Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Clinical and epidemiological features and severity markers in children admitted with multisystem inflammatory syndrome in children (MISC) in a tertiary care center in the United Arab Emirates.

BACKGROUND: Multisystem inflammatory syndrome in children (MISC) is a phenomenon that appeared in children infected with or exposed to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response. METHODS: Our study retrospectively analyzed data from a tertiary center in United Arab Emirates of MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post-PICU admission) from May 2020 to August 2021. RESULTS: The total sample size was 50 patients, and the study included a comparison of MISC-PICU admissions with MISC-non-PICU admissions. The MISC-PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. MISC-PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. MISC-PICU patients presented with relatively higher inflammatory markers: C-reactive protein, procalcitonin, ferritin, and d-dimer. Immunological studies were significantly higher for interleukin-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in MISC-PICU patients. Likewise, MISC-PICU patients were provided with more extensive therapy. As part of our study course, we reevaluated our MISC-PICU patients twice, once at 48 h post-PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort. CONCLUSION: This study evaluated risk factors of MISC and potential severity features. Follow-up of patients on discharge showed improvement across all domains.

Genetic determinants of severe COVID-19 in young Asian and Middle Eastern patients: a case series.

Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we clinically characterize a case series of patients with COVID-19, who were otherwise healthy, young adults (N = 55; mean age 34.1 ± SD 5.0 years) from 16 Asian, Middle Eastern, and North African countries. Using whole exome sequencing, we identify rare, likely deleterious variants affecting 16 immune-related genes in 17 out of 55 patients (31%), including 7 patients (41% of all carriers or 12.7% of all patients) who harbored multiple such variants mainly in interferon and toll-like receptor genes. Protein network analysis as well as transcriptomic analysis of nasopharyngeal swabs from an independent COVID-19 cohort (N = 50; 42% Asians and 22% Arabs) revealed that most of the altered genes, as identified by whole exome sequencing, and the associated molecular pathways were significantly altered in COVID-19 patients. Genetic variants tended to be associated with mortality, intensive care admission, and ventilation support. Our clinical cases series, genomic and transcriptomic findings suggest a possible role for interferon pathway genes in severe COVID-19 and highlight the importance of extending genetic studies to diverse populations to better understand the human genetics of disease.

A Rare Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation Associated With Typical Cystic Fibrosis in an Arab Child.

Cystic fibrosis (CF) is a progressive genetic disorder, inherited by the autosomal recessive mode of inheritance and more frequently seen in the Caucasian population with a carrier rate of 1:29 in Caucasian-Americans. Over 1800 cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations have been identified so far and the delta F 508 del mutation is the most common mutation. Gene sequencing and deletion/duplication analysis can detect mutations in 99% of people with a clinical diagnosis of CF. However, diagnostic testing can be challenging, as screening tests may be inconclusive and the routine gene mutation panel analysis may be negative due to some rare or undocumented mutations. We report a case of a two-year-old boy of Palestinian-Lebanese descent, with a history of raised immunoreactive trypsin test (IRT), positive sweat test, and phenotypical CF manifestations, found to have rare CF apparent homozygous CFTR (NM_000492.3) variant, c.3623del (p.Gly1208AlafsX3). In our case, genetic testing for 139 mutations done in Germany could not identify any defect. Only CFTR gene sequencing identified the above pathogenic variant. This reinforces the practice for a broad range of CFTR mutation analyses to detect ethnic-specific rare variants. This is the second case of this particular genetic mutation identified and the first to be reported in detail.

COVID-19 under 19: A meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to cause global havoc posing uncertainty to educational institutions worldwide. Understanding the clinical characteristics of COVID-19 in children is important because of the potential impact on clinical management and public health decisions. METHODS: A meta-analysis was conducted for pediatric COVID-19 studies using PubMed and Scopus. It reviewed demographics, co-morbidities, clinical manifestations, laboratory investigations, radiological investigations, treatment, and outcomes. The 95% confidence interval (CI) was utilized. RESULTS: Out of 3927 articles, 31 articles comprising of 1816 patients were selected from December 2019 to early October 2020 and were defined by 77 variables. Of these studies 58% originated from China and the remainder from North America, Europe and the Middle East. This meta-analysis revealed that 19.2% (CI 13.6%-26.4%) of patients were asymptomatic. Fever (57%, CI 49.7%-64%) and cough (44.1%, CI 38.3%-50.2%) were the most common symptoms. The most frequently encountered white blood count abnormalities were lymphopenia 13.5% (CI 8.2%-21.4%) and leukopenia 12.6% (CI 8.5%-18.3%). Ground glass opacities were the most common radiological finding of children with COVID-19 (35.5%, CI 28.9%-42.7%). Hospitalization rate was 96.3% (CI 92.4%-98.2%) of which 10.8% (CI 4.2%-25.3%) were ICU admissions, and 2.4% (CI 1.7%-3.4%) died. CONCLUSION: The majority of pediatric patients with COVID-19 were asymptomatic or had mild manifestations. Among hospitalized patients there remains a significant number that require intensive care unit care. Overall across the literature, a considerable level of understanding of COVID-19 in children was reached, yet emerging data related to multisystemic inflammatory syndrome in children should be explored.

Clinical Characteristics of Children With COVID-19 in the United Arab Emirates: Cross-sectional Multicenter Study.

BACKGROUND: COVID-19 has infected over 123 million people globally. The first confirmed case in the United Arab Emirates (UAE) was reported on January 29, 2020. According to studies conducted in the early epicenters of the pandemic, COVID-19 has fared mildly in the pediatric population. To date, there is a lack of published data about COVID-19 infection among children in the Arabian region. OBJECTIVE: This study aims to investigate the clinical characteristics, laboratory findings, treatment, and outcomes of children with COVID-19. METHODS: This cross-sectional, multicenter study included children with confirmed COVID-19 infection admitted to 3 large hospitals in Dubai, UAE, between March 1 and June 15, 2020. Serial COVID-19 polymerase chain reaction (PCR) testing data were collected, and patients' demographics, premorbid clinical characteristics, and inpatient hospital courses were examined. RESULTS: In all, 111 children were included in our study and represented 22 nationalities. Of these, 59 (53.2%) were boys. The mean age of the participants was 7 (SD 5.3) years. About 15.3% of children were younger than 1 year. Only 4 (3.6%) of them had pre-existing asthma, all of whom had uneventful courses. At presentation, of the 111 children, 43 (38.7%) were asymptomatic, 68 (61.2%) had mild or moderate symptoms, and none (0%) had severe illness requiring intensive care. Fever (23/111, 20.7%), cough (22/111, 19.8%), and rhinorrhea (17/111, 15.3%) were the most common presenting symptoms, and most reported symptoms resolved by day 5 of hospitalization. Most patients had no abnormality on chest x-ray. The most common laboratory abnormalities on admission included variations in neutrophil count (22/111, 24.7%), aspartate transaminase (18/111, 22.5%), alkaline phosphatase (29/111, 36.7%), and lactate dehydrogenase (31/111, 42.5%). Children were infrequently prescribed targeted medications, with only 4 (3.6%) receiving antibiotics. None of the 52 patients tested for viral coinfections were positive. COVID-19 PCR testing turned negative at a median of 10 days (IQR: 6-14) after the first positive test. Overall, there was no significant difference of time to negative PCR results between symptomatic and asymptomatic children. CONCLUSIONS: This study of COVID-19 presentations and characteristics presents a first look into the burden of COVID-19 infection in the pediatric population in the UAE. We conclude that a large percentage of children experienced no symptoms and that severe COVID-19 disease is uncommon in the UAE. Various laboratory abnormalities were observed despite clinical stability. Ongoing surveillance, contact tracing, and public health measures will be important to contain future outbreaks.

An interesting case of dysautonomia presenting with dyspnea.

Dysautonomia such as POTS syndrome presenting with respiratory symptoms can often be misdiagnosed for other common pulmonary conditions. It can be diagnosed with a comprehensive history and orthostatic vital measurement. Simple diagnostic test such as diffusing capacity in supine and standing position can emerge as a noninvasive tool to guide the long-term monitoring and treatment response.

Primary Ciliary Dyskinesia: An Update on New Diagnostic Modalities and Review of the Literature.

Primary ciliary dyskinesia (PCD) is a genetic condition affecting approximately 1 in 15,000-20,000 individuals, and the majority of cases exhibit an autosomal recessive inheritance pattern. However, genetic heterogenicity is seen in PCD and reflects the complexity of ciliary structure and biogenesis. There have been many recent advances in the diagnosis and management of PCD in the last few years, including advanced genetic sequencing, nasal nitric oxide assay, and ciliary motility tests. This article focuses on the ultrastructure and pathophysiology of ciliary dyskinesias, along with a review of clinical features, screening, and diagnostic tests. It also reflects upon the diagnostic challenge caused by the diverse clinical presentation, which will be of great value to pediatricians for considering PCD in their differential list, henceforth leading to early recognition and management, along with awareness of the recent advances in the field of genetics and other techniques for diagnosis of this condition.