Are we overdiagnosing multisystem inflammatory syndrome in children (MIS-C)? A case series of children with bacterial infection mimicking MIS-C.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a serious hyperinflammatory condition associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Usually, the diagnosis of MIS-C is made by criteria defined by international organizations, which include specific clinical features, laboratory findings, and evidence of SARS-CoV-2 infection. We hereby present a case series of three children. The objective of this case series, involving chart review of medical records of children admitted with MIS-C, is to emphasize that the features of MIS-C may overlap with other conditions. CASE PRESENTATION: Three children were presented with MIS-C based on World Health Organization (WHO) criteria and given treatment for the same. However, due to persistent symptoms, they were further worked up and diagnosed to have underlying bacterial infections which included liver abscess, enteric fever, or urinary tract infection. CONCLUSIONS: The criteria for MIS-C may overlap with other conditions, particularly bacterial infection that may lead to overdiagnosis of MIS-C. Therefore, one should be very careful in making an MIS-C diagnosis and other differential diagnoses should be considered when the symptoms persist or worsen.

Role of nebulised magnesium sulfate in treating acute asthma in children: a systematic review and meta-analysis.

OBJECTIVES: To review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children. METHODS: The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO4 as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them. RESULTS: 10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO4/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I2=21%). Children in the MgSO4 group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I2=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups. CONCLUSIONS: There is low-certainty evidence that nebulised MgSO4 as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO4 in paediatric acute asthma management. PROSPERO REGISTRATION NUMBER: CRD42022373692.

Association of vitamin D with disease severity in infants with bronchiolitis.

Vitamin D's role in immune system regulation and its contribution to host defenses against respiratory infections may have implications for bronchiolitis pathophysiology. This cross-sectional study aimed to determine the association between the clinical severity of bronchiolitis and serum vitamin D levels in infants. Infants aged 1 month to 12 months, diagnosed with bronchiolitis, and healthy controls attending routine immunization were enrolled. Baseline characteristics were recorded, including clinical details, bronchiolitis severity, and course during hospital stay. Bronchiolitis severity score (BSS) was used to score the severity. A 1-2 ml serum sample was obtained for vitamin D levels estimation. The median age of cases (n = 64; 65.6% male) was 5 [3, 8] months, and that of the control group (n = 30) was 3 [2, 9] months. No statistically significant differences were observed between the two groups in age, gender, weight, mode of delivery, family history of atopy/asthma, feeding pattern, smoke exposure, and daily vitamin D supplementation. The median vitamin D levels were not significantly different between the groups (p = 0.68). Among infants with bronchiolitis, 62.5% had vitamin D insufficiency (≤ 20 ng/ml). A significantly higher median BSS indicates that infants with vitamin D insufficiency exhibited more severe disease (p = 0.019). Although a negative correlation between BSS and vitamin D levels was noted, it did not reach statistical significance [rs = (-)0.17; p = 0.16]. CONCLUSION:  Infants with Vitamin D insufficiency experienced more severe bronchiolitis with elevated BSS scores. It highlights the potential role of vitamin D deficiency in severe bronchiolitis. WHAT IS KNOWN: • Vitamin D level is low in infants with bronchiolitis. WHAT IS NEW: • Infant with low vitamin D level experienced more severe bronchiolitis.

Comparison of Telemedicine versus In-Person Visit for Control of Asthma in Children aged 7-17 years: A Randomized Controlled Trial.

OBJECTIVES: To compare asthma control between telemedicine and in-person visit in children aged 7 to 17 y. METHODS: A non-inferiority randomized-controlled trial was conducted at a pediatric chest clinic, involving a total of 192 patients, with 96 children in each group of telemedicine and in-person follow-up. RESULTS: There was a significant improvement in the mean asthma control test (ACT)/ Childhood asthma control test (C-ACT) scores from baseline to three months in both groups, with no significant difference in the change of means between the two groups. The mean difference in ACT/C-ACT score at three months in the telemedicine and in-person visit group was -0.35; 95% CI (-1.30 to +0.10) [p-value 0.09]. There was a significant change in the mean Pediatric Quality of Life index (PQLI) scores from 57.2 ± 10.2 to 66.82 ± 7.99 in the telemedicine group and from 56.1 ± 11.7 to 66.71 ± 4.66 in the in-person visit group, however the mean difference in PQLI score in both the groups was not significant (p = 0.91). There was no significant difference in the number of asthma exacerbations (4 vs. 1) between telemedicine and in-person visit (p = 0.10). The mean telemedicine satisfaction questionnaire score in this study was 3.8 ± 0.7, which indicates that most of the parents were satisfied with the telemedicine follow-up process. CONCLUSIONS: This study revealed that telemedicine is non-inferior to in-person visit for follow-up of children with asthma and can be used as an alternative to in-person visit for the management of asthma, especially in remote settings and pandemic situations.

Effect of Long-term Inhaled Corticosteroids on the Hypothalamic-Pituitary-Adrenal Axis in Children with Asthma.

OBJECTIVES: To assess the effect of the long-term use of inhaled corticosteroids (ICS) on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: Children (5-18 y) diagnosed with asthma and on ICS therapy for ≥6 mo were included. In the first step, screening with fasting at 8 AM, cortisol level was measured; a value <15 mcg/dl was considered low. Children with low fasting cortisol levels were subjected to adreno-corticotropic hormone (ACTH) stimulation test in the second step. Post-ACTH stimulation, cortisol level <18 mcg/dl was considered to have HPA axis suppression. RESULTS: A total of 78 children (males 55, 70.5%) diagnosed with asthma, with a median age of 11.5 (8, 14) y, were enrolled. The median duration of ICS use was 12 (12-24) mo. The median value of post-ACTH stimulation cortisol level was 22.5 (20.6, 25.5) mcg/dl, and a value <18 mcg/dl was observed in 4 (5.1%; 95% CI 0.2-10%) children. There was statistically no significant correlation between low post-ACTH stimulation cortisol level with ICS dose (p = 0.23) and asthma control (p = 0.67). None of the children had clinical features of adrenal insufficiency. CONCLUSIONS: In this study, a few children had low post-ACTH stimulation cortisol values; however, none had clinical evidence of HPA axis suppression. Therefore, ICS is a safe drug in children for treating asthma, even for long-term use.

Evaluation of Chronic Cough in Children Using Management Algorithm: A Prospective Cohort Study.

OBJECTIVE: To assess the use of a standardized evaluation algorithm [American College of Chest Physician (ACCP) 2006] in children with chronic cough. METHODS: In this prospective cohort study, children with chronic cough were evaluated as per the ACCP 2006 diagnostic algorithm. All children were followed regularly at an interval of 2-4 wk. The study's endpoint was for the patient being cough free for four weeks either following treatment or naturally. RESULTS: The mean age of the 87 studied children (52 male, 35 female) was 11.9±3 y. Forty children (45.9%) had specific cough pointers on history and examination. Radiograph showed abnormalities in 12 (13.8%) children, and spirometry showed a reversible obstructive pattern on spirometry in 6 (6.9%) among 47 (54%) children without specific cough pointers. After a detailed evaluation, 16 (18.3%) children had no remarkable findings and were reviewed after two weeks. Spontaneous resolution of cough occurred in 6 children. A trial of inhalational corticosteroids (ICS) (9 children) or antibiotics (1 child) was given to the rest of the ten children. Specific underlying diagnoses could be established in 80 (91.9%) children. The most common etiology identified in the study was asthma and asthma-like illnesses (n = 52; 59.8%), followed by upper airway cough syndrome (n = 13; 14.9%) and tuberculosis (n = 9; 10.4%). Eighty-four (96.5%) children had complete resolution of cough during follow-up. The mean time to resolution in the study was 33.6±16.8 d. CONCLUSIONS: This study demonstrated that the ACCP 2006 algorithm is effective in establishing the underlying etiology and managing children with chronic cough.

Vitamin D and Respiratory Diseases : Based on 11th Dr. I. C. Verma Excellence in Research Award for Young Pediatricians Delivered as Oration on 15th Oct. 2023.

The significance of Vitamin D has been appreciated beyond bone health and calcium metabolism. The importance of Vitamin D in respiratory health has been recognized due to its immunomodulatory and anti-microbial properties. The hypothesis is that Vitamin D could have a significant role in the pathogenesis of respiratory diseases and may represent a novel preventive and therapeutic strategy. Furthermore, enumerable observational studies established the association of Vitamin D deficiency with respiratory diseases such as asthma, bronchiolitis, pneumonia, tuberculosis, etc. However, experimental studies have not shown the encouraging results. This brief review will summarize and discuss the synthesis and metabolism of Vitamin D, the prevalence of Vitamin D deficiency in children, its role in the pathogenesis of various childhood respiratory diseases, and an overview of the therapeutic trials assessing the role of Vitamin D supplementation in childhood respiratory diseases.

Expert group recommendation on inhaled mucoactive drugs in pediatric respiratory diseases: an Indian perspective.

Background: Currently, there are no guidelines or consensus statements about the usage of inhaled mucoactive drugs in pediatric respiratory disease conditions from an Indian perspective. Objective: To develop a practical consensus document to help pediatricians in clinical decision-making when choosing an appropriate mucoactive drug for the management of specific respiratory disease conditions. Methods: A committee of nine experts with significant experience in pediatric respiratory disease conditions and a microbiological expert constituted the panel. An electronic search of the PubMed/MEDLINE, Cochrane Library, Scopus, and Embase databases was undertaken to identify relevant articles. Various combinations of keywords such as inhaled, nebulized, mucoactive, mucolytic, mucokinetic, expectorants, mucoregulators, mucociliary clearance, respiratory disorders, pediatric, cystic fibrosis (CF), non-CF bronchiectasis, acute wheezing, asthma, primary ciliary dyskinesia (PCD), critically ill, mechanical ventilation, tracheomalacia, tracheobronchomalacia, esophageal atresia (EA), tracheoesophageal fistula (TEF), acute bronchiolitis, sputum induction, guideline, and management were used. Twelve questions were drafted for discussion. A roundtable meeting of experts was conducted to arrive at a consensus. The level of evidence and class of recommendation were weighed and graded. Conclusions: Inhaled mucoactive drugs (hypertonic saline, dry powder mannitol, and dornase alfa) can enhance mucociliary clearance in children with CF. Experts opined that hypertonic saline could be beneficial in non-CF bronchiectasis, acute bronchiolitis, and PCD. The current state of evidence is inadequate to support the use of inhaled mucoactive drugs in asthma, acute wheezing, tracheomalacia, tracheobronchomalacia, and EA with TEF.

Utility of systemic immune-inflammation Index as a serum biomarker to differentiate between complicated and simple para-pneumonic effusion.

The systemic immune-inflammation index (SII) is a novel inflammatory biomarker. Simple and complicated para-pneumonic effusion (PPE) are two significant complications of pneumonia. We evaluated the efficacy of the systemic immune inflammation index (SII) to differentiate between the two. Records of all children up to 18 years of age admitted between April 2019 and September 2022 and diagnosed with Simple or complicated PPE were retrospectively evaluated. SII and other biomarkers were compared between both groups. ROC with the Youden index was used to estimate the discriminative value of SII. Fifty children were enrolled with a median (IQR) age of 81.5 (36.7, 133.5) months; 31 (62%) were male. Thirty-one (62%) had complicated PPE, and 19 (38%) had simple PPE. SII was significantly higher in complicated PPE (p=0.007). Good areas under the curve (AUCs) were found for CRP (0.771) and SII (0.736) to differentiate complicated from simple PPE. The best cut-off value for SII to differentiate complicated PPE from simple PPE was 1557×103µL, with a sensitivity of 82.4% and specificity of 57.6%. SII can be used as a screening tool to differentiate between complicated and simple PPE at the time of presentation.

Relationship of Serum Periostin With Asthma Control in Children: Single Center Experience.

OBJECTIVE: To determine the association between serum periostin levels and asthma control in children. METHODS: Children aged 6-17 years with physician-diagnosed asthma were enrolled in the study. Age-matched (±2 years) control children, who visited our outpatient department with non-respiratory complaints, were also enrolled. RESULTS: A total of 90 children (60 with asthma and 30 control subjects) with a mean (SD) age of 12.1 (2.77) years were enrolled. Children with asthma had significantly higher median (IQR) periostin levels than the controls [23.5 (22,26) vs 22 (19.4, 22.96); P= 0.04]. On multivariable logistic regression analysis, serum periostin levels were associated with poor asthma control in children [OR (95% CI), 1.12 (1.01-1.24); P= 0.02]. Age, body mass index, IgE levels, eosinophil count, forced expiratory volume in first minute (FEV1) and presence of allergic rhinitis did not have any association with asthma control. CONCLUSION: Asthmatic children have a high serum periostin level, and its higher levels are associated with poor asthma control.

Clinical Profile, Follow-up, and Role of Neuroimaging in Pediatric Guillain-Barré Syndrome in the COVID Era: An Ambispective Study.

Background: To define the varied presentations of Guillain-Barré syndrome in children in the COVID era and 6 months' follow-up outcome. Methods: Ambispective study of 15 months' duration involving children with Guillain-Barré syndrome aged 1 month to 18 years at a tertiary care pediatric hospital. They were categorized into groups A and B based on COVID-19 serology testing. Hughes Disability Scale was used for disability assessment. Modified Rankin scale was used for improvement assessment in follow-up. Results: Of 19 children with Guillain-Barré syndrome, 9 (47%) were females and 10 (53%) were males. Groups A and B had children with negative (8) and positive serology (11), respectively. The most common presentation in both groups was motor weakness. Post-COVID pediatric Guillain-Barré syndrome presented with variants of Guillain-Barré syndrome rather than the classical form (P = .03). In group B, patients with elevated inflammatory markers had poor response to intravenous immunoglobulin, and 5 of 11 patients had good response to pulse steroids, probably depicting an inflammation-predominant pathology. Conclusion: Post-COVID Guillain-Barré syndrome in children presented with Guillain-Barré syndrome variants rather than the classic form. Neuroimaging is of great value in both confirming Guillain-Barré syndrome diagnosis and excluding differentials. Patients with elevated inflammatory markers and residual weakness may be given a pulse steroid trial.