Interstitial Lung Disease in childhood (chILD) is rare and no longer solely a childhood issue. Many are surviving into adult life. Therefore, many affected with chILD need to transition from paediatric to adult healthcare services. Transition is a significant life event that has the potential to impact on physical and mental health outcomes and across Europe this is a haphazard process for chILD. This qualitative study explores how young people and parents in the United Kingdom experienced transition from paediatric to adult healthcare services for chILD. Participants (n = 7) were recruited from chILD patient organisations and online communities. We focused on the experience of transition and whether there were any information packs or support provided for the transition. The data was analysed by constructivist grounded theory. The study presents a lived experience of transition with themes of lack of transition preparation and planning, challenges of learning how to adapt to adult services and a changing healthcare scene. Due to the complexity of ChILD, parents discussed their need to remain, in part, as an advocate for the young person. Respondents provided recommendations for how transition could be improved along with tips for young people who are new to the transition process, which include educating oneself about the condition and learning medical terminology, being open if there are issues and reaching out for support.

Dystrophin-deficiency results in a cardiomyopathy of variable onset and deficiency. Myocardial scarring commonly results in cardiac dysfunction, with both atrial and ventricular dysrhythmias. Heart failure, rather than arrhythmia burden, remains the strongest cardiac predictor of mortality in this patient population. Current data suggests the overall rate of sudden cardiac death in pediatric dilated cardiomyopathy is significantly lower than adults. Specifically in the Duchenne cardiomyopathy population, sudden death from an arrhythmic cause appears to be rare, even in patients with previously diagnosed arrhythmias. Despite this, recommendations for implantable cardioverter-defibrillator (ICD) placement in patients with Duchenne cardiomyopathy has traditionally been extrapolated from adult heart failure recommendations based on decreased left-ventricular ejection fraction less than 35%. Early involvement of the cardiologist in the care for patients with dystrophin-deficient cardiomyopathy is recommended for this reason. The indications for ICD placement to prevent sudden death in patients with Duchenne cardiomyopathy are not well defined. There is little evidence to suggest placement meaningfully prolongs life in this population, and should be carefully considered in accordance with the care goals of the patient and his family.

Objectives: Airway clearance therapy (ACT) is an important component of therapy for cystic fibrosis (CF) but is associated with significant treatment burden. Highly effective CFTR modulator therapy (HEMT) has improved pulmonary function for many people with CF(pwCF). We sought to understand changes in attitudes and practices about ACT in the post-HEMT era. Study design: Surveys of CF community members and CF care team members Methodology: Separate surveys were created for the CF community and CF care providers to evaluate attitudes towards ACT and exercise in the post-HEMT era. We solicited answers from pwCF via the CF Foundation’s Community Voice and from CF care providers via CF Foundation listservs. Surveys were available between July 20 and August 3, 2021. Results: Surveys were completed by 153 community members (parents of children and pwCF) and 192 CF care providers. Belief that exercise can substitute partially for ACT was endorsed similarly by community members (59%) and providers (68%) . After starting HEMT, 36% of parents of children and 51% of adults did fewer ACT treatments including 13% who stopped ACT. Adults reported altering their ACT regimen more than parents of children. Half of providers had changed their ACT recommendations for those on HEMT. Fifty-three percent of respondents had discussed changing ACT with their care team (36% of parents, 58% of pwCF). Conclusions: Providers should be aware that ACT management changes may have been undertaken by pwCF who have pulmonary benefits of HEMT. Treatment burden should be considered in co-management decisions regarding ACT and exercise.

BACKGROUND: High-flow nasal cannula therapy (HFNC) is increasingly used for children with bronchiolitis, but its optimal role remains relatively uncertain. Our institution created and later revised a ward-based clinical pathway guiding initiation and weaning of HFNC. METHODS: A retrospective review of 664 encounters was conducted. Total duration of HFNC, duration of weaning from maximum flow rate, hospital length of stay (LOS), and escalation of care were compared across 3 study periods using generalized linear models: Baseline (HFNC managed at provider discretion, 5/1/2015-4/30/2017, n = 215), Intervention 1 (first pathway, initiation at 0.5 L/kg/min and escalation up to 2 L/kg/min, 5/1/2017-2/28/2018, n = 155), and Intervention 2 (revised pathway, initiation at the maximum rate of 2 L/kg/min, 3/1/2018-1/31/2020, n = 294). Both pathway iterations provided specific titration and weaning guidance. Models controlled for initial SpO2 and maximum respiratory rate to adjust for the possibility of differing case severity. RESULTS: After adjustment for severity, total duration of HFNC was significantly reduced in the second intervention, but not the first. Adjusted LOS was shorter in Intervention 1 and Intervention 2 compared to the baseline period. Adjusted weaning time and escalation of care did not differ significantly between periods. CONCLUSION: Pathway implementation was associated with modestly decreased LOS and – when initial flow rates were increased to 2 L/kg/min – reduced duration of HFNC, without differences in escalation of care or weaning time. These findings highlight the potential role of standardization of practice with clinical pathways in safely reducing unnecessary care.

We read with great interest recent research by Anderson et al.1 on how NICU respiratory support affects infant feeding, and by Behnke et al.2 on the potential interference of infant feeding with successful respiratory stabilization of the preterm infant. Since both preclinical and human studies have established that nutrition plays a key role in preterm lung growth and development, a crucial aspect of any research undertaken in the field of neonatal respiratory outcomes should be the breastfeeding history. It is now becoming well established that human milk feeding actively contributes in limiting lung injury among vulnerable neonates.

with other laboratory and clinical investigations. Early and accurate diagnosis of inherited conditions generally leads to better medical care for patients and their families, with improved knowledge of the natural history of the condition and early intervention. It is therefore essential that equitable access to such testing is established for indigenous and isolated populations, in order to further narrow the health disparity gap. Although supported by funding from a few sources, this study signals a success for the Silent Genomes Project, with one of the cases having been identified by whole genome sequencing within that project, after negative whole exome sequencing. Furthermore the study has potential life-changing clinical consequences and provides starting points for possible interventions for respiratory medicine in the Inuit population. These include increased awareness of the possibility of PCD in patients presenting with neonatal respiratory distress, bronchiectasis or otitis media leading to early intervention; and in conjunction with Inuit organizations and public health officials, targeted analysis of the DNAH11 variant in the population with the possible introduction of newborn screening for PCD.

Background: Hispanic people with cystic fibrosis (CF) have decreased life expectancy and earlier acquisition of Pseudomonas aeruginosa compared to non-Hispanic white individuals with CF. Racial and ethnic differences in the airway microbiome of CF may contribute to known health disparity, but have not been studied. The objective was to describe differences in the upper airway microbial community in Hispanic and non-Hispanic white children with CF. Methods: This prospective, observational cohort study of fifty-nine Hispanic and non-Hispanic white children with CF, ages 2-10 years old, was performed at Texas Children’s Hospital (TCH) from February 2019 to January 2020. Oropharyngeal swabs were collected from the cohort during clinic visit. Swab samples underwent sequencing (16S V4 rRNA), diversity analysis, and taxonomic profiling. Key demographic and clinical data were collected from the electronic medical record and the Cystic Fibrosis Foundation Patient Registry (CFFPR). Statistical analysis compared sequencing, demographic, and clinical data. Results: We found no significant difference in Shannon diversity or relative abundance of bacterial phyla between Hispanic and non-Hispanic children with CF. However, a low abundant taxa- “uncultured bacterium” belonging to the order Saccharimonadales was significantly higher in Hispanic children (mean relative abundance=0.13%) compared to the non-Hispanic children (0.03%). Hispanic children had increased incidence of Pseudomonas aeruginosa (p=0.045) compared to non-Hispanic children. Conclusion: We did not find a significant difference in the airway microbial diversity between Hispanic and non-Hispanic white children with CF. However, we found a greater relative abundance of Saccharimonadales and higher incidence of Pseudomonas aeruginosa in Hispanic children with CF.

Backround: Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation and this may increase morbidities. Objective: To evaluate the association of symptomatic patent ductus arteriosus with failure of extubation among preterm infants. Methods: This was a retrospective study on preterm infants (birth weight <1,250 grams and gestational age ≥23weeks) born between January 2009 and December 2016, who were mechanically ventilated and extubated within the first 60 days of age. Results: 360 infants were evaluated, of these, 26% failed and 74% succeeded the initial extubation attempt. On adjusted analysis, symptomatic ductus was associated with an increased risk of extubation failure. Conclusion(s): Presence of symptomatic patent ductus arteriosus was associated with extubation failure. Further investigations are needed to establish whether screening for presence of ductus and treatment of the same, prior to extubation among these infants, improves chances of successful extubation and cardiorespiratory outcomes.

Introduction: The reliability of breath sound analysis using an improved method in infants has been reported. Objective: Breath sounds of infants with respiratory syncytial virus (RSV)-induced acute bronchiolitis were analyzed to evaluate their specificity and examine their relationship with the severity. Subjects and methods: We evaluated the inspiratory and expiratory breath sound parameters of 33 infants (median age=2 months old) diagnosed with RSV-induced acute bronchiolitis. The sound powers of inspiration and expiration and the spectrum curve indices (ratio of the third and fourth area to the total area under the curve and ratio of the power and frequency at 50% and 75% of the highest frequency were evaluated at the acute phase and recovery phase. Furthermore, the relationship between the breath sound parameters and the clinical severity of acute bronchiolitis was examined. Results: Analyses of the breath sound spectrogram showed that the power of expiration at the acute phase was large, and was the expiration-to-inspiration sound power ratio in a mid-frequency range (E/I MF), with values decreased in the recovery phase. Data of the inspiratory sound spectrum curve showed the improvement of airway stenosis during the recovery period. Furthermore, there were significant relationships between the E/I MF and SpO2 and the severity score of acute bronchiolitis. Conclusion: In RSV-induced acute bronchiolitis, specificity of breath sounds was observed in the expiration sound and the reversible airway stenosis was evaluated. Breath sound analyses are expected to be useful for the diagnosis and clinical evaluation of the severity of acute bronchiolitis.

Pilot Study of Nuclear Scintigraphy To Assess Cough Clearance in DMDTo the Editor:Respiratory muscle weakness as a consequence of neuromuscular disease results in ineffective cough, atelectasis, and pneumonia. Augmented airway clearance treatments such as mechanical in-exsufflation and high frequency chest compression have been shown to decrease morbidity and mortality in children with neuromuscular disease, although the evidence supporting these therapies in clearance of airway secretions is indirect.We sought to pilot the use of nuclear imaging of the clearance of pulmonary secretions before and after voluntary coughing and airway clearance treatment to explore the role of measures of pulmonary function to predict airway clearance. This technique has been used for some time in patients with cystic fibrosis but has not been applied to patients with neuromuscular disease or to assess the utility of airway clearance devices. To this end, we recruited 7 outpatient subjects (7.8-21 years of age) with Duchenne Muscular Dystrophy when clinically well and categorized as “Early Ambulatory” (requiring minimal assistive devices, n=4); “Early Non-ambulatory” (using wheelchair some of time, n=2); and “Late Non-Ambulatory” (always using wheelchair, n=1). This study was approved by local Institutional Review Board.Spirometry was performed according to ATS specifications and normalized using Global Lung Initiative equations. Peak cough flow was measured from total lung capacity (TLC) and data was normalized with previously published equations[1]. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured at the mouth using a hand-held pressure manometer and maximal pressure from FRC was also be measured at the nares (SNIP) during a sniff maneuver[2] using a small nasal occluder and handheld transducer Maximal static pressures and SNIP pressures were normalized using previously published data.For imaging of mucus clearance, 4 mCi of Technetium [Tc-99m] sulfur-colloid particles in 2 ml of normal saline were delivered by nebulizer using a defined breathing pattern for 2 minutes [3]. During continuous imaging, subjects were asked to voluntarily cough every 10 seconds for 1 minute using guidance from a metronome, and this sequence was repeated 3 times. The subject then received an airway clearance treatment for 30 minutes using a high frequency chest compression device with pressure adjusted between 80-100% of maximum, and compression frequencies cycled between 5Hz-15Hz. The device was paused every 10 minutes at which time the patient was asked to cough every 10 seconds over 1 minute.Image analysis was performed according to previously published methods. Measurements of radioactivity in the right lung were corrected for background and radioactive decay and normalized by starting radioactive counts. A single retention curve was generated from the initial cough clearance period and the period during which the high frequency chest compression device was operated. Cough clearance (CC) represents the percent of total deposited radioactivity cleared during the associated period. We designated the percentage cleared by 18 voluntary coughs over 3 minutes as CCvol, and the percentage cleared during three 10 min periods of HFCC and 18 voluntary coughs over 3 minutes as CCHFCC. CCvol and CCHFCCwere correlated with physiologic measures including peak cough flow (PCF), MIP/MEP, and SNIP using Spearman’s correlation.Pulmonary function was overall well preserved (FVC 92% ± 35%). Respiratory muscle strength (in cmH2O) decreased with disease severity (e.g. MIP EA 73.5 ± 26, ENA 62.5 ± 14.8, LNA 47). Peak cough flow (% predicted) decreased with severity (EA 94±11, ENA 79±9, LNA 46). Complete details are provided in the online supplement.Representative imaging of two subjects is shown (Figure 1). Significant intra-subject differences were seen in clearance with voluntary cough and with cough augmented with HFCC vest (Figure 2). Voluntary cough was responsible for 46-96% of the total clearance and HFCC-augmented clearance for 3-53% of total clearance. For most patients, the kinetics of clearance with HFCC-augmented cough did not appear very different than for voluntary cough.Statistical comparisons between disease stages were hampered by the small sample size in each group. Nonetheless, while there appeared to be a trend for decreasing CCvol with stage of disease (Figure 2), age, and PCF, we found no statistically significant correlations between voluntary cough clearance and measures of pulmonary function (FVC, r=0.39), respiratory muscle strength (PCF, r=-0.63; SNIP r=-0.12, MIP r=0.43, MEP r=0.29), age (r=-0.57), height (r=-0.49), weight (r=-0.37). Additionally, we did not find statistically significant correlations between augmented cough clearance and measures of pulmonary function (FVC, r=0.40), respiratory muscle strength (PCF, r=-0.08; SNIP r=-.02, MIP r=-0.07, MEP r=0.05), age (r=-0.39), height (r=-0.75), weight (r=-0.03).This study is the first we are aware of to directly examine cough clearance of secretions using nuclear scintigraphy in patients with DMD. Importantly, the measurements were well tolerated by subjects. We did not find a relationship between CPF, respiratory muscle strength, or spirometry and voluntary cough clearance. However, these results must be qualified based on the small number of enrolled subjects. We do note that many of the patients had good cough clearance. Additionally, HFCC did not consistently alter the rate of secretion clearance above noted with voluntary cough.While Bach et al[4] showed that PCF >160 L/min was a predictor of successful tracheal decannulation in adults with neuromuscular disease, Airen et al[5] found that the majority of healthy children <13 years old generated PCFs < 270 l/min despite having the ability to generate MEP > 60 cmH2O. This suggests that PCF may change with age and that an absolute threshold cannot be used across the age span. There are no studies specifically examining use of HFCC in patients with DMD. As patients with DMD are expected to have impairment in cough, mechanical in-exsufflation would be expected to assist with airway clearance by replacing the function of weak respiratory muscles in a way that HFCC does not. Lechtzin et al[6] showed that in adults with neuromuscular diseases, HFCC decreased inpatient costs and costs for treating pneumonia compared to the year prior to initiating HFCC. Measures of pulmonary function, including PCF, were not assessed. It would be of interest to examine secretion removal with in-exsufflation using this nuclear imaging method.While we were not able to demonstrate a relationship between cough clearance and measures of respiratory muscle strength, peak cough flow, or FVC, it is possible that this relationship exists and would be demonstrated in a larger population. However, the longstanding assumption that PCF is a reliable indicator of need for airway clearance, especially in children, is not supported by these data. The biggest limitation of our pilot study is the small sample size. We suspect enrollment was limited due to preference for interventional studies. Another limitation is that for our population, the impairment of respiratory muscle strength was mild for most subjects. Additional subjects with more advanced weakness may have helped clarify the relationship between respiratory muscle strength and airway clearance. Finally, there can be day-to-day variations of clearance.There are now a number of airway clearance technologies being proposed for patients with neuromuscular and airway diseases (e.g. cystic fibrosis, ciliary dyskinesia). These include high frequency chest compression vests, battery-powered vests, in-exsufflation devices (with or without oscillation), intrapulmonary percussive ventilation devices, and handheld oscillating positive expiratory pressure devices. We propose that the imaging methodology used in this study could be utilized to compare these different techniques, some of which are costly and with limited or no comparison data. In addition, there are patients that will be unable to cooperate with pulmonary function measurements and an imaging assessment of airway clearance may be useful to determine optimal strategies.In conclusion, we demonstrated that use of nuclear scintigraphy is a feasible technique to examine airway clearance for patients with respiratory muscle weakness, as it has been used for patients with cystic fibrosis. Additional studies will be needed to further examine the relationship between pulmonary function measures and secretion removal.Daniel J. Weiner MD1,Hoda Abdel Hamid MD2,Timothy E. Corcoran PhD3Divisions of Pediatric Pulmonology1 and Neurology2, Department of PediatricsUPMC Children’s Hospital of PittsburghDivision of Pulmonary, Allergy and Critical Care Medicine3, Department of MedicineUniversity of Pittsburgh School of Medicine

Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth and the most common cause of chronic lung disease in infancy. Previous studies have shown that children with a history of BPD have impaired lung function in childhood compared to their term counterparts. However, little is known about potential modifiable factors that alter lung function trajectories and subsequent respiratory morbidity in this population. Objectives: To identify potential modifiable risk factors for the development of impaired lung function in patients with a history of prematurity and BPD. Methods: Growth parameters (birth, 2yo, 6yo) and pulmonary function testing (6yo) were retrospectively reviewed for subjects (n=598) recruited from an outpatient BPD clinic who were born ≤36 weeks gestation and were ≥5 years of age. Results: Of the 598 recruited subjects, 88 (14.7%) performed adequate pulmonary function testing at approximately six years of age. The mean FEV1% predicted was 84.5% with lower values associated with lower median household income, Nissen fundoplication, and higher weight percentiles at 2yo. The mean FVC % predicted was 94.2% with lower values associated with higher amounts of oxygen required at time of initial hospital discharge, Nissen fundoplication, and higher weight percentiles at 2yo. Conclusions: Our study found that children with BPD have different long-term pulmonary trajectories than full-term controls. Supplemental oxygen, lower income, and Nissen fundoplication at discharge were associated with lower lung function at 6 years of age. Prospective studies should focus on modifiable risk factors that could minimize the impact of BPD on later lung function.

The diagnosis of primary ciliary dyskinesia (PCD) is made through a combination of clinical features supported by a panel of diagnostic tests. Our cases highlight the similarities in the clinical presentation of patients with the specific immunodeficiency activated phosphatidylinositol 3-kinase delta syndrome 1 (APDS1 or PIK3CD) and PCD. We highlight the importance of repeating nasal nitric oxide testing (nNO) when PCD has not been confirmed by genetic or ciliary electron micrograph (EM) analysis in the setting of an expanded suppurative lung disease differential that includes considerations for immunodeficiency as well as PCD.

Background International consensus statements on depression and anxiety in adolescents and adults with CF recommend assessment for comorbid substance misuse. However, at CF centers, the frequency and impact of substance misuse have not been well characterized, and best practices for prevention, identification, and evidence-based treatment have not been routinely implemented. Methods Medical records of 148 adults with CF over 3 years were reviewed to determine the prevalence of substance misuse (alcohol or opiates) and its relationship with clinical variables and healthcare utilization. Independent-sample t-test for continuous outcomes and chi-square test for binary outcomes were used to compare groups with and without substance misuse. Results Substance misuse was documented in 28 (19%) adults with CF, equally distributed between alcohol (n=13) and opiates (n=15). Adults with substance misuse were more likely to be male. The prevalence of diagnosed anxiety and depression did not differ significantly between groups, but those with substance misuse had more severe anxiety (GAD-7: 10.0±6.1 vs. 3.3±4.4; p<0.001) and depressive symptoms (PHQ-9: 10.4±6.5 vs. 4.0±4.8; p<0.001). Adults with substance misuse had higher annual rates of missed outpatient CF visits and inpatient hospitalizations, with hospital admissions of longer mean duration. Conclusions In adults with CF, substance misuse is common and is associated with adverse indicators of emotional and physical health and service utilization, suggesting that systematic approaches to addressing substance misuse in CF clinics should be considered. Prospective, longitudinal study is warranted to elucidate the complex relationships between depression, anxiety, substance misuse, and health outcomes in individuals with CF.

Introduction. Respiratory syncytial virus infection is the leading cause of lower respiratory infection globally. Recently, nirsevimab has been approved to prevent RSV infection. This study explores the economically justifiable price of nirsevimab for preventing RSV infection in Colombia’s children under one year of age. Materials and methods. A static model was developed using the decision tree microsimulation to estimate the quality-adjusted costs and life years of two interventions: a single intramuscular dose of nirsevimab versus not applying nirsevimab. This analysis was made during a time horizon of 1 year and from a societal perspective. Results The annual savings in Colombia associated with this cost per dose ranged from U$ 2.5 to 4.1 million. Based on thresholds of U$4828, U$ 5128, and U$19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 21.88, U$ 25.04, and U$ 44.02 per dose of nirsevimab. Conclusion the economically justifiable cost for nirsevimab in Colombia is between U$21 to U$44 per dose, depending on the WTP used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.

As the population of ventilator-dependent children (VDC) with tracheostomies due to underlying severe BPD grows, there is an increasing need to shift the care of these children from hospital to home. Transitioning the ventilator-dependent child from the hospital to home is a complex process that requires coordination between the medical team and the family. One crucial step in the process is transitioning from an Intensive care unit (ICU) ventilator to a portable home ventilator (PHV). The Clinical team needs to understand the nuances in transitioning to PHV, including assessing readiness to transition and choosing the optimum settings on an available home ventilator. In recent years, various ventilator modes have been available in PHV that can help achieve synchronous breathing to allow for adequate gas exchange for the infant. This review details some approaches to asses readiness to transition and the process of Transition along with commonly used modes of support available in PHV, as well as the primary and secondary settings in which we should be mindful in supporting a child with chronic respiratory failure in the home setting.

Objective: This retrospective observational cohort study aimed to assess the real-life application of bronchial challenge test (BCT) in the management of preschool children presenting with atypical recurrent respiratory symptoms (ARRS). Methods: We included children, aged 0.5-6 years referred to a pediatric-pulmonology clinic, who underwent BCT using methacholine or adenosine between 2012-2018 due to ARRS including uncertain severity of airway hyperactivity. BCT was considered positive based on spirometry results and/or wheezing, desaturation, and tachypnea reactions. We collected data on demographics, BCT results, pre-BCT treatment, post-BCT treatment change and post-BCT symptoms control. The primary outcome measure was the change in treatment post-BCT (step-up or step-down). Secondary outcome included clinical improvement observed 3-6 months after BCT. Results: A total of 228 children (55% males) with a mean age of 4.2±0.6 years underwent BCT (52% adenosine-BCT, 48% methacholine-BCT). Children referred for methacholine were significantly younger compared to adenosine (3.6±1.2 vs. 4.2±1.2 years, P<0.01). Methacholine and adenosine BCTs were positive in 95% and 61%, respectively. Overall, changes in management were observed in 122(53.5%) children following BCT, with 83(36.4%) being stepped up and 37(17%) being stepped down. Significantly more children in the methacholine group were stepped up compared to the adenosine (46% vs 28%, p=0.004). During the follow-up assessment, we observed a clinical improvement in 119/162 (73.4%) of the children. Conclusion: This study demonstrates the importance of BCT in the management of preschool children presenting to pediatric pulmonary-units with ARRS. The change in treatment and subsequent clinical improvement observed, highlight the added-value of BCT in this populations.

Editorial: Long-term respiratory complications of OA-TOF: The need for better data and a more specialised multidisciplinary approach