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This part reviews the management of chronic cough and proposes a management algorithm. Despite proven improvements in quality of life following chronic cough treatment, a clear understanding of the disease and the evidence for the efficacy of some treatments remain vague. Eight key questions regarding the treatment in the uncertain areas were systematically addressed based on the PICO framework and applying the GRADE system for evidence synthesis to provide the strength of recommendation and quality of evidence for key questions, with narrative components for the description of other chronic cough treatment including non-pharmacological therapy. Practical diagrams were developed to facilitate clinical decision-making on treatment. Our guideline introduces the concept of the cough management process for guiding practitioners to assess chronic cough using a holistic approach.

Chronic cough is a common clinical condition requiring comprehensive assessment. This review employs a symptom-focused approach, prioritizing the presenting symptom of "chronic cough" to mirror real-world clinical practice. Ten key questions regarding the investigations in the uncertain areas were systematically addressed based on the PICO framework and applying the GRADE system for evidence synthesis to provide the strength of recommendation and quality of evidence for key questions. Practical diagrams were developed to facilitate clinical decision-making. The initial evaluation involves screening for red flag signs requiring urgent attention, followed by a detailed history-taking and physical examination. A chest radiograph is recommended as the first-line investigation. The primary objective of the initial evaluation is to identify the cause and initiate appropriate treatment. If history and physical examination prove insufficient for a definitive diagnosis, referral to a specialist is advised for further specific testing. The recommendations on specific testing include fractional exhaled nitric oxide for cough variant asthma, nasal endoscopy or digital endoscopy (optional) for upper airway cough syndrome, paranasal sinus computed tomography (CT) for chronic rhinosinusitis, and laryngoscopy for hoarseness. Spirometry is for the diagnosis of obstructive airway diseases, and peak flow variability or bronchial challenge tests are complements particularly if asthma is suspected. Gastroesophageal reflux (GERD) investigations are for patients with chronic cough without typical GERD symptoms. Sinus radiographs and chest CT are not routinely recommended. Our guideline distinguishes itself by prioritizing a symptom-based clinical evaluation to guide clinicians toward the most probable diagnosis, streamlining the diagnostic process.

Background: Barrier disruption in the airway mucosae has been implicated in allergic type 2 inflammatory diseases such as allergic rhinitis and asthma. Zingiber cassumunar Roxb. has long been used in traditional medicine to treat allergic diseases. The active compound, namely compound D, has proven anti-inflammatory benefits. However, the effect of compound D on allergic inflammation remains unclear., Objective: This study aimed to investigate the protective effects of compound D on allergic inflammation-induced barrier disruption., Methods: Type 2 cytokine (IL-4 and IL-13)-exposed 16HBE human bronchial epithelial cells were treated with compound D. After 24, 48, and 72 h, cytotoxicity, epithelial integrity, and tight junction (TJ) disruption were determined by viability assays, transepithelial electrical resistance measurement, and immunofluorescence staining, respectively. Moreover, the mechanism of action of compound D was investigated by western blotting., Results: Compound D (100 and 200 µM) prevented IL-4/IL-13-induced barrier disruption at 24 and 48 h with no effect on cell viability. Compound D rescued the localization of ZO-1 to pericellular areas, and the barrier-protective effect of compound D was mediated by inhibiting STAT6 signaling., Conclusions: Compound D can suppress IL-4/IL-13-induced epithelial inflammation and TJ disruption through STAT6 inhibition. The agent is a promising candidate for therapeutic or adjunctive treatment of type 2 inflammation-associated diseases, including asthma.

Introduction: Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management., Methods: This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens., Results: Overall, 1400 patients (mean age, 34 years) and 599 physicians (mean age, 43 years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score < 20) and high symptom burden (39% reported nighttime awakenings or early mornings ≥ 2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting β 2 -agonist (LABA) with as-needed inhaled short-acting β 2 -agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever., Conclusions: Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA., (© 2024. The Author(s).)

Background: Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated., Objective: This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa., Methods: This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients., Results: We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo., Conclusions: These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.

Background: Asthma and allergic rhinitis (AR) can coexist and cause disabilities. This study aimed to assess the association between AR, asthma control, asthma-related quality of life, and other comorbidities., Methods: A cross-sectional study was conducted in adults with asthma in six hospitals in Thailand. The outcomes were association of asthma control assessed by the asthma control test (ACT), AR, and asthma comorbidities. Not-well-controlled asthma was defined as ACT scores ≤22. The severity of AR was determined by visual analog scale (VAS). Severe AR was defined as VAS ≥5. Asthma-related quality of life (AQLQ), comorbidities, and total IgE were recorded., Results: A total of 682 asthmatic patients were included. Median (IQR) age was 58.0 (47.0-64.0) years. 69.9% were female. Not-well-controlled asthma was present in 44.7%. The prevalence of AR was 86.1%. Moderate/severe persistent AR was diagnosed in 21.7% and severe AR was diagnosed in 30.2% of the patients. Inhaled corticosteroid-containing regimens were prescribed in 97.7% of patients. Intranasal corticosteroid and antihistamine were prescribed in 65.7 and 31.7%, respectively. Patients with not-well-controlled asthma had higher body mass index, VAS scores, proportions of pollution exposure, aeroallergen sensitization, severe AR, nasal polyp, urticaria, food allergy, gastroesophageal reflux disease, depression and anxiety, peptic ulcer, and asthma exacerbations, but younger age, lower AQLQ scores, and lower FEV 1 . Correlation was found between AR severity and ACT ( r  = -0.461, p  < 0.001), AQLQ ( r  = -0.512, p  < 0.001), and total IgE ( r  = 0.246, p  < 0.023). Multiple regression analysis revealed that ACT, AQLQ, and percentage of FEV 1 /FVC were significantly associated with severe AR., Conclusion: Allergic rhinitis is prevalent in Thai asthmatic patients. AR severity is associated with asthma control, quality of life, and pulmonary function. Comprehensive care is essential for patients with uncontrolled asthma, particularly when coexisting with conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sriprasart, Saiphoklang, Kawamatawong, Boonsawat, Mitthamsiri, Chirakalwasan, Chiewchalermsri, Athipongarporn, Kamalaporn, Kornthatchapong, Kulpraneet, Sompornrattanaphan, Oer-Areemitr, Rerkpattanapipat, Silairatana, Thawanaphong, Gaensan, Jirakran and Poachanukoon.)

Background: Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce., Objective: To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma., Methods: A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients., Results: Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years., Conclusions: ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.

Background: Preclinical studies demonstrated anti-inflammatory effects of Zingiber montanum (J.König) Link ex Dietr.(Phlai). However, its clinical effect on allergic rhinitis (AR) is not evident., Objective: We sought to assess the efficacy and safety of Phlai for treating AR., Methods: A phase 3, randomized, double-blind, placebo-controlled study was conducted. Patients with AR were randomized into three groups and received Phlai 100 mg or Phlai 200 mg or placebo once a day for four weeks. The primary outcome was a change in the reflective total five symptom score (rT5SS). The secondary outcomes were the change in the instantaneous total five symptom score (iT5SS), the reflective individual symptom scores (rhinorrhea, nasal congestion, sneezing, itchy nose, itchy eyes), Rhinoconjunctivitis Quality of Life-36 Questionnaire (RCQ-36) score, peak nasal inspiratory flow (PNIF), and adverse events., Results: Two hundred and sixty-two patients were enrolled. Compared with placebo, Phlai 100 mg improved rT5SS [adjusted mean difference (aMD) -0.62; 95%CI -1.22, -0.03; p = 0.039], rhinorrhea (aMD -0.19; 95%CI -0.37, 0.002; p = 0.048), itchy nose (aMD -0.24; 95%CI -0.43, -0.05; p = 0.011), and itchy eyes (aMD -0.19; 95%CI -0.36, -0.02; p = 0.033) at week 4. Nasal obstruction, sneezing, iT5SS, overall RCQ-36 score, PNIF did not reach statistical significance. Phlai 200 mg did not bring additional benefits compared to 100 mg. Adverse events were similar among groups., Conclusions: Phlai was safe. At four weeks, there were small improvements in rT5SS, together with the individual symptoms of rhinorrhea, itchy nose, and itchy eyes.

Background: The accuracy of an atopy patch test (APT) for fresh cow's milk allergy is controversial. Few studies have focused on commercial extract solutions. We aimed to evaluate the diagnostic performance of the APT in cow's milk allergic children using fresh cow's milk and commercial extracts of cow's milk and its components including casein, α-lactalbumin, and β-lactoglobulin., Methods: A prospective study was carried out in children with a history of cow's milk allergy. Children underwent the skin prick test (SPT) and APT with fresh cow's milk, powdered cow's milk, and commercial extracts of cow's milk, casein, α-lactalbumin, and β-lactoglobulin. Oral food challenge (OFC) was confirmed in all children., Results: A total of 37 patients participated (mean age 13.14 ± 7.26 months). Only 5 (13.51%) patients had positive OFC to cow's milk. The sensitivity of the APT using fresh cow's milk was 40%, specificity was 65.6%, PPV was 15.4%, and NPV was 87.5%. The sensitivity of the APT using powdered cow's milk was 40%, 60.7% for specificity, 15.4% for PPV, and 58% for NPV. The sensitivity and PPV of the APT using commercial solutions of cow's milk, casein, α-lactalbumin, and β-lactoglobulin were zero. The specificities were 90.6%, 93.8%, 100%, and 100% for α-lactalbumin, cow's milk, casein, and β-lactoglobulin, respectively., Conclusions: APT using commercial solutions showed higher specificity than fresh milk. The specificity increased using a protein component allergen., (© 2023. The Author(s).)

Objective: In order to understand the role of regular controller inhaled corticosteroids (ICS) versus as-needed ICS-formoterol in managing mild asthma, we performed a modified Delphi procedure., Methods: Opinions from 16 respiratory experts to three surveys and during a virtual scientific workshop helped to develop final consensus statements (pre-defined as 70% agreement)., Results: Thirteen participants completed all rounds (response rate 81%). At the end of the procedure, there was final consensus on: regular daily ICS being the recommended treatment approach in mild persistent asthma, with better symptom control and robust long-term clinical data compared with as-needed ICS-formoterol (85%); to avoid noncompliance, frequently seen in mild asthma patients, regular ICS dosing should be accompanied by ongoing education on treatment adherence (100%); treatment aims should be targeting asthma control (92%) and reduction of exacerbation risk (85%). No consensus was reached on whether GINA or national guidelines most influence prescribing decisions., Conclusions: It is important to encourage patients to be adherent and to target both asthma control and exacerbation risk reduction. There is robust clinical evidence to support proactive regular dosing with ICS controller therapy plus as-needed short-acting beta-agonists for the management of patients with mild asthma.

Background: Patterns of aeroallergen sensitization vary by countries. Testing with the minimum number of allergens is important to identify sensitized patients for a cost-effective approach. We aimed to assess the minimal skin prick test (SPT) panel to identify sensitized children with allergic respiratory diseases., Methods: The SPT results from January 2020 to December 2021 in children aged 2-18 years with symptoms of asthma or allergic rhinitis or both were retrospectively reviewed. All children received 11 allergen extracts (Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f], American cockroach, German cockroach, cat, dog, Bermuda grass, careless weed, Timothy, Acacia, and molds). The conditional approach was used to determine the allergen selection for the SPT panel., Results: A total of 688 children were enrolled (mean age = 8.14 ± 3.91 years). The sensitization results were Der p (57.85%), Der f (55.09%), German cockroach (18.02%), American cockroach (17.01%), cat (11.77%), Acacia (3.49%), Bermuda grass (3.34%), molds (3.05%), Timothy (2.33%), dog (1.89%), and careless weed (1.60%). Der p, Der f, and German cockroach were required to detect at least 95% of sensitized children. If the SPT panel added Acacia, cat, American cockroach, Bermuda grass, and careless weed, sensitization was detected in 99-100% of cases., Conclusions: Indoor allergens (Der p, cockroach, and cat) were common causes of sensitization in Thai children with allergic respiratory diseases. Eight allergens were sufficient for sensitization identification in Thai children with asthma or allergic rhinitis or both in clinical practice., (© 2022. The Author(s).)

Background: Nasal irrigation is an effective component of sino-nasal disease management. Nonetheless, bacterial contamination is worrisome., Objective: To study bacterial colonization incidence using squeeze-bottle nasal irrigation devices, after disinfection with soap or soap-plus-microwave technique, in pediatric acute rhinosinusitis., Methods: A randomized, prospective, controlled study was conducted on acute rhinosinusitis children, aged 2-15 years. Each participant was randomized into a soap-cleaning or soap-plus- microwave group. For a two-week period, participants irrigated their nostrils with NSS twice daily and cleaned the bottle after each use. In the end, bottles were sent to a microbiological laboratory for bacterial identification., Results: The mean 5S Score and satisfaction score gradually improved in both groups with no significant differences between groups. Bacterial identification frequency in the soap group was slightly higher than in the soap-plus-microwave one, without statistical significance. For safety and tolerability, all participants reported 100% adherence to nasal irrigation. The soap-plus-microwave group reported more minor adverse outcomes than the soap-cleaning one. No thermal deformation of irrigation bottles was observed., Conclusions: Regular cleaning of nasal irrigation devices is needed to minimize bacterial contamination. Only soap or soap plus microwave disinfection appeared simple and safe for disinfection. Both techniques can equally minimize the rate of bacterial contamination. Although no gross thermal deformation at optimal power and duration, chemical irritants after high power or long microwave durations may be a concern.

The multidisciplinary experts in Thailand developed an asthma management recommendation that was relevant to low-middle income countries (LMICS). Populations level consideration about asthma management is emphasized. The healthcare systems, access to and availability of treatments as well as the asthma populations vary from country to country in LMICS. The feasibility in clinical practice for implementation is also a major issue. For these reasons, the practice guidelines that are relevant to local contexts are essential to improve better asthma control. Furthermore, integrative and collaboration between asthma experts and the public health sector to implement and discriminate such guidelines will help to achieve these challenging goals. The topics covered include the current asthma situation in Thailand and the Asia-Pacific region, the definition of asthma, asthma diagnosis, assessment of asthma patients, asthma treatment - both pharmacological and non-pharmacological, management of asthma exacerbation, management of asthma comorbidities, treatment of asthma in special conditions, severe and uncontrolled asthma, Thai alternative medicine and asthma, and asthma and coronavirus disease-19 (COVID-19).

Objective: The aim of this study was to determine if there is an association between the salivary protein profile and disease control in asthma., Methods: Thirty asthmatic patients (17 adults and 13 children) participated in this study. Saliva samples were collected from healthy subjects, controlled and uncontrolled asthmatics. Individual samples from each group were combined to form a pooled sample, from which proteomic analysis was performed using gel-based quantitative proteomics., Results: Fourteen out of thirty asthmatics were classified to be controlled asthma. Most of asthmatics received inhaled corticosteroids as the controller medications. SDS-PAGE showed predominant bands at high molecular weight in asthmatic saliva compared to that of the controls. Shotgun proteomic analyses indicated that 193 salivary proteins were expressed in both controlled and uncontrolled asthmatics. They were predicted to associate with proteins involved in pathogenesis of asthma including IL-5, IL-6, MCP-1, VEGF, and periostin and asthma medicines (Cromolyn, Nedocromil, and Theophylline). Nucleoside diphosphate kinase (NME1-NME2) only expressed in controlled asthmatics whereas polycystic kidney and hepatic disease 1 (PKHD1)/fibrocystin, zinc finger protein 263 (ZNF263), uncharacterized LOC101060047 (ENSG00000268865), desmoglein 2 (DSG2) and S100 calcium binding protein A2 (S100A2) were only found in uncontrolled asthma. Therefore, the six proteins were associated with disease control in children and adults with asthma., Conclusion: Our findings suggest that NME1-NME2, PKHD1, ZNF 263, uncharacterized LOC101060047, DSG 2 and S100 A2 in saliva are associated with disease control in asthma.

Background: Allergic rhinitis (AR) has substantially negative impacts on patients' quality of life. Besides conventional medicines, many patients use alternative approaches, which sometimes were misconception., Objective: This study aims to explore and compare the beliefs about AR and its treatment options between 2 different groups; control and AR patient groups., Methods: A cross-sectional study of 518 respondents residing in the central region of Thailand has been conducted using a self-reported questionnaire which consists of 3 parts; personal profile, the International Study of Asthma and Allergies in Childhood (ISAAC) questions, and the beliefs. ISAAC is applied for identifying respondents as the control or the AR group., Results: From a total of 518 respondents, 311 (60.0%) were identified as the AR group. The demographic data between the control and the AR group has no statistical difference ( p > 0.05). Regarding the beliefs about AR characteristics, 56.1% of the AR group believe that low immunity causes AR while the number of the control group reaches 56%. Thirty-nine point two percent for the AR group and 38.6% for the control group believe that AR is a fatal disease. The belief that AR can be spread by droplet/airborne transmission is 22.8% and 28.5% for the AR and the control group, respectively. About AR treatment options, 60.1% of the AR group and 43% of the control group believe that taking vitamin C can relieve AR symptoms, which has a statistical difference ( p < 0.05) between the 2 groups. The belief that prolonged use of antihistamine drugs can cause drug resistance is 29.9% and 24.6% for AR and control groups, respectively., Conclusion: Both groups of respondents mostly share common beliefs about AR characteristics and treatment options in which the AR group has higher percentage in some beliefs. Therefore, health literacy should be promoted in order to improve patient's care., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Acute asthmatic exacerbation in children causes economic burdens both directly and indirectly. The GINA guideline does mention the use of inhaled or oral corticosteroids in the treatment of asthmatic exacerbation, it provides little practical guidance on the use of nebulized corticosteroid., Objective: To review and recommend the practical considerations in the use of nebulized corticosteroid in children with acute asthmatic exacerbation., Methods: This consensus was developed by a group of expert pediatricians in respiratory and allergy fields in Thailand. The recommendations were made based on a review of published studies and clinical opinions. The eligible studies were confined to those published in English, and randomized controlled trials and meta-analyses involving nebulized corticosteroids in asthmatic exacerbation in children aged between 1-18 years., Results: There were 13 randomized controlled-trial studies published from 1998 to 2017. Nine of the 13 studies compared nebulized with systemic corticosteroid conducted in moderate to severe exacerbation, while the remaining four compared nebulized corticosteroid with placebo conducted in mild to severe exacerbation. The admission rate was significantly lower in severe exacerbation (one study) and pooled four mild to severe exacerbation studies comparing with placebo (p 0.022). Other clinical parameters were significantly improved with nebulized corticosteroid such as clinical scores, systemic corticosteroid/bronchodilator use, or shorter ER stays. Only one study used fluticasone, while the other 12 studies conducted by budesonide (92.31%)., Conclusions: Nebulized corticosteroid may offer an effective therapeutic option for the management of acute exacerbation of asthma in all severities. Nebulized budesonide is the preferred corticosteroid.

Background: In vitro studies have demonstrated cross-reactivity among indoor allergen proteins in children with allergic respiratory diseases. However, there are only few studies evaluating in vivo response. A skin prick test (SPT) with commercial indoor solutions is widely used in clinical practice. We aimed to evaluate SPT agreement in children with allergic respiratory disease between pairs of common indoor allergens., Methods: We reviewed SPT results of children 2 to 18 years old, diagnosed with respiratory allergic disease. Results from house dust mite (Dermatophagoides farinae, Dermatophagoides pteronyssinus), cockroach (Periplaneta americana, Blatella germanica), cat and dog were collected. Sensitization was defined as ≥ 3 mm in wheal diameter. Kappa coefficient (κ) was used to analyze sensitization concordance for each allergen pair., Results: The charts of 300 children, 187 (62.33%) males, were reviewed. Mean age was 7.43 ± 3.29 years with 183 (61%), 140 (46.67%), 45 (15%), 30 (10%) sensitizations to house dust mite (HDM), cockroach, cat and dog, respectively. Sensitization concordance between HDM and cockroach was moderate: κ = 0.53 (95% CI: 0.42-0.64). Moderate agreement occurred between dog and cat: κ = 0.41 (95%CI: 0.30-0.52). HDM-sensitized children showed poor concordance with both cat κ = 0.17 (95%CI: 0.09-0.24) and dog κ = 0.09 (95%CI: 0.03-0.14). There was also poor concordance between cockroach-sensitized children to cat κ = 0.19 (95%CI; 0.11-0.28) and dog κ = 0.11 (95%CI; 0.04-0.18)., Conclusion: We demonstrated moderate agreement of SPT response between HDM and cockroach as well as dog and cat. This may be due to cross-reactivity. Component-resolved diagnosis should be considered in children with co-sensitization of these allergen pairs., (© 2021. The Author(s).)

Cigarette smoking has negative effects on the respiratory system, particularly pulmonary functions. This study aimed to determine smoking prevalence and characteristics among university athletes. We conducted a cross-sectional study of Thammasat University athletes in Thailand from July to October 2018. Demographic and smoking data were recorded. Exhaled carbon monoxide (CO) levels and lung function data were analysed. A total of 433 subjects (56% men) were included. Mean age was 19.8 ± 1.3 years. Asthma was reported in 5.5%. The prevalence of current cigarette smoking was 23.8%. Tobacco use was 3.0 ± 3.2 cigarettes per day. The Fagerstrom score for nicotine dependence was 0.76 ± 1.47. Compared to non-smokers, smokers were predominately males (70.6% vs 29.4%, P < 0.001), had higher exhaled CO levels (3.75 ± 3.08 ppm vs 2.18 ± 0.73 ppm, P < 0.001), higher FVC (89.65 ± 17.61% vs 83.22 ± 15.72%, P = 0.001), higher FEV 1 (92.60 ± 15.36% vs 87.77 ± 11.23%, P = 0.002), but lower FEV 1 /FVC (78.21 ± 5.38% vs 79.70 ± 5.60%, P = 0.015). Moreover, athletes who smoke, were more likely to: drink alcohol, have a family member who smokes, have a friend who smokes or have a university instructor who smokes. In conclusion, smoking prevalence among university athletes was relatively high, although low nicotine addiction level and good lung functions were found. Home and institute environments had important influences on cigarette use in students.Trial registration: TCTR20180917001.

Purpose of Review: Pediatric and adult chronic rhinosinusitis (CRS) have some similarities but a number of differences. This article reviews the similarities and differences between pediatric and adult CRS., Recent Findings: Rhinosinusitis is an inflammatory disease of the nose and the paranasal sinuses. In adults, inflammation in CRS without polyps (CRSsNP) mainly manifests with T-helper 1 lymphocytes while in CRS with polyps (CRSwNP) manifests with T-helper 2 lymphocytes and eosinophilic inflammation. In children, CRS inflammation manifests with neutrophils, macrophages, and lymphocytes. The associations between the ostiomeatal complex occlusion and CRS are revealed in adults but are not so evident in children. Although the relationship between the CRS and allergic rhinitis is still controversial, recent findings have shown an association between allergen sensitization and a specific group of adults with rhinosinusitis. Intranasal corticosteroids and saline constitute the first-line of medical treatment for both pediatric and adult rhinosinusitis. Low-dose macrolides are used for immunomodulatory activities and beneficial effects to adult patients with CRSsNP were demonstrated by recent meta-analyses. For surgical treatment, adenoidectomy is a key strategy to eradicate mature biofilms in pediatric CRS and effective in treating children with CRS regardless of the adenoid size. Although endoscopic sinus surgery has been proven to improve quality of life outcomes in adult CRS, it should be only considered in the pediatric CRS after failure of adenoidectomy. Pediatric and adult CRS are different in many aspects, including immunopathogenesis and management. Investigations should be considered in specific cases. After failure of medical treatments, endoscopic sinus surgery is recommended for adults, while adenoidectomy is primarily considered for children.

Purpose: Reported associations of interleukin-18 (IL-18) single-nucleotide polymorphisms (SNPs) with allergic rhinitis (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates., Methods: We synthesized data from 8 articles and examined 3 IL-18 SNPs. Two SNPs (rs360721 and rs187238), in linkage disequilibrium, were combined and termed RS1. The rs1946518 SNP was analyzed separately (termed RS2). The recessive, dominant, and codominant (multiplicative) genetic models were used to estimate ORs and 95% CIs. Subgroup analysis was ethnicity-based. Sources of heterogeneity were investigated with outlier treatment. Sensitivity analysis was used to assess robustness of the associative effects. Multiple comparisons were Holm-Bonferroni corrected., Results: All significant (pa < 0.05) outcomes indicating increased risks were found in the dominant/codominant models in RS1 and RS2. Five aspects of differences marked the significant African (RS1) and overall (RS2) outcomes: (i) magnitude of effect (ORs): greater (3.01-5.15) versus less (1.20-1.47); (ii) precision of -effects (95% CIs): less (1.07-21.52) versus more (1.01-1.89); (iii) outlier treated: no versus yes; (iv) sensitivity outcomes: nonrobust versus robust (dominant model only); and (v) greater evidential strength for RS2 (pa = 0.002) compared to RS1 (pa = 0.02) rendered RS2 our core finding. These levels of statistical significance for RS1/RS2 enabled both to survive the Holm-Bonferroni correction., Conclusions: The core outcome indicating a 1.5-fold increased risk could render the IL-18 polymorphisms useful in the clinical genetics of AR. Future studies that could focus on other IL-18 SNPs may find deeper associations with AR than what we found here., (© 2020 S. Karger AG, Basel.)

Objective: To determine whether the measurement of exhaled nitric oxide (eNO) can help distinguish children with allergic rhinitis (AR) from healthy controls and whether eNO in children with AR correlates with disease severity., Methods: From August 2015 to 2016, children aged 5-15 years of age grouped into those with allergic rhinitis (n = 40) and those classified as healthy control subjects (n = 40) had exhaled nitric oxide (eNO) levels measured. The eNO level was additionally compared to the patient's clinical disease severity according to the ARIA (Allergic Rhinitis and its Impact on Asthma) classification., Results: Mean eNO in children with AR (12.64 ± 14.67 ppb) was significantly higher than that in the healthy control group (7.00 ± 6.33 ppb) (p-value = 0.046). In the persistent AR group (17.11 ± 18.40 ppb), eNO level was significantly higher than individuals in the intermittent AR group (8.59 ± 8.88 ppb, p-value = 0.024) and the healthy control group (7.00 ± 6.33 ppb, p-value = 0.008). Among children with AR, eNo was not significantly different with relationship to gender, age, weight and passive smoking exposure., Conclusions: Exhaled nitric oxide may be elevated in children with AR that do not have concomitant asthma. This suggests exhaled nitric oxide may show utility as a parameter to monitor the severity of allergic rhinitis and to monitor the efficacy of the treatment. Physicians should consider comorbid AR when utilizing exhaled nitric oxide as a monitoring parameter in the treatment of asthma., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To evaluate long-term effectiveness of omalizumab in 'real-life' setting of Thai asthmatic patients., Methods: We conducted multi-center, observational study in severe asthma patients who received omalizumab in Thailand. Outcomes were asthma exacerbation (hospitalization and ER visit), asthma control test (ACT), and daily ICS dose. Data were evaluated at baseline, 16 Week, and 52 Week., Results: A total of 78 patients received omalizumab treatment (average duration 16.9 months with range 16 weeks-2 years). The mean annualized rate of exacerbations was reduced from baseline (3.79) at Week 16 (3.54) and Week 52 (1.16), (p<0.05), respectively. The mean hospitalization rate was reduced from 0.49 in previous year to 0.15 at Week 16 and 0.19 at Week 52. A reduction in ER visit rates was observed at Week 16 (0.15) and Week 52 (0.97) respectively from baseline (1.44) (p<0.05). The ACT score increased from 15.4 at baseline to 20.6 at Week 16 (p<0.001) and increased to 21.5 at Week 52 (p<0.001). The number of patients with controlled asthma (ACT≥20) increased from 16 of 51 at baseline to 32 of 45 at Week 16 and 25 of 32 at week 52, respectively. The median daily dose of ICS equivalent to fluticasone was reduced from baseline 680 mcg to 500 mcg at Week 52. In all, 22 patients discontinued omalizumab after 1 year. Six patients who discontinued omalizumab were restarted due to relapse of symptoms., Conclusions: These data confirms the effectiveness of one-year duration of omalizumab treatment in Thai severe asthmatic patients. Furthermore, 27% of patients who discontinued treatment required restarting due to relapse of symptoms.

Introduction: Compound D and DMPBD are compounds extracted from Plai or Zingiber cassumunar Roxb., which have antiasthmatic properties. Thai herbal pharmacopoeia have indicated that approximate 50% of Thai prescriptions for asthma contain Plai. However, the inhibition mechanisms of these compounds are not clearly known., Methods: In this study, molecular docking and molecular dynamics (MD) simulations have been used to simulate complex systems and analyze molecular interactions between these compounds and protein target, 5-lipoxygenase (5-LO) enzyme, which is an enzyme involved with asthma symptoms., Results: From our MD simulations, Compound D and DMPBD molecules bind at the same binding site of its natural substrate (arachidonic acid) on 5-LO enzyme, which is similar to the binding of commercial asthma drug (Zileuton). Molecular mechanics generalized born surface area binding energy calculations of the 5-LO complex with Compound D and DMPBD are -26.83 and -29.15 kcal/mol, respectively., Conclusions: This work indicated that Compound D and DMPBD are competitive inhibitors, which are able to bind at the same 5-LO substrate binding site. This reveals opportunities for using Compound D and DMPBD as novel antiasthmatic drugs., (© Biomedical Engineering Society 2017.)

Background: Zingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease., Objective: The purpose of this study was to assess the antihistaminic effect of Phlai on skin testing., Design, Setting, Participants and Intervention: This was a randomized, open-label, three-way crossover study. Twenty allergic rhinitis (AR) patients were enrolled. In randomized sequence, patients received a single dose of Phlai capsules (100 or 200 mg) or loratadine (10 mg) with a washout period of 1 week between each treatment., Main Outcome Measures: Skin prick testing for histamine and common aeroallergen (house dust mite) were performed before treatment and after 1, 2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment., Results: Both 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that loratadine caused more wheal and flare suppression than Phlai capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and loratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse events., Conclusion: Both 100 mg (compound D 4 mg) and 200 mg (compound D 8 mg) Phlai capsules, when taken as a single therapeutic dose, inhibited skin reactivity to histamine and mite skin prick tests in AR patients., Trial Registration: Thai clinical trial registry (TCTR20160510001).

Objective: To evaluate the efficacy of positive-pressure nasal irrigation devices in children with acute sinusitis, in addition to bacterial colonization of the irrigation device., Method: We performed a randomized, prospective, controlled study of 80 children with acute sinusitis, aged between 3 and 15 years. Participants were randomly separated into two groups, where one group was treated using a squeezable bottle and the other group treated using a syringe. All patients were instructed to use a 1.25% buffered hypertonic solution for nasal irrigation twice daily for 2 weeks, in addition to amoxicillin-clavulanic acid. During this period, all participants recorded a 5S score, satisfaction score, any side effects and use of antihistamines. Parents were instructed to clean the device with soap after each use. After this period, the nasal irrigation devices were sent to a microbiological laboratory for bacterial identification., Results: At the 2-week follow-up, improvement in both 5S and satisfaction scores were observed in both groups compared to baseline, which were significantly higher in the group treated with the squeezable bottle compared to the syringe. Few complaints were reported, and side effects were equal in both groups. The overall rate of bacterial contamination for both treatments was approximately 80%, but this did not translate into higher rates of infection amongst patients., Conclusions: The use of a squeezable bottle for nasal irrigation in children with acute sinusitis was associated with further improvements in 5S and satisfaction scores compared to syringe use, and there were no significant differences in bacterial contamination between methods.

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor α (TNF-α) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported., Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-α in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone (1 µg/mL) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-α in culture supernatants were measured using enzyme-linked immunosorbent assay., Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-α., Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-α production in PMA-induced human airway epithelial cells., Competing Interests: No potential conflict of interest relevant to this article was reported.

Rhizomes of Zingiber cassumunar have been used for many years in traditional Thai medicine as an anti-inflammatory agent. The major bioactive component of this plant is Compound D [E-4-(3', 4'-dimethoxyphenyl)but-3-en-1-ol], which is a strong smooth muscle relaxant, and has antihistamine and anti-inflammatory actions. There is, however, incomplete information available for the pharmacokinetics of Compound D in mammals. In this study, we examined the pharmacokinetic profiles of Compound D in male Wistar rats. A standardized extract of Z. cassumunar containing 4 % w/w Compound D was administered intravenously at 25 mg/kg or by oral gavage at 25, 75, or 250 mg/kg to Wistar rats. Blood, tissues, urine, and feces were collected from 0 to 48 h after dosing and the level of Compound D was determined by liquid chromatography-tandem mass spectrometry. The concentration of Compound D ranged from 10-100 µg/L, reached a maximum approximately 0.15 h after oral dosing. Compound D exhibited an excellent tissue to plasma ratio, ranging from 1- to 1000 in several organs at 1-4 h after oral dosing. Less than 1 % of unchanged Compound D was excreted in the urine and feces. Further studies on tissue uptake and metabolite identification are required to obtain complete pharmacokinetic information and to develop appropriate dosing strategies of Compound D and the standardized extract of Z. cassumunar., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Inhaled bronchodilator treatment given via the pressurized metered-dose inhaler (pMDI) with spacer has been recommended for an acute asthma treatment. Unfortunately, most of commercially available spacers are at high cost while a do-it-yourself (DIY) spacer has lower cost as it is made from plastic bottle and siphon pump which are inexpensive and easilyfound materials., Objective: This study aims to compare treatment response in nebulizer and DIY spacer used for asthmatic children., Material and Method: A prospective, randomized control study was conducted in children aged 1-15 years old hospitalized for mild to moderate asthmatic attack at Thammasat University Hospital between June 2014 and March 2015. The patients were divided into 2 groups, receiving β2-agonist via nebulization and via pMDI with DIY spacer. Their vital signs and oxygen saturation were monitored and asthma scores were also recorded at admission, 24 hours, 48 hours, and before discharge. The satisfaction of equipment use was evaluated employing questionnaires., Results: 40 childrens were enrolled with male at 72.5% and mean age at 3.1±1.6 years old. There was no significant difference in efficacy of β2-agonist among 2 groups when comparing in consideration of vital signs, oximetry, asthma scores and hospital stay. However, there were significantly different on side effect in which the DIY spacer had less tachycardia and agitation. Satisfaction of parents and healthcare workers were higher in DIY spacer., Conclusion: MDI with DIY spacer was able to be used effectively when compared with nebulization to treat mild to moderate acute exacerbations of asthma in children admitted in hospital.

Background: The prevalence of allergic rhinitis (AR) in Thailand continues to rise. We report the prevalence and evaluate its impact upon quality of life (QoL) in students on a metropolitan campus., Methods: From March 2013 to February 2014, 222 students from Thammasat University Medical School were evaluated using the International Study of Asthma and Allergies in Childhood Questionnaire (ISAAC) questionnaire and the rhinoconjunctivitis QoL questionnaire (Rcq-36) to assess subjective symptoms. Those students with clinical symptoms of AR underwent skin prick testing (SPT) using 5 common allergens found in Thailand. The association between AR and QoL was then determined using a paired t test., Results: A total of 222 students were enrolled in the study; 86 (38.7%) were men. There were 183 (81.9%) students with AR symptoms and 130 (71.4%) students with positive results for SPT. The students' QoL as defined by the Rcq-36 revealed a significant worsening in students who self-reported rhinitis symptoms within the past 12 months. Compared to the non-AR group, in those with AR, eye symptoms were significantly more common., Conclusion: The prevalence of AR at a college campus was 58.5%. The presence of rhinitis symptoms was the highest predictor of the presence of AR, with 67.7% having subsequent positive SPT. Students with AR had poorer scores in every dimension of QoL as defined by the Rcq-36 when compared to their non-AR counterparts. Educational performances among the 2 groups were unaffected., (© 2015 ARS-AAOA, LLC.)

Objectives: Cefditoren pivoxil (CDT) has been used in the treatment of rhinosinusitis. However, little is known about the efficacy of this drug at low and high doses. This study was to compare the efficacy and safety of low dose (8-12 mg/kg/day) and high dose (16-20 mg/kg/day) CDT in the treatment of children with uncomplicated acute rhinosinusitis (ARS)., Methods: This investigation was a randomized, investigator-blinded, and parallel study, conducted in patients (aged 1-15 years) with a clinical diagnosis of uncomplicated ARS. Two groups of patients randomly received low dose or high dose CDT for 14 days. Patients' symptoms were assessed quantitatively using a quantitative symptom score (the S5 score). The changes in sinus symptoms and adverse events were provided by patients and their parents/caregivers. The response rate and adverse effects were evaluated at days 7 and 14. The relapse rate was recorded at days 21 and 28. The recurrences of sinus symptoms at day 60 were also assessed., Results: One hundred forty patients were recruited and randomized; 72 received low dose CDT (group I) and 68 received high dose CDT (group II). There were no significant differences in demographic data including sex, age, presenting symptoms, medical history, and X-ray findings between two groups. The responses rate at day 14 in groups I and II were 95.5% and 95.4%, respectively (P>0.99). There were no significant differences between groups in relapse rate at day 28 and no recurrence at day 60 in either group. The most common treatment-related adverse events were diarrhea (4.2% in group I vs. 2.9% in group II) and vomiting (2.8% in group I vs. 10.3% in group II). There was no statistically significant difference in adverse events between groups., Conclusion: Both low and high doses regimens of CDT appeared a similar clinical outcome for treatment in uncomplicated ARS in pediatric patients.

Background: The assessment of the quality of life among patients and their parents is increasingly recognized as an important chronic disease such as asthma., Objective: The present study assessed the validity and reliability of the Thai Mini PAQLQ in Thai asthmatic children by comparison with the PAQLQ., Material and Method: The authors performed a 9-week Descriptive cross sectional study. The mini PAQLQ (Thai version) consists of11 items which are categorized into symptoms, activities, emotions. Cronbach 's alpha was used to test for internal consistency reliability. The Pearson's correlation co-efficients was used to test Criterion validity., Results: 58 patients, aged 7-17 years were recruited in the study. 45 patients completed the study. The mean age ofpatients was 10.5 +/- 2.7 years. The intraclass correlation between PAQLQ andMiniPAQLQfor total, activities and symptoms were moderately strong except in emotion domain (ICC = 0.65). The correlations between the PAQLQ and MiniPAQLQ were 0.80-0.72. Both quality of life questionnaires correlated strongly with the asthma control questionnaire but not with PEFR., Conclusion: The MiniPAQLQ is valid and reliable when compared to the PAQLQ. It can be used with confidencefor monitoring in a pediatric asthma clinic.

Background: House dust mite (HDM) induced matrix metalloproteinase (MMP)-9 plays a role in asthma. Zingiber cassumunar Roxb. (Phlai in Thai) has been used in folk medicine for asthma treatment., Objective: We investigated effects of Phlai and its constituent (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D) on the cleavage of pro- MMP-9 by HDM. The effects of these compounds on phorbol 12-myristate 13-acetate (PMA)- induced MMP-9 gene and protein expression in airway epithelial cells (NCI-H292) were also investigated., Methods: Pro-MMP-9 was directly activated in vitro with HDM in the presence or absence of the ethanolic extracts of Phlai or compound D for 1 hour. The amount of activated MMP-9 was determined using gelatin zymography. To study the cellular response of Phlai, NCI-H292 cells were pretreated with crude Phlai extracts or compound D for 2 hours, and then the cells were stimulated with PMA for 48 hours. The mRNA RT-PCR and Western blotting, respectively. MMP-9 activity was determined by gelatin zymography., Results: Crude Phlai extracts (0.25 - 2.0 mg/ml) and compound D (0.5 - 4.0 mg/ml) inhibited pro- MMP-9 cleavage by HDM. Furthermore, crude Phlai extracts (100 mg/ml) and compound D, at concentrations of 50 and 100 mg/ml, attenuated the PMA-induced MMP-9 gene and expression in NCI-H292 cells. These compound also suppressed MMP-9 release from PMA-induced NCI-H292 cells., Conclusion: The crude ethanolic extract of Z. cassumunar and its active constituent compound D inhibited the cleavage of pro-MMP-9 by HDM. They also inhibited PMA-induced MMP-9 gene and protein synthesis in human airway epithelial cells.

Objective: To compare the sleep problems between children with and without allergic rhinitis (AR)., Material and Method: A case-control study was conducted in 65 children aged 6-15 years with allergic rhinitis and 104 control subjects matched individually by age, height and weight. Cases were recruited from the Pediatric Allergy Clinic at Thammasat University Hospital. The selection of cases was based on clinical history, physical examination and skin prick test. Matched healthy control children were recruited from the Thammasat primary school. Children and their caregivers who usually sleep with them completed the questionnaire., Results: 86.2% of allergic rhinitis was classified as persistent rhinitis and 63.1% had moderate to severe disease. The most common presenting symptom was nasal blockage (66.2%). Allergic rhinitis patients had significant sleep problems with snoring, sleep apnea, restless, night sweating, mouth breathing, dry throat, morning headache, falling asleep in class, difficulty in waking up and not refreshed in the morning (p<0.05). Patients who categorized as blockers had significantly more restless sleep and dry mouth on waking up compared to that of non-blockers (p<0.05)., Conclusion: There was a higher prevalence of sleep problems in children with AR then those without AR.

Background: Over expression of mucin often leads to serious airway pathologies. The rhizome of Zingiber cassumunar Roxb. ("Phlai" in Thai) has been used as an anti-asthmatic drug in Thai traditional medicine. However, the effect of this plant on mucin production has not been reported., Objective: The aim of the present study was to investigate whether crude ethanolic extracts of Zingiber cassumunar (CEZE) suppress phorbol12-myristate 13-acetate (PMA)-induced mucin production and gene expression in human airway epithelial cells and if so, to examine whether the suppression of mucin gene expression is mediated via the mitogen-activated protein kinase (MAPK) signal transduction pathways., Methods: Confluent NCI-H292 cells were pretreated with CEZE for 2 hours and then stimulated with 100 or 200 nmol/l PMA for 8 h. The levels of MUC2 and MUC5AC mRNA were determined by RT-PCR and real-time PCR. Levels of total mucin; MUC2 and MUC5AC inculture supernatants were measured using ELLA and ELISA assays, respectively. Extracellular signal-regulated kinase (ERK), JNK, p38 MAPK protein levels were analyzed by Western blotting., Results: CEZE (5-100?g/ml) significantly inhibited total mucin production, including MUC2 and MUC5AC mRNA and proteins induced by PMA in NCI-H292 cells. The extracts obviously inhibited the phosphorylation of ERK, but not JNK and p38 in PMA-stimulated NCI-H292 cells. Our results suggest that Z. cassumunar-mediated suppression of PMA-induced MUC2 and MUC5AC mRNA operates via ERK inhibition., Conclusion: Z. cassumunar suppresses PMA-induced MUC2 and MUC5AC gene expression in human airway epithelial cells via inhibition of ERK MAPK-dependent pathway.

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.

Thalassemia major is an inherited form of chronic hemolytic anemia that results in iron overload due to regular blood transfusions. Deferoxamine is used as chelating agentfor treatment ofpatients with chronic iron overload worldwide. Anaphylactic reaction to deferoxamine is rare, and the mechanism ofdeferoxamine-induced anaphylaxis is not well understood. Only afewpediatric cases ofsuccessful desensitization for deferoxamine hypersensitivity have been described, and a different protocol has been used in each report. We report a case ofanaphylaxis to deferoxamine in a thirteen-years-old Thai boy with Hemoglobin E/β-thalassemia disease who underwent successful desensitization. He had been receiving blood transfusions since the age often months. At age eleven, the patient began treatment with deferoxamine. Treatment was interrupted after the occurrence ofanaphylaxis, with urticaria, wheezing and gastrointestinal symptoms. A skin prick test was positive, indicating a type 1 hypersensitivity reaction. Deferoxamine desensitization was attempted with various differentprotocols. Finally, the patient could tolerate deferoxamine therapy at the dose previously administered. We proposed this modified subcutaneous desensitization protocolforpediatric cases that develop allergic reactions to deferoxamine.

Objectives: The aim of this study was to observe the caries activities of allergic rhinitis patients in relation to salivary properties, salivary levels of mutans streptococci (MS) and lactobacillus (LB), oral hygiene and dietary habits., Methods: The study groups composed of 40 allergic rhinitis children and 40 healthy controls aged between 6 and 13 years old. Demographic data, oral hygiene practices and dietary habits were recorded by questionnaire. For permanent teeth, caries experience was expressed as DMFT (D=decayed; M=missing; F=filled; T=teeth) index. The dmft (d=decayed; m=missing; f=filling; t=teeth) index was used for caries prevalence in primary teeth. Unstimulated salivary flow rate, salivary buffering capacity, and salivary MS and LB were also determined in children with allergic rhinitis and controls., Results: There were no significant differences in combined DMFT/dmft, salivary flow rate, buffer capacity of saliva, salivary LB levels, and sugary food consumption between cases and controls (p>0.05). However, higher salivary MS levels were observed in allergic rhinitis patients, compared to controls (P<0.05)., Conclusions: Our results demonstrated that patients with allergic rhinitis had an increase in the level of salivary MS., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: Macrolide antibiotics are effective drugs in chronic bronchiolitis and chronic rhinosinusitis with mucus hypersecretion. However, the mechanism of action is unclear. This study was designed to investigate the effect of azithromycin (AZM; 15-membered) and midecamycin acetate (MDM; 16-membered) on MUC5AC and MUC2 gene expression and secretion from human airway epithelial cells. The effects of the two macrolides on tumor necrosis factor-α (TNF-α) release were also examined., Methods: Confluent NCI-H292 human mucoepidermoid airways epithelial cells were pretreated with AZM or MDM for 2 h and then stimulated with 200 nmol/l phorbol 12-myristate 13-acetate (PMA) for 8 h. The MUC5AC and MUC2 gene expression was measured by real-time quantitative RT-PCR. Total mucin in culture supernatants was measured using enzyme-linked lectin assay. Enzyme-linked immunosorbent assay was used to determine MUC5AC, MUC2 and TNF-α released by the cells., Results: AZM and MDM attenuated PMA-induced MUC5AC and MUC2 gene and protein expression in NCI-H292 cells. They also suppressed PMA-mediated TNF-α in the cells., Conclusion: The present study demonstrates that AZM and MDM suppress the synthesis of mucin and TNF-α from human airway epithelial cells., (© 2014 S. Karger AG, Basel.)

Background: Rhinosinusitis (RS) is a common problem in children. There are very few published studies comparing acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) in children., Objective: To determine the clinical manifestations in children with ARS and CRS., Methods: One hundred and fifty-four patients with a clinical diagnosis of RS were enrolled. ARS was defined as persistent symptoms for more than 10 days but less than 4 weeks and CRS was defined as persistent symptoms for longer than 8 weeks. Patients were interviewed to obtain demographic and clinical data. Physical findings and medications were recorded. All patients underwent radiographic studies. Allergy and immunological testing were done in selected case. All data were compared between the ARS and CRS groups., Results: One hundred and three patients were classified as having ARS and fifty-one had CRS. Their mean (+/- SD) age was 5.9 +/- 3.3 years. Allergic rhinitis was common in the chronic rhinosinusitis group. The most common main complaints in acute and chronic rhinosinusitis were cough and rhinorrhea. There was no significant difference in symptoms between both groups, except for periorbital pain and sleep apnea which were found more frequently in the chronic group. Sixty five percents of ARS and 58.8% of CRS had abnormal x-ray findings. Adenoid hypertrophy was found in the CRS group. There was overall improvement after 14.6 +/- 3.82 days and 22.35 +/- 5.04 days (mean) of antibiotic treatment in the ARS and CRS groups, respectively. None of the patient underwent sinus surgery., Conclusion: The most common RS symptoms were rhinorrhea and cough. Patients with allergic rhinitis had a higher risk of developing chronic rhinosinusitis. Patients with ARS and CRS were successfully treated with medical treatment.

Background: The recommended treatment for acute bacterial rhinosinusitis in adults and children is 10 to 14 days of high doses of oral cephalosporins or amoxicillin/clavulanate., Objective: This study compared the clinical efficacy and tolerability of cefditoren pivoxil and amoxicillin/clavulanate in children with uncomplicated acute bacterial rhinosinusitis., Methods: This was a randomized, investigator-blinded, controlled study in pediatric patients (age 1-15 years) with clinical and radiographic signs and symptoms of acute rhinosinusitis. Patients were allocated to receive either cefditoren (8-12 mg/kg daily) or amoxicillin/clavulanate (80-90 mg/kg amoxicillin daily) for 14 days. Changes in sinus symptoms were assessed daily by patients or their parents using a quantitative symptom score (the S5 score). Rates of improvement, the primary efficacy measure, were also evaluated by the study investigators 7 and 14 days after the initial visit. Secondary outcome measures included time to improvement, adverse effects, and rates of relapse (assessed at days 21 and 28) and recurrence (assessed at day 60) of sinus symptoms. Relapse was defined as a subjective rating of lack of improvement at day 21 or 28 in a patient rated as improved on day 14, and recurrence was defined as sinus symptoms lasting for >or=10 days during the second month of follow-up in a patient rated as improved on day 28. Time to improvement was defined as the number of days between the initial visit and the time at which caregivers noted an improvement in patients' symptoms. Adverse events were monitored by parents/caregivers using a self-administered questionnaire and were also elicited by telephone contact., Results: The study enrolled 142 pediatric patients: 70 in the cefditoren group (42 males, 28 females; median age, 7.15 years) and 72 in the amoxicillin/clavulanate group (37 males, 35 females; median age, 6.60 years). Four patients in the cefditoren group were excluded from the study analyses (2 who were noncompliant [used <80% of the assigned medication] and 2 who developed infection at other sites). There were no significant differences in baseline medical history or signs and symptoms between the 2 groups. Rates of improvement at day 14 in the cefditoren and amoxicillin/clavulanate groups were 78.8% (52/66) and 84.7% (61/72), respectively (P = NS). There was no significant difference in the change in S5 scores between groups at day 14. The median time to improvement was 3.0 days in both groups. There were no significant differences between groups in rates of relapse (9.1% and 11.1%) or recurrence (3.0% and 5.6%) of sinus symptoms. The most common adverse event in both groups was diarrhea, occurring in 4.5% of the cefditoren group and 18.1 % of the amoxicillin/clavulanate group (P = 0.02)., Conclusion: In these children with acute bacterial rhinosinusitis, there were no significant differences between cefditoren and amoxicillin/clavulanate, the currently recommended treatment, in terms of rates of response, relapse, or recurrence.