A document by Miles Weinberger. Click on the document to view its contents.

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.

Introduction: Congenital diaphragmatic hernia (CDH) is known with high mortality rates and significant pulmonary morbidities. The objective of this study was to describe the histopathological findings of necropsy and clinical manifestations in CDH patients to find the clinicopathological correlations. Methods: We reviewed the postmortem findings with associated clinical characteristics retrospectively in 8 CDH cases from 2017 to2022 July. Results: Of the eight cases, one was bilateral congenital eventration diagnosed by autopsy. Severe pulmonary hypertension with a right to left shunting of large patent ductus arteriosus (PDA) obtained from echocardiogram were most common. And the average time of survive was 46 (8-624) h. According to the autopsy reports, the major pathological lung changes were diffuse alveolar damages (congestion and hemorrhage) and hyaline membrane formation. Notably, although the lung volume was significantly reduced, pulmonary structural dysplasia was not observed at all, presented normal lung development (50%); bilateral (25%) or ipsilateral (25%). Lobulated deformities were accompanied in three (37.5%) cases. All patients exhibited large PDA and a patent foramen ovale with increased right ventricle (RV) volume, and the myocardial fibers were slightly congested and swollen. Pulmonary vessels showed mild to moderate arterial media thickening. Lung hypoplasia and diffuse lung damages reduced gas exchange, meanwhile the PDA and PH caused RV failure, contributed a clinical picture of organ dysfunction, which lead to death. Conclusions: Pulmonary structures have certain heterogeneity in CDH. The arteries’ pathological changes are not consistent with clinical diagnosis. And the adverse outcome may should be due to the cardiopulmonary vicious cycle.

Title: Reply to Migration is not the perfect answer: Optimised methodology to assess LCI agreement between corrected legacy multiple breath nitrogen washout data and that directly collected on updated software.

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.

Cryptococcosis is an invasive, opportunistic, fungal infection that predominantly effects the respiratory tract and central nervous system in immunocompromised patients. It is classically associated with defects in cellular immunity such as acquired immunodeficiency syndrome. Here we describe a case of life-threatening laryngitis, endobronchitis and pneumonia due to Cryptococcus neoformans in a teenager with hypogammaglobulinaemia. To the best of our knowledge, no previous cases of laryngeal cryptococcosis have been reported in the paediatric population.

Introduction: Assessment of and intervention for sleep-disordered breathing and malnutrition are related to respiratory management for preventing recurrent respiratory tract infections (RRTIs) and acute respiratory failure (ARF) in children with spinal muscular atrophy (SMA). However, the specific standard has not been clarified. Purpose: The study aimed to obtain the risk factors and the predictive index for RRTIs and/or ARF in children with SMA. Methods: In this retrospective study, the differences in clinical characteristics in patients with or without RRTIs and ARF were compared, and binary logistic regression analysis was carried out. The best cutoff points of the positive predictive index were obtained. Results: Type 1 (OR = 4.12, 95% CI 1.30-13.07, P =.016) and apnea hypopnea index (AHI) (OR = 1.14, 95% CI 1.05-1.24, P =.001) were risk factors, while body mass index z score (BMIz) (OR = 0.68, 95% CI 0.49-0.94, P =.018) and mean pulse oxygen saturation (MSpO 2) (OR = 0.67, 95% CI 0.50-0.91, P =.010) were protective factors. The sensitivity and specificity of the standard of MSpO 2 < 96% and AHI > 10 events/h or BMIz < -1 with the occurrence of RRTIs and/or ARF were 0.513 and 0.957, respectively. Conclusion: SMA Type 1, BMIz, AHI and MSpO 2 should be used to estimate the risk for RRTI or ARF in children with SMA. MSpO 2 < 96%, and AHI > 10 events/h or BMIz < -1 should be used as the intervention standard.

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.

6 month old child presented with complaints of recurrent respiratory infection, tachypnea and decreased air entry on right side . Xray chest AP view (Fig[1](#fig-cap-0001)) showed opaque right hemithorax with ipsilateral mediastinal shift and compensatory hyperinflation of left lung. Further evaluation with CECT thorax (Fig [2](#fig-cap-0002)) showed hypoplastic right lung with collapse consolidation and right sided mediastinal shift. Bifurcation of trachea was not seen with trachea continuing as left main bronchus with normal segmental division. Right bronchus appears to be arising from lower part of esophagus, precise communication was not demonstrated (Fig [3](#fig-cap-0003)). Conventional contrast (non ionic) esophagogram was performed and free flow of contrast was seen from lower third of esophagus to the right main bronchus (Fig [4](#fig-cap-0004)) confirming the diagnosis of Congenital bronchopulmonary foregut malformation (CBPFM)

Our case was a pediatric patient with very extensive lung involvement who also had involvement in other organs. We believe our case demonstrates clinical features that are complementary for the case series by Mfingwana L and colleagues and thus, will be beneficial for the readers.

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

Right and left ventricular dysfunction are commonly encountered in pulmonary disorders. Pulmonary hypertension exerts pressure load on the right ventricle, subsequent RV-LV interactions through shared septum, pericardium and blood supply lead to LV dysfunction. The early detection and treatment of pulmonary hypertension is crucial to improve outcomes of pulmonary disorders. New advanced echocardiographic techniques such as pulmonary artery circumferential strain and pulmonary artery blood speckle tracking might help in replacing invasive hemodynamics, for early detection of pulmonary vasculopathy in pulmonary disorders.

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.

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.

Background: Inhaler technique (IT) knowledge among healthcare providers is poor. The aim was to improve PED healthcare providers’ IT technique by carrying out an education intervention, and sustain it for 6 months. Methods: open-label, quasi-experimental, prospective and unicentric study. Healthcare professionals working at the Pediatric Emergency Department (PED) were enrolled. The study was developed in three phases: baseline evaluation and education intervention (P1) and reevaluation 1 month (P2) and 6 months (P3) after the education intervention. Participants fulfilled an eight-question theoretical test. Practical skills were evaluated by demonstrating IT in all three phases. The education intervention consisted in a verbal explanation of IT followed by a demonstration of IT with metered-dose inhaler using a mannequin. Results: 84 healthcare providers (medical residents, nurses and nursing assistants) were involved. In the theoretical questionnaire, the mean score at baseline was 4.4/8 (SD 1.7) improving to 6.3/8 (SD 1.2) in P2 and 6.47/8 (SD 1.1) in P3. In the IT evaluation for children <7 years old, the score improved from 5.7/7 (SD1.3) to 6.5/7 in P2 and 6.7/7 in P3 (p<0.001). For children >7 years old, the mean score of IT at baseline was 3.1/10 (SD 4), which improved to 7.4/10 (SD3) and 8.2/10 in P2 and P3 respectively (p<0.001). Only laboral category influenced results at baseline. Conclusion: Healthcare providers’ theoretical knowledge and practical skills on IT are low. The education intervention performed is a useful strategy to ameliorate IT among healthcare providers.

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.

A Pediatric Case of Neuromyelitis Optica and Pulmonary Inflammatory Myofibroblastic TumorAlyson Win, BS ([email protected])a : Conceptualization; writing- original draft; writing- review and editing.Jesper Jiang, BS ([email protected])a:Conceptualization; writing- original draft. John Fitzwater, MD ([email protected])b : writing- review and editing; supervision. Edwin Hernandez Caro, MD ([email protected])c : writing- review and editing. Amy Cruickshank, DO ([email protected])d : writing- review and editing. Duriel Hardy, MD ([email protected])e : writing- review and editing. Ydamis Estrella Perez, MD ([email protected])f : writing- review and editing. Michele Prater, PNP ([email protected])c: writing- review and editing. Malvika Sagar, MD ([email protected])c : Conceptualization; writing- review and editing; supervision.a: Texas A&M Health Science Center School of Medicine, Temple, TXb: Department of Pediatric Surgery, Baylor Scott and White McClane Children’s Medical Center, Temple, TXc: Department of Pediatric Pulmonology, Baylor Scott and White McClane Children’s Medical Center, Temple, TXd: Department of Pediatric Hematology/Oncology, Baylor Scott and White McClane Children’s Medical Center, Temple, TXe: Department of Pediatric Neurology, Dell Children’s Medical Center, Austin, TXf: Department of Pathology, Baylor Scott and White Medical Center, Temple, TX

Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO)) were performed at 6 months corrected age. Results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into non-severe (N=41) and severe (N=105) groups. There was no significant difference in DCLO and DLCO/aveolar volume amongst the three groups. Forced vital capacity was similar amongst the three groups, but the non-severe Pre-E group had significantly higher forced expiratory flows that the other two. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.