Weaning strategies for children on home invasive mechanical ventilation.

Children who require home mechanical ventilation (HMV) with an artificial airway or invasive mechanical ventilation (HMV) have a possibility of successful weaning due to the potential of compensatory lung growth. Internationally accepted guidelines on how to wean from HMV in children is not available, we summarize the weaning strategies from the literature reviews combined with our 27-year experience in the Pediatric Home Respiratory Care program at the tertiary care center in Thailand. The readiness to wean is considered in patients with hemodynamic stability, having effective cough measured by maximal inspiratory pressure, requiring a fraction of inspired oxygen (FiO2) < 40%, positive end expiratory pressure <5 cmH2O, and acceptable arterial blood gases. The strategies of weaning is start weaning during the daytime while the child is awake and close monitoring is feasible. Disconnect time is gradually increased through naps and sleeping hours. Weaning from the conventional mechanical ventilator to Bilevel PAP or CPAP are optional. Factors affected the successful weaning are mainly the underlying diseases, complications, growth and development, caregivers, and resources. Weaning should be stopped during acute illness or increased work of breathing. The readiness for decannulation could be determined by using the speaking devices, tracheostomy capping, and measurement of end-expiratory pressure. Polysomnography and airway evaluation by bronchoscopy are recommended before decannulation. Weaning when the child is ready is crucial because living with HMV can be challenging and stressful. Failure to remove a tracheostomy when indicated can result in delayed speech, social problems as well as risk for infection.

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.

Allergic rhinitis and other comorbidities associated with asthma control in Thailand.

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 FEV1. 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 FEV1/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.

Development and validation of the predictive score for pediatric COVID-19 pneumonia: A nationwide, multicenter study.

BACKGROUND: Due to the possibility of asymptomatic pneumonia in children with COVID-19 leading to overexposure to radiation and problems in limited-resource settings, we conducted a nationwide, multi-center study to determine the risk factors of pneumonia in children with COVID-19 in order to create a pediatric pneumonia predictive score, with score validation. METHODS: This was a retrospective cohort study done by chart review of all children aged 0-15 years admitted to 13 medical centers across Thailand during the study period. Univariate and multivariate analyses as well as backward and forward stepwise logistic regression were used to generate a final prediction model of the pneumonia score. Data during the pre-Delta era was used to create a prediction model whilst data from the Delta one was used as a validation cohort. RESULTS: The score development cohort consisted of 1,076 patients in the pre-Delta era, and the validation cohort included 2,856 patients in the Delta one. Four predictors remained after backward and forward stepwise logistic regression: age < 5 years, number of comorbidities, fever, and dyspnea symptoms. The predictive ability of the novel pneumonia score was acceptable with the area under the receiver operating characteristics curve of 0.677 and a well-calibrated goodness-of-fit test (p = 0.098). The positive likelihood ratio for pneumonia was 0.544 (95% confidence interval (CI): 0.491-0.602) in the low-risk category, 1.563 (95% CI: 1.454-1.679) in the moderate, and 4.339 (95% CI: 2.527-7.449) in the high-risk. CONCLUSION: This study created an acceptable clinical prediction model which can aid clinicians in performing an appropriate triage for children with COVID-19.

Spatial Estimation of PM2.5 Exposure and its Association with Asthma Exacerbation: A Prospective Study in Thai Children.

Background: The acceptable fine particulate matter (PM2.5) level in Thailand is double the recommendation of the World Health Organization. It is necessary to have an accurate measure of PM2.5 exposure and its association with health problems in vulnerable groups such as asthma exacerbation in Thai children to urge the Clean Air Act in Thailand, which is currently in the process of revision. Objective: To study the association between PM2.5 exposure and asthma exacerbation in children living in Bangkok Metropolitan Region and Chiang Mai Province. Methods: A pilot prospective observational study was conducted at the Chest and Allergy clinic at Ramathibodi Hospital, Mahidol University, Bangkok and at the Chest Clinic at Nakornping Hospital, Chiang Mai, Thailand, from June 2020 to February 2021. Children with asthma, aged 5-18 years old, were recruited. Respiratory symptoms, including cough, chest tightness, dyspnea or wheezing, peak expiratory flow rate, and asthma exacerbation, were recorded twice daily by caregivers. Estimated average daily PM2.5 exposure levels were calculated using ArcGIS® at exacerbation day, three days before exacerbation (lag day 3), and 7 days before exacerbation (lag day 7). Regression analysis was applied to examine the association between PM2.5 exposure and asthma exacerbation. Findings: Seventy asthmatic patients were enrolled. The median age was 9.7 (IQR 5-18) years old. There were 53 respiratory symptoms, 5 admissions, and 1 intensive care unit admission. Daily PM2.5 levels above 12 mcg/m3 (the US cut-off level for the sensitive group) has higher sensitivity to detect asthma exacerbation compared to Thai cut-off level for the sensitive group (37 mcg/m3) (sensitivity 98.2% vs 32.1%). The average daily PM2.5 level exposure at lag day 3 in the exacerbation vs the non-exacerbation group was 27.5 and 13.6 mcg/m3 (p < 0.01), respectively. The daily PM2.5 level at lag day 3 was also correlated with an acute asthmatic attack (r = 0.62, p < 0.01) with the 0.2 events increasing of asthmatic exacerbation every 10 mcg/m3 of increment of daily PM2.5 level. Conclusions: Our findings suggest that asthmatic children are sensitive to daily PM2.5 levels above 12 mcg/m3. Exposure to high daily PM2.5 levels can lead to asthma exacerbation within three days. Further participant recruitment is needed to emphasize this association and establish the national data.

Efficacy of a newly developed cartoon video on dry powder inhaler technique: a multicenter study.

BACKGROUND: One of the factors associated with uncontrolled pediatric asthma is inadequate delivery of inhaled medication to the lungs. Incorrect inhaler technique has been reported. We developed a 2-minute cartoon video instruction aiming to improve dry powder inhaler (DPI) technique. OBJECTIVE: To assess the efficacy of video instruction in improvement of DPI technique in Thai children with asthma. METHODS: The prospective multicenter cohort study was conducted during March 2018 - February 2019. Children with asthma aged 6-15 years were recruited from the outpatient departments. Five videotapes demonstrated how the patients use DPI devices were recorded as the followings: before and after watching video (V1pre and V1post), at one-month (V2post), at three-month (V3post) after watching the video and at 5-month follow-up without watching the video (V4pre). Scoring of correct DPI steps were evaluated by two independent respiratory specialists. RESULTS: Of 57 patients recruited, 30 used Accuhaler™ while 27 used Easyhaler™. In Accuhaler™ group, the median age (range) of 10 (8, 11) year. The mean score of V1pre, V1post, V2post and V3post were 10.7, 12.3, 12.4, and 12.2 out of 14 respectively. In Easyhaler™ group, the median age (range) of 11 (9-12) year. The mean score of V1pre, V1post, V2post and V3post were 8.6, 10.4, 11.2 and 11.4 out of 12 respectively. At the five-month follow-up, without watching video, the V4pre score was still as high as 12.9 ± 1.3 in Accuhaler™ and 11.8 ± 0.4 in Easyhaler™. CONCLUSIONS: Our video instruction could improve Accuhaler± and Easyhaler± technique among Thai children with asthma.

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).

Efficacy and safety of inhaled nebulized sodium nitrite in asthmatic patients.

BACKGROUND: Nitrite is a physiologic nitric oxide (NO) derivative that can be bioactivated to NO. NO has been shown to attenuate airway inflammation and enhance the anti-inflammatory effect of corticosteroids in the animal model of asthma. Here, we aimed to investigate the efficacy and safety of inhaled sodium nitrite as add-on therapy with inhaled corticosteroid (ICS) in adult patients with persistent asthma. METHODS: In protocol 1, 10 asthmatic patients were administered a single dose of nebulized 15-mg sodium nitrite to assess safety, effect on lung function, and pharmacokinetics of nitrite within 120 min. In protocol 2, 20 patients were randomly assigned to a nitrite (15 mg twice daily) group or a placebo group to assess the efficacy over 12 weeks. The primary outcome was the forced expiratory volume in 1 s (FEV1). The secondary outcomes were other lung function parameters, unplanned asthma-related visits at the emergency department (ED) or outpatient department (OPD), admission days, asthma control test (ACT), and safety. RESULTS: Nebulized sodium nitrite had neither acute adverse effect nor effect on lung function test within 120 min. No blood pressure change was seen. At week 12, FEV1 increased in the nitrite group, whereas there was no change in the placebo group. There were 5 events of asthma exacerbation, 4 ED visits, and one unplanned OPD visit in the placebo group, but none of these was noted in the nitrite group. There was no change in ACT scores in both groups. No adverse event was reported during 12 weeks in the nitrite group. There was no change in methemoglobin levels and sputum inflammatory markers. CONCLUSION: From our pilot trial, nebulized sodium nitrite is safe in asthmatic patients, and shows the potential to reduce asthma exacerbation compared with placebo.

The effectiveness of newly developed written asthma action plan in improvement of asthma outcome in children.

BACKGROUND: Providing asthma education about controller medication use and appropriate management of asthma exacerbation are the keys to improving the disease outcome. Many asthma guidelines recommend that physicians provide written asthma action plan (WAAP) to all of their asthmatic patients. However, the benefit of WAAP is unclear. Thus, we have created a new WAAP which is simplified in Thai and more user friendly. OBJECTIVE: To determine the effectiveness of the newly developed asthma action plan in management of children with asthma. METHODS: Asthmatic children who meet inclusion criteria all received the WAAP and they were followed up for 6 months with measurement of outcome variables, such as asthma exacerbation that required emergency room visit, unscheduled OPD visit, admission and school absence in order to compare with the past 6 months before receiving the WAAP. RESULTS: The analyzed outcomes of forty-nine children show significantly reduced emergency room visit (P-value 0.005), unscheduled OPD visit (P-value 0.046), admission days (P-value 0.026) and school absence days (P-value 0.022). Well controlled group and mild severity group were not the factors that contribute to decreased emergency room visit but step up therapy may be the co-factor to decreased ER visit. CONCLUSIONS: The results of this study suggest that the provision of newly developed WAAP is useful for improving self- care of asthma patients and reducing asthma exacerbation.

Thai pediatricians' current practice toward childhood asthma.

BACKGROUND: Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). OBJECTIVES: We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. METHODS: A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians. Asthma diagnosis and management were evaluated for compliance with standard guidelines. The practices of PCP and RS were compared. RESULTS: From 800 surveys distributed, there were 405 respondents (51%). Most respondents (81%) were PCP, who preferred to use clinical diagnosis rather than laboratory investigations to diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians prescribed at least one controller. For exercise-induced bronchospasm, 55% of the pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p < 0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of an acute asthmatic attack. CONCLUSIONS: Most of the Thai pediatricians' practices toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics, and antihistamines than RS.

Using non-invasive bi-level positive airway pressure ventilator via tracheostomy in children with congenital central hypoventilation syndrome: two case reports.

INTRODUCTION: Due to the economic downturn in Thailand, two baby girls with congenital central hypoventilation syndrome had to wait for several months to obtain definite diagnosis and long-term mechanical ventilation. Genetic investigation later revealed 20/25 polyalanine expansion of PHOX2B gene in both girls. In this report we highlight the use of non-invasive bi-level positive airway pressure ventilators via tracheostomy, overnight end-tidal carbon dioxide trend graphs and outcomes of the patients whose diagnosis and treatment were delayed. CASE PRESENTATION: Case 1: A Thai baby girl showed symptoms of apnea and cyanosis from birth and required invasive mechanical ventilation via tracheostomy during sleep. At 5 months, she unfortunately was discharged from the hospital without any ventilatory support due to financial problems. She subsequently developed cor pulmonale, respiratory failure and generalized edema and was referred to us when she was 9-months old. An overnight polysomnogram was consistent with a central hypoventilation disorder, in which the severity of oxygen desaturation and hypercapnia was worsening during non-rapid eye movement compared to rapid eye movement sleep. At 12 months she was allowed to go home with a conventional home ventilator. The ventilator was changed to bi-level positive airway pressure when she was 4-years old. After she received adequate home ventilation, she thrived with normal growth and development. Case 2: A Thai baby girl developed apnea and cyanosis from the age of 5 weeks, requiring ventilatory support (on and off) for 5 months. After being extubated, she had been put on supplemental oxygen via nasal cannula for 2 months. She was then referred to us when she was 7-months old. An overnight end-tidal carbon dioxide trend graph revealed marked hypercapnia without increase in respiratory rate. An overnight polysomnogram was consistent with a central hypoventilation disorder. Since 9 months of age she has been on home bi-level positive airway pressure via tracheostomy without any complications. Genetic testing confirmed 20/25 polyalanine expansions of PHOX2B gene in both girls. CONCLUSIONS: Bi-level positive airway pressure, originally designed as a non-invasive ventilator, was found to work effectively and safely, and may be used as an invasive ventilator via tracheostomy in young children with congenital central hypoventilation syndrome.

Aerosolized liposomal Amphotericin B: a potential prophylaxis of invasive pulmonary aspergillosis in immunocompromised patients.

BACKGROUND: Aerosolized liposomal Amphotericin B may reduce the incidence of invasive pulmonary Aspergillosis in adults with chemotherapy-induced prolonged neutropenia with less nephrotoxicity. The breath-actuated AeroEclipse® BAN nebulizer is very efficient and minimizes environmental drug contamination since no aerosol is produced, unless the patient is inspiring through the device. Our aim is to develop an appropriate delivery system suitable for children that does not disrupt the liposomes due to the shear forces in nebulization. METHODS: This is an in vitro experimental study in vitro. Six ml of 4 mg/ml liposomal Amphotericin B solution (AmBisome®; Astellas Pharma Inc., Markham, Ontario, CA) was nebulized with the breath-actuated nebulizer (AeroEclipse®; Trudell Medical International, Canada) and captured by the glass liquid impinger. Sodium dodecyl sulfate was used as detergent to disrupt the liposomes in control samples. Gel filtration, electron microscopy, and high performance liquid chromatography (HPLC) were used to compare the size and shape of the liposomes, and amount of the drug before and after nebulization. The aerosol particle size was obtained by the laser diffraction. RESULTS: After nebulization, 97.5% of amphotericin B was captured by the liquid impinger and detected by HPLC. Gel filtration and electron microscopy demonstrated that the drug remained in its liposomal configuration after nebulization. The mass median diameter (MMD) was 3.7 µm and 66% of aerosol particles were less than 5 µm in diameter. CONCLUSIONS: We demonstrated that liposomal Amphotericin B can be nebulized successfully without disrupting the liposomes and minimize drug loss by using the breath-actuated nebulizer.