Background: Depression and anxiety symptoms in patients with cystic fibrosis (CF) and their caregivers are 2-3 times higher than in the normal population. This study aims to evaluate the frequency and severity of depression and anxiety symptoms and to determine possible risk factors in CF patients and their mother and/or fathers at Marmara University CF center. Methods: The study included 132 CF patients who were followed up at our CF center. Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Questionnaire (GAD-7) were used to screen depression and anxiety. The questionnaires were completed by 50 CF patients (aged 12 - 17 years) and 132 parents of patients (aged 0-17 years). Results: While moderate to severe depression were seen in 25.5% of patients, 33.7% of mothers and 14.6% of fathers; moderate to severe anxiety were present in 17.6%, 21.8% and 8.5%, respectively. None of the demographic characteristics was identified as a predictor of depression or anxiety. GAD-7 scores have shown a higher incidence of anxiety in mothers of patients with chronic methicillin-resistant Staphylococcus Aureus (p = 0.034). Additionally, hospitalization in the last 12 months was statistically significantly higher in PHQ-9 scores of fathers (p = 0.043). Analysis of patients’ adherence to medical treatment and airway clearance showed higher depression and anxiety in mothers of the non-adherent group (p = 0.002). Conclusion: Depression and anxiety were common in CF patients and their parents. These results illustrate the importance of depression/anxiety screening and psychosocial support for the CF patient and their parents.

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation (CCAM), is a rare developmental lung abnormality with the potential for malignant transformation. Bronchioloalveolar carcinoma (BAC), pleuropulmonary blastoma (PPB), rhabdomyomatous dysplasia/rhabdomyosarcoma (RMS) have been associated with CPAM. We report an unusual case of a 1-day-old male newborn who underwent lobectomy for a cystic lung lesion, which was found to be a mucinous BAC with K-ras mutation in a type 1 CPAM. The case supports the relationship between type 1 CPAM and BAC/KRAS mutant, and highlights that the malignant transformation can occur in very early stage of the infancy.

We used the lung ultrasound score (LUSS) to analyze the ultrasound images and assess the lesions and aeration loss in 12 lung regions of 11 COVID-19 neonates born to mother with COVID-19 and 11 age- and gender-matched controls. In the COVID-19 group, 132 regions were reviewed and 83 regions (62.8%) detected abnormalities. Compared with controls, COVID-19 neonates showed more increased B-lines (83 regions), abnormal A-lines (83 regions), abnormal pleural line (29 regions) and subpleural consolidation (5 regions). among which 49 regions (37%) were normal, 73 regions (55%) scored 1, and 10 regions (8%) scored 2. The LUSS was significantly higher in COVID-19 group. All the lesions were bilateral, multiple regions involved, and mainly located in bilateral lower lobes and right middle lobe. The intra-observer and inter-observer reproducibility of LUSS were excellent. Lung ultrasound is a noninvasive and convenient method for the assessment of neonatal COVID-19 pneumonia and presents typical signs. LUSS provides valuable semi-quantitative information about the lesion distribution and severity.

A 16-Year old with Lemierre’s Syndrome and Multiple Septic Pulmonary EmboliChristopher M Oermann, MDDepartment of Pediatrics, Children’s Mercy Kansas City, Kansas City MOCorresponding Author:Christopher M Oermann, MDChildren’s Mercy Kansas City2401 Gillham RoadKansas City, MO 64108816-302-3354 (telephone)816-302-9736 (fax)[email protected] Head: Pulmonary Septic Emboli in Lemierre SnKey Words: Lemierre Syndrome, Septic EmboliWord Count: 1035To the Editor,Lemierre’s syndrome (LS) is a rare disease resulting from infective thrombophlebitis of the internal jugular vein (JV) following oropharyngeal infection. The incidence of LS has increased after decades of decline. Septic pulmonary emboli (PE) are common, but all organ systems can be involved. Although LS is most often caused byFusobacterium necrophorum , other pathogens have been implicated. Persistent high fever and organ-specific signs and symptoms result from the septic emboli (SE). The diagnosis is often suspected following growth of Fusobacterium from blood cultures and is confirmed by head/neck imaging. Therapy includes antimicrobials, drainage of abscesses, and anticoagulation. Significant morbidity/mortality occur if diagnosis and treatment are delayed. Pediatric pulmonologists must be familiar with the diagnosis and management of LS.A previously healthy 16-year old male was admitted to hospital following two weeks of fever, myalgia, nausea/vomiting/diarrhea with 10-pound weight loss, and dry cough. He had been evaluated by his primary care provider (PCP) ten days prior to admission for pharyngitis and fever of 40oC. Rapid streptococcal antigen and SARS-CoV-2 testing were negative, and he was treated with antipyretics. Continued symptoms led to PCP reevaluation after 7 days. Chest imaging demonstrated a single round pneumonia in the right lower lobe, and he received 3 days of azithromycin. He failed to improve and was referred to the emergency department 3 days later. Computed tomography (CT) of the chest/abdomen/pelvis demonstrated bilateral pulmonary nodules. He was admitted for evaluation and treatment.Considerations from the admitting team included atypical infection (fungal or mycobacterial) versus e-cigarette or vaping product use associated lung injury (EVALI), so Pulmonary Medicine service was consulted. EVALI was thought unlikely based on the radiographic appearance of the lesions (Figure 1). Additional considerations included septic PE, paragonimiasis, autoimmune disease with small vessel vasculitis (polyangiitis with granulomatosis), and inflammatory bowel disease. Evaluation for these potential diagnoses was initiated and empiric therapy with vancomycin and ceftriaxone was commenced. Echocardiogram, infectious diseases testing, and autoimmune evaluation were all normal. Painful swelling in the right, anterior neck and a tender spot on his upper right back developed the day after admission. His blood culture grew gram-negative anaerobic rods, raising concern for LS. Doppler ultrasound of the neck demonstrated occlusive thrombus within the right external JV with extension into the internal JV. Metronidazole was added to his intravenous antimicrobial regimen and anticoagulation therapy was initiated.CT Imaging demonstrated normal CNS with confirmation of thrombosis of the JVs and inflammation over the surrounding soft tissues of the anterior right neck and a large abscess involving the posterior spinal musculature of the upper thorax. A drain was placed, and 25 cc of pus removed. Magnetic resonance imaging of the spine demonstrated extension of the abscess into the T1 spinous process suggesting osteomyelitis. The blood culture grew Fusobacterium necrophorum and antibiotic coverage was changed to ampicillin/sulbactam to treat potential polymicrobial infection. Fevers resolved, pain and other symptoms improved, and the drain was removed after 3 days. He was discharged to continue 6 weeks of ampicillin/sulbactam and anticoagulation therapy.LS is a rare complication of infections of the head/neck, with a reported incidence of one per million people per year.1 Common during the “pre-antibiotic era”, LS had decreased in incidence for decades but has increased since the 1990s. This is possibly due to better antimicrobial stewardship and decreased use of antimicrobials for pharyngitis.1Disease is attributed to infections of the tonsils and peritonsillar tissue in 87% of cases and infections of the pharynx, parotid glands, sinuses, mastoids, middle ears, and teeth/gums in 13%.2 Males and females are equally affected.3 LS has been reported in individuals aged 2 months to 78 years, although it is most commonly reported among previously healthy adolescents and young adults.2,3LS originates with primary infection of the head/neck.4 This is followed by spread of the infection through the soft tissues of the neck resulting in thrombophlebitis of the internal JV. Dissemination of infection via SE occurs, with lung involvement in up to 80% and bones/joints in up to 27%.1-4 Additional sites of infection include cardiovascular, skin/muscles, central nervous system, abdominal organs (liver and spleen), and kidneys. Pulmonary involvement has included septic PE, abscess formation, necrotizing pneumonia, empyema, pneumothorax, pulmonary embolism, and acute respiratory distress syndrome. LS is most often caused by Fusobacterium necrophorum , part of the normal flora of the pharynx, accounting for up to 85%. Additional causes include other Fusobacterium species, anaerobes (Bacteroides , Peptococcus , and Peptostreptococcusspecies), and aerobes (Streptococcus , and Staphylococcusspecies), among others. Polymicrobial infections are reported in up to 30%.2 Significant morbidity results from delayed diagnosis. Mortality has been reported as 4-18%; more recent reviews suggest a lower rate.3,5LS often presents 4-12 days after the initiating oropharyngeal infection, which may have resolved by presentation. Symptoms include high fever (up to 80%), gastrointestinal (50%), pharyngitis with cervical adenopathy or neck pain/swelling, myalgia/arthralgia, rigors, and respiratory symptoms (cough or dyspnea).1,2,5Additional symptoms may be secondary to organ dysfunction caused by SE. Diagnosis is often made via Doppler ultrasound or CT imaging of the head/neck or the growth of Fusobacterium from blood/abscess cultures.Therapy for LS involves long term, intravenous antibiotics, surgical drainage of abscesses, and anticoagulation.1-5Metronidazole is often reported as standard therapy for LS. Other antibiotic considerations include carbapenems or penicillin/beta-lactamase inhibitor combinations, which provide broader coverage for polymicrobial infections. Duration of therapy is 4-6 weeks, allowing for adequate penetration of thrombi and treatment of secondary problems such as osteomyelitis. Anticoagulation therapy is more controversial; some data suggest that anticoagulation hastens overall response while others indicate adequate clinical response without additional therapy.LS is a rare disorder of the head/neck that may be associated with significant morbidity/mortality if diagnosis and treatment are delayed. Pediatric pulmonologists will typically encounter LS in patients hospitalized with prolonged fever and multiple septic PE. LS must be considered in every child with multiple cavitary nodules identified on chest imaging. This is particularly true if there is a history of preceding oropharyngeal infection or signs/symptoms suggesting pathology in the head/neck. The growth of Fusobacterium species from blood culture or abscesses should also suggest LS. Doppler ultrasound examination of the neck and CT imaging of the head/neck should be obtained. Therapy is long-term, intravenous antibiotics. Adjuvant therapy includes surgical incision and drainage of abscesses and anticoagulation therapy.

Aims:  In infants with chronic neonatal lung disease (CNLD), we aimed to identify predictors of home oxygen duration, predictors of discharge oxygen flow rates and the association of oxygen flow rates with respiratory outcomes.Methods:  Retrospective review of infants with CNLD requiring home oxygen in 2016 and 2017.  Hazard ratios (HR) were estimated from Cox proportional hazards regression models in the cohort.  A multinomial logistic regression model examined the effects of maternal and infant variables on discharge oxygen flow rates.  Kruskal-Wallis test with univariate linear regression and Fisher’s exact test with binomial univariate logistic regression were used to examine associations between oxygen flow groups and post-discharge clinical variables.Results:  149 infants were included.  Median corrected gestational age (CGA) at oxygen cessation was 6.8 months (IQR 4.4) with 87.2% of infants weaned by 12 months CGA.  Shorter initial neonatal intensive care unit (NICU) stay predicted faster oxygen weaning at 9 months (HR 0.99, 95%CI 0.98-1.00, p=0.02) and 12 months (HR 0.99, 95%CI 0.98-1.00, p=0.02).  Infants with hypercarbia at discharge or discharged from NICU at higher CGA had higher odds of requiring ≥200mL/min relative to ≤125 mL/min oxygen.  Infants discharged with >250mL/min oxygen were more likely to have a respiratory related admission before two years chronologic age. Conclusion:  Shorter initial NICU stay was the best predictor of earlier home oxygen cessation.  At NICU discharge, infants with hypercarbia or a higher CGA may require more home oxygen and experience more respiratory related hospital admission in the first two years of chronological age.

Plastic bronchitis in a toddler born preterm Jinfang Yuan M.D, Ling Liu M.D, Wei Zhou M.D, Xiaomei Tong M.D, Tongyan Han M.D Department of Pediatric, Peking University Third Hospital, Beijing, China

Background: The aim of this study was to evaluate diaphragmatic parameters in bronchiolitis patients and identify correlations between clinical and sonographic severity scores and outcomes in order to develop a more objective and useful tool in the emergency department. Methods: Children aged between 1 and 24 months and diagnosed with acute bronchiolitis were included in the study. The Modified Respiratory Distress Assessment Instrument (mRDAI) score was used to quantify the clinical severity of the disease. Lung ultrasound was performed and a bronchiolitis ultrasound score (BUS) was calculated. Diaphragm ultrasound was then performed and diaphragm thickness at the end of inspiration and expiration, thickening fraction, diaphragm excursion (EXC), inspiratory slope (IS), expiratory slope (ES), and total duration time of the respiratory cycle were measured. Results: There were 104 patients evaluated in this study. The mRDAI score and BUS had a significant positive correlation. There was a positive correlation between IS and respiratory rate at admission. As the clinical score increased, IS, ES, and EXC measurements rose and they were positively correlated. Values of IS, ES, and EXC were higher in the moderate-severe group than the mild group for both mRDAI and BUS scores. Inspiratory slope values were correlated with the length of stay in the hospital. Conclusion: Values of IS and ES were correlated with clinical and sonographic severity scores. Moreover, IS was a good predictor of outcome. Diaphragm ultrasound appears to be an objective and useful tool to help the physician make decisions regarding the evaluation and management of bronchiolitis.

Mainstem bronchial atresia (MBA) is a rare and fatal entity with no survivors reported to date. We describe a neonate born at 36 weeks gestational age (GA) with right MBA who underwent successful slide tracheobronchoplasty at 32 days of life. It is theorized that during fetal life a transient fistulous connection developed, allowing right lung decompression and left lung development.

Improving synchrony in young infant supported by noninvasive ventilation for severe bronchiolitis: Yes we can… so we should!C Milési, MD1, J Baleine, MD1, G Cambonie, MD, PhD11Department of Neonatal Medicine and Pediatric Intensive Care, Arnaud de Villeneuve Hospital, Montpellier University Hospital Center, Montpellier, FranceCorrespondence: Christophe Milési, MD, Department of Neonatal Medicine and Pediatric Intensive Care Unit, Arnaud de Villeneuve Hospital, Montpellier University Hospital, 371 Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, FranceTel: +33 467 336 556, Fax: +33 467 336 228, e-mail:[email protected] count: 1391; references: 43Keywords: asynchrony, bronchiolitis, noninvasive ventilation, neurally adjusted ventilatory assist, infantAdmission to a pediatric intensive care unit (PICU) is required for 9-14% of infants with acute viral bronchiolitis (AVB) and evolving respiratory distress.1,2 In this context, AVB generally presents as severe obstructive lung disease, which causes an increased load on the respiratory muscles.3,4 As no pharmaceutical treatment currently in use is able to rapidly reduce airway obstruction, the management of these patients is focused on providing respiratory support to reduce respiratory muscle fatigue and prevent intubation. Noninvasive ventilation (NIV), delivered by continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP), has traditionally been applied and is associated with reductions in intubation rates, ventilation-associated complications, and duration and cost of hospitalization.5,6 More recently, a third device was introduced to administer a heated and humidified mixture of air and oxygen with high-flow nasal cannulae (HFNC). PICU clinicians thus currently have at their disposal several respiratory assistance modalities for infants with moderate to severe AVB, but few high-grade evidence studies to guide their choice.7 Indeed, most of the studies carried out in this field have been observational, with comparisons with historical cohorts,5,6,8-10 or physiological, assessing differences with and without noninvasive respiratory support.4,11-13 In this issue of Pediatric Pulmonology , Delacroix et al. re-evaluates the use of BiPAP as the first-line respiratory support in less-than-6-months patients with bronchiolitis.14 In their single-center retrospective study, they report longer durations of noninvasive support and longer PICU stays in the patients supported with BiPAP compared with CPAP and HFNC. The authors should be congratulated for this analysis covering more than 250 infants, one of the largest cohorts treated with this device. This work usefully complements the information provided by two recent observational studies that focused on the comparison of these three techniques in this specific group of patients.15,16 The inherent limitation of these retrospective studies, whether monocentric14,16 or database-driven,15 is the presence of confounders, which influence both the choice of the initial respiratory support and the outcome. It was particularly interesting to note in Delacroix et al.’s study that the clinicians’ preferred choice was BiPAP, although no local written protocol required it in this situation. However, the BiPAP-treated group also included a higher rate of premature infants, a condition associated with the immaturity of immune defenses and airway development and ventilation-induced airway injury that predisposes to more severe bronchiolitis.17Several national and multinational surveys have demonstrated that pediatric intensivists currently select HFNC for initial respiratory care in cases of severe bronchiolitis.18,19 This popularity among caregivers appears to be associated with the perception of a technique that is easy to implement, with comparable effectiveness and fewer complications than CPAP.20 The physiological background for using CPAP in this instance is that the application of nearly constant pressure support is associated with rapid unloading of respiratory muscles, increased expiratory time, and concomitantly improved respiratory distress.4,11,21 Reduced respiratory effort and a change in breathing pattern suggest that CPAP improves the work of breathing by offsetting the patient’s inspiratory effort to overcome intrinsic end-expiratory pressure (PEEPi). In addition, positive airway pressure helps maintain airway patency and alleviate bronchiolar obstruction, a ‘stenting’ effect that in turn reduces respiratory system resistance. HFNC also generates some degree of airway distenting pressure, which supports inspiratory effort. The reduced diaphragmatic electrical activity and decreased esophageal pressure swings also confirm the effectiveness of HFNC to reduce the work of breathing in AVB.12,13 Randomized controlled trials, however, have found that neither CPAP nor HFNC reduces the need for intubation in infants with bronchiolitis, probably due to the current low occurrence of this event1,2,21-24 In practice, CPAP and HFNC are introduced early in the course of the disease—even as a preemptive measure in some cases—in infants generally not exhausted. While NIV is widely used to treat bronchiolitis,25 most clinicians, unlike in Delacroix et al.’s study,14 consider BiPAP the next step for patients failing with HFNC or CPAP.19 Failure rates vary widely, from 10% to 50% in the major randomized controlled studies,1,2,22-24and depend on multiple factors, the most important probably related to the criteria and delays in defining failure. According to the TRAMONTANE study, the main causes of failure are worsening respiratory distress, especially in patients supported by HFNC; patient discomfort, the leading cause in patients treated with CPAP; and the occurrence of apnea in a minority of cases in both groups.22 The very large cohort of almost 6500 patients collected by Clayton et al.15 in more than 90 PICUs in North America and Saudi Arabia gives credit to clinicians who turn to NIV in the event of failure, since this strategy seems to avoid escalation to invasive mechanical ventilation (IMV) in more than 70% of cases. There is a rationale for using BiPAP in infants with bronchiolitis and worsening respiratory failure, but is this technique being used optimally?Delacroix et al. point out that the unfavorable results in their BiPAP group may have resulted from a suboptimal patient-ventilator interaction.14 Indeed, use of pressure support in spontaneous/timed modes requires inspiratory synchrony, expiratory synchrony, and rapid compensation for leaks in order to reach pre-established pressure values during inspiration.26Infants, especially when exhausted, have a higher respiratory rate, lower tidal volume, and weaker inspiratory efforts, making synchronization with their ventilator more complex.27Patient-ventilator asynchrony is frequent during IMV or NIV with pressure support in infants and children.28,29 In an elegant physiological study performed in infants with AVB, Baudin et al. characterized the main inspiratory asynchronies with noninvasive pressure assist control ventilation from diaphragmatic electrical activity recordings.30 Autotriggering, double triggering, and above all non-triggered breaths were observed for nearly 40% of the respiratory cycles, highlighting difficulties in detecting inspiratory effort in patients younger than 6 months, the targeted population in the study by Delacroix et al.14 These triggering asynchronies are associated with leaks, notably when BiPAP is performed with a nasal interface.31 This issue is explained by the insufficient sensitivity of the triggers with regard to the modest volumes and flows generated during inspiration at this young age.32 In addition, airway obstruction and dynamic hyperinflation may increase the frequency of ineffective respiratory efforts.30 The asynchrony index could be even higher if premature and late cycling are considered, i.e., asynchronies related to excessively long or short ventilator inspiratory times in relation to the neural command.28 These expiratory asynchronies are influenced by the ventilator’s mode and algorithm and may be improved by adjustments of the cycling-off criterion, which remains a difficult bedside challenge.28 In adults, patient-ventilator asynchrony has been associated with increased duration of mechanical ventilation, sleep disorders, prolonged ICU stay, and increased mortality.33 Such a demonstration has not been made in pediatrics, but recognition of this phenomenon and the analysis of its risk factors and consequences are much more recent.34 Currently, technological advances in ventilators have opened new horizons regarding synchronization, even in this group of patients. NIV software, management of leaks, and turbines specifically dedicated to NIV are indisputable advances.35 Neurally adjusted ventilatory assist (NAVA), initially developed for intubated patients, offers another option. In the field of severe AVB, an early report highlighted the interest of NAVA in providing less aggressive IMV and more comfort to the child.36 Discomfort during NIV is common in infants,22 and the prescription of sedatives is systematically considered by some teams.37 The discomfort may have multiple origins, including intolerance of the interface, skin breakdown, conjunctivitis, and gastric distension.38 Patient-ventilator asynchrony is another important source,39 which can be significantly improved with NAVA. Indeed, the direct analysis of diaphragmatic depolarization reduces the trigger delay, leading to more effective synchronization than with conventional NIV, even after careful optimization of the expiratory trigger setting.28,30,40 The asynchrony index may be reduced to 2%-8%, i.e., lower than the critical threshold of 10% defined in the adult population,41 with a nasal interface and in the presence of large leaks. One of the restraints on using NAVA is the extra cost it entails. However, the targeted population is limited to HFNC or CPAP failure, corresponding to 10-15% of moderate to severe AVB.15 A recent physiological study in severe AVB infants found that, compared to CPAP, NAVA was associated with a decreased work of breathing, lower neural drive and lower Ti/Ttot ratio.42 The promising results of this study suggest that pediatric intensivists must be as ambitious in combating asynchrony as they have been in combating pain and discomfort.43The impact on patient outcome will be judged in randomized controlled trials targeting severe forms of the disease.Disclosure: The authors declare no conflict of interest.

Pediatric pulmonologists, and, indeed, general pediatricians, are exposed to the causative virus of Covid-19 , SARS-CoV2, in their daily outpatient practices from both symptomatic and asymptomatic patients. This risk naturally increases with multiple exposures over time. We have developed a simple equation to calculate the probability of a practitioner remaining Covid free over a specified time interval, given the local population prevalence of virus, the transmissibility of the organism or “attack rate,” the mitigating effects of personal protective equipment (PPE), and the number of patients seen over the time interval. The equation can be used to construct a Kaplan Meier -like plot for remaining Covid free. Since studies of transmission of SARS-CoV2 suggest a spectrum between droplet and aerosol spread, even in asymptomatic patients and absence of aerosol generating procedures, the type of masks protection worn by medical practitioners may mitigate risk to different degrees. Eye protection may mitigate the risk further. While the risk of acquiring Covid-19 in a year of practice is low, it is not negligible. However it can be minimized. These considerations may be helpful in deciding local risk to the practitioner according to practice volume and in choosing the level of PPE that would result in minimizing that risk.

Background: Pneumonia is one of the most common serious infections in children. Scoring systems have been adopted to quantify the severity of the disease, but they were based on clinical findings that can vary according to the subjective assessment of the clinician. We hypothesized that diaphragm ultrasound (DUS) parameters may be a new useful tool to objectively score the severity of the disease and predict outcomes in children with pneumonia. Methods: Children diagnosed with pneumonia, aged between 1 month and 18 years, were prospectively evaluated in the pediatric emergency department. The Pediatric Respiratory Severity Score was used to indicate the severity of the disease and DUS was performed. Diaphragm thickness at the end of inspiration and expiration, thickening fraction (TF), diaphragm excursion, inspiratory slope (IS), expiratory slope (ES), and total duration time of the respiratory cycle were calculated. Results: There were 96 patients enrolled in the study. Inspiratory slope and ES measurements had positive correlations with respiratory rate and length of stay in the hospital and negative correlations with oxygen saturation levels. Furthermore, TF values were negatively correlated with respiratory rate and length of stay in the emergency department. Patients with higher clinical scores had increased IS and ES and decreased TF values. Conclusion: Diaphragm ultrasound can be a promising and useful tool to assess diaphragmatic dysfunction in patients diagnosed with pneumonia. Diaphragm parameters, especially TF, IS, and ES, may provide objective and reliable information to predict the severity of the illness, the need for respiratory support, and outcomes.

Background: Bronchiolitis obliterans syndrome (BOS) is a life-threatening respiratory complication of allogeneic hematopoietic stem cell transplant (HSCT). Even though a lung function test is crucial in monitoring BOS, little information exists on the test’s association with prognosis in children with BOS. Objectives: The purpose of this study was to determine the correlation between changes in lung function after BOS diagnosis and long term outcomes. Methods: A total of 428 children received allogeneic HSCT from January 2006 to December 2017 at Asan Medical Center. Twenty-three of those children (5.4%) were diagnosed with BOS after allogeneic HSCT, and their clinical data were reviewed. Twenty-one subjects underwent regular pulmonary function tests for 24 months after the occurrence of BOS. Results: Among the 21 children with BOS, eight died, five underwent a lung transplant (TPL), and 15 required oxygen (O2) therapy. The FEV1% predicted (pred), FVC% pred, and FEF25-75% pred were 37.8±12.7% (mean±SD), 62.2±16.2%, and 16.4±9.6%, respectively, upon BOS diagnosis. Changes in the FEV1% pred were greater in the death and lung TPL group (-24.8±22.3%) than the survival without lung TPL group (5.7±21.8%), and greater in the O2 therapy (-19.4±23.4%) group than the group without O2 therapy (14.2±20.0%) during the first three months after BOS diagnosis. Conclusion: The change of FEV1 during the first three months after BOS correlated with the prognosis including survival, lung transplantation, and O2 therapy. These results suggest more active intervention in the first three months after BOS diagnosis may be needed to improve prognosis.

Background/Objectives: Adults with heart failure (HF) have high prevalence of central sleep apnea (CSA). While this has been repeatedly investigated in adults, there is a deficiency of similar research in the pediatric population. The goal of this study was to compare prevalence of CSA in children with and without HF and correlate central apnea events with heart function. Methods: Retrospective analysis of data from children with and without HF was conducted. Eligible children were <18 years old with echocardiogram and polysomnogram within 6 months of each other. Children were separated into groups with and without HF and groups with and without elevated central apnea index (CAI) for comparative study. Results: 120 children (+HF:19, -HF:101) were included. The +HF group was younger, with higher prevalence of trisomy 21, muscular dystrophy, oromotor incoordination, and structural heart disease and lower Apnea Hypopnea Index and lower CAI. Prevalence of CSA was similar in both the groups. LogCAI was inversely correlated to age at time of sleep study. Children with elevated CAI were younger and had higher prevalence of prematurity. There was no difference in left ventricular ejection fraction (LVEF) between groups with and without elevated CAI. Conclusion: In contrast to adults, after adjusting for age, there is no difference in frequency of central apneic events in children with and without heart failure. Unlike in adults, LVEF does not correlate with CAI in children. Overall, it appears that CAI may be more a function of age rather than of heart function in the pediatric population.

Rationale: Aerosolized albuterol is widely used, but its safety and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. Objectives: To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. Methods: Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25mg, 2.5mg) and 3ml of normal saline were administered every 4 hours during separate 24-hour treatment periods assigned in random order with a 6-hour washout phase between periods. The primary outcome was the absolute change (post–pre therapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. Results: Average within subject EF75 values improved with each therapy: saline placebo (+0.45L/min  2.5, p=0.04), 1.25mg of albuterol (+0.70L/min  2.4, p<0.001), and 2.5mg of albuterol (+0.38L/min  2.4, p=0.06). However, 1.25mg of albuterol (0.26L/min; 95% CI -0.19, 0.72) and 2.5mg (-0.10L/min; 95% CI -0.77, 0.57) produced similar changes in EF75 when compared to saline. All secondary outcomes were similar between saline and 1.25mg of albuterol. Peak inspiratory pressure needed to deliver goal tidal volumes (7.5% relative decrease, 95% CI 2.6, 12.3) and heart rate (6.5% increase, 95% CI 2.2, 10.8) differed significantly between albuterol 2.5mg and saline. Conclusion: Albuterol at 1.25mg and 2.5mg, compared to aerosolized saline, did not affect EF75 in infants with sBPD receiving invasive ventilation. Greater improvement in inspiratory pressures with albuterol 2.5mg suggests benefit, but close heart monitoring is indicated.

Duchene muscular dystrophies (DMD) is a rare but devastating disease resulting in progressive loss of ambulation, respiratory failure, DMD-associated cardiomyopathy (DMD-CM) and premature death. The use of corticosteroid and supportive respiratory care has improved outcomes, such that DMD-CM is now the leading cause of death. Historically, most programs have focused on the skeletal myopathy with less attention to the cardiac phenotype. This omission is rather astonishing since boys with DMD possess an absolute genetic risk of developing cardiomyopathy. Unfortunately, heart failure signs and symptoms are vague due to skeletal muscle myopathy leading to limited ambulation and traditional assessment of cardiac symptoms by the New York Heart Association classification is of limited utility even in advance stages. Echocardiographic assessment can detect cardiac dysfunction late in the disease course, but this has proven to be a poor surrogate marker of early cardiovascular disease and an inadequate predictor of DMD-CM. Indeed, one explanation for the paucity of cardiac therapeutic trials for DMD-CM has been the lack of a suitable end-point. Improve outcomes requires a better proactive treatment strategy, however the barrier to treatment is lack of a sensitive and specific tool to assess efficacy of treatment. The use of cardiac imaging has evolve from echocardiography to cardiac magnetic resonance imaging to assess cardiac performance. The purpose of this article is to review the role of cardiac imaging in characterizing the cardiac natural history of DMD-CM, highlighting the prognostic implications and an outlook on how this field might evolve in the future.

We explain our concerns on using plain LU score to predict extubation failure in preterm infants, as gestational age at birth can be an important confounder.

Asthma assessment by spirometry is challenging in children as forced expiratory volume in one second (FEV1) is frequently normal at baseline. Bronchodilator (BD) reversibility testing may reinforce asthma diagnosis but FEV1 sensitivity in children is controversial. Ventilation inhomogeneity, an early sign of airway obstruction, is described by the upward concavity of the descending limb of the forced expiratory flow-volume loop (FVL)s, not detected by FEV1. The aim was to test the diagnosis ability of FVL shape indexes as β-angle and forced expiratory flow at 50% of the forced vital capacity (FEF50)/peak expiratory flow (PEF) ratio, to identify asthmatics from healthy children in comparison to “usual” spirometric parameters. Seventy-two asthmatic children and twenty-nine controls aged 8 to 11 years were prospectively included. Children performed forced spirometry at baseline and after BD inhalation. Parameters were expressed at baseline as z-scores and BD reversibility as percentage of change reported to baseline value (Δ%). Receiver operating characteristic curves were generated and sensitivity and specificity at respective thresholds reported. Asthmatics presented significantly smaller zβ-angle, zFEF50/PEF and zFEV1 (p≤0.04) and higher BD reversibility, significant for Δ%FEF50/PEF (p=0.02) with no difference for Δ%FEV1. zβ-angle and zFEF50/PEF exhibited better sensitivity (0.58, respectively 0.60) than zFEV1 (0.50), and similar specificity (0.72). Δ%β-angle showed higher sensitivity compared to Δ%FEV1 (0.72 vs 0.42), but low specificity (0.52 vs 0.86). Quantitative and qualitative assessment of FVL by adding shape indexes to spirometry interpretation may improve the ability to detect an airway obstruction, FEV1 reflecting more proximal while shape indexes peripheral bronchial obstruction.

ABSTRACT Background: Necrotizing pneumonia (NP) is a severe complication of community-acquired pneumonia. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the epidemiology of NP in children has not been formally assessed. Patients and methods: Medical records of children <18 years admitted with NP to two pediatric hospitals in Italy between 2005 through 2019 were retrospectively reviewed. The following 4 periods were defined: 2005-2010 (pre-PCV13), 2011-2013 (early post-PCV13), 2014-2016 (intermediate post-PCV13), and 2017-2019 (late post-PCV13). Results: Forty-three children (median age, 44 months) were included. Most of them (93%) were previously healthy. No differences in age, sex, season of admission, comorbidity, clinical presentation, or hospital course were identified between pre-PCV13 and post-PCV13 periods. A significant decrease in the rate of NP-associated hospitalizations was found between the early (1.5/1000 admissions/year) and the intermediate (0.35/1000 admissions/year) post-PCV13 period (p=0.001). Streptococcus pneumoniae was the most common agent detected in both periods (pre-PCV13: 11/18, 61%; post-PCV13: 13/25, 52%). Serotype 3 was the most common strain in both periods (pre-PCV13: 3/11, 27%; post-PCV13; 4/13, 31%). There were no changes in the bacterial etiology over time, but most patients with Streptococcus pyogenes or Staphylococcus aureus infection were admitted during the post-PCV13 period. Conclusions: The hospitalization rate for NP in children decreased a few years after the implementation of PCV13 immunization in Italy. However, an increased trend in admissions was found thereafter. S. pneumoniae was the most frequent causal agent in both pre- and post-PCV13 periods. Pneumococcal serotypes were mainly represented by strain 3.