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.

Incidence of Respiratory Syncytial Virus Lower Respiratory Tract Infections During the First 2 Years of Life: A Prospective Study Across Diverse Global Settings.

BACKGROUND: The true burden of lower respiratory tract infections (LRTIs) due to respiratory syncytial virus (RSV) remains unclear. This study aimed to provide more robust, multinational data on RSV-LRTI incidence and burden in the first 2 years of life. METHODS: This prospective, observational cohort study was conducted in Argentina, Bangladesh, Canada, Finland, Honduras, South Africa, Thailand, and United States. Children were followed for 24 months from birth. Suspected LRTIs were detected via active (through regular contacts) and passive surveillance. RSV and other viruses were detected from nasopharyngeal swabs using PCR-based methods. RESULTS: Of 2401 children, 206 (8.6%) had 227 episodes of RSV-LRTI. Incidence rates (IRs) of first episode of RSV-LRTI were 7.35 (95% confidence interval [CI], 5.88-9.08), 5.50 (95% CI, 4.21-7.07), and 2.87 (95% CI, 2.18-3.70) cases/100 person-years in children aged 0-5, 6-11, and 12-23 months. IRs for RSV-LRTI, severe RSV-LRTI, and RSV hospitalization tended to be higher among 0-5 month olds and in lower-income settings. RSV was detected for 40% of LRTIs in 0-2 month olds and for approximately 20% of LRTIs in older children. Other viruses were codetected in 29.2% of RSV-positive nasopharyngeal swabs. CONCLUSIONS: A substantial burden of RSV-LRTI was observed across diverse settings, impacting the youngest infants the most. Clinical Trials Registration. NCT01995175.

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.

Assessment of small airway function and reversibility in symptom-controlled asthma in pediatric patients.

BACKGROUND: The goals of asthma management aim to control the symptoms and minimize future risk. There is, however, an option to stop controller medication if the patient has been well-controlled for at least 6-12 months. To assess control, both clinical symptom assessment and lung function should be monitored periodically. In practical clinical practice of pediatric patients, lung function is not available at all health centers. OBJECTIVES: to determine lung function with a focus on small airway function and the risk of reversibility among children who have been symptom-controlled. METHODS: Our participants were symptom-controlled asthmatic children according to GINA Guideline for at least 6 months with low dose inhaled corticosteroid. Written informed-consent was given by the parents and the children. They performed a self-evaluated symptom-controlled test (C-ACT) and a spirometric assessment. Abnormal lung function was defined as FEV1±80%, FEV1/FVC < 80%, and FEF25-75 <65% predicted. Airway reversibility was determined by the change of FEV1 >12% and FEF25-75 >30% post bronchodilator. RESULTS: Forty children (65% male) were enrolled. Age ranged between 6.7 and 15.0 years. The mean C-ACT score was 25.2 ± 1.7. Spirometry results were: mean FEV1 84.0 %, FEV1/FVC 87.8%, and FEF25-75 85.5% predicted. Normal FEV1 was found among 72.5% of participants compared to normal FEF25-75 in 87.5%. Among the abnormal FEV1 and FEF25-75, all were of mild severity as 10% retained airway reversibility. CONCLUSION: Children with well-controlled asthma, based on their symptom assessment, may have persistent abnormal lung function. Spirometry should be performed before considering cessation of controller medication.

COMPARISONS OF THE CLINICAL FEATURES AND OUTCOMES OF CHILDREN PRESENTING WITH INFLUENZA-LIKE ILLNESSES, INCLUDING A (H1N1) PDM09 AND SEASONAL INFLUENZA, IN A UNIVERSITY HOSPITAL, THAILAND.

In Thailand, during the A(H1N1)pdm2009 pandemic, 82% of fatal cases did not received the specific treatment within 48 hours of the onset of symptoms. Specific diagnostic tests, especially RT-PCR, were not available throughout the country. To assist early clinical diagnosis and treatment, this study compared the clinical features and treatment outcomes of children presenting with influenza-like illness (ILIs). These included confirmed cases of A(H1N1)pdm2009, as well as seasonal influenza and cases for which no cause could be specified. The medical records of patients aged less than 15 years with ILIs, who had RT-PCR performed for influenza virus between May 2009 and December 2011 at Srinagarind Hospital, were reviewed. Clinical features, chest radiographs and treatment outcomes were compared between those positive for A(H1N1)pdm2009, and those with seasonal influenza and/or the unspecified causes group. In 179 complete medical records, 27.4% were positive for A(H1N1)pdm2009, 13.4% for seasonal influenza and the cause of illness in the remainder was unspecified. Both A(H1N1)pdm2009 and seasonal influenza viruses infected older children more than did the unspecified group (group median ages 96,48 and 24 months, respectively). Sore throat, headache and myalgia were significantly more frequent in the A(H1N1)pdm2009 group than in the other two groups (p < 0.001). Half of all children had pneumonia but there were no significant differences among groups. There was no mortality in this study. In conclusion, sore throat, headache and myalgia were the significant clinical features suggestive of A(H1N1)pdm2009 infection in children and might be helpful indicators prompting early administration of specific treatments in the settings where definitive laboratory tests are not available.

Bacterial etiology of empyema thoracis and parapneumonic pleural effusion in Thai children aged less than 16 years.

This study aimed to identify the bacterial etiology of empyema thoracis or parapneumonic pleural effusions in Thai children, with a focus on pneumococcus. This hospital-based, descriptive study included children aged < or = 16 years, diagnosed with empyema thoracis or parapneumonic pleural effusion, from whom a pleural fluid (PF) sample was taken between January 2008 and November 2009. PF and blood samples were cultured and PF samples were also tested by polymerase chain reaction (PCR) to assess whether evidence of an infection might be identified among culture-negative samples. Serotyping of Streptococcus pneumoniae-positive samples was performed by molecular techniques and Quellung reaction. In this study, 29 children with empyema thoracis and 42 children with parapneumonic pleural effusion were enrolled. Potentially pathogenic bacteria were cultured in 13/71 samples at local or central laboratories; the most common bacteria were Staphylococcus aureus (8 children) and S. pneumoniae (2 children). Molecular techniques detected one or more targeted respiratory pathogens in 18/71 PF samples. S. pneumoniae and Haemophilus influenzae were identified by PCR in 13 and 6 children, respectively; PCR for S. aureus was not performed. The pneumococcal serotypes identified were 1, 3, 5, 6A/B, 9A/V, 14, 15A, 19F and 23A. This study shows that among Thai children with empyema thoracis and parapneumonic pleural effusions, S. aureus and S. pneumoniae were the most common pathogens identified by culture and PCR, respectively. These findings confirmed that molecular techniques are more sensitive for identification of S. pneumoniae and H. influenzae and enhance detection of important bacterial causes of empyema.

Rhinovirus infection in children hospitalized with acute bronchiolitis and its impact on subsequent wheezing or asthma: a comparison of etiologies.

BACKGROUD: Children who suffer a viral lower respiratory infection early in life are prone to subsequent wheezing and asthma: RSV and rhinovirus are thought to be the primary causative pathogens. Epidemiologic and long-term data on these pathogens in Thailand are limited. OBJECTIVES: To detect the causative pathogens in children hospitalized with a first episode of acute wheezing and to compare the respective impact on the recurrence of wheezing and development of asthma. METHOD: We conducted a 5-year cohort study of children under 2 hospitalized with acute bronchiolitis at two tertiary hospitals. Nasopharyngeal secretions were collected at admission to determine the causative pathogens by RT-PCR. RESULTS: 145/170 samples (85%) were positive for pathogens. RSV, rhinovirus, influenza, bacteria and hMPV was found in 64.7%, 18.2%, 17.6%, 12.9% and 3.5% of children respectively. The majority (94/152; 62%) of participants reported having recurrent wheezing within the first year of follow-up (mean duration 5.5 ± 7.2 months). Only 16% still had wheezing episodes after 5 years. Asthma was diagnosed in 41 children (45%), most of whom were treated with inhaled corticosteroid. There were no statistically significant differences among the various etiologies. CONCLUSION: Rhinovirus ranked second after RSV as the cause of hospitalizations of children with acute bronchiolitis. More than half of these children had recurrent wheezing which mostly disappeared before the age of 6. Nearly half were subsequently diagnosed with asthma at the 5th year of follow-up. The specific pathogens did not account for a statistically significant difference in subsequent wheezing or asthma development.

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children.

BACKGROUND: Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015). METHODS: In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen's κ statistics. RESULTS: Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs. CONCLUSIONS: Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI. CLINICAL TRIAL REGISTRATION: NCT01995175.

Burden of acute lower respiratory infection in children in Thailand in 2010: have we achieved the national target in under-five morbidity and mortality?

BACKGROUND: National reports indicate that morbidity and mortality from pneumonia among Thai children has decreased dramatically since the turn of the millennia; notwithstanding, pneumonia remains the leading cause of admission and death in Thai children under five years of age. OBJECTIVE: To assess the burden and pattern of acute lower respiratory infection in under-fives in Thailand from the health data in 2010. MATERIAL AND METHOD: Information on respiratory infection using the ICD10: J09-J22 was evaluated for the number of OPD visits, admissions, mortality, monthly incidence and co-morbidities of the mortality. RESULTS: 73% of all OPD visits with ALRI were in under-fives: one-fourth of whom required hospitalization. Pneumonia is the leading cause of both admissions and mortality (3.22% and 11.29/100,000 population for this age group, respectively). The highest mortality was in the first year of life (39/100,000). One-fourth of the children (168/639) died within 24 hours of admission and septicemia was the most common co-morbidity. CONCLUSION: The respective morbidity and mortality of pneumonia in under-fives fell far short of national targets. To achieve these targets, many key aspects are needed; such as, strengthening the knowledge of healthcare personnel, the cost-effectiveness researches on the causative organism detection and the expanding coverage of the preventable-vaccine.

Health situation analysis of Thai children aged 1-5 years in 2010: implications for health education and health service reform.

BACKGROUND: To make the world fit for children is a task necessarily involves all organizations working with children. The real health situation will be useful for strategic planning for them. OBJECTIVE: To emphasize Thailand's health burdens of children between 1 and 5 years in 2010. MATERIAL AND METHOD: The authors analyzed the fiscal 2010 data from the three health insurance schemes from hospitals nationwide for information on: out-patient and in-patient visits, common illnesses of Thai children between 1 and 5 years, lengths of stay, hospital charges and deaths. Most (96%) of the population was represented in this data. RESULTS: Respiratory infection was the most common admission (225,183 times) while intestinal infection was the second (83,293 times). Respiratory infection was the second most common for an out-patient visit (7, 387,132 times = 23.6%) after other factors influencing health (17,384,963 times = 55.5%). The most common causes of death were injury and poisoning (178 patients) and respiratory infection (175 patients). Pneumonia required the most budget and resulted in the longest stays. Among accidents, accidental drowning and submersion caused the most deaths. CONCLUSION: Respiratory infection, pneumonia, intestinal infection, injuries, poisoning and accidental drowning were the most common health burdens among children between 1 and 5 years of age.

Comparison between the radiographic findings in pulmonary tuberculosis of children with or without HIV infection.

OBJECTIVE: Identify the difference between radiographic findings in children with pulmonary tuberculosis with and without HIV infection. MATERIAL AND METHOD: The authors retrospectively reviewed the chest radiography of 93 children (under 15 years of age) with pulmonary tuberculosis between January 2000 and June 2005. Fifty-two of the children had an HIV co-infection while the remaining 41 children did not. The chest radiographic findings were assessed for parenchymal changes, lymphadenopathy, and pleural effusion. RESULTS: The radiographic manifestations in the HIV-infected group included interstitial infiltration in 39 patients (75%), alveolar infiltration in five patients (9.6%), combined interstitial and alveolar infiltration in seven patients (13.4%), miliary infiltration in one patient (1.9%), and hilar/mediastinal lymphadenopathy in 17 patients (32.6%). One patient had extensive alveolar infiltration in conjunction with multiple cavitatary formations. The findings in the non-HIV-infected group were interstitial infiltration in 30 patients (73.1%), hilar/mediastinal lymphadenopathy in 13 patients (31.7%, 3 of whom had adenopathy without parenchymal infiltration), and pleural effusion in two patients (4.8%). Other less frequent abnormalities included bronchiectasis, peribronchial thickening in the HIV-infected group, and atelectasis and granuloma in the non-HIV-infected group. There was no statistically significant difference in the radiographic findings between the two groups, except the association of hilar/mediastinal lymphadenopathy and pulmonary infiltration. Regarding hilar/mediastinal lymphadenopathy with or without pulmonary infiltration between the two groups, all cases in the HIV-infected group with hilar/mediastinal lymphadenopathy were significantly more associated with pulmonary infiltration (17 patients) than the other group (8 patients) (p = 0.009). CONCLUSION: Hilar/mediastinal lymphadenopathy with pulmonary infiltration strongly suggests the presence of HIV infection in children with pulmonary tuberculosis.

Epidemiology of acute lower respiratory tract infection hospitalizations in Thai children: A 5-year national data analysis.

BACKGROUND: Lower respiratory tract infections (LRTIs) are the most common cause for hospitalization in pediatric patients. Pediatric patients with LRTIs are at an increased risk of morbidity and mortality. The national data analysis of epidemiologic variations facilitates awareness and develops solutions to prevent these conditions in the future. OBJECTIVE: This study aims to evaluate the epidemiology, causative pathogens, morbidity, and mortality of LRTIs in pediatric patients of Thailand from 2015 to 2019. METHODS: This was a retrospective study among pediatric patients aged between 0 and 18 years old admitted in hospitals due to LRTIs in Thailand from January 2015 to December 2019. The data were extracted from National Health Security Office using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification; ICD-10-TM of J09 to J22. RESULTS: A total of 1,423,509 children hospitalized due to LRTIs were identified. Most of the patients were of age 1-5 years. Pneumonia was the most common LRTI (876,557 children, 61.58%) in hospitalized children. Respiratory syncytial virus (RSV) is the main etiologic pathogen of bronchiolitis, which presents in approximately 10.86% of all episodes. Influenza viruses were found predominantly in children with pneumonia (15.52%). The mortality rate since 2015-2019 was highest in pneumonia under 1 year old (P < 0.001). Pneumonia in children under 5 years old had the highest mortality rate, which accounted for 11.85 per 100,000 children in 2019. CONCLUSIONS: LRTIs had a high incidence rate of hospitalization and mortality, especially in children under 5 years old. Influenza virus was the most common pathogen of pneumonia.

Effect of the COVID-19 Pandemic on Lower Respiratory Tract Infection Determinants in Thai Hospitalized Children: National Data Analysis 2015-2020.

Background: The COVID-19 outbreak emerged in January 2020 and remains present in 2022. During this period, nonpharmaceutical interventions (NPIs) have been used to reduce the spread of COVID-19 infection. Nationwide data analysis should be pushed as the new standard to demonstrate the impact of COVID-19 infection on other respiratory illnesses and the reliability of NPIs during treatment. Objective: This study aims to identify and compare the incidence of lower respiratory tract infections (LRTIs) among children in Thailand before and after the emergence of COVID-19. Methods: A retrospective study was carried out in hospitalized children under the age of 18 in Thailand from October 2015 to September 2020. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification, was used to identify patient diagnoses (ICD-10-TM). The data were extracted from the Universal Coverage Health Security Scheme Database. Results: A total of 1,610,160 admissions were attributed to LRTIs. The most common diagnosis was pneumonia (61.9%). Compared to the 2019 fiscal year, the number of hospitalizations due to LRTIs decreased by 33.9% in the 2020 fiscal year (COVID-19 period) (282,590 vs. 186,651). The incidence of all three diagnostic groupings was substantially lower in the pre- and post-COVID-19 eras, with a decrease of 28% in the pneumonia group (incidence rate ratio (IRR) = 0.72; 95% confidence interval (CI): 0.71 to 0.72), 44% in the bronchiolitis group (IRR = 0.56; 95% CI: 0.55 to 0.57), and 34% in the bronchitis group (IRR = 0.66; 95% CI: 0.65 to 0.67). Between fiscal years 2019 and 2020, the overall monthly cost of all hospitalizations for LRTIs decreased considerably (p value < 0.001). Conclusions: NPIs may decrease the number of pediatric hospitalizations related to LRTIs. All policies designed to prevent the spread of COVID-19 must be continually utilized to maintain the prevention of LRTIs.

Burden of Respiratory Syncytial Virus Related Acute Lower Respiratory Tract Infection in Hospitalized Thai Children: A 6-Year National Data Analysis.

Objectives: This study sought to determine the epidemiology, seasonal variations, morbidity, and mortality of respiratory syncytial virus (RSV) infection among hospitalized children with lower respiratory tract infection in Thailand. In addition, we assessed the risk factors associated with severe RSV lower respiratory tract infection (LRTI)-related morbidity and mortality. Methods: The data were reviewed retrospectively from the National Health Security Office for hospitalized children younger than 18 years old diagnosed with RSV-related LRTI in Thailand, between the fiscal years of 2015 to 2020. The RSV-related LRTIs were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification. ICD-10-TM codes J12.1, J20.5, and J21.0, which represent respiratory syncytial virus pneumonia, acute bronchitis due to respiratory syncytial virus, and acute bronchiolitis due to respiratory syncytial virus, respectively, were studied. Results: During the study period, RSV-related LRTI accounted for 19,340 of the 1,610,160 hospital admissions due to LRTI. RSV pneumonia was the leading cause of hospitalization (13,684/19,340; 70.76%), followed by bronchiolitis (2849/19,340; 14.73%) and bronchitis (2807/19,340; 14.51%), respectively. The highest peak incidence of 73.55 percent occurred during Thailand's rainy season, from August to October. The mortality rate of RSV-related LRTI in infants younger than 1 year of age was 1.75 per 100,000 person years, which was significantly higher than that of children 1 to younger than 5 years old and children 5 to younger than 18 years old (0.21 per 100,000 person years and 0.01 per 100,000 person years, respectively, p-value < 0.001). Factors associated with mortality were congenital heart disease, hematologic malignancy, malnutrition, and neurological disease. Conclusions: In children with RSV LRTI, pneumonia was the leading cause of hospitalization. The admission rate was highest during the rainy season. Mortality from RSV-related LRTI was higher in children under 1 year old and in children with underlying illnesses; future preventive interventions should target these groups of patients.

Localized melioidosis in children in Thailand: treatment and long-term outcome.

Melioidosis, an infection caused by Burkholderia pseudomallei, can present as severe septicemia or localized infection. Data on optimum antibiotic treatment regimen for localized melioidosis in children is limited. This is a report on localized melioidosis in children, regarding clinical presentation, treatment and the long-term outcomes. We reviewed 37 cases of localized melioidosis in children treated between 1994 and 2006 and followed up them prospectively until 1 October 2007. The two most common presentations were skin/soft tissue infections and suppurative parotitis. Oral eradication antibiotics after initial parenteral therapy included trimetroprim-sulfamethoxazole (10 patients) and trimetroprim-sulfamethoxazole in combination with doxycycline (four patients). Patients who did not get any parenteral antibiotics for B. pseudomallei were treated with oral trimetroprim-sulfamethoxazole (10 patients) and trimetroprim-sulfamethoxazole in combination with doxycycline (one patient). No adverse effects were reported. We were able to follow-up 32 patients, all recovered except one patient reported a history of possible relapse.

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.

Immunogenicity and safety of a 12-valent pneumococcal conjugate vaccine in infants aged 6-10 weeks: a randomized double-blind active-controlled trial.

BACKGROUND: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates. PURPOSE: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants. METHODS: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group. RESULTS: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 µg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 µg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). CONCLUSION: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

Hemostatic alterations in splenectomized and non-splenectomized patients with beta-thalassemia/hemoglobin E disease.

Beta-thalassemia/hemoglobin (Hb) E is a hereditary hemolytic anemia with varying degrees of severity. Severely affected patients are treated with blood transfusion and/or splenectomy in order to maintain an optimum level of hemoglobin for normal growth and physical activities. As thrombosis has been observed among splenectomized patients, we have investigated alterations in coagulation and fibrinolysis in beta-thalassemia/Hb E patients. Plasma levels of prothrombin, fibrinogen, factors V, VII, VIII, IX and XI, protein C, protein S, thrombin activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1+2 were determined in 61 patients (21 non-severe non-splenectomized, 18 severe non-splenectomized, 22 severe splenectomized) and 28 healthy individuals. Serum levels of D-dimer, ferritin, aspartate transaminase and alanine transaminase were also measured. All severe patients received regular blood transfusion. Prothrombin fragment 1+2 and D-dimer were significantly elevated in splenectomized patients compared to the healthy control subjects, whereas levels of proteins C, protein S, TAFI, fibrinogen, and factors V and VIII in the splenectomized groups were statistically lower than those in control group. There are no statistical differences for the other parameters measured between patients and controls. Coagulation tests showed only significantly reduction in TAFI and factor V and VIII levels in severe splenectomized group in comparison with severe non-splenectomized patients. These results demonstrate the existence of a low grade consumptive coagulopathy among blood-transfused splenectomized patients with severe clinical manifestations, indicating that these patients may have a higher risk for thrombosis than comparable patients with intact spleen.

Efficacy of dexamethasone injection for acute bronchiolitis in hospitalized children: a randomized, double-blind, placebo-controlled trial.

Controversy over the efficacy of systemic corticosteroids for acute bronchiolitis initiated this study. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy of single dexamethasone injection for the treatment of acute bronchiolitis in young hospitalized children. The study, performed at the pediatric wards of a University Hospital and its affiliated hospital in Thailand, included 174 previously healthy children under 2 years of age, hospitalized with acute bronchiolitis. Each child received either a single intramuscular injection of 0.6 mg/kg dexamethasone or a placebo in addition to regular management. The primary outcome was the time from study entry to resolution of respiratory distress, determined by a clinical score derived from the respiratory rate, occurrence of wheezing, chest retraction, and oxygen saturation. Survival analysis using the Kaplan-Meier method and a log-rank test were performed. A single-dose, dexamethasone injection versus placebo produced a significant: (1) decrease in the time needed for resolution of respiratory distress (hazard ratio 1.56; 95% CI, 1.14-2.13; P = 0.005), (2) decrease in the mean duration of symptoms of 11.8 hr (95% CI, 3.9-19.7; P = 0.004), (3) decrease in the mean duration of oxygen therapy of 14.9 hr (95% CI, 5.3-24.4; P = 0.003), and (4) decrease in the mean length of hospital stay of 13.4 hr (95%CI, 2.6-24.2; P = 0.02). In conclusion, a single injection of dexamethasone yielded a significant clinical benefit for the treatment of previously healthy, young children hospitalized with acute bronchiolitis.

Human metapneumovirus and respiratory syncytial virus detection in young children with acute bronchiolitis.

This study was conducted to detect human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in young children hospitalized with acute bronchiolitis, using reverse transcriptase polymerase chain reaction (RT-PCR). Nasopharyngeal secretions were collected from 170 children between 1 and 24 months of age admitted to two tertiary hospitals in northeastern Thailand, between 2002 and 2004. Acute bronchiolitis was defined as the first episode of wheezing associated with tachypnea, increased respiratory effort and an upper respiratory tract infection. Two-thirds (115/170) were positive for viral etiologies: 64.7% RSV (110/170) and 3.5% hMPV (6/170). One patient had a dual infection. hMPV was detected between August and November, while RSV was prevalent from July through March. The clinical manifestations among the 6 hMPV, RSV and non-RSV-infected children were similar. RSV was the leading cause of acute bronchiolitis in young children and hMPV had a low prevalence in northeastern Thailand.