Clinical approach for pulmonary alveolar proteinosis in children.

In this editorial, we discuss the clinical implications of the article by Zhang et al. Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by excessive surfactant accumulation in the alveoli. It is classified into four categories: Primary, secondary, congenital, and unclassified forms. Primary PAP is caused by the disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor signaling, which is necessary for the clearance of surfactant by alveolar macrophages. It is further divided into autoimmune PAP, caused by anti-GM-CSF antibodies blocking alveolar macrophage activation, and hereditary PAP, resulting from mutations in genes encoding GM-CSF receptors. Secondary PAP develops due to conditions affecting the number or function of alveolar macrophages, such as infections, immunodeficiency, hematological disorders, or exposure to inhaled toxins. Congenital PAP is linked to mutations in genes involved in surfactant protein production. Notably, the causes of PAP differ between children and adults. Diagnostic features include a characteristic "crazy-paving" pattern on high-resolution computed tomography, accompanied by diffuse ground-glass opacities and interlobular septal thickening. The presence of PAP can be identified by the milky appearance of bronchoalveolar lavage fluid and histological evaluation. However, these methods cannot definitively determine the cause of PAP. Whole lung lavage remains the standard treatment, often combined with specific therapies based on the underlying cause.

Clinical approach for pulmonary lymphatic disorders.

In this editorial, we discuss the clinical implications of the article "Lymphatic plastic bronchitis and primary chylothorax: A study based on computed tomography lymphangiography" published by Li et al. Pulmonary lymphatic disorders involve abnormalities in the lymphatic tissues within the thoracic cavity. Specifically, pulmonary lymphatic perfusion syndrome describes a condition where the flow of lymphatic fluid in the lungs is redirected towards abnormally widened lymphatic vessels. Clinically, individuals with this syndrome may experience symptoms such as chyloptysis, plastic bronchitis (PB), chylothorax, chylopericardium, and interstitial lung disease. These disorders can be caused by various factors, including PB, chylothorax, and complex lymphatic malformations. Advancements in lymphatic imaging techniques, such as intranodal lymphangiography, computed tomography lymphangiography, and dynamic contrast-enhanced magnetic resonance lymphangiography, have enabled the detection of abnormal lymphatic flow. This has enhanced our understanding of the pathophysiology of these conditions. Additionally, innovative minimally invasive treatments, such as thoracic duct embolization, selective embolization of lymphatic channels, and surgical procedures aim to improve clinical condition of patients and address their dietary needs.

Chest X-ray findings of COVID-19 pneumonia in children: Experiences in a multicenter study in Thailand.

INTRODUCTION: Although chest X-ray is commonly used to diagnose COVID-19 pneumonia, few studies have explored findings in pediatric patients. This study aimed to reveal chest X-ray characteristics in children with COVID-19 pneumonia and compare between non-severe and severe cases. METHODS: This multicenter, nationwide retrospective study included all children aged 0 to 15 years who were admitted to 13 medical facilities throughout Thailand with COVID-19 pneumonia between January 2020 and October 2021. We analyzed the demographics, clinical features, and chest X-ray results of these children, and compared differences between the non-severe and severe groups. RESULTS: During the study period, 1018 children (52% male, median age 5 years) were admitted with COVID-19 pneumonia. Most chest radiographic findings showed bilateral (51%) patchy/ground glass opacities (61%) in the central area (64%). Only 12% of the children exhibited typical classification for COVID-19 pneumonia, whereas 74% of chest radiographs were categorized as indeterminate. Comorbidities including chronic lung diseases [adjusted OR (95%CI): 14.56 (3.80-55.75), P-value <0.001], cardiovascular diseases [adjusted OR (95%CI): 7.54 (1.44-39.48), P-value 0.017], genetic diseases [adjusted OR (95%CI): 28.39 (4.55-177.23), P-value <0.001], clinical dyspnea [adjusted OR (95%CI): 12.13 (5.94-24.77), P-value <0.001], tachypnea [adjusted OR (95%CI): 3.92 (1.79-8.55), P-value 0.001], and bilateral chest X-ray infiltrations [adjusted OR (95%CI): 1.99 (1.05-3.78), P-value 0.036] were factors associated with severe COVID-19 pneumonia. CONCLUSION: Most children with COVID-19 pneumonia had indeterminate chest X-rays according to the previous classification. We suggest using chest X-rays in conjunction with clinical presentation to screen high-risk patients for early detection of COVID-19 pneumonia.

Incidence and risk factors for long COVID in children with COVID-19 pneumonia.

BACKGROUND AND OBJECTIVE: There are only a few reports of long COVID including pulmonary function in children after COVID-19 pneumonia. We determined the incidence of long COVID and abnormal pulmonary function in those children and identify risk factors. METHODS: This cohort study enrolled children admitted with COVID-19 pneumonia during 2021-2022. We gathered clinical characteristics during admission and at follow-up 3 months after. RESULTS: We determined the incidence of long COVID at 39.7% (95% confidence interval [CI]: 30.7%-49.1%). All severe pneumonia cases consistently reported persistent symptoms. Exercise intolerance, cough, and fatigue were the three most common persistent symptoms in 26 (22.4%), 21 (18.1%), and 18 (15.5%) of the patients, respectively. At the follow-up, 21 cases (18.1%) demonstrated persistent abnormal chest radiographs. Three cases (6.9%) demonstrated restrictive ventilatory defects. Among those, one case (2.3%) demonstrated concomitant diffusion defect. Three cases (6.0%) demonstrated exercise-induced hypoxemia after the 6-minute walk test. Comparing spirometry variables between children with long COVID and without revealed significant difference of FEF25-75 (z score) between two groups. Age [adjusted OR (95% CI): 1.13 (1.05-1.22), p value 0.002], allergic diseases [adjusted OR (95% CI): 4.05 (1.36-12.06), p value 0.012], and living in polluted areas [adjusted OR (95% CI): 2.73 (1.18-6.33), p value 0.019] were significantly associated with long COVID. CONCLUSION: A significant percentage of children developed long COVID after COVID-19 pneumonia. We should give additional attention to those who have exercise intolerance, chronic cough, or fatigue, especially older children, severe cases, children with allergic diseases, and those living in polluted areas.

Impact of respiratory care training and family support using telemedicine on tracheostomized children admitted with respiratory infection after discharge.

OBJECTIVE: Children with tracheostomies usually require a long hospital stay, high healthcare costs and caregiver burden. With the help of telemedicine, this study attempted to determine how home respiratory care training and family support affected admission days, admission costs, ICU admission rates, and caregivers' confidence. METHODS: We enrolled children with tracheostomies who were admitted between 2020 and 2022 with respiratory infections. Before discharge, we evaluated the knowledge and skills of the caregivers and gave them practice in home respiratory care while providing them with structured feedback using a checklist, a peer-to-peer mentor assignment, a virtual home visit, teleeducation, and teleconsultation via a mobile application. We compared the admission days, admission costs, and ICU admission rates one year following the program with the historical control one year earlier. RESULTS: Forty-eight children with tracheostomies were enrolled. Thirteen percent of those had a 1-year readmission. The median [IQR] number of admission days decreased from 55 [15-140] to 6 [4-17] days (p value < 0.001). The median [IQR] admission costs decreased from 300,759 [97,032 - 1,132,323] to 33,367 [17,898-164,951] baht (p value < 0.001). The ICU admission rates decreased from 43.8% to 2.1% (p value < 0.001). Immediately after the program, caregivers' confidence increased from 47.9% to 85.5% (p value < 0.001). CONCLUSIONS: This respiratory care training and telehealth program decreased admission days, admission costs, and ICU admission rates for children with tracheostomies admitted with respiratory infections. The confidence of caregivers was also increased immediately after the program.

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.

Effect of Threshold Inspiratory Muscle Training on Functional Fitness and Respiratory Muscle Strength Compared to Incentive Spirometry in Children and Adolescents With Obesity: A Randomized Controlled Trial.

Background: To determine the effect of threshold inspiratory muscle training (IMT) on functional fitness and respiratory muscle strength (RMS) compared to incentive spirometry (IS) in children/adolescents with obesity. Methods: A total of 60 obese children/adolescents aged 8-15 years were randomized into the threshold IMT group (n = 20), the IS group (n = 20), or the control group (n = 20). The IMT group performed 30 inspiratory breaths with the intensity set at 40% of baseline maximal inspiratory pressure (MIP) twice daily for 8 weeks; the IS group performed 30 breaths with sustained maximum inspiration twice daily for 8 weeks; and, the control group was assigned no training device for 8 weeks. Six-min walk test (6-MWT), RMS, and spirometry were compared between baseline and 8 weeks. Results: Six-MWT distance (528.5 ± 36.2 vs. 561.5 ± 35.2 m, p = 0.002) and MIP (121.2 ± 26.8 vs. 135.3 ± 32.1%Predicted, p = 0.03) were significantly improved after 8 weeks of IMT training. There was no significant difference in any evaluated pulmonary function parameters between baseline and 8 weeks in the IS or control groups; however, 6-MWT distance demonstrated a trend toward significant improvement in the IS group (526.9 ± 59.1 vs.549.0 ± 50.6 m, p = 0.10). No significant difference among groups was found for any variable relative to change from baseline to post-training. Conclusion: Eight weeks of threshold IMT training significantly improved both inspiratory muscle strength (MIP) and functional fitness (6-MWT) in children/adolescents with obesity. Eight weeks of IS training yielded a trend toward significantly improved functional fitness.

Prevalence and Risk Factors for Rapid Eye Movement-Related Obstructive Sleep Apnea in Children.

Objectives: Different pathophysiological mechanisms and the distribution of respiratory events among rapid eye movement (REM) and non-rapid eye movement (NREM) sleep modulate the effect of obstructive sleep apnea (OSA). We aimed to study the prevalence and risk factors for REM-related OSA in children. Study Design: Retrospective, cross-sectional study. Methods: We recruited 366 children with OSA confirmed by polysomnography (PSG) over a 5-year period. REM-related OSA is defined by an obstructive apnea-hypopnea index (OAHI) in the REM sleep ≥2× than during NREM sleep. Results: The prevalence of REM-related OSA in children was 50.3%. Children with REM-related OSA were more likely to be female (P = 0.042), and had lower prevalence of adenotonsillar hypertrophy (P = 0.043) compared with children with other OSA subtypes. Children with REM-related OSA slept longer in the supine position (P = 0.003), had shorter duration of NREM1 sleep (P = 0.018), lower nadir SpO2 (P = 0.005), and a higher oxygen desaturation index 3% (ODI3%) (P = 0.014), and lower arousal index (P = 0.034) compared with other OSA subtypes. Female gender and supine sleep was the independent risk factors for REM-related OSA. Conclusion: The prevalence of REM-related OSA was 50.3%. OAHIREM should be considered as an important parameter in future clinical research studies done in children with OSA.

Tuberculosis-immune reconstitution inflammatory syndrome in HIV-negative children.

Even though tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is usually found in HIV-positive patients receiving antiviral treatment, it can also occur in HIV-negative patients especially if they have risk factors. We report a unique case of TB-IRIS in an immunocompetent child presenting with new onset of pleuritic chest pain after receiving anti-TB drugs. TB-IRIS should be considered as a differential diagnosis in case of clinical deterioration or appearance of new typical lesions despite appropriate anti-TB treatment for more than 2 weeks in the absence of persistently active TB or any other alternative causes. This will prevent physicians from misdiagnosis as superimposed infections, treatment failure or TB relapse.

Comparing Adherence of Continuous and Automatic Positive Airway Pressure (CPAP and APAP) in Obstructive Sleep Apnea (OSA) Children.

OBJECTIVES: The treatment outcomes of pediatric obstructive sleep apnea (OSA) are affected by positive airway pressure (PAP) therapy adherence, which may be affected by the type of device used. Continuous PAP (CPAP) devices deliver a continuous and fixed air pressure level, whereas automatic PAP (APAP) devices automatically adjust the pressure to meet changing needs during sleep. The adherence, tolerance and consistency of OSA-children's use of CPAP and APAP devices were compared. STUDY DESIGN: One-year, observational cohort study. METHODS: Twenty-seven OSA-children were enrolled. Fourteen (52%) used CPAP, and 13 (48%) used APAP. The adherence, tolerance, and consistency of the PAP usage by the two groups were compared. RESULTS: Overall, 11 of the 27 children (41%) showed good PAP adherence. The CPAP patients averaged 4.9 h of device usage on the days used, for 60% of days, with 6 of 14 (43%) demonstrating good adherence. In comparison, the APAP patients averaged 3.2 h for 55% of days, with 5 of 13 (38%) exhibiting good adherence. The 2 groups showed no differences in their adherence, tolerance, or consistency of device usage (P values, 0.816, 0.609, and 0.720, respectively). Although the adherence of both groups improved in the second 6 months, it was without statistical significance (P values, 0.400 and 0.724). Age, sex, baseline apnea-hypopnea index, comorbidities, prescribed period, device type, mask type, and caregiver education-level were not risk factors for poor PAP adherence. CONCLUSIONS: No differences in the adherence, tolerance, or consistency of the children's use of CPAP and APAP were revealed in this small inhomogeneous cohort study with limited resources.

Rare cause of neonatal apnea from congenital central hypoventilation syndrome.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by mutations in the Paired-Like Homeobox 2B (PHOX2B) gene. It causes alveolar hypoventilation and autonomic dysregulation. This report aimed to raise awareness of this rare cause of neonatal apnea and hypoventilation as well as described the diagnostic work up to confirm the diagnosis in resource-limited setting where polysomnography for neonate is unavailable. CASE PRESENTATION: A late preterm female newborn born from a non-consanguineous primigravida 31-year-old mother had desaturation soon after birth followed by apnea and bradycardia. After becoming clinically stable, she still had extubation failure from apnea without hypercapnic ventilatory response which worsened during non-rapid eye movement (NREM) sleep. After exclusion of other etiologies, we suspected congenital central hypoventilation syndrome and sent genetic testing. The result showed a PHOX2B gene mutation which confirmed the diagnosis of CCHS. We gave the patient's caregivers multidisciplinary home respiratory care training including tracheostomy care, basic life support, and simulation training for respiratory problem solving. Then, the patient was discharged and scheduled for follow-up surveillance for associated conditions. CONCLUSION: Diagnosis of CCHS in neonates includes the main clue of the absence of hypercapnic ventilatory response which worsens during non-rapid eye movement (NREM) sleep after exclusion of other causes. Molecular testing for PHOX2B gene mutation was used to confirm the diagnosis.

A rare case of mediastinal lymphatic venous malformations in children.

We report a case of mediastinal lymphatic venous malformations (LVM) in a 11-year-old boy who presented with chest pain after jumping into a swimming pool, with review of the literature. A superior mediastinal mass was incidentally found from the chest x-ray. Chest computed tomography revealed a large heterogenous mass at the left-sided mediastinum containing fat, minimal enhancing solid portion, non-enhancing cystic portion and calcification. Because of the large size of the mass, the patient underwent tumour removal. Operative findings gave a definitive diagnosis of mediastinal LVM. The patient had an uneventful clinical course and was discharged without complication. This report highlights that it is possible to misdiagnose mediastinal LVM especially if its predominant portion is lymphatic tissue with only minimal contrast enhancement. Tissue biopsy must be avoided because it may lead to haemorrhagic complication.

Paediatric haemoptysis from multiple pulmonary artery aneurysms.

The case of multiple peripheral pulmonary artery aneurysms in children presenting with haemoptysis following an episode of bacterial endocarditis is presented. They are extremely rare and clinically non-specific but critical because early diagnosis is crucial for preventing sudden death from their rupture. Computed tomography pulmonary angiography remains the investigation of choice. Despite no consensus recommendation on the management, a multidisciplinary team should plan the beneficial approach with minimal procedure-related morbidity and mortality to improve survival. This case report aimed to emphasize the recognition of this rare cause of haemoptysis in children.

Pancreaticopleural fistula in a child with chronic pancreatitis harboring compound SPINK1 variants.

BACKGROUND: Pancreaticopleural fistula (PPF) is a rare complication of chronic pancreatitis (CP) that requires a high index of clinical suspicion in the patient who presents with a pleural effusion. Visualizing the fistula tract from the pancreatic duct to the pleural space by radiological imaging provides confirmation of this complication. CASE PRESENTATION: A 9-year-old boy who presented with massive right pleural effusion secondary to PPF, a complication of CP from a genetic mutation involving two mutations of SPINK1. We successfully managed the case with by endoscopic pancreatic duct stent placement after failure of conservative treatment approaches. CONCLUSIONS: PPF is a rare but serious complication of CP in all ages. The diagnosis of PPF in children requires a high index of clinical suspicion and should be considered in the differential diagnosis of massive pleural effusion where pancreatic pathology is present. A high level of pleural fluid amylase and the results from radiological imaging when the patients have symptoms play essential roles in the diagnosis of PPF. Currently, Magnetic resonance cholangiopancreatigraphy (MRCP) is the imaging modality of choice. Endoscopic therapy and surgery are treatment options for patients who do not respond to conservative therapy.

Obesity Indices for Predicting Functional Fitness in Children and Adolescents With Obesity.

Objectives: We aimed to determine the obesity indices that affect 6-min walk test (6-MWT) distance in children and adolescents with obesity and to compare the 6-MWT distance of obese subjects with that of normal-weight subjects. Methods: Obese children and adolescents aged 8-15 years and normal-weight age- and gender-matched controls were enrolled. All participants performed the 6-MWT; respiratory muscle strength (RMS), including maximal inspiratory pressure and maximal expiratory pressure; and spirometry. Data between groups were compared. In the obesity group, correlation between obesity indices and pulmonary function testing (6-MWT, RMS, and spirometry) was analyzed. Results: The study included 37 obese and 31 normal-weight participants. The following parameters were all significantly lower in the obesity group than in the normal-weight group: 6-MWT distance (472.1 ± 66.2 vs. 513.7 ± 72.9 m; p = 0.02), forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (85.3 ± 6.7 vs. 90.8 ± 4.5%; p < 0.001), forced expiratory flow rate within 25-75% of vital capacity (FEF25-75%) (89.8 ± 23.1 vs. 100.4 ± 17.3 %predicted; p = 0.04), and peak expiratory flow (PEF) (81.2 ± 15 vs. 92.5 ± 19.6 %predicted; p = 0.01). The obesity indices that significantly correlated with 6-MWT distance in obese children and adolescents were waist circumference-to-height ratio (WC/Ht) (r = -0.51; p = 0.001), waist circumference (r = -0.39; p = 0.002), body mass index (BMI) (r = -0.36; p = 0.03), and chest circumference (r = -0.35; p = 0.04). WC/Ht was the only independent predictor of 6-MWT distance by multiple linear regression. Conclusions: Children and adolescents with obesity had a significantly shorter 6-MWT distance compared with normal-weight subjects. WC/Ht was the only independent predictor of 6-MWT distance in the obesity group.