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.

Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children.

Talaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.

Prevalence of food allergy among preschool children in northern Thailand.

BACKGROUND: The epidemiology and clinical spectrum of food allergies (FA) confirmed by oral food challenge tests (OFC) in the Southeast Asian countries are limited. The aim of the present study was to examine the prevalence and characteristics of FA among preschool children in northern Thailand. METHODS: Five hundred and forty-six children aged 3-7 years living in Chiang Mai, Thailand participated in this study. A cross-sectional parent questionnaire survey was conducted. Families with children reporting FA were invited to undergo further investigations with skin prick testing, serum specific IgE, and OFC. RESULTS: A total of 452 out of 546 questionnaires (82.8%) were returned. Forty-two children (9.3%) were reported to have FA. The five leading allergic foods reported were shrimp, cow's milk, fish, chicken eggs, and ant eggs. The most commonly reported symptom was a skin rash (78.0%), followed by abdominal pain and vomiting (31.1%). Anaphylaxis was found in two children (3.4%), from ant eggs allergy. Eighteen children underwent OFC; five of them were positive to shrimp, fish, and crab. Either skin prick test or serum-specific IgE was positive in these children. Factors associated with parent-reported FA included personal and family history of atopic dermatitis. CONCLUSIONS: The prevalence of IgE-mediated FA confirmed on OFC was ≥ 1.11% (95% confidence interval: 0.41-2.98%). The most common causative food was shrimp. Ant eggs were a unique food allergen causing severe reactions in preschool children in northern Thailand.

Comparison of salbutamol efficacy in children--via the metered-dose inhaler (MDI) with Volumatic spacer and via the dry powder inhaler, Easyhaler, with the nebulizer--in mild to moderate asthma exacerbation: a multicenter, randomized study.

BACKGROUND: Beta(2) agonist administered via a nebulizer is the standard treatment for acute asthma exacerbation. There are some limitations for the use of nebulization. We conducted a study to determine the efficacy of salbutamol administered via the pMDI with Volumatic spacer and the Easyhaler (DPI) compared to nebulization in mild to moderate asthma exacerbations in children. METHODS: A multicenter, randomized, controlled study was conducted in children between 5 and 18 years of age who presented at an emergency or outpatient department. They were randomized to receive either 6 puffs of salbutamol via the pMDI with Volumatic spacer, or via the Easyhaler, or 0.15 mg/kg of salbutamol nebulized via oxygen (or compressed air). The primary outcome was the clinical response which was assessed using the modified Wood's asthma score. The secondary outcomes were: hospitalization, asthma revisit within 3 days, systemic corticosteroid use and adverse events. The clinical score, oxygen saturation, PR, RR, BP and adverse events were recorded at time 0 (before treatment) and 20, 40 and 60 minutes after drug administration. RESULTS: There were no statistically significant differences in the clinical response between the three groups at the 1st, 2nd or 3rd dose or for the SpO(2) or the respiratory rate while the children in the Easyhaler group had significantly less tachycardia after the 2nd dose. No significant adverse events were noted among the three groups. CONCLUSIONS: Salbutamol administered via pMDI with Volumatic spacer or DPI (Easyhaler) are as effective as salbutamol given via a nebulizer in providing effective relief of mild to moderate severity acute asthma exacerbation in children between 5 and 18 years of age.

Allergic rhinitis and immunoglobulin deficiency in preschool children with frequent upper respiratory illness.

BACKGROUND: Frequent upper respiratory illness (URI) is a common problem in preschool children. Allergic rhinitis and immunoglobulin (Ig) deficiency are usually suspected as underlying etiologies. OBJECTIVE: To determine the prevalence of allergic rhinitis and Ig and IgG subclass deficiency in preschool children with frequent URI. METHODS: Two thousand eight hundred and seventy-six questionnaires were distributed to the parents of children aged 3-6 years in 24 kindergartens. Firstly, they determined the frequency of URI in the previous year and secondly the prevalence of rhinitis according to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The skin prick test (SPT) was performed and serum Ig and IgG subclasses were measured in children with frequent URI (> or = 10 episodes per year). Allergic rhinitis was diagnosed when the child had had rhinitis in the previous 12 months and positive SPT for at least 1 aeroallergen. RESULTS: Two thousand three hundred and one questionnaires (80.01%) were returned. Ninety-four out of 219 children with frequent URI participated in the study. The prevalence of allergic rhinitis in the participants was 42.55%. Exclusive breastfeeding for at least 6 months had a protective effect, while paternal history of rhinitis was a risk factor. All participants had normal serum IgG, IgA, IgM and IgG subclass levels for age. CONCLUSION: The prevalence of allergic rhinitis in preschool children with frequent URI in our study was 42.55%. Allergic rhinitis should be considered if they have a family history of allergic rhinitis. Immunoglobulin deficiency was not found in our study.

Air pollution-related peak expiratory flow rates among asthmatic children in Chiang Mai, Thailand.

The severity of air pollution in northern Thailand has long been recognized; in spite of that there have been no epidemiological studies regarding the associations between the air pollution and health effects in the area. The authors followed a cohort of 31 asthmatic children (4-11 years of age) residing in Muang district, Chiang Mai, Thailand, from 29 August 2005 to 30 June 2006, for 306 days. The daily air pollutants, including particulate matter with aerodynamic diameter < 2.5 microm, particulate matter with aerodynamic diameter < 10 microm, carbon monoxide, ozone (O(3)), nitrogen dioxide, and sulfur dioxide (SO(2)), and the meteorological parameters, including pressure, temperature, relative humidity, rain quantity, and sunshine duration, were recorded. The peak expiratory flow rates (PEFRs) were fitted with pollutants and meteorological covariates using general linear mixed models to account for random effects and autocorrelation. The authors found that there were inverse associations of SO(2) and evening PEFR, with a coefficient of -2.12 (95% confidence interval (CI) = -3.22 to -0.28); of SO(2) and daily percent deviation of PEFR, with a coefficient of -0.73 (95% CI = -1.33 to -0.12); and of O(3) combining with SO(2) and daily average PEFR, with a coefficient of -0.16 (95% CI = -0.31 to -0.00) and -1.60 (95% CI = -3.10 to -0.11), respectively. The associations of O(3) and SO(2) with PEFR were found even when SO(2) concentrations never exceeded the standard level.

Time trends of the prevalence of asthma, rhinitis and eczema in Thai children-ISAAC (International Study of Asthma and Allergies in Childhood) Phase Three.

Using the same questionnaire as in ISAAC Phase One study conducted in 1995, the ISAAC Phase Three was carried out in Bangkok and Chiang Mai, Thailand, in 2001, among children aged 6-7 and 13-14 years. There was an increase in the prevalence of the three diseases in the younger age group, i.e., current asthma, rhinitis, rhinoconjunctivitis, and flexural eczema. In the older age group, the prevalence of rhinitis and rhinoconjunctivitis increased. There was no change of prevalence of asthma in Bangkok, but prevalence decreased in Chiang Mai. Prevalence of eczema in older children increased in Bangkok, but remained the same in Chiang Mai.

X-linked agammaglobulinemia in northern Thailand.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by a failure to generate immunoglobulins of all isotypes due to the absence of mature B cells and plasma cells, secondary to mutations in the Bruton's tyrosine kinase (Btk) gene. We report six patients with XLA, confirmed by mutation analysis, from northern Thailand. The mean age of onset was 2.5 years and the mean age at diagnosis was 7.3 years. All patients had a history of otitis media, pneumonia and arthritis at the time of diagnosis, five patients had developed bronchiectasis and 3 patients septicemia. Other infections reported included sinusitis (5/6), pericarditis (1/6), meningitis (1/6) and pyoderma (1/6). Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus were isolated on multiple occasions. One patient died of sepsis at the age of 16 years. These observations demonstrate that early diagnosis and treatment can improve prognosis and quality of life.

House dust mite allergen levels in Chiang Mai homes.

The quantitative assays for house dust mite (HDM) allergens provide a valid index of exposure and can be used for risk evaluation. We assessed group I HDM allergen levels in mattress and living room floor dust from 35 Chiang Mai homes and identified factors associated with high allergen levels. One-third of mattress and living room floor dust had group I HDM allergen levels of between 2-10 microg/g. Two-thirds of mattress dust and a small amount of living room floor dust had group I HDM allergen levels of over 10 microg/g. The geometric means of Der p I, Der f I and total group I allergens in mattress and living room floor dust were 8.61, 2.88, and 15.81 microg/g and 1.61, 0.27 and 2.43 microg/g, respectively. Mattresses made of kapok and rugs kept in the living room were associated with high group I allergen levels.

The determinants of dust mite allergen and its relationship to the prevalence of symptoms of asthma in the Asia-Pacific region.

The role that house dust mites play in the primary causation of asthma is controversial. Approximately thirty-six 10-yr-old children in each of 10 centres in the Asia-Pacific region participated. Researchers collected dust from mattresses and living room floors using standardized procedures. Der p1 and Der f1 were analysed using a double monoclonal antibody enzyme-linked immunosorbent assay. Geometric mean allergen levels were calculated for each centre. An ecological analysis was conducted to show the regression of the geometric mean allergen level, using the highest household level, against asthma symptom and severity prevalence data from the International Study of Asthma and Allergies in Childhood, Phase I. Among children aged 13-14 yr, the change in asthma symptom prevalence was associated with per unit change in Der p1 microg/g (1.08, 95% CI 0.10-2.06) and Der 1 microg/g (Der p1 + Der f1) (0.64, 95% CI 0.02-1.26). The change in having four or more attacks of asthma in the last 12 months was associated with per unit change in Der p 1 microg/g (0.29, 95% CI -0.02 to 0.60) and Der 1 microg/g (0.20, 95% CI 0.01-0.38). There was no effect for total Der p1 or Der f1 (total or microg/g). Among children aged 6-7 yr, neither allergen was related to symptoms or severity prevalence. While our findings suggest that Dermatophagoides pteronyssinus may have a role in the primary causation of asthma, the complexity of this association reinforces the need for prospective studies.

An extensive study of human IgE cross-reactivity of Blo t 5 and Der p 5.

BACKGROUND: Dual sensitization by Blomia tropicalis and Dermatophagoides pteronyssinus mites is common in tropical and subtropical countries. The human IgE cross-reactivity between clinical important group 5 allergens, Blo t 5 and Der p 5, remains controversial. OBJECTIVE: This study was undertaken to assess the levels of the IgE cross-reactivity between Blo t 5 and Der p 5 by using sera from a large cohort of asthmatic children in subtropical and tropical countries. METHODS: Purified recombinant Blo t 5 and Der p 5 were produced in Pichia pastoris and tested against sera from 195 asthmatic children. The IgE cross-reactivity was examined by direct, inhibitory and competitive human IgE enzyme-linked immunosorbent assay as well as skin prick tests. RESULTS: The Blo t 5 IgE responses were 91.8% (134 of 146) and 73.5% (36 of 49) for Taiwanese and Malaysian sera, respectively. The Blo t 5 specific IgE titers were significantly higher than those of Der p 5 (P <.02). The correlation of IgE reactivity between Blo t 5 and Der p 5 was low, and only limited cross-reactivity was observed. This was further confirmed by the dose-response inhibition studies. Skin prick tests performed on asthmatic children in Thailand also showed differential IgE response to Blo t 5 and Der p 5. CONCLUSION: By using a large panel of asthmatic sera and a combination of in vitro and in vivo assays, the major allergen of B tropicalis in tropical and subtropical regions, Blo t 5, exhibits low levels of IgE cross-reactivity with homologous Der p 5. These findings suggest that highly specific clinical reagents are necessary for precise diagnosis and immunotherapeutic treatment of sensitization to group 5 mite allergens.

Sensitization to Dermatophagoides pteronyssinus and Blomia tropicalis extracts and recombinant mite allergens in atopic Thai patients.

Mite surveys in Thailand indicated that Dermatophagoides pteronyssinus (Dp) is predominant, but so far there were no data available on Blomia tropicalis (Bt), which is prevalent in the Asia Pacific region. Skin prick testing (SPT) was performed in 40 atopic children, 45 atopic adults and 17 non-atopic volunteers. Skin reactions to Dp were found in 25/40 (62.5%) and 23/45 (51.1%); skin reactions to Bt were found in 15/40 (37.5%) and 18/45 (40%) in atopic children and adults, respectively. SPT to the major sensitizing allergens Der p 1, Der p 2, Der p 5, and Blo t 5 showed positive results in 14/40 (35%), 12/40 (30%), 1/40 (2.5%) and 4/40 (10%) of atopic children, and in 12/45 (26.7%), 13/45 (28.9%), 5/45 (11.1%), 6/45 (13.3%) of atopic adults, respectively. The results indicate that Dp is one of the major sources of allergy, while Bt is a minor one and that Der p 1 and Der p 2 are important mite allergens in Chiang Mai, Thailand.