Hai-Lun Sun

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study.

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double‐blind, placebo‐controlled study for 6 months. Patients (aged 6–12 yr) with mild‐to‐moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild‐to‐moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.

Randomized placebo‐controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.

Efficacy of nasal irrigation in the treatment of acute sinusitis in children.

BACKGROUND Nasal irrigation has been used as an adjunctive therapy of sinonasal disease including acute/chronic sinusitis and allergic rhinitis. Several published articles reported it also improves clinical sinus symptoms. OBJECTIVE To evaluate the effectiveness of normal saline nasal irrigation in the management of acute sinusitis in children. DESIGN This was a randomized, prospective placebo-controlled study. METHODS We included 69 participants with acute sinusitis. 30 of 69 participants underwent normal saline nasal irrigation. 39 of 69 participants were not receiving nasal irrigation. All participants performed nasal peak expiratory flow rate (nPEFR) test, nasal smear examination, radiography (Waters projection) and requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ) at the baseline visit. All participants were requested to record the symptom diary card every day and were followed-up every 1 week during this period. A physical examination, nasal smear and nPEFR were performed at each visit, and all daily diary cards collected. At the final visit, the symptoms diaries were reviewed and participants were requested to complete the PRQLQ again. The nPEFR, radiography (Waters projection) and nasal smear were also repeated. RESULTS Normal saline irrigation group significantly improved mean PRQLQ values and nPEFR values at medium (T=2.816, P<0.05) and final period (T=2.767, P<0.05) compared with the other group. Although there were no statically significant improving rate of radiography (Waters projection) in among two groups (T=0.545, P>0.05), but normal saline irrigation group was better than the other group. The improval rate of mean TSS in the irrigation group significantly improved all symptoms compared with the placebo group, in which rhinorrhea, nasal congestion, throat itching, cough and sleep quality improved. 27 of 66 (40.9%) participants with atopy, 16 of 27 (53.33%) participants underwent normal saline irrigation. Normal saline irrigation atopy group significantly improved rhinorrhea, nasal congestion, throat itching and sleep quality symptoms compared with non-irrigation atopy group. Normal saline irrigation atopy group significantly improved nPEFR values at final period (Z=2.53, P<0.05). CONCLUSION This study evidence that normal saline nasal irrigation improves Pediatric Rhinoconjunctivitis Quality of Life and decreases acute sinusitis symptoms. Nasal irrigation is an effective adjunctive treatment for pediatric acute sinusitis. Normal saline nasal irrigation in atopy children also improves allergic-related symptoms. We may need larger, longer and extended study to assess the conclusion.

A trial of adding Lactobacillus johnsonii EM1 to levocetirizine for treatment of perennial allergic rhinitis in children aged 7-12 years.

BACKGROUND Supplementary consumption of probiotics may temporarily alter the intestinal microflora of infants and children, thereby preventing and treating allergic disorders. OBJECTIVE To compare the clinical efficacy of levocetirizine with that of levocetirizine plus Lactobacillus johnsonii EM1 (Lj EM1) for treating perennial allergic rhinitis (PAR) in children. METHODS Sixty-three children aged 7-12 years fulfilled the entry criteria for the study and had moderate to severe PAR of at least 1 years duration. The treatment followed a randomized, open-label crossover design: all subjects were randomized to 2 crossover treatment regimens of levocetirizine with Lj EM1 (group 1) or levocetirizine alone (group 2) for 12 weeks; subsequently, treatments were reversed for a further 12 weeks. The effects of the 2 regimens were compared using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and the total symptom score (TSS) from diary cards. The parameters evaluated were nasal peak expiratory flow rate (nPEFR), FVC, FEV1, serum immunoglobulin E (IgE), mite-specific IgE, eosinophilic cationic protein (ECP), resistin, blood eosinophils, eosinophil percentage in nasal smears, IL-4, IL-10, interferon-γ (IFN-γ), and transforming growth factor-β (TGF-β). RESULTS After the first 12 weeks of treatment, TSS in both groups had improved progressively compared with that in the run-in period. Both groups had improved TSS at weeks 4, 8, and 12 (P<0.05), and group 1 was more efficacious than group 2 at week 4 (P=0.014), week 8 (P=0.011), and week 12 (P<0.009). During the second 12-week period, group 2 showed continual and progressive improvement, while group 1 did not. The PRQLQ scores were significantly decreased in both groups (P<0.05), but there was no statistically significant difference between the 2 groups (P=0.446). The eosinophil percentage in nasal smears decreased in both groups compared with that in the run-in period, and significant differences were detected in groups 2 and 1at 16 and 24 weeks of treatment, respectively (P<0.05). Both groups showed significant improvement in nPEFR at weeks 4, 8, 12, 16, and 24 (P<0.01), and the treatment for group 1 appeared to be more efficacious than that for group 2 at weeks 12, 16, and 20 (P<0.05). FVC and FEV1 were improved in both groups at weeks 8 through 24 (P<0.05), but there was no significant difference between the 2 groups. In cytokine measurements, IFN-γ and IL-10 increased significantly and IL-4 decreased significantly in both groups, while elevation of TGF-β was seen only in group 1 at 12 weeks (P<0.001). However, the difference in TGF-β disappeared after 24 weeks treatment. There was no difference in serum resistin levels. No serious adverse events were recorded in either treatment group. CONCLUSION The 24-week, 2-phase, crossover treatment program showed that levocetirizine plus Lj EM1 was more effective for PAR than levocetirizine and that this difference persisted for at least 3 months after discontinuation of Lj EM1.

Prevalence of childhood allergic diseases in central Taiwan over the past 15 years.

BACKGROUND 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.

Uric Acid Levels Can Predict Metabolic Syndrome and Hypertension in Adolescents: A 10-Year Longitudinal Study.

The relationships between uric acid and chronic disease risk factors such as metabolic syndrome, type 2 diabetes mellitus, and hypertension have been studied in adults. However, whether these relationships exist in adolescents is unknown. We randomly selected 8,005 subjects who were between 10 to 15 years old at baseline. Measurements of uric acid were used to predict the future occurrence of metabolic syndrome, hypertension, and type 2 diabetes. In total, 5,748 adolescents were enrolled and followed for a median of 7.2 years. Using cutoff points of uric acid for males and females (7.3 and 6.2 mg/dl, respectively), a high level of uric acid was either the second or third best predictor for hypertension in both genders (hazard ratio: 2.920 for males, 5.222 for females; p<0.05). However, uric acid levels failed to predict type 2 diabetes mellitus, and only predicted metabolic syndrome in males (hazard ratio: 1.658; p<0.05). The same results were found in multivariate adjusted analysis. In conclusion, a high level of uric acid indicated a higher likelihood of developing hypertension in both genders and metabolic syndrome in males after 10 years of follow-up. However, uric acid levels did not affect the occurrence of type 2 diabetes in both genders.

The comparison of cetirizine, levocetirizine and placebo for the treatment of childhood perennial allergic rhinitis.

Cetirizine (Zyrtec) is a potent and long‐acting second‐generation histamine H1‐ receptor antagonist for the treatment of allergic disease, such as allergic rhinitis and chronic idiopathic urticaria, in adult and child. It is a racemic mixture of levocetirizine (Xyzal) and dextrocetirizine. The purpose of this present study was to compare the efficacy of cetirizine, levocetirizine and placebo for the treatment of pediatric perennial allergic rhinitis. 74 perennial allergic rhinitis patients, aged 6 to 12 years old, assigned to 1 of 3 treatment groups for 12 weeks randomly. The effects of the three agents were compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. Nasal peak expiratory flow rate (nPEFR) and laboratory examinations including serum immunoglobulin E level, eosinophil cationic protein (ECP), blood eosinophil counts and eosinophil percentage in a nasal smear were evaluated among the three groups. The results revealed that both cetirizine and levocetirizine improved TSS in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine at week 8 and week 12. The PRQLQ score showed significant decreased both in cetirizine and levocetirizine group, but there was no statistic significant difference between both groups. The eosinophil proportion in a nasal smear significantly decreased among the cetirizine in comparison with the placebo group but there was no statistic significant in levocetirizine groups. Both cetirizine and levocetirizine showed significant improvement in nPEFR in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine. The 12‐week treatment program showed that cetirizine was more effectious than levocetirizine.

Comparison of the effects of air pollution on outpatient and inpatient visits for asthma: a population-based study in Taiwan.

Background A nationwide asthma survey on the effects of air pollution is lacking in Taiwan. The purpose of this study was to evaluate the time trend and the relationship between air pollution and health care services for asthma in Taiwan. Methods Health care services for asthma and ambient air pollution data were obtained from the National Health Insurance Research database and Environmental Protection Administration from 2000 through 2009, respectively. Health care services, including those related to the outpatient and inpatient visits were compared according to the concentration of air pollutants. Results The number of asthma-patient visits to health-care facilities continue to increase in Taiwan. Relative to the respective lowest quartile of air pollutants, the adjusted relative risks (RRs) of the outpatient visits in the highest quartile were 1.10 (P-trend  = 0.013) for carbon monoxide (CO), 1.10 (P-trend  = 0.015) for nitrogen dioxide (NO2), and 1.20 (P-trend <0.0001) for particulate matter with an aerodynamic diameter ≦10µm (PM10) in the child group (aged 0–18). For adults aged 19–44, the RRs of outpatient visits were 1.13 (P-trend = 0.078) for CO, 1.17 (P-trend = 0.002) for NO2, and 1.13 (P-trend <0.0001) for PM10. For adults aged 45–64, the RRs of outpatient visits were 1.15 (P-trend = 0.003) for CO, 1.19 (P-trend = 0.0002) for NO2, and 1.10 (P-trend = 0.001) for PM10. For the elderly (aged≥ 65), the RRs of outpatient visits in were 1.12 (P-trend  = 0.003) for NO2 and 1.10 (P-trend  = 0.006) for PM10. For inpatient visits, the RRs across quartiles of CO level were 1.00, 1.70, 1.92, and 1.86 (P-trend  = 0.0001) in the child group. There were no significant linear associations between inpatient visits and air pollutants in other groups. Conclusions There were positive associations between CO levels and childhood inpatient visits as well as NO2, CO and PM10 and outpatient visits.

Inhibition of lysosome degradation on autophagosome formation and responses to GMI, an immunomodulatory protein from Ganoderma microsporum

BACKGROUND AND PURPOSE Autophagic cell death is considered a self‐destructive process that results from large amounts of autophagic flux. In our previous study, GMI, a recombinant fungal immunomodulatory protein cloned from Ganoderma microsporum, induced autophagic cell death in lung cancer cells. The aim of this study was to examine the role of autophagosome accumulation in GMI‐mediated cell death.

Effects of the Immunomodulatory Agent Cordyceps militaris on Airway Inflammation in a Mouse Asthma Model

BACKGROUND 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.