Objectives: Although albuterol, the most frequently used bronchodilator, has been traditionally and generally delivered via nebulization (NEB) with compressed air/oxygen, the benefits of metered‐dose inhalers with a spacer (MDI+S) have been widely recognized as an alternative method for albuterol administration. The aim of this systematic review was to compare the response to albuterol delivered through NEB with albuterol delivered through MDI+S in pediatric patients with asthma exacerbations. Methods: We conducted an electronic search in MEDLINE/PubMed, EMBASE, Ovid and ClinicalTrials. To be included in the review, a study had to a randomized clinical trial comparing albuterol delivered via NEB versus MDI+S; and had to report the rate of hospital admission (primary outcome), or any of the following secondary outcomes: oxygen arterial saturation, heart rate (HR), respiratory rate, the pulmonary index score (PIS), adverse effects, and need for additional treatment. Results: Fifteen studies (n=2057) met inclusion criteria. No significant differences were found between the two albuterol delivery methods in terms of hospital admission (RR 0.89; 95% CI 0.55 to 1.46; I2=32%; p=0.65). There was a significant reduction in the PIS score (MD -0.63; 95% CI -0.91 to -0.35; I2=0%; p < 0.00001), and a significantly smaller increase in HR (better) (MD -6.47; 95% CI -11.69 to -1.25; I2=0%; p=0.02) when albuterol was delivered through MDI+S than when it was delivered through NEB. Conclusions: This review showed a significant reduction in the PIS and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB.

Introduction: COVID-19 emerged in China leading to worldwide morbidity and mortality, including depression and anxiety. As the pandemic spread throughout Italy and Europe, mental health concerns emerged for people with cystic fibrosis (pwCF), who are at increased risk. This led to development of a Telehealth Psychological Support Intervention to help adolescents/young adults with CF and caregivers cope with the stress and emotional challenges of the lockdown which began in Italy in March 2020. Methods: This intervention utilized cognitive behavioral skills (e.g., relaxation training, cognitive reframing). Participants included 16 adolescents/adults and 14 parents, who completed 4 individual video sessions with a psychologist. Stress ratings, PHQ-8 and GAD-7 were completed electronically. Feasibility and Satisfaction were rated. Results: Ratings of stress significantly decreased from pre to post-testing for both pwCF (paired t=-4.06 (14), p<.01) and parents (paired t=-5.2, p< 001). Most participants reported clinically elevated depression and anxiety at the pre-test, with statistically significant reductions in depression for pwCF (pre: M=8.0 to post M=4.7; paired t (14)=2.8, p <.05) but not anxiety (pre: M=6.9 to post: M=5.6, t (14)=1.2, p=NS). Reductions in depression were found for parents (pre: M=6.4 to post: M 5.1, (14) t=-2.5, p<.05) but not anxiety (pre: M=8.1 to post: M=7.9, t (14)=-0.2, p=ns). Positive ratings of Feasibility and Satisfaction were documented. Conclusion: This brief telehealth intervention yielded significant reductions in stress and depression for participants. Anxiety was not reduced, possibly because COVID was ongoing. This intervention was effective for improving mental health and was highly feasible and satisfactory.

International guidelines have recommended the use of inhaled beta-2 agonists and systemic corticosteroids (SC) as the first-line treatment for acute asthma. Objective: To evaluate the evidence for the efficacy of inhaled corticosteroids (ICS) in addition to SC compared to SC alone in children with acute asthma in the ED or during hospitalization. Data sources: Five electronic databases were searched. Study Selection: All RCTs that compared ICS (via nebulizer or metered dose inhaler) plus SC (oral or parenteral) with placebo (or standard care) plus SC were included without language restriction. Data extraction: Two reviewers independently reviewed all studies. The primary outcomes were hospital admission or hospital length of stay [LOS], and secondary outcomes were readmissions during follow-up, ED-LOS, lung function, asthma clinical score, oxygen saturation, and heart and respiratory rates. Results: Nine studies (n=1473) met the inclusion criteria. In all the studies, the ICS was budesonide. Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreased hospital LOS by more than one day (MD= -29.08 hours [-39.9 to -18.3]; I2=0%, p=<0.00001). Moreover, adding budesonide (especially with ≥2mg doses) significantly improved the acute asthma severity score among patients at ED. Conclusions: Compared to SC alone, adding budesonide to SC did not affect hospitalization rate, but decreases the LOS and improves the acute asthma score in children at ED setting.

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased d-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 PCR and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic.

It was recently reported that due to the COVID-19 pandemic, in the European winter 2020-2021, bronchiolitis had practically disappeared. But early reports from the southern hemisphere (Australia) raised concerns about a late spring / summer peak. After a full winter season and now ending the summer, we report that there was no peak of common respiratory viruses in late spring / summer in South America.

Objectives: Pleuropulmonary blastoma (PPB) is a very rare, characteristic and highly aggressive neoplasm occurring in children, most under 6 years of age. We assessed the clinical characteristics, treatment modalities, treatment outcomes, and prognostic factors affecting survival in patients with PPB treated at our institution over a 10-year period to improve the prognosis of PPB. Methods: From November 2008 to November 2019, 31 children (21 boys and 10 girls) with a median age of 30 months (range, 22 days-54 months) were treated at our institution. Here, we describe the patient characteristics, treatment modalities and treatment outcomes. The Kaplan-Meier method was used to estimate the progression free survival probability (PFS) and overall survival (OS). Log-rank test was performed for comparison between groups. Results: 3 children were lost to follow-up and 2 were dead of postoperative complications. Of the 26 patients included in the follow-up, 16 PPB patients displayed tumor-free survival. The 6-month, 1-, 3-, and 5-year PFS were 80.8%, 69.0%, 60.4% and 60.4%, respectively. Accordingly, the 6-month, 1-, 3-, and 5-year OS were 84.6%, 72.7%, 60.1% and 60.1%, respectively. Sex, extent of surgery and chemotherapy/irradiation appeared to affect the survival, while age and pathology type appeared not to do. Conclusions: PPB is an aggressive neoplasm. To improve the prognosis of PPB, we should promote radical resection and improve the auxiliary treatment measures.

Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.

Abstract Aim: To evaluate the respiratory functions of children with nephrotic syndrome (NS) by IOS and its correlation with spirometry. Methods: Fifty-five NS patients aged 3–18 years were included as the study group and 40 healthy children of the same age formed the control group. Patients were divided into nephrotic phase (first attack and relapse) and remission. Demographic, anthropometric and laboratory data of the children were recorded. Respiratory functions were evaluated by IOS and spirometry. Children over 6 years old performed both IOS and spirometry while children under 6 years performed only IOS. Results: The R (R5%, R10%, R5-20) and AX and Z5% values of IOS in patients with nephrotic phase were higher than remission patients and control group while spirometry indices of FEV1%, FEV1/FVC, PEF% and MEF25-75% were lower. FEV1% showed negative correlation with R5%, R10%, R15%, X10% and X15% results, FEV1/FVC% showed negative correlation with R5%, R5-20 and X15% results, FVC showed negative correlation with X10% results, MEF25-75% showed negative correlation with, R5%, R10%, R5-20, X15%, F res, Z5% and AX results. Conclusion: Our study demonstrated that respiratory functions measured by IOS and spirometry were affected at the time of nephrotic phase in NS patients. And IOS, a novel method easily applicable even in small children, is a valuable and reliable tool to detect this condition; given its good correlation with spirometry. Keywords Nephrotic syndrome, Respiratory functions, Spirometry, Impulse Oscillometry

Background: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. Methods: Children diagnosed by the method of RT-PCR for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. Results: One hundred and five patients children with the mean age of 108.64±65.61 were enrolled in this study. The most common cause of transmission in pediatric patients was contacting with a family member diagnosed with COVID-19 (n=91, 86.7%).The most common admission complaints were dry cough (n=17, 16.2%), fever (n=16, 15.2%), lassitude and fatigue (n=14, 13.3%) respectively. More than 95 % of all children with Covid-19 had asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. Conclusion: The results of this study show preliminary results of a study investigating the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors is critical for the successful implementation of the prevention and control program.

Pneumonia is a frequent manifestation of COVID-19 in hospitalized children. Methods The study involved 80 hospitals in the SARS-CoV-2 Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from 2012 to 2019. Results In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP included. Main clinical features of SARS-CoV-2-associated CAP were cough 117/151(77%), fever 115/151(76%) and dyspnea 63/151(46%); 22/151(15%) patients were admitted to a pediatric intensive care unit (PICU), and 5/151(3%) patients died. Lymphopenia was found in 63/147(43%) patients. Chest X-ray revealed condensation (64/151[42%]) and other infiltrates (87/151[58%]). Compared with CAP from other viral pathogens, COVID-19 patients were older (8 vs.1 year; odds ratio [OR] 1.42 [95% confidence interval, CI 1.23;1.42]), with lower CRP levels (23 vs.48 mg/L; OR 1 [95%CI 0.99;1]), less wheezing (17 vs.53%; OR 0.18 [95%CI 0.11;0.31]) and greater need of mechanical ventilation, MV (7 vs.0.7%, OR 10.8 [95%CI 1.3;85). Patients with non-SARS-CoV-2-associated CAP had a greater need for oxygen therapy (77 vs.44%, OR 0.24 [95%CI 0.14;0.40]). There were no differences in the use of CPAP or HVF or PICU admission between groups. Conclusion SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap, and differentiating the etiology may be difficult. The overall prognosis is good.

We describe the demographic, clinical, and laboratory characteristics of children with COVID 19 in comparison with those of not-laboratory-confirmed cases. We conducted a cross-sectional study on the epidemiological, clinical, radiological, and laboratory characteristics, and outcome of 422 children (aged 0–18 years) with suspected and confirmed COVID 19 admitted to the pediatric emergency department from March 23rd to July 23rd, 2020. Of the 422 children with suspected COVID-19 included in this study, COVID-19 was PCR-confirmed in 78 (18.4%). Fever (51.2%) and cough (43.5%) were the most prominent symptoms in children with confirmed cases. The clinical status of the patients with confirmed COVID-19 was significantly milder than that of those with suspected COVID-19. The proportion of COVID-19 pneumonia cases was 44.4%, 5.5%, 18.7%, and 8.5% for the age groups of ≤ 1, 2–6, 7–12, and ≥ 12 years, respectively. Of the 422 children, 128 (30.3%) underwent nasopharyngeal PCR testing for other respiratory viral pathogens; 21 (16.4%) were infected with viral pathogens other than severe acute respiratory syndrome-related coronavirus-2. Only one patient (4.7%) with confirmed COVID-19 had coinfection with respiratory syncytial virus and rhinovirus. The areas under the receiver-operating characteristics curves were 0.812 for WBCs, 0.752 for neutrophils, 0.717 for lactate dehydrogenase, and 0.708 for lymphocyte for predicting COVID-19 (p ≤ 0.001). Fever and cough or other clinical symptoms or signs should not be considered hallmarks of COVID 19. In this study, the WBC, neutrophil, and lymphocyte counts were predictive of COVID-19 positivity.

To our knowledge this is the first published case of NP associated with COVID-19 in an individual with CF and the first associated with Nocardia infection. We suspect the combination of cystic fibrosis, COVID-19 pneumonitis and co-infection with Nocardia farcinia caused this young man’s NP and ultimately his untimely death. We hope this case will highlight individuals with CF of all ages are at risk of severe COVID-19 infection.

Background: Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), a subset of ANCA, are associated with a multisystem vasculitis affecting small blood vessels in the body. A handful of adult patients who developed vasculitis post-COVID-19 infection have been reported. Although COVID-19 infection has been shown to drive an exaggerated immune response in the pediatric population, such as MIS-C (multisystem inflammatory syndrome in children), only one case of vasculitis following COVID-19 infection has been reported previously in children. Case presentation: Seventeen-year-old male with a past medical history of COVID-19 pneumonia two months prior presented with acute kidney injury/failure and diffuse alveolar hemorrhage (DAH). Rheumatologic workup revealed P-ANCA and Myeloperoxidase (MPO) positivity. Kidney biopsy showed necrotizing glomerulonephritis with limited immune complex deposition. Subsequently, he was treated with pulse steroids, plasmapheresis, and ultimately started on cyclophosphamide. Conclusions: To our knowledge, this report presents the second reported pediatric case of P-ANCA / MPO vasculitis following COVID-19 infection.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease caused by a combination of prenatal and postnatal factors that leads to the disruption of lung development and abnormal repair, this is a condition that is commonly seen in premature infants. With the improvement of treatment technology, the survival rate of very early preterm infants has increased significantly compared with before, and the incidence of severe BPD has decreased, however, the prevalence of BPD has not decreased. The overall prevalence of BPD is 45%.The prevention of prematurity, the systematic use of non-aggressive ventilator measures, the avoidance of supra-physiological oxygen exposure, and the administration of diuretics, caffeine and vitamin A have all been shown to lead to a significant reduction in the risk of BPD development. A growing number of clinical studies have shown that caffeine not only prevents apnea, but also reduces the incidence of BPD. We review the clinical value of caffeine in the treatment of BPD and its potential mechanisms of action, include anti-inflammatory, antioxidant, anti-fibrotic, anti-apoptotic pathways, and the regulation of angiogenesis. Our aim was to provide a new theoretical basis for the clinical treatment of BPD.

Objetives. To perform a description of the etiology of hospitalized children with community-acquired pneumonia (CAP) in Spain and analyze predictors related to etiology. Hypothesis. The different etiological groups of pediatric CAP are associated to different clinical, radiographic and analytical data. Design. Observational, multi-center, prospective study. Patient selection. Patients from 1 month to 17 years admitted because of CAP from April 2012 to May 2019. Methods. An extensive microbiological workup was done. Clinical, radiographic and analytical parameters were analyzed in order to differentiate viral, atypical bacteria (AB) and typical bacteria (TyB) pneumonia. Results. 495 children were enrolled. At least one likely causative pathogen was identified in 262 (52.9%). Pathogenic viruses in 155/262 (59.2%), AB in 84/262 (32.1%) and TyB in 40/262 (15.3%). Consolidation was found in 89/138 (64.5%) CAP attributed to virus only, in 74/84 (88.1%) of CAP attributed to AB and 40/40 (100%) of CAP attributed to TyB. Para-pneumonic pleural effusion (PPE) was found in 112/495 (22.6%) patients, 61/112 (54.5%) with a likely causative pathogen: virus 12/61 (19.7%), AB 23/61 (37.7%) and TyB 26/61 (42.6%). Viral etiology was significantly more frequent in younger patients and those with lower oxygen saturation, wheezing, no-consolidation and higher lymphocyte counts. Patients with AB were significantly more likely to have more days of fever at admission and a higher rate of use of antibiotics before admission. Conclusions. Viruses and AB are the main cause of pediatric CAP in Spain. Wheezing, younger age and no-consolidation on the X-ray support viral etiology. Viruses and AB can also cause PPE. The use of antibiotic in pediatric CAP can be restricted.

Background: A series of repeated questionnaire surveys among 8- and 9-year-old schoolchildren in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment during the last decade. Methods: Two further identical cross-sectional surveys were conducted in 2013 (N=2554) and 2018 (N=2648). Physician-diagnosed wheeze and asthma were analysed separately and in relation to their occurrence (recent-onset: solely within the last two years; non-current: prior to the last two years; persistent: both before and within the last two years). In addition, in 2018, spirometry was performed in participants reporting relevant symptoms and in a random sample of healthy controls. Results: The prevalence of current wheeze/asthma declined from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018. The persistent and non-current wheeze/asthma groups (both including children with symptoms at preschool age) followed this overall trend, while the prevalence of recent-onset wheeze/asthma remained unchanged. Persistent and non-current wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. Children with recent-onset wheeze/asthma and a considerable fraction of those with persistent symptoms had lower lung function. Conclusions: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. Our analysis suggests that the reversing trend is most likely attributed to changing asthma perceptions among physicians and/or parents, especially in the case of preschool children with troublesome respiratory symptoms.

The difference in morbidity and mortality between adult and pediatric COVID-19 infections is dramatic. Understanding pediatric-specific acute and delayed immune responses to SARS-CoV-2 is critical for the development of vaccination strategies, immune-targeted therapies, and treatment and prevention of MIS-C. The goal of this review is to highlight research developments in understanding of the immune responses to SARS-CoV-2 infections, with a specific focus on age-related immune responses.

Background: Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat sweat testing in the first year of life. Methods: This multicentre, prospective study analysed clinical data and outcomes in CRMS/CFSPID infants born between September 1, 2018 and December 31, 2019, and followed until June 30, 2020. All subjects underwent CF transmembrane conductance regulator (CFTR) gene sequencing and the search for CFTR macrodeletions/macroduplications, and repeat sweat testing in the first year of life. Results: Fifty subjects (median age at end of follow-up, 16 months [range, 7–21 months]) were enrolled. Forty-one (82%) had the first sweat chloride in the intermediate range. During follow up, 150 sweat tests were performed (range, 1–7/infant). After a median follow-up of 8.5 months (range 1–16.2 months), 11 (22%) subjects were definitively diagnosed as follows: CF (n=2 [4%]) at 2 and 5 months, respectively; healthy carrier (n=8 [16%]), at a median age of 4 months (range 2–8 months); and healthy (n=1 [2%]) at 2 months of age. Inconclusive diagnosis remained in 39 (78%) infants. Conclusions: Early repeat sweat testing in the first year of life can shorten the time to definitive diagnosis in screening positive subjects with initial sweat chloride levels in the intermediate range.