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Atopic dermatitis (also known as atopic eczema) is a chronic relapsing inflammatory skin disease commonly seen in children, with increasing prevalence over the past few decades in many countries including Taiwan. The management of pediatric atopic dermatitis can be challenging, particularly as treatment options are expanding with the emergence of novel systemic and topical anti-inflammatory medications in recent years. The Taiwan Academy of Pediatric Allergy, Asthma and Immunology (TAPAAI) has developed the Taiwan guidelines for the diagnosis and management of pediatric atopic dermatitis, which provides a concise overview of its epidemiology, clinical characteristics and diagnosis, mechanisms, treatments, and education. The contents of this guideline integrate the principles of recent national and international guidelines for the diagnosis and management of atopic dermatitis, latest research findings, and expert opinions of experienced pediatric allergy specialists in Taiwan. For practical purposes, this guideline presents simplified and easy-to-use diagnostic criteria and severity grading for pediatric atopic dermatitis. A stepwise treatment algorithm is also proposed to expedite rational, cost-effective, and evidence-based management strategy. This guideline, developed based on current best evidence and real-world experience of pediatric allergy experts in Taiwan, is intended to facilitate practical, up-to-date management of pediatric atopic dermatitis among physicians.

Background: Asthma is a complex multifactorial chronic airway inflammatory disease with diverse phenotypes and levels of severity and is associated with significant health and economic burden. In a certain population of asthma patients, the symptoms cannot be well controlled with steroid. There has been long standing interest in the use of probiotics for treating allergic diseases. The purpose of this study is to investigate whether the combination of Lactobacillus rhamnosus GG (LGG) with prednisolone could reduce the dosage of glucocorticoid in controlling airway inflammation in a murine model for allergic asthma. Material and methods: We used Der p 2-sensitized asthma model in female BALB/c mice. The animals were treated with 75 μl or 50 μl oral prednisolone or combination treatment of these two doses of oral prednisolone with LGG. Airway hyperresponsiveness, serum specific IgE/IgG1/IgG2a, infiltrating inflammatory cells in lung and cytokines were assessed. Results: Compared to 75 μl prednisolone, a lower dose of prednisolone with 50 μl was less satisfactory in suppressing airway hyperresponsives, serum IgE and IgG1, Th2 cytokines and inflammatory cytokines such as IL-6, IL-8 and IL-17 as well as infiltrating inflammatory cells. However, combination of 50 μl prednisolone and LGG decreased airway resistance and serum IgE and IgG1, inhibited the production of IL-4, IL-5, IL-6, IL-8, IL-13 and IL-17, upregulated serum IgG2a and enhanced Th1 immune response. Conclusions: LGG may reduce the dosage of prednisolone and thus may be beneficial in the treatment of asthma.

Background: The prevalence of allergic diseases in children has increased globally. Early-life exposure to inorganic arsenic has been found to be associated with impaired immune function and decreased lung function in children; however, the results are inconsistent. We aimed to evaluate the effect of prenatal and childhood exposure to inorganic arsenic on allergic diseases in children, through a 15-year follow-up birth cohort study, conducted in central Taiwan. Methods: Children born to women enrolled in the Taiwan Maternal and Infant Cohort Study (TMICS-pilot) from December 2000 to November 2001 were recruited and followed every 2–3 years until the age of 14 years. Urinary specimens were collected in the pregnant women during the 3rd trimester and the followed children. Diagnoses of allergic diseases were based on physician diagnoses using the International Study of Asthma and Allergies in Childhood questionnaire. Urinary arsenic speciation was performed using high-performance liquid chromatography and inductively coupled plasma dynamic reaction cell mass spectrophotometry. Results: Of the 261 children from 358 mother-infant pairs for this study, those with asthma and allergic rhinitis reported a higher prevalence of maternal allergy (49.47%) than did non-allergic children (29.81%). In the fully adjusted model, levels of maternal urine (iAs + MMA + DMA) greater than the median were found to be significantly associated with an increased risk of asthma (OR = 4.28; 95% CI 1.32, 13.85). Levels of urinary (iAs + MMA + DMA) in children higher than the median were associated with an increased risk of allergic rhinitis (OR = 2.26; 95% CI 1.20, 4.26). Conclusion: Prenatal and childhood exposure to inorganic arsenic were found to be significantly associated with the occurrence of asthma and allergic rhinitis in children, respectively. Further large cohort follow-up studies are important to validate the association between inorganic arsenic exposure and allergic diseases in children.

Background: Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. Objective: We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. Methods: The chronic asthma animal model was established with 6–8 weeks female Balb/c mice. After intranasal challenges with OVA, the airway inflammation and AHR were determined by a BUXCO system. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathologic changes and Collagen deposition were assayed with H&E, Masson's trichrome and IHC stain. Results: FIP-fve significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines and increased Th1 cytokines in BALF and serum compared with the OVA sensitized mice. FIP-fve had a better effect than corticosteroid could reduce infiltrating cells in lung especially neutrophils and eosinophils. We also found that the oral FIP-fve group suppressed IL-17 and enhanced IL-22 in the serum and BALF. In addition, oral FIP-fve decreased MMP9 expression, collagen expression and airway remodeling in lung tissues. Conclusion: FIP-fve had anti-inflammatory effects on OVA-induced airway inflammation and an effect to inhibited Th17 cells to reduced airway remodeling and collagen expression. Moreover, FIP-fve might be a potential alternative therapy for allergic airway diseases. Keywords: Asthma, Airway remodeling, Collagen deposition, FIP-fve, IL-17, IL-22

Objective: The main objective of this study was to evaluate the efficacy and safety of Lactobacillus rhamnosus in children aged 4–48 months with atopic dermatitis. Methods: The design of this study was a two-center, double-blind, randomized, and placebo-controlled study with two parallel groups to evaluate the efficacy and safety profile of L. rhamnosus in children aged 4–48 months with atopic dermatitis diagnosed using Hanifin and Rajka criteria and with a Scoring of Atopic Dermatitis (SCORAD) ≥ 15 at enrollment. The duration of this study was 8 weeks with a total of five visits. The enrolled patients were allocated into either a treatment group (one ComProbi capsule containing L. rhamnosus a day) or a control group (one capsule of placebo a day) at a ratio of 1:1. The primary endpoint was to compare the mean change from baseline in SCORAD after 8 weeks of treatment. The other secondary end points were to compare the following: the mean changes from baseline in SCORAD at postbaseline visits, the frequency and total amount of the use of corticosteroids during the 8-week treatment, the frequency of atopic dermatitis and the symptom-free duration, the mean changes from baseline in Infant Dermatitis Quality of Life Questionnaire at Week 4 and Week 8, and the mean changes from baseline in the Dermatitis Family Impact Questionnaire at Week 4 and Week 8. Results: The mean changes in SCORAD from baseline at Week 8 was −21.69 ± 16.56 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group for the intent-to-treat population (p = 0.014). For the per-protocol population, the mean change of SCORAD from baseline was −23.20 ± 15.24 in the L. rhamnosus group and −12.35 ± 12.82 in the placebo group (p = 0.003). Significant differences were demonstrated between groups at Week 8 in intensity in the intent-to-treat population and per-protocol population. Throughout the period, the amount of topical corticosteroids used showed no difference between groups. No significant difference was noted in the overall symptom-free durations compared with the placebo group. Infant Dermatitis Quality of Life Questionnaires and Dermatitis Family Impact Questionnaires scores improved significantly at Week 4 and Week 8 but did not reach statistical significance. Adverse events were documented in 14/33 patients in the L. rhamnosus group (42.42%, 35 events) and in 15/33 placebo patients (45.45%, 37 events). Conclusions: The results of this study indicated that L. rhamnosus was effective in decreasing symptoms of atopic dermatitis after an 8-week treatment by comparing the mean change of SCORAD from baseline with a placebo (p

Background/Purpose: House dust mite (HDM) is well known as one of the major indoor allergens that trigger allergic inflammation, especially asthma, and accounts for 85% of all cases. So far, asthma has been thought of as a condition of imbalance between T helper (Th)1 and Th2. Fungal immunomodulatory protein-Flammulina velutipes (FIP-fve) has been seemingly demonstrated to modulate the response to Th1 cytokine production. The aim of this study was to investigate if the oral administration of FIP-fve can inhibit HDM-induced asthma inflammation in the mouse model. Methods: We divided the mice (female BALB/c, 4–6 weeks) into four groups: the prevention group, which consisted of mice sensitized by HDM (intraperitoneally on Day 1, Day 7, and Day 14, and intranasally on Day 14, Day 17, Day 21, Day 24, and Day 27) fed with FIP-fve from Day 1 to Day 14; the treatment group, which comprised mice that received treatment from Day 14 to Day 28; the positive control (PC, sensitized by HDM fed without FIP-fve) group; and the negative control group (NC, nonsensitized). Airway hyperresponsiveness induced by methacholine challenge was determined using whole-body barometric plethysmography. In addition, cytokines were analyzed from bronchoalveolar lavage fluid and serum. Histopathological studies and Liu's staining method in mice lungs were also performed. Results: The results showed that both pre- and posttreated FIP-fve groups had significantly reduced airway hyperresponsiveness compared with the PC group after methacholine challenge. In addition, a significantly decreased level of HDM-specific immunoglobulin E in serum and decreased production of Th2 cytokines in bronchoalveolar lavage fluid and serum were observed in these two FIP-fve fed groups. Moreover, more decreased amounts of infiltrating inflammatory cells were present in the lungs of FIP-fve fed groups than those of the PC group. Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

Various studies have investigated the efficacies of mometasone furoate monohydrate (MFM) and fluticasone propionate (FP) nasal sprays for adults. However, research on their effectiveness for children is limited. This study compares the efficacies of MFM and FP nasal sprays in pediatric patients with perennial-allergic rhinitis. Materials and methods: For this study, 94 perennial allergic rhinitis patients aged 6–12 years were randomly assigned to two treatment groups: an MFM group and an FP group. Treatment was provided for 4 weeks. The effects of the two agents were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and total symptom scores (TSSs). Nasal-peak expiratory flow rates and eosinophil percentage in nasal smears were also compared between the two groups. Results: Patients in the MFM group exhibited significant improvement in their TSS (t = −2.65, p

Data on hospital admissions for children under 5 years old, concerning the admission rate, leading diagnoses, categories of disease, average hospitalization days, costs and between-year differences are scarce. Our study aims to investigate such admission profiles. Methods: Five percent of admission data for children under 5 years old in 2000 and 2009 was collected from the National Health Insurance Research Database in Taiwan. We calculated the admission rate in regards to total admission, the patients' gender, the ten leading diagnoses, the ten most systemic common categories of disease, and the average hospitalization days and costs. The differences of the rates between 2000 and 2009 were evaluated by incidence rate ratios (IRR). Results: The admission rate per thousand children (population) was higher in 2009 (172.9) than 2000 (153.1). The ten most common systemic categories of disease were similar in both years. Furthermore, it was observed that the hospitalization days decreased by 3.7% in 2009, while medical expenditures increased by 10.9%. Conclusions: Efforts should be made to decrease the admission rate and hospitalization days in Taiwan to the levels of well-developed countries. Our data may serve as baseline data for future evaluations of child morbidity.

Cysteinyl leukotrienes (CysLTs) play a major role in the pathogenic changes of airway inflammation in asthma treatment. The matrix metalloproteinase (MMP) family, especially MMP-9 and MMP-2 levels, can reflect the status of airway remodeling. This study was undertaken to determine the role of a specific CysLT receptor antagonist in inhibition of airway inflammation and reversal of airway remodeling. Methods: Ovalbumin (OVA)-sensitized BALB/c mice were fed with a specific leukotriene receptor antagonist (MK-679), prednisolone or placebo from Days 15 to 27. Airway hyperreactivity, bronchoalveolar lavage fluid (BALF), and sera were analyzed. Pulmonary histology was obtained, and the levels of MMP-2 and MMP-9 in BALF were measured. Results: The OVA-sensitized mice developed significant airway inflammatory responses, including extensive eosinophils trafficking into BALF and lung interstitium, goblet cell hyperplasia, mucus hypersecretion, elevated serum immunoglobulin (Ig) E, and decreased level of serum IgG2a. Administration of MK-679 could reduce airway inflammation but was not as effective as prednisolone. However, MK-679 was more effective than prednisolone for reversing subepithelial fibrotic and myofibrotic reactions of airway remodeling. The levels of MMP-2 and -9 in BALF were proportional to the extent of airway remodeling, which can reflect the effects of treatment. Both prednisolone and MK-679 reverse airway hyperresponsiveness induced by OVA-sensitized mice. Conclusion: Cysteinyl leukotriene receptor plays a more important role than CysLT in the pathogenesis of allergic airway inflammation. MMP-2 and -9 may be more sensitive indicators of airway remodeling.

The prevalence of asthma, allergic rhinitis and atopic eczema in children from the developed and developing countries has been increasing. Methods: Three epidemiological surveys of the prevalence of bronchial asthma, allergic rhinitis and atopic eczema in schoolchildren in Taichung, located in central Taiwan, were conducted in 1987, 1994, and 2002. The first questionnaire was used before the International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire was developed; the last two surveys were modified using ISAAC questionnaires. Results: A total of 37,801, 75,960, and 11,580 children were studied in 1987, 1994 and 2002, respectively. The prevalence of allergic diseases had increased in the past two decades. Results indicate that the prevalence of bronchial asthma had risen, from 2.19% in 1987, and 3.54% in 1994, to 6.99% in 2002. Regardless of sex, the prevalence of bronchial asthma decreased with increasing age. The prevalence of allergic rhinitis was 5.1% in 1987, 12.46% in 1987, and 27.59% in 2002, and the prevalence of atopic eczema was 1.10% in 1987, 1.88% in 1994, and 3.35% in 2002. Conclusion: There has been a significant increase in the prevalence of bronchial asthma, allergic rhinitis and atopic dermatitis in Taichung schoolchildren from 1987 to 2002.

Cordyceps militaris is a well-known fungus with immunomodulatory activity. It is generally used in traditional Chinese medicine to treat hemoptysis, bronchial or lung inflammation, and urogenital disorders. The purpose of our study was to evaluate the effect of cultivated C. militaris on airway inflammation in a mouse asthma model. Methods: BALB/c mice were sensitized with intraperitoneal ovalbumin (OVA) on Days 0 and 14, and were then given intranasal OVA on Day 14 and Days 25-27. Randomized treatment groups of sensitized mice were administered C. militaris, prednisolone, montelukast, or placebo by gavage from Days 15-27. Airway hyperreactivity to aerosolized methacholine was determined. Bronchoalveolar lavage fluid and serum were analyzed to assess airway inflammation. Results: OVA-sensitized mice developed a significant airway inflammatory response that was inhibited by prednisolone and montelukast, whilst C. militaris reduced airway inflammation less effectively. Airway hyperresponsiveness to methacholine was observed in OVA-sensitized mice and was reversed by both prednisolone and montelukast. C. militaris initially reversed airway hyperreactivity, but this effect disappeared at higher methacholine doses. Conclusion: C. militaris can modulate airway inflammation in asthma, but it is less effective than prednisolone or montelukast. These results demonstrate that C. militaris is unable to adequately block the potent mediators of asthmatic airway inflammation.

The lymphotoxin-α (LT-α) gene is located on chromosome 6 (6p21.1–6p21.3) and it may regulate tumor necrosis factor (TNF) production. TNF is a potent cytokine in the airway inflammatory response. Polymorphisms of TNF-associated genes have been related to asthma. This study investigated an LT-α-NcoI polymorphism in the first intron of the LT-α gene (LT-α-NcoI*1 allele, as a variant type; and LT-α-NcoI*2 allele), which may predispose individuals to asthma and atopy. Methods: Polymerase chain reaction-based assays were performed to determine LT-α-NcoI genotypes among our subjects. A genetic case control analysis was then performed on 114 atopic asthmatic and 155 non-asthmatic unrelated children. Results: There was a statistically higher frequency of LT-α-NcoI*1 allele carriers (1/1 + 1/2) in the subjects with atopic asthma than in controls (OR = 1.923; 95% CI = 1.061–3.484; p = 0.031). Conclusion: The results indicate that LT-α-NcoI*1 may be a risk factor for atopic asthma in Taiwanese children.

Prescription patterns of anti-asthma medications in children vary among doctors in different disciplines and settings, and may reflect differences in treatment outcome. The purpose of this study was to analyze the prescribing patterns of anti-asthma drugs by pediatricians, family physicians and other practitioners. Methods: Data for a total of 225,537 anti-asthma prescriptions were collected from the National Health Insurance Research Database for the period from January 1, 2002 to March 31, 2002. These medications included inhaled and oral adrenergics, inhaled and oral corticosteroids, xanthine derivatives, and leuko-triene receptor antagonists prescribed by general pediatricians, family physicians and physicians in other disciplines. Results: Oral p2-agonist was the most commonly prescribed drug used as monotherapy, with prescription rates of 70.4%, 46.9% and 58.0% by pediatricians, family physicians and other physicians, respectively. A xanthine derivative was the next most commonly prescribed monotherapy. Oral corticosteroid combined with oral p2-agonist, followed by oral p2-agonist combined with a xanthine derivative were the two most commonly prescribed dual-agent combined therapies by all three physician categories. The prescription rate for inhaled corticosteroid monotherapy was 7.8% by pediatricians, 5.6% by family physicians, and 8.0% by other physicians. The prescription rate for inhaled adrenergic was the highest in family physicians (14.9%), followed by the other physicians (7.2%), and was lowest in pediatricians (3.1%). Conclusion: Pediatricians and family physicians appeared to share similar opinions on the medical management of children with asthma in that both most commonly prescribed oral p2-agonists and xanthine derivatives, either alone or in combination. Family physicians were least likely to prescribe an inhaled corticosteroid and most likely to prescribe an inhaled adrenergic agent.