Inhibitory effect of Zingiber cassumunar Roxb. (Phlai) on nasal cytokine productions and eosinophilic recruitment in patients with allergic rhinitis.

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.

Consensus on mild asthma management: results of a modified Delphi study.

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.

Diagnostic accuracy of atopy patch test in children with cow's milk allergy.

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 ß-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 ß-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 ß-lactoglobulin were zero. The specificities were 90.6%, 93.8%, 100%, and 100% for α-lactalbumin, cow's milk, casein, and ß-lactoglobulin, respectively. CONCLUSIONS: APT using commercial solutions showed higher specificity than fresh milk. The specificity increased using a protein component allergen.

Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.

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.

Phase III study of Phlai capsules in the treatment of allergic rhinitis: A randomized, double-blind, placebo-controlled trial.

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.

A shotgun proteomic approach reveals novel potential salivary protein biomarkers for asthma.

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.

A randomized controlled study comparing the efficacy of soap versus soap-plus-microwave disinfection for irrigation device in children with acute rhinosinusitis.

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.

Guidelines for the management of asthma in adults: Evidence and recommendations.

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).

Concordance of skin test reactivity between indoor inhalant allergens among children with allergic respiratory disease.

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.

Practical considerations of nebulized corticosteroid in children with acute asthmatic exacerbation: A consensus.

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.

Influence of Polymorphisms in the Interleukin-18 Gene on Allergic Rhinitis: A Meta-Analysis.

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.

Pediatric Versus Adult Chronic Rhinosinusitis.

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.

Long-term effectiveness of omalizumab treatment in Thai severe asthmatic patients: A real-life experience.

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.

A randomized controlled study comparing the efficacy of nasal saline irrigation devices in children with acute rhinosinusitis.

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.

Pharmacokinetics of Compound D, the Major Bioactive Component of Zingiber cassumunar, in Rats.

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.

MDI with DIY Spacer versus Nebulizer for Bronchodilator Therapy in Children Admitted with Asthmatic Attack.

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 ß2-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 ß2-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.

Zingiber cassumunar ROXb. and its active constituent inhibit MMP-9 direct activation by house dust mite allergens and MMP-9 expression in PMA-stimulated human airway epithelial cells.

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.

Mini version of the pediatric asthma quality of life questionnaire (MiniPAQLQ): validity among Thai asthmatic children.

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.

Snoring and sleep problems in children with and without allergic rhinitis: a case control study.

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.

Macrolides attenuate phorbol ester-induced tumor necrosis factor-α and mucin production from human airway epithelial cells.

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.