Abstract: Aim: Recent literature has shown epidemiological changes in bronchiolitis with an increased incidence in the post-SARS-CoV-2 pandemic period but reports regarding disease severity are conflicting. We aimed to describe the epidemiology, disease severity, and microbiology of bronchiolitis during the 2022-2023 cold season compared to the previous five years. Methods: This single-center retrospective observational study at IRCCS Gaslini, Italy, included all children aged 0-2 years hospitalized for bronchiolitis from September 1st, 2017, to August 31, 2023. Findings from the 2022-2023 season were compared to the previous five years. Results: We observed a statistically significant increase in the 2022-2023 season in the absolute number of bronchiolitis admissions. Children who required mechanical ventilation dramatically increased from a total of 7 patients in the previous five seasons to 17 in the 2022-2023 season alone ( p=0.001). All other severity parameters significantly increased: the need for respiratory support ( p=0.002) , the median length of stay (5 vs. 4, p=0.001), and the median duration of respiratory support (4 vs. 3, p=0.016). Conclusions: We report a substantial increase in the severity of bronchiolitis in the season 2022-2023 with a remarkable number of previously healthy infants requiring mechanical ventilation. Our data represents a call in our setting for urgent measures to plan prophylactic and therapeutic strategies and prepare healthcare systems. Further studies are needed to confirm whether our findings are an isolated phenomenon or part of a true global trend. Health systems need to be prepared and protective preventive measures should be implemented for all newborns.

Primary ciliary dyskinesia is a rare genetic ciliopathy characterized by impaired clearance of the airway, leading to recurrent airway infections and various pulmonary conditions. The underlying cause of PCD is complex and involves diverse mechanisms. On one hand, advancements in genetic analysis techniques have significantly contributed to identifying the mutated genes associated with PCD, which in turn, can aid in understanding the variable clinical presentations of the disease. On the other hand, based on the mutated gene, disease manifestation may change and this makes it more challenging to establish a standardized diagnosis approach. Hence, it is important to approach it with a comprehensive perspective. In this study, 8 Turkish individuals with PCD were subjected to whole-exome sequencing (WES) analysis, as well as other diagnostic tests such as ciliary beat frequency measurement, immunofluorescence staining (IF), and confocal microscopy. The findings from this study not only contribute to the enlightenment of PCD aetiology but also emphasize the importance of a multidisciplinary approach when diagnosing and understanding this complex genetic disorder.

Background: Vitamin D may contribute to the balance in between regulatory and suppressive functions of T cells to modulate the inflammatory process in asthma. Objective: To assess serum vitamin D levels and their relationship with asthma control, asthma severity and its anti-inflammatory effect in children. Methods: This systematic review was based on articles published between 2009 and August 2022. Children under 18 years old with asthma were included. Results: The initial database search identified 2,015 manuscripts. Through screening identified only 25 eligible articles, but only eight studies met criteria for inclusion in the meta-analysis. The analysis revealed that in six studies involving 588 participants, mean 25-hydroxyvitamin D levels were lower in children with uncontrolled asthma compared to those with controlled asthma, with a mean difference of -5.07 (-8.57, -1.57) and a high rate of heterogeneity I 2 = 89%. In five studies comprising 362 patients, the relationship between vitamin D and asthma severity was assessed. Lower levels of vitamin D were associated with a higher risk of severe asthma in children, with a mean difference of -6.00 (-8.09, -3.90) and substantial heterogeneity (90%, p<0.00001). In most patients, no significant correlation was found between vitamin D and lung function. Furthermore, serum vitamin D showed an association with interleukins and with regulatory T lymphocytes. Conclusion: Vitamin D plays a critical role in reducing asthma attacks. However, more randomized studies are necessary for a thorough evaluation and definitive recommendation for vitamin D supplementation.

Childhood interstitial lung disease associated with connective tissue disease and immune mediated is the second most common chILD diagnostic category. As knowledge of the molecular and genetic underpinnings of these rare disorders advances, the recognized clinical spectrum of pulmonary manifestations that can be associated with them continues to broaden. This review will focus on chILD and other pulmonary complications associated with primary immune disorders, namely monogenic inborn errors of immunity as well as acquired systemic autoimmune and autoinflammatory diseases. Pulmonary complications, including ILD in these diseases can confer increased risk for morbidity and mortality and can be complex to manage due to the multiple organ systems that can be impacted in these systemic disorders. Thankfully, pulmonologists do not have to work alone. These diseases often have stereotypical patterns of extra-pulmonary features which aid in their recognition. In collaboration with a multidisciplinary team of subspecialists, the pulmonary and other systemic manifestations can be managed effectively together. The goal of this review is to familiarize the reader with the distinct patterns of ILD and associated systemic/immunologic features that are characteristic of monogenic inborn errors of immunity and systemic autoimmune and autoinflammatory diseases. In addition, this review will highlight current, emergent and innovative therapeutic strategies and will underscore the important role of multidisciplinary management to improving outcomes for these patients.

Objective: Acute bronchiolitis, primarily caused by Respiratory syncytial virus (RSV), is the most common cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity. We aim to evaluate the association between C-reactive protein (CRP) levels at admission and disease severity in children hospitalized due to RSV bronchiolitis. Study design: This single center retrospective cohort study included children (0-24 months old) who were hospitalized due to RSV bronchiolitis (January 2018 – March 2022) with CRP levels taken upon admission. Clinical data and severity parameters were extracted using MD-clone platform and the clinical research unit at SUMC. Results: 1,874 children (mean age of 6.7 months, 59% males) with a median CRP level of 1.92mg/dL were included. Children with elevated CRP (>1.92mg/dL) were significantly older (5.1 vs. 3.8 months, p<0.001), had higher rates of pneumonia (9.4% vs. 4.3%, p<0.001 ), urinary tract infection (UTI), (2.2% vs. 0.2%, p<0.001), acute otitis media (AOM), (1.7% vs 0.2%, p<0.001), admissions to pediatric intensive care unit (PICU) (7.4% vs 3.7%, p<0.001), antibiotic treatment (49.8% vs 37.2%, p<0.001) and longer hospitalizations (3.83 vs 3.31 days, p=0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk of 11.6, 2.25, 1.98, 1.44, respectively, p<0.001)). CRP thresholds of 3.51, 1.9, and 2.81 mg/dL for PICU admission, UTI, and pneumonia, were calculated using Youden’s index with AUC of 0.72, 0.62, and 0.61, respectively. Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Introduction: Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this quality improvement project was to implement a systematic gross motor assessment in children with CF ages 4-12 years. Methods: Physical therapists aimed to evaluate at least 50% of eligible children at our CF Center over 1 year using the Bruininks-Oseretsky Test of motor Proficiency, second edition (BOT-2), a norm referenced assessment for gross motor skills, with delays defined by scores less than 18 th percentile. Demographic and clinical data including body mass index, hospitalizations, genotype, and comorbidities were collected. Basic descriptive statistics summarized patient information. Parametric and non-parametric methods compared groups of interest. Linear regression assessed associations between BOT-2 measures and clinical characteristics. Results: Of the 105 eligible children, 72 (69%) completed the BOT-2 over 1 year. Forty-five (62.5%) scored below average in at least one category. Impaired strength (22.2%) was most common, followed by impaired balance (16.7%), running speed and agility (15.3%), and bilateral coordination (8.3%). Eleven (15.5%) scored below average on their total motor composite score (TMC). Increased age, comorbidities and hospitalizations were associated with a lower TMC. Conclusions: The BOT-2 was successfully implemented as part of routine CF care to screen for gross motor delays. Results suggest that a high percentage of children with CF, especially older children with comorbid conditions or a history of hospitalization, have impaired gross motor function. These findings support the need for routine gross motor evaluations and physical therapy interventions within pediatric CF clinics.

Background: Despite advancements in vaccination and the transition from pandemic to endemic, SARS-CoV-2 continues to pose a medical challenge, particularly among children. In this context, imaging diagnostics, such as chest x-rays, are crucial to the initial treatment of patients. This study aims to characterize the radiological findings in pediatric patients with confirmed SARS-CoV-2 infection in Colombia between April 2020 and November 2021, as well as their potential association with intensive care admission. Methods: In Colombia, a multicenter cohort comprised patients aged 29 days to 17 years with confirmed SARS-CoV-2 infection and chest X-ray administered within 72 hours of hospitalization. In two separate groups, four radiologists evaluated the images. A fifth radiologist reviewed all the X-rays; and subsequently, these readings were used to calculate the kappa coefficient and to resolve discrepancies among the other radiologists. The results were compared to admission to intensive care. Results: Analysis was conducted on 392 patients with a mean age of 2 years, the majority of whom (42%) were infants. Sixty-eight percent of the radiographs had normal results. Peribronchial thickening and interstitial opacity were the most common aberrant findings (59%), followed by alveolar opacity (12%). 88 percent of findings were bilateral. The most common association between peribronchial thickening and intensive care admission was ventilatory failure. Interobserver agreement was low for peribronchial thickening (kappa = 0.1), but higher for consolidations and alveolar opacities (kappa = 0.4 and 0.5, respectively). Conclusion: In pediatric patients with SARS-CoV-2, radiological findings are nonspecific and interobserver agreement is minimal. Although consolidation and alveolar opacities demonstrated greater concordance, they were not associated with clinical differences; therefore, chest radiography is not considered useful for determining the severity of COVID-19 in children.

Background: As the population of people with CF (pwCF) continues to age, attention is shifting towards addressing the unique challenges teenagers and adults face, including substance use. Changing attitudes and legality regarding marijuana and CBD may influence their use among pwCF, but data on their prevalence, reasons for use, and administration methods are lacking. Objective: Investigate marijuana, cannabidiol (CBD), e-cigarette, and cigarette usage among pwCF and explore differences in demographics, disease severity, and CFTR modulator use between current and non-users. Methods: This cross-sectional study used a one-time electronic survey to assess marijuana, CBD, e-cigarette, and cigarette use in pwCF aged >13 years. Demographic and clinical characteristics were compared between current users and non-users. The association between current substance use and CFTR modulator use was analyzed using logistic regressions. Results: Among 226 participants, 29% used marijuana, 22% used CBD, 27% used e-cigarettes, and 22% used cigarettes. Current users of all substances were more likely to be college-educated, Black, or aged 29-39 years than non-users. Current e-cigarette users were 2.9 times more likely to use CFTR modulators (95% CI 0.98-11.00, p=0.08) and current marijuana users were 2.5 times more likely to use CFTR modulators compared to non-users, adjusted for confounders. Current users of CBD, e-cigarettes, and cigarettes were more likely to have an abnormal mental health screen compared to non-users. A high proportion of never-users of marijuana and CBD expressed interest in using. Conclusion: Substance use is more prevalent among pwCF than previously reported and needs to be addressed by healthcare providers.

Background Adolescents living with obesity (AlwO) can have limited exercise capacity. Exercise capacity can be predicted by a 2-factor model comprising lung function and leg muscle function, but no study has looked at cycling leg muscle function and its contribution to cycling exercise capacity in AlwO. Methods 22 nonobese adolescents and 22 AlwO (BMI>95 percentile) were studied. Anthropometry, body composition (DEXA), spirometry, 30-sec isokinetic work capacity, and maximal exercise (cycle ergometry) were measured. Results AlwO had greater lean leg mass (LLM) (14.8±4.1 vs 21.0±4.3 kg, Con vs AlwO p<0.001). Lung function did not differ, although FEV 1 trended higher in AlwO (101.0±13.1 vs 107.9±12.7 percent predicted, p=0.08). Leg 30-second work output did not differ in absolute terms or per allometrically scaled LLM. Peak oxygen consumption did not differ between the groups in absolute terms or as percent predicted values (78.5±15.4 vs 82.1±16.5 percent predicted), but was lower in AlwO when expressed per scaled kg of LLM. Peak oxygen consumption related to both lung function and 30-second work capacity, with no observed group effect. 30-second leg work capacity related to the scaled muscle mass, with a small group effect. There was some correlation between leg work capacity and time spent in moderate to vigorous physical activity in AlwO (r s=0.39, p=0.07). Conclusion AlwO have larger LLM and preserved exercise capacity, when expressed as percentage of predicted, but not per allometrically scaled LLM. Increasing time spent in moderate to vigorous activity may benefit AlwO.

Introduction High flow nasal cannula (HFNC) is commonly used as first step respiratory support in infants with moderate-to-severe acute viral bronchiolitis (AVB). This device, however, fails to effectively manage respiratory distress in about a third of patients, and data are limited on determinants of patient response. The respiratory rate-oxygenation (ROX) index is a relevant tool to predict the risk for HFNC failure in adult patients with lower respiratory tract infections. The primary objective of this study was to assess the relationship between ROX indexes collected before and 1 hour after HFNC initiation, and HFNC failure occurring in the following 48 hours in infants with AVB. Method: This is an ancillary study to the multicenter randomized controlled trial TRAMONTANE 2, that included 286 infants of less than 6 months with moderate-to-severe AVB. Collection of physiological variables at baseline (H0), and 1 hour after HFNC (H1), included heart rate (HR), respiratory rate (RR), fraction of inspired oxygen (FiO 2), respiratory distress score (mWCAS), and pain and discomfort scale (EDIN). ROX was calculated as SpO 2/FiO 2 to RR. Predefined HFNC failure criteria included increase in respiratory distress score or respiratory rate, increase in discomfort, and severe apnea episodes. The accuracy of ROX index to predict HFNC failure was assessed using receiver operating curve analysis. Result: HFNC failure occurred in 111/286 (39%) infants, and for 56 (50% of the failure) of them within the first 6 hours. The area under the curve of ROX indexes at H0 and H1 were, respectively, 0.56 (95% CI 0.48-0.63, p =0.14), 0.56 (95% CI 0.49- 0.64, p =0.09). HFNC failure was associated with higher mWCAS score at H1 (p<0.01) and lower decrease in EDIN scale during the first hour of HFNC delivery (p = 0.02), but none of the physiological variables were predictive of HFNC failure. Conclusion: In this study, neither ROX index, nor physiological variables usually collected in infants with AVB had early discriminatory capacity to predict HFNC failure.

Introduction: Children with tracheostomies are high risk for morbidity and mortality. Pediatric resident physicians are not routinely taught skills to care for this vulnerable patient population. Few reports link educational interventions to improved patient outcomes. This study evaluates the impact of an intensive educational training program on pediatric residents’ observed skills and tracheostomy-dependent patient outcomes. Methods: Pediatric post-graduate year 2 (PGY2) resident physicians rotating through the inpatient pediatric pulmonology month at Children’s Hospital Colorado July 2018-2019 participated in the Pediatric Resident Education in Pulmonary (PREP) Boot Camp, an intensive educational program with an interactive lecture and simulation experience on patients with tracheostomy-dependence. PGY2s who partook in PREP and PGY3s who rotated prior to PREP initiation were invited to be studied. Primary outcomes included: 1) resident skills assessed by direct observation during simulation encounters and 2) rates of intensive care unit (ICU) transfers in tracheostomy-dependent patients following acute events before and after introduction of PREP. We hypothesized that increased education would enhance resident skills and improve patient outcomes by decreasing the rate of ICU transfers. Results: PGY2 residents retained skills learned during PREP up to 11 months following initial participation, and significantly outperformed their PGY3 counterparts. There was a significant decrease in ICU transfer rate in patients with tracheostomies admitted to the pulmonary team during the 19 months following initiation of PREP. Conclusions: Enhanced early education improves resident physicians’ ability to care for complex patients with tracheostomies and improves outcomes in this high-risk population.

Cystic fibrosis-related hepatobiliary involvement (CFHBI) is a term used to describe a spectrum of hepatobiliary involvement ranging from benign elevation of transaminase levels to advanced cystic fibrosis associated liver disease (aCFLD). While CFHBI is common among people with cystic fibrosis (PwCF), aCFLD is rare impacting only approximately 5-10% of the CF population. Importantly though, aCFLD is the third leading cause of death among PwCF, is an independent predictor of all-cause mortality and is associated with significant morbidity. Despite this recognition, our ability to predict those patients at greatest risk for aCFLD, identify early aCFLD and monitor incremental progression of CFHBI is lacking. Here we review the strengths and weaknesses of the common biomarkers and imaging modalities used in the evaluation and monitoring of CFHBI, as well as the current understanding of genetic modifiers related to aCFLD.

Children with home invasive mechanical ventilation need special health care and rehabilitation services due to complications caused by both the pulmonary system and limitation of movement. The need for rehabilitation in this patient group is increasing day by day. In this treatment method, whose importance and application area is increasing, life expectancy is prolonged, respiratory morbidity decreases and quality of life increases with effective rehabilitation. The main purpose of rehabilitation is to reduce morbidity, increase the independence of the child in activities, and improve the quality of daily life and life as much as possible. Physical therapy and exercise practices applied in this patient group can be divided into two; those for the whole body and those for the pulmonary system. Parent and/or caregiver education is important to ensure effective invasive mechanical ventilation. In this review, although full standard approaches have not been determined yet, rehabilitation approaches for children dependent on home-type invasive mechanical ventilator will be discussed.

The management of respiratory problems in children on home invasive mechanical ventilation (HIMV) is a complex and challenging task. In recent years, with appropriate family education, these patients have been able to be discharged from the hospital and continue their treatment at home. The population of pediatric patients dependent on HIMV has been increasing worldwide, presenting unique and varying care needs. Management of these patients involves addressing ventilator settings, monitoring respiratory status, ensuring airway safety, and providing continuous support and education to patients and their caregivers. Despite the completion of home settings and family education, children on HIMV may encounter various respiratory problems during home follow-up. Prevention and timely management of these complications are crucial to improving patient outcomes. This article summarizes the most significant respiratory problems in children on HIMV and the management strategies for each problem are discussed, emphasizing the importance of appropriate aspiration techniques, regular monitoring, adequate training of caregivers, and a well-prepared emergency plan.

Children with home invasive mechanical ventilation face numerous difficulties, including endocrine problems that can arise as a consequence of their condition. Endocrine problems seen in children treated with HIMV may develop due to the underlying disease, drugs used, or prolonged mechanical ventilation. This manuscript will discuss the most common endocrine problems encountered in children with home invasive mechanical ventilation, including problems in glucose metabolism, thyroid dysfunction, bone metabolism, adrenal dysfunctions, growth and puberty. Close monitoring, multidisciplinary care, and regular assessments are essential to optimize the endocrin system functions of children requiring HMV. By understanding these complications, it can develop effective management strategies to optimize the health and well-being of these vulnerable individuals.

Background: There is a lack of research that has focused on ADHD in people with cystic fibrosis (pwCF). Given ADHD is associated with executive functioning impairments, exploring ADHD in the context of living with CF is of great importance. The purpose of the current systematic review was to examine ADHD in pwCF across the lifespan in terms of its prevalence, its impact on various health outcomes, and treatments for managing ADHD. Methods: This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting studies of any design that focused on ADHD in pwCF were included. Studies were excluded if they did not meet this criterion and if they were written in languages other than English. PsycINFO, MEDLINE, EMBASE, and CINAHL databases were searched. Search items were based on three concepts: 1) terms related to CF, 2) terms related to ADHD, and 3) terms related to age. Results: Ten studies were included in this systematic review. Reported prevalence rates of ADHD in people with CF ranged from 5.26% to 21.9%. The reported relationships between ADHD in pwCF and other health outcomes is also inconsistent. In terms of treatment considerations, pharmacological interventions and behavioural strategies for managing ADHD in the context of living with CF have been reported as being successful. Conclusions: The presence of ADHD in pwCF should be evaluated when symptoms are impacting treatment adherence and health outcomes. Additional research is needed to further explore ADHD in the CF population and health variables that may be associated with CF prognosis.

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert’s Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert’s Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF.

Beginning in the early 2010s, an increased incidence of interstitial lung disease in systemic juvenile idiopathic arthritis (sJIA-LD) in pediatric patients has been identified. Despite the increase in prevalence of sJIA-LD, little is known about this disease process and effective therapeutic management. In this single-center, retrospective case series of 9 patients, we analyze demographic, clinical, radiographic, and laboratory data to corroborate common clinical characteristics and describe an approach for diagnosis and monitoring of interstitial lung disease in children with sJIA. Our results were similar to other described cases of sJIA-LD as patients in our cohort were more likely to be younger, have a history of macrophage activation syndrome and prior use of biologic therapies. In contrast to prior studies, they did not present with lymphadenopathy and hepatosplenomegaly. We discuss our management of this rare disease process. More research is necessary to understand the increased incidence and treatment of sJIA-LD in pediatric population.