by ingestion of orange].

The patient was a 10-year-old girl who presented with a history of anaphylactic episodes on three occasions, that developed in association with exercise after she ate citrus fruit. She underwent tolerance tests, as food-dependent exercise-induced anaphylaxis (FDEIA) induced by citrus fruit was suspected. The result of the test for the combination of intake of oranges and exercise was negative. The patient presented with swollen eyelid and wheezing following combined intake of orange and aspirin, based on which she was diagnosed as having FDEIA. Many patients developing an allergic reaction to fruit are diagnosed as having oral allergy syndrome (OAS), and only few cases of FDEIA are reported. Immunoblot tests revealed antigens of 9 kDa, 39 kDa and 53 kDa in this patient, and an inhibition study with oranges revealed that the 39 kDa and 53 kDa antigens were probably antigen-specific allergens. Although the studied patient showed a strongly positive result for IgE antibodies specifically directed at cedar pollen, no common antigenicity with cedar pollen could be recognized. The final diagnosis was a type of FDEIA caused by 39 kDa and 53 kDa proteins, which are different from antigens previously identified in patients with citrus fruits allergy. It should be the first report of such a case.

Lung sound analysis in a patient with vocal cord dysfunction and bronchial asthma.

OBJECTIVE: Vocal cord dysfunction (VCD) is a condition characterized by adduction of the vocal cords, resulting in narrowing or even closure of the glottis during inspiration. This can cause wheezing that originates at the site of narrowing. Some patients have both VCD and asthma. In such cases, an acute episode of VCD can be difficult to differentiate from that of asthma. We tested the usefulness of lung sound analysis (LSA) in such a condition. METHODS: We performed an LSA in a patient with asthma and coexisting VCD diagnosed using laryngoscopy. RESULTS AND CONCLUSION: The LSA during an acute VCD episode revealed monophonic continuous adventitious sounds that were distributed symmetrically over both lung fields. The time domain analysis revealed that the adventitious sounds originated in the neck. These LSA findings clearly indicated that the acute episode was not due to asthma but due to VCD. This case illustrates that the LSA may be a useful tool to differentiate between an acute episode of asthma and that of VCD.

Relationship among airborne pollen, sensitization, and pollen food allergy syndrome in Asian allergic children.

Background: Causes of pediatric pollen food allergy syndrome (PFAS) differ depending on airborne pollen levels in a particular region. We aimed to analyze airborne pollen counts, IgE sensitization rates, and PFAS incidence among children with allergies in South Korea and Japan. Methods: This cross-sectional study included children aged 5-17 years with allergies in 2017. Airborne pollen samples were collected from Busan in South Korea, and Fukuoka and Tochigi in Japan. Questionnaires were used to assess bronchial asthma, seasonal allergic rhinitis, atopic dermatitis, food allergy, and PFAS. The serum IgE specific to Dermatophagoides pteronyssinus, pollen, tomato, and peach were investigated. Results: In total, 57, 56, and 20 patients from Busan, Fukuoka, and Tochigi, respectively, were enrolled. Airborne Japanese cedar and cypress pollen were predominant in Fukuoka and Tochigi, whereas pine and alder pollen were predominant in Busan. Children with allergies in Fukuoka and Tochigi had a significantly higher sensitization rate to Japanese cedar, cypress, juniper, orchard grass, ragweed, Japanese hop, and tomato compared with children in Busan. In Fukuoka and Tochigi, where Japanese cedar and cypress pollen were frequently scattered, high sensitizations among allergic children were observed. The sensitization rate was not affected by the pollen count in alder, grass, ragweed, and Japanese hop. In multivariable analysis, only alder sensitization was found to be associated with PFAS (odds ratio: 6.62, 95% confidence interval: 1.63-26.87, p = 0.008). In patients with PFAS in Busan and Tochigi, peach associated with birch allergen Bet v 1 was a causative food item for PFAS. Moreover, PFAS was associated with ragweed and Japanese hop pollen sensitization in Fukuoka. Conclusion: Regardless of pollen counts, alder pollen sensitization was associated with PFAS in children. Ragweed and Japanese hop pollen sensitization were associated with PFAS, particularly among children in southern Japan.

Changes in clinical features of food-related anaphylaxis in children during 5 years.

Background: Despite being frequently recommended, adrenaline auto-injectors (AAIs) are insufficiently prescribed and used for the prehospital management of anaphylaxis. Objective: This study aimed to investigate recent changes in the clinical features and prehospital management of food-related anaphylaxis in children. Methods: We retrospectively compared the clinical features of children who were hospitalized for food-related anaphylaxis in 2013 and 2018. The patients' medical records were reviewed for causative foods, triggers, location, AAI prescription, and/or use, wheezing on admission, and treatment. Results: Overall, 62 consecutive patients (43 males; median age, 5.6 years) hospitalized in 2018 were compared with 57 patients (37 males; median age, 4.3 years) hospitalized in 2013. There were no significant differences between the cohorts in age, gender, causative foods, or wheezing on admission. Cow's milk, wheat, and egg represented over half of the causative foods in both groups. Compared with 2013, the incidence of anaphylaxis decreased at home but increased at nurseries and schools in 2018. Exercise was a significantly more common trigger for anaphylaxis in 2018. Furthermore, a significant increase was observed in AAI administration by lay helpers or the patients themselves and in ambulance transportation. After admission, intramuscular adrenaline was administered to 26 patients in 2013 and 12 patients in 2018. Patients receiving prehospital adrenaline were significantly less likely to require in-hospital adrenaline injections. Conclusion: Food-related anaphylaxis triggered by exercise and AAI use have increased. Hence, raising awareness and educating caregivers, patients, teachers, and medical professionals are essential for the optimal management of this disorder.

Risk Factors for Lung Function Decline in Pediatric Asthma under Treatment: A Retrospective, Multicenter, Observational Study.

Background: Childhood asthma is a major risk for low lung function in later adulthood, but what factors in asthma are associated with the poor lung function during childhood is not known. Objective: To identify clinical factors in children with asthma associated with low or declining lung function during the treatment. Methods: We enrolled children with asthma who had been treated throughout three age periods, i.e., 6−9, 10−12, and 13−15 years old, at seven specialized hospitals in Japan. Clinical information and lung function measurements were retrieved from the electronic chart systems. To characterize the lung function trajectories during each age period, we evaluated the forced expiratory volume 1 (FEV1) with % predicted values and individual changes by the slope (S) from linear regression. We defined four trajectory patterns: normal (Group N) and low (Group L), showing %FEV1 ≥80% or <80% throughout all three periods; upward (Group U) and downward (Group D), showing S ≥ 0 or S < 0%. Logistic regression analysis was performed to compare factors associated with the unfavorable (D/L) versus favorable (N/U) groups. Results: Among 273 eligible patients, 197 (72%) were classified into Group N (n = 150)/U (n = 47), while 76 (28%) were in Group D (n = 66)/L (n = 10). A history of poor asthma control, long-acting beta2 agonist use, and a lower height Z-score during 13−15 years were associated with an unfavorable outcome (Group D/L). Conversely, inhaled corticosteroid (ICS) use during 10−12 years and high-dose ICS use during 13−15 years were associated with a favorable outcome (Group N/U). Conclusion: We identified several factors that are associated with unfavorable lung function changes in pediatric asthma. Attention should be paid to the possible relationship between yearly changes in lung function and poor asthma control, use of ICS (and its dose) and use of LABA.

Clinical evaluation of a new rapid immunochromatographic test for detection of Bordetella pertussis antigen.

A more rapid and less complicated test to diagnose pertussis is required in clinical settings. We need to detect Bordetella pertussis, which mainly causes pertussis, as early as possible, because pertussis is more likely to become severe in infants, and people around them can easily become a source of infection due to its strong infectivity. Nevertheless, methods that can detect B. pertussis rapidly and efficiently are lacking. Therefore, we developed a new immunochromatographic antigen kit (ICkit) for the early diagnosis of pertussis. The ICkit detects B. pertussis antigens in a nasopharyngeal swab without equipment and provides the result in about 15 min with a simple procedure. Additionally, a prospective study to evaluate the ICkit was conducted in 11 medical institutions, involving 195 cases with suspected pertussis. Compared with the real-time polymerase chain reaction (rPCR), the sensitivity and specificity of the ICkit were 86.4% (19/22) and 97.1% (168/173), respectively. The ICkit detected the antigen in both children and adults. Furthermore, the ICkit detected the antigen until the 25th day from the onset of cough, when rPCR detected the antigen. Thus, the ICkit demonstrated a high correlation with rPCR and would help diagnose pertussis more rapidly and efficiently.

[Effect of weight reduction on respiratory function in obese children with asthma].

BACKGROUND: Though the epidemiological relationship between obesity and asthma has been widely investigated, the mechanism is less known. Several studies have examined that weight loss improved lung function in adults. However, it has not been systematically studied in children. We investigated the effect of weight reduction on respiratory function in obese children with asthma. METHODS: We selected 10 obese children aged 7-13 years with physician diagnosed asthma who was subjected the weight reduction program in Fukuoka National Hospital in 2003-2007. Obesity was defined by BMI >90 percentile of the same age population. Before and after the program, they performed the spirometry. And they were measured the height, the weight, the %Fat, and the Fat volume. Logistic linear analysis was conducted to determine the correlation between relative change in each obesity markers and relative change in each respiratory parameter. RESULTS: Reduction of BMI, %Fat, and Fat volume correlated with relative changes in %FVC and %FEV1. Reduction of %Fat and Fat volume also correlated with relative changes in %PEF and %V50. CONCLUSION: Reduction of BMI, %Fat, and Fat volume can improve respiratory function in obese children with asthma. Obesity may be contribute to aggravate the symptoms of asthma.

[Relationship between compliance with inhaled corticosteroids and changes in the fraction of exhaled nitric oxide during summer camp for asthmatic children].

BACKGROUND: Recently, the fraction of exhaled nitric oxide (FENO), which can be measured easily and noninvasively even in children, has attracted attention as a method of evaluating airway inflammation. The aim of this study was to investigate the relationship between compliance with inhaled corticosteroids (ICS) before a summer camp for asthmatic children and the changes in the FENO during camp. METHODS: Fifty asthmatic children (26 boys and 24 girls) aged 6-12 years old were recruited from the Fukuoka National Hospital Summer Camp between 2008 and 2010. We measured their FENO on the first and last day of camp. The children were taught appropriate inhalation methods by pediatric pulmonologists and nurses and performed ICS under their supervision every day during the camp. Before the camp, we asked the participants to complete a questionnaire regarding the use of ICS. The participants were classified into four groups according to their adherence to this therapy. The changes in FENO were then examined and compared among the groups. RESULTS: The FENO measured on the last day of camp was significantly lower than that measured on the first day of camp among children who tended to forget to perform ICS. However, no significant difference in the FENO measurements were observed during the camp, when the children were performing ICS every day. CONCLUSION: The FENO decreased significantly after only four days of camp in the poor compliance group. Therefore, teaching children the appropriate method for inhaling ICS is important, especially for children who tend to forget to perform ICS.

Exercise-induced anaphylaxis unrelated to food ingestion and with hyperleukotrieneuria during challenge testing.

BACKGROUND: Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder that can develop independently without food ingestion. Cold drinks can also trigger symptoms in some patients with cold-induced anaphylaxis. We present a case of a patient with EIA that was diagnosed on the basis of positive exercise loading test with hyperleukotrieneuria. CASE PRESENTATION: A 12-year-old girl presented with acute flushing, cyanosis, swollen eyelids, and dyspnea after an endurance run in winter or swimming in a cold-water pool. She also developed dyspnea after having a cold drink. She had no history of food allergies, atopy, or asthma. No association was noted between anaphylaxis and food intake in her history. On the first day, she ingested 200 mL of 5 °C cold water in 30 s, which did not trigger symptomatic responses, but her urinary leukotriene E4 (LTE4) level increased (pre-challenge test: 295 pg/mg-creatinine (cr), post-challenge test: 400 pg/mg-cr). On the second day, she underwent the exercise loading test according to the Bruce protocol by using an ergometer to increase the power of exercise every 2 min. She had been fasting for > 15 h and did not have breakfast. Just after the exercise loading test, the plasma adrenaline and noradrenaline increased. At 15 min after the exercise loading test, her plasma adrenaline and histamine (pre-challenge test: 0.7 ng/mL, 15 min post-challenge test: 81 ng/mL) rose sharply with anaphylaxis symptoms accompanied by increasing urinary LTE4 (pre-challenge test: 579 pg/mg-cr, post-challenge test: 846 pg/mg-cr). After she was discharged, she was restricted from strenuous exercise especially in cold environments and prescribed an adrenaline autoinjector. CONCLUSION: Cold stimulation can become a co-effector of EIA. Measurements of urinary LTE4 levels during challenge testing are useful for diagnosing EIA and capture the pre-anaphylaxis stage.

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan.

OBJECTIVE: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program. METHODS: Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis. RESULTS: Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0-8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01). CONCLUSION: Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.

Annual changes in the prevalence of asthma may be related to air pollution in Fukuoka: 29†years of observation.

The relationship between the annual changes of the prevalence of bronchial asthma (BA) and that of concentrations of air pollutants has not been reported. We studied the annual prevalence of BA, remission of BA, and wheeze in children at the same five elementary schools in Fukuoka city, Japan, in October to November from 1988 to 2016 by the same methods using the same questionnaire. Annual changes in the prevalence of asthma among boys were related to changes in the air concentrations of NO (r=0.708), NO2 (r=0.665) suspended particulate matter (SPM) (r=0.803), and smoking rate (r=0.741), but there were no such relationships among girls. Annual changes in the prevalence of wheeze were related to changes of NO, NO2, SPM, and smoking rate among boys and girls (NO: r=0.650, 0.660; NO2: r=0.556, 0.490; SPM: r=0.582, 0.518; smoking rate: r=0.656, 0.593, respectively) (all of the above are significant with p<0.05). There was no relationship between remission of BA and any of the pollutants. Annual changes in the prevalence of boys' BA and boys' and girls' wheeze among first-grade children (age 6 or 7 years) in Fukuoka were correlated with changes in the concentration of air pollutants (SPM, NO, NO2 or smoking rate). Recent decrease of asthma prevalence in this area might be related to the decreasing tendency of air pollutant concentration. The causal relationship between the two will need to be verified in the future.

[Efficacy and safety of budesonide inhalation suspension nebulization by mesh nebulizer in Japanese infants and young children with bronchial asthma in 12-week, randomised, open study].

OBJECTIVE: This study evaluated the efficacy and safety of Budesonide Inhalation Suspension (BIS) nebulazation by mesh nebulizer in children ages 6 months to 4 years with moderate to severe persistent asthma. METHOD: This 12-week, randomized, open study involved 30 asthmatic children. They were randomized 3 different nebulizer groups, Pari TurboBoy +LC Plus nebulizer, Pari eMotion and Omron MicroAir NE-22U. BIS administered 0.25 mg once daily (qd). Efficacy was assessed by daily card. Safety was assessed by adverse event, plasma cortisol and growth. RESULT: Baseline concentrations of plasma cortisol were significantly high in the group of Omron MicroAir NE-22U compared to other group. Plasma cortisol were decreased significantly at 4 weeks in Omron MicroAir NE-22U compared with baseline, but those in no subjects decreased under normal range. Asthma symptoms were improved significantly from baseline to 12-week. CONCLUSION: This study demonstrate that usage of mesh nebulizer in BIS 0.25 mg qd is effective and safe in young asthmatic children.