Seasonal epidemics of influenza and the respiratory syncytial virus are the cause of substantial morbidity and mortality among children. During the global COVID-19 pandemic, the epidemiology of these viruses seems to have changed dramatically. In Australia and New Zealand, a significant decrease in both influenza and bronchiolities have been noticed during usual peak seasons. Data from early months of winter seasons in Europe are showing similar trends. This current scenario imposes a reconsideration of the paradigm that toddlers and young schoolchildren are the main drivers of seasonal RSV outbreaks and respiratory epidemics in general. In this paper, we summarize current literature, address current knowledge or role of adults in the respiratory syncitial virus epidemiology, describe the lessons learned from pertussis epidemics and call the international community to better understand the community transmission dynamics of respiratory infections in all age-groups. This can allow the establishment of better and more affordable preventive measures in the whole population level, which can ultimately save millions of child lives.

Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Awareness of the multisystem concerns that face persons with CF (PwCF) has also continued to be recognized as an important aspect of the burden of the disease. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, an understanding of worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served, ranging from the advances in care in the United States (US) to the challenges of disease recognition and diagnosis in low-and-middle-income countries (LMIC). This review is the third in a three-part CF Year in Review 2020 series, focusing on the multi-system effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three has been split into two individual parts, Part 3A presented here, and Part 3B related to CF specific nutrition and gastrointestinal publications will also be published this year. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.

The multisystemic manifestations of cystic fibrosis (CF) involve all parts of the gastrointestinal (GI) system, including the pancreas, intestine and liver. As providers who care for people with CF (PwCF), knowledge of the manifestations, treatment and research related to nutrition and GI disease is important. This review is last installment of the CF Year in Review 2020 series, focusing on the multisystem effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three was split into Part 3A, focusing on the multisystem impact of CF, and this review, Part 3B, focusing on nutritional, gastrointestinal and hepatobiliary articles. Articles were chosen from Pediatric Pulmonology but also include articles published in 2020 from other journals that are of particular interest to clinicians.

Background: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments. Objective: We aimed to predict progression of bronchiectasis in preschool children with CF. Methods: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. Results: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with a positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively. Conclusion: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool.

Introduction: In the era of data-driven decision-making, an unacceptable haziness and inconsistency surrounds the yearlong scientific and public debate on the school closure policy in the COVID-19 pandemic mitigation efforts. Aim: The present literature review stems out of the need for a clear scaffold collecting in one place all current evidence, as well as helping organizing incoming future evidence, concerning both the role of schools in driving the Sars-CoV-2 community spread and the cost-effectiveness of school closure in containing such spread. Methods: References for this review were initially identified through searches of PubMed, Scopus and Cochrane Library for articles published from March, 2020, to March, 2021 by use of the terms “Schools” “COVID-19” “pandemic” “clusters” “outbreak” “seroprevalence”. Further search was undertaken through Google Scholar and ResearchGate, and finally through Google. Results: School closure at times of high background prevalence of COVID-19 should not be considered a measure implemented to protect the health of children. Children had lower secondary attack rates than adults and that they infrequently represented the index case. One year of pandemic has been sufficient for the emergence of one indication of concern: a potentially increased burden of paediatric mental health disorders. Conclusions: A fact-based understanding of what is currently known on such a consequential policy is required to provide a basis of evidence for an advocacy of either school closure or school opening at times of high intensity community transmission of Sars-CoV-2.

Objective: Asthma is a recognized comorbidity in children with sickle cell disease (SCD). It increases risk of acute chest syndrome (ACS), vaso-occlusive episodes, and early mortality. We aim to determine whether evaluation and management of children with sickle cell disease (SCD) and asthma by a pulmonologist reduces rate of asthma exacerbation and ACS. Methods: The study included 192 patients with SCD (0-21 years) followed at Children’s Hospital of Philadelphia Hematology between 01/01/2015 and 12/31/2018 with a diagnosis of asthma, wheeze, or cough. Patients were placed in two groups: those evaluated by a pulmonologist (SCD-A-P) and those not (SCD-A). Rates of emergency department (ED) visits and hospitalizations for asthma exacerbation and ACS were compared between groups and before/after initial pulmonology visit. Results: SCD-A-P (n=70) had lower baseline pulmonary function, hemoglobin, and hematocrit compared to SCD-A (n=122). SCD-A-P had a higher average rate of hospital visits for asthma exacerbation and ACS per year compared to SCD-A: 0.84 [0.56-1.12] versus 0.31 [0.18-0.43], (p<0.001). For SCD-A-P patients with at least one hospital visit (n=48), the average rate decreased from 3.93 [1.57-6.29] before initial pulmonary visit to 0.85 [0.48-1.23] after the visit (p=0.014). Conclusion: SCD-A-P had more severe baseline disease and higher rates of ED visits and hospitalizations for asthma exacerbation and ACS compared to SCD-A, but the rates significantly decreased following pulmonology consultation. These findings support the pulmonologist’s role in the multidisciplinary care of SCD patients. Further studies are needed to help establish evidence-based asthma guidelines for children with SCD.

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.

Objective: To analyze the proportion of backup ventilation during neurally adjusted ventilatory assist (NAVA) in preterm infants at different gestational ages and to analyze the trends in backup ventilation in relation to clinical deteriorations. Methods: A prospective observational study was conducted in 18 preterm infants born at a median (range) 27+4 (23+4–34+4) weeks of gestation with a median (range) birth weight of 1,100 (460–2,820) g, who received respiratory support with either invasive or noninvasive NAVA. Data on ventilator settings and respiratory variables were collected daily; the mean values of each 24-hour recording were computed for each respiratory variable. For clinical deterioration, ventilator data were reviewed at 6-hour intervals for 30 hours prior to the event. Results: A total of 354 ventilator days were included: 269 and 85 days during invasive and noninvasive NAVA, respectively. The time on backup ventilation (%/min) significantly decreased, and the neural respiratory rate increased with increasing postmenstrual age during both invasive and noninvasive NAVA. The median time on backup ventilation was less than 15%/min, and the median neural respiratory rate was more than 45 breaths/min for infants above 26+0 weeks of gestation during invasive NAVA. The relative backup ventilation significantly increased prior to the episode of clinical deterioration. Conclusion: The proportion of backup ventilation during NAVA showed how the control of breathing matured with increasing gestational age. Even the most immature infants triggered most of their breaths by their own respiratory effort. An acute increase in the proportion of backup ventilation anticipated clinical deterioration.

Background: Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia, with better understanding of cerebral autoregulation (CAR). integrating NIRS and pulse oximetry (SpO2) for titrating inspired oxygen is a novel approach. Methods: We aimed to study the impact of integrated monitoring of oxygen saturation by SpO2 and cerebral regional tissue oxygen (crRTO) by NIRS during oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO2 with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r>0.5) were determined during the assessment period, and was considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO2 at 72 hours after start of the integrated monitoring. Results: Total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR), (group 1) in whom SpO2 was poorly correlating with cerebral regional tissue oxygen (crRTO) with (r<0.5) and had significantly greater percentage of reduction below baseline in FiO2 (Mean:34%). Eleven infants had impaired CAR (group 2) with SpO2 significantly correlating with crRTO (r>0.5) and had a linear trend of FOE inverse to SpO2 and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO2). Conclusion: Integrated monitoring of preterm infants by SpO2 and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia.

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.

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Pulmonary actinomycosis is very rarely seen in the paediatric population. The classic radiological presentation of thoracic involvement of actinomycosis includes lower lobe consolidation, empyema and periostitis of the ribs. We report a case of endobronchial pulmonary actinomycosis in a child diagnosed on endobronchial biopsy and broncho-alveolar lavage taken during bronchoscopy. Bronchoscopy can be dangerous when performed on these cases, as there is a risk of severe bleeding and large airway obstruction, as was the case with this patient.

Background: Chronic pulmonary infection is the leading cause of mortality and morbidity in patients with cystic fibrosis (CF). The most common pathogens isolated in CF are Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa). Chronic infection of P. aeruginosa and MRSA are associated with worse survival and antibiotic eradication treatment is recommended for both. This study evaluates the efficacy of intravenous (IV) vs. non-IV antibiotics in the eradication of P. aeruginosa and MRSA. Methods: This was a single-center retrospective study at a large CF center. All respiratory specimen cultures of 309 CF patients and eradication regimens between 2015-2019 were reviewed. The primary analysis was the comparison of the percentage of successful eradication after receiving IV and non-IV eradication regimens. Demographic and clinical risk factors for eradication failure were also analyzed. Results: 102 patients with P. aeruginosa isolations and 48 patients with MRSA were analyzed. At one year, 21.6% in P. aeruginosa group and 35.4% in MRSA group were successfully eradicated. There was not any statistically significant difference between IV vs. non-IV antibiotic regimens on eradication in either group. Additionally, none of the clinical risk factors was significantly associated with eradication failure in P. aeruginosa and MRSA groups. Conclusion: In the eradication of P. aeruginosa and MRSA, IV and non-IV treatment regimens did not show any superiority to one another. Non-parenteral eradication could be a better option in eradication considering the cost-effectiveness and the treatment burden of IV treatments due to hospitalization and the need for IV access.

Pediatric palliative care (PPC) is an active and total approach to the care of children with life-limiting conditions and to their families. PPC programs provide ongoing care for children with medical complexity (CMC), many of whom will reach adulthood. The aim of the study is to describe a population of CMC afferent in 4 months to the Intermediate Care Unit of a tertiary referral hospital for southern and central Italy. We enrolled all CMC patients admitted at our unit in 4 randomized months. We registered pathologies and different categories of childhood diseases, devices and needs, hospitalization and home care plan. Among 195 admitted to our unit, 87 CMC were included. Median age was 9 (0.1 – 35.7) years. The main pathologies recorded were neuromuscular, neurological, respiratory, metabolic, malformative, genetic syndromes and outcomes of prematurity. Comorbidity made by respiratory, digestive, neurological, cardiac and urological involvement was present in a high percentage of cases. Among our patients, only 24 hadn’t any devices. The average length of hospitalization was 7.0 (1.0 – 270.0) days with 2 (1.0 – 7.0) admissions per year for patient. Home care activation was not required for only 24 of 87 patients. Children eligible for CPP are increasing and their survival results in a rise in comorbidities and special needs demanding multi-level interventions. Respiratory symptoms are the most recurrent observed demonstrating the need for an expert in CPP to have respiratory skills. Sharing data and knowledge of CMC needs may help to improve care coordination and interventions.

Reintubation in the pediatric intensive care unit (PICU) increases morbidity, mortality, and the overall cost of care. Post-extubation airway obstruction (PEAO) is a potentially predictable cause of extubation failure and may be prevented by the use of corticosteroids. Defining which patients are most at risk for the development of POAE as well as the optimal dose and timing of corticosteroids for prevention is critical. We review the current literature regarding the use of corticosteroids surrounding extubation in the PICU and discuss the implications that a clear algorithm for identification and treatment of these patients would have in the care of critically ill children.

Objectives: Discharging a child home on long term ventilation (LTV) via tracheostomy is complex and involves multiple healthcare providers across healthcare sectors. To date, patient and family feedback of a newly developed LTV discharge pathway has been anecdotal. Our objective was to explore the perceptions of family caregivers (FCs) that have completed the LTV pathway to home with respect to their: (1) experience with transitions across the pathway (2) perceptions of competency attainment and, (3) viewed opportunities for improvement. Methods: We conducted 11 semi structured interviews with FCs. Interviews focused on FCs experience with the training process, perception of competency from a knowledge and skill perspective and opportunities for improvement. Interviews were audiotaped, transcribed verbatim, coded and analyzed using an inductive thematic analysis approach. Results: Eight mothers and 3 fathers of 10 children participated. Six primary themes were identified: 1) making an informed decision, 2) transitioning to rehabilitation, 3) building capacity for self-care, 4) coordinating case management, 5) readying for discharge home and, 6) experiencing home care. Conclusion: Overall, FCs felt that the preparation and transition support obtained through the application of a standardized LTV discharge pathway allowed successful attainment of new knowledge and skills necessary to care for their child with LTV at home.

Diagnosing asthma in preschool children remains an unsolved challenge, at a time when early identification would allow for better education and treatment to prevent morbidity and lung function deterioration. Objective: To evaluate if the Asthma Predictive Index (API) can be used as surrogate for asthma diagnosis in preschoolers. Methods: Birth cohort of 339 pregnant women enrolled at delivery and their offspring, who were followed for atopy, wheezing, and other respiratory illnesses through 30 months of age. The API was determined at 30 months of age by the researchers; and examined its association with physician-diagnosed asthma during the first 30 months, made independently by the primary care physician not involved in the study. Results: Among 307 offspring with complete follow-up, 44 (14.3%) were API+. Maternal body mass index, maternal education, past oral contraceptive use, birthweight, placenta weight, age of daycare at 12m, gastroesophageal reflux disease at 12m, acute otitis media at 18m, bronchiolitis, croup and pneumonia, cord blood adiponectin were all associated with API+. In the multivariable analysis, API+ was associated with almost 6-fold odds of asthma diagnosis (adjusted OR= 5.7, 95% CI [2.6-12.3]), after adjusting for the relevant covariates above including respiratory infections like bronchiolitis and pneumonia. The API sensitivity was 48%, specificity 92%, 61% PPV, 88% NPV, 6.4 LR+, 0.56 LR-, 0.84 diagnosis accuracy. The adjusted odds for asthma was 11.4. Conclusions: This longitudinal birth cohort suggests, for first time, that API could be used as a diagnostic tool, not only as a prognostic tool, in toddlers and preschoolers.

Background There are limited data in paediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of COVID-19. We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive (SARS-CoV-2[+]) compared to those testing negative (SARS-CoV-2[-]) at our institution. Method Prospective cohort with nested case-control study of all children tested by PCR for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. Results In total, 179 SARS-CoV-2[+] children (44% female, median age 3.5 yrs, range 0.1 to 19.0 yrs) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 yrs, range 0.1 to 18.3 yrs). The commonest co-morbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs n = 10, 2.3%, p = 0.82). In the SARS-CoV-2 group, the prevalence of symptomatic disease was similar amongst children with and without cardiorespiratory comorbidities (n = 12, 75% vs n = 103, 57%, p = 0.35) who tested positive. A high proportion of children hospitalised with SARS-CoV-2 infection had cardiac comorbidities (23.8%). Conclusions In this single site dataset, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. High rates of comorbid cardiac disease were observed amongst hospitalised children with COVID-19, warranting further research to inform public health measures and vaccine prioritisation.

Background & local problem: Acute wheezing attacks are a leading cause of Pediatric Emergency Department (PED) attendances and inpatient admissions and are a considerable burden on the healthcare providers. Almost one-third of children vomit prednisolone in the PED, requiring anti-emetics and repeat dosing. Aim: This quality improvement (QI) intervention aimed to improve oral corticosteroid (OCS) tolerability, reduce emergency department length of stay (LOS), and reduce OCS drug costs for acute wheeze attendances in a PED, while not adversely affecting admissions, re-attendance, or mortality rates. QI Interventions: Included (1) a departmental protocol and (2) modification of the OCS type and dosage from prednisolone (3-day course of 1 mg/kg) to dexamethasone (600 mcg/kg, then single dose 300 mcg/kg). Methods: The study team reviewed the evidence and implemented the interventions. To assess the scale of improvement, we retrospectively collected data on attendance records for patients aged 2-14 years with acute wheeze requiring OCS. We collected data on 100 children who attended the PED between October and December for each year (2016, 2017, and 2018). We then assessed OCS tolerability, LOS, OCS drug costs, and, admission, re-attendance, and mortality rates. Results: Over a 48-month period, we increased OCS tolerability by 67.2% and achieved an 85.8% reduction in OCS drug costs (saving £41,553.14). There was no change in the LOS, admission, re-attendance, and mortality rates. Conclusions: Improved tolerability and substantial cost savings can be achieved by implementing a structured acute pediatric wheeze protocol and modifying the OCS to single-dose dexamethasone (300 mcg/kg).