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

As our understanding of the uncommon group of disorders called plastic bronchitis has evolved, so too has the classification of these disorders.

Background: Globally, observational studies have demonstrated an association between high levels of air pollution and asthma attacks in children. It remains unclear whether and to what extent exposure may be associated with increased near fatal and fatal attacks. Objective: To systematically review the evidence for an association between ambient outdoor air pollution and fatal and/or near fatal asthma (NFA). Methods: Following Cochrane methodology, we searched MEDLINE, EMBASE, Web of Science, Scopus and Open Grey electronic databases for studies reporting the association of fatal/NFA and air pollution (Particulate Matter (PM), sulphur dioxide, nitrogen dioxide, black carbon and ozone) in children. NFA was defined as requiring intensive care (ICU) management. Results: Two reviewers independently screened 1,358 papers. 276 studies identified asthma attacks related to air pollution, 272 did not meet inclusion criteria after full text review. Four observational studies described fatal/NFA, of which 3 addressed NFA. PM2.5 and ozone (22ppb) were associated with NFA in one study (RR 1.26 CI (1.10-1.44)). PM10 was associated with ICU admission in the context of thunderstorm asthma. Elemental carbon was associated equally with NFA that did not require an ICU admission (p=0.67). Studies of fatal asthma including children did not demarcate age within analysis. Conclusions: Ozone and PM2.5 have been associated with NFA in children but synthesis is limited by the paucity of studies and methodological heterogeneity. Poor reporting of severities of asthma attack does not enable assessment of whether outdoor air pollution is associated with an increased number of NFA and fatal attacks in children.

Advanced cystic fibrosis liver disease (aCFLD) with portal hypertension develops in a minority of people (5-7.5%) with Cystic Fibrosis (CF), necessitating surgical interventions, including portosystemic shunting, gastrostomy tube placement, and in some cases, liver transplantation. This manuscript also aims to explore the different endoscopic, endovascular and surgical procedures needed to diagnose and manage aCFLD, including liver biopsy, endoscopic retrograde cholangiopancreatography, intraoperative cholangiograms, hepatic venous pressure gradient measurement and portosystemic shunt procedures in patients with aCFLD. By utilizing advanced diagnostic and surgical techniques, healthcare professionals can effectively manage aCFLD and improve patient outcomes.

Tracheostomies are indicated in children to facilitate long-term ventilatory support, aid in the management of secretions, or to manage upper airway obstruction. Children with tracheostomies often experience ongoing airway complications, of which respiratory tract infections are common. They subsequently receive frequent courses of broad spectrum antimicrobials for the prevention or treatment of respiratory tract infections. However, there is little consensus in practice with regard to the indication for treatment/ prophylactic antimicrobial use, choice of antimicrobial, route of administration, or duration of treatment between different centres. Routine antibiotic use is associated with adverse effects and an increased risk of antimicrobial resistance. Tracheal cultures are commonly obtained from paediatric tracheostomy patients, with the aim of helping guide antimicrobial therapy choice. However, a positive culture alone is not diagnostic of infection and the role of routine surveillance cultures remains contentious. Inhaled antimicrobial use is also widespread in the management of tracheostomy associated infections; this is largely based upon theoretical benefits of higher airway antibiotic concentrations. The role of prophylactic inhaled antimicrobial use for tracheostomy associated infections remains largely unproven. This systematic review summarises the current evidence base for antimicrobial selection, duration, and administration route in paediatric tracheostomy associated infections. It also highlights significant variation in practice between centres and the urgent need for further prospective evidence to guide the management of these vulnerable patients.

Background: CFTR-Related Metabolic Syndrome/ Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) is the diagnosis in infants who have a positive Cystic Fibrosis (CF) newborn screen (NBS), 2 CF-causing mutations, and borderline or normal sweat test. NY State implemented a new CF NBS algorithm (IRT-DNA-SEQ) in December 2017 with significant improvement in positive predictive value. This algorithm also resulted in detection of more CRMS cases. For these infants repeat sweat testing is recommended at 6, 12, and 18 months to monitor for risk of rising sweat chloride over time and 6-48% of infants with CRMS develop clinical features suggestive of CF. Infants with CRMS and sweat test results in the normal range are often lost to follow and parents were unwilling to return for recommended repeat sweat testing during the statewide lockdown during the peak of COVID-19 pandemic. We recognized the practice gap exacerbated during the pandemic and underscore the importance of establishing a medical home in a CF Center for longitudinal care. Methods: Retrospective analysis of infants with CRMS from December 2017 to December 2020 were collected by 10 NY CF Centers and the NBS program with NYU as the data collection and statistical analysis site. Infants with CRMS without repeat sweat chloride testing at 6 months of age were considered lost to follow up, and their parents were contacted via mail or telephone. Families completed a questionnaire that was developed with the assistance of CF Voice to evaluate parental understanding of CRMS and the recommendation for repeat sweat chloride testing. Primary care providers (PCPs) caring for infants with CRMS were also contacted and provided educational materials about CRMS. A subcommittee of CF Center Directors met to develop a statewide approach for the management of infants with CRMS. Results: Of 350 infants diagnosed with CRMS, 179 (51.1%) infants were lost to follow up. As an outcome of this QI effort 31 (17.3%) were scheduled for repeat sweat tests and follow up at CF Centers. This QI effort explored the knowledge and practice gap among PCPs with limited understanding of the implications of a CRMS diagnosis. CF Center Directors subcommittee issued a consensus statement regarding evaluation and follow up for infants with CRMS in NY. Conclusions: This QI effort effectively recaptured infants with CRMS previously lost to follow up. Consensus recommendations for CRMS include annual visits until 2-6 years of age for repeat sweat testing and in adolescence to educate the patient about clinical and reproductive implications of CRMS.

Pathogenic variants in the Surfactant Protein C gene ( SFTPC) result in fibrotic childhood interstitial lung disease (chILD). We previously reported three children with SFTPC pathogenic variants with respiratory failure who were supported by chronic invasive ventilation via tracheostomy as an alternative to lung transplantation or comfort care [(1)](#ref-0001). We present two children with SFTPC pathogenic variants treated with non-invasive ventilation (NIV) (Figure 1).

In recent decades, the patient survival is increased due to the advances in intensive care units and development of modern mechanic ventilators. Unfortunately, it is not always possible to wean these children from mechanical ventilation. Recently, after placement a tracheostomy tube, they can support at home with non-invasive or invasive mechanical ventilation. Most of the children who need ventilation support at home have neurological impairment. The nutritional issues and gastrointestinal complications are well defined in critically ill patients, but there are very limited studies on the children with tracheostomy. Considering that majority of the patients has neuromuscular disorders, the nutritional and gastrointestinal problems of the children with tracheostomy are discussed, in the light of the knowledge on critically ill patients.

We are presenting a teenage girl with a recent history of virilism who presented with tension pneumothorax. Subsequent contrast-enhanced chest CT revealed multiple bilateral irregular thin-walled cysts of varying sizes with numerous solid noncalcified pulmonary nodules and pulmonary artery pseudoaneurysms. Lung biopsy revealed trophoblastic neoplasm with metastasis to both lungs. We discussed the differential diagnosis of diffuse cystic lung diseases. While diffuse cystic lung diseases in children are rarely due to malignancy, we emphasize that clinicians be aware of the possibility of metastatic lung diseases and their radiologic features when encountering diffuse cystic lung diseases.

Introduction: Elective flexible bronchoscopy (FB) is now widely available and standard practice for a variety of indications in children with respiratory conditions. However, there is limited evidence regarding the utility of elective FB in children. This systematic review aimed to determine the utility of FB on its impact in clinical decision making and patient-reported outcome measures (PROMs). Methods: We searched Pubmed, Cochrane central register of controlled trials, Embase, World Health Organisation Clinical Trials Registry Platform and Cochrane database of systematic reviews from inception to 20 th April 2023. We included systematic reviews (SRs) and randomised controlled trials (RCTs) that used parallel group design (comparing use of elective FB versus no FB, or a wait-list approach [early FB versus usual wait FB]) in children aged ≤ 18 years. Our protocol was prospectively registered and used Cochrane methodology for systemic reviews of interventions. Results: Our search identified 859 articles; 102 duplicates were removed, and 753 articles were excluded by title and abstract. Four full text articles were reviewed and subsequently excluded, as none met the inclusion criteria outlined in our PICO framework. Conclusions: Given the paucity of data, there is need for high-quality evidence to support the routine use of elective FB in children with respiratory conditions. We recommend clinicians adhere to current international guidelines until such evidence emerges. Registration: PROSPERO CRD42021291305.

We believe that the data in this letter clearly demonstrate that even with CFTR2 expansion to 719 variants, striving to achieve equity of early diagnosis of CF via screening requires states to perform a sweat test in all infants with a high IRT level and one identified CFTR variant. This recommended policy can be debated but sweat testing overload should not be the argued as the barrier and CF specialists need to recognize that CFTR2 may never include all of the very rare, “private” pathogenic variants nor will next generation sequencing cover the structural variants such as deletions and duplications.

This is an editorial on the article by Drs. Hnaini et al. in this month’s issue of Pediatric Pulmonology reporting respiratory data in patients with Duchernne muscular dystrophy from a large, real-world database– The Canadian Neuromuscular Disease Registry (CNDR).

Introduction: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. Methods: Participants aged 6-23 born ≤32 (N=288; 132 with bronchopulmonary dysplasia) and ≥37 weeks’ gestation (N=76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400mcg salbutamol was classified according to published criteria. Results: A BDR was identified in 30.9% (n=85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k=0.26; 95%CI 0.18 to 0.40, p<0.001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs 11%, p=0.010) and baseline resistance (Rrs 5 z-score mean difference (MD)= 0.86, 95%CI 0.07 to 1.65, p=0.025), but similar spirometry to the group without a BDR (FEV 1 z-score MD= -0.01, 95%CI -0.66 to 0.68, p>0.999). Oscillometry was more feasible than spirometry (95% vs 85% (FEV 1), 69% (FVC), p<0.001), however being born preterm did not affect test feasibility. Conclusion: In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to that measured by spirometry and thus these tests should not be used interchangeably.

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene typically cause severe health complications in multiple organ systems, including the respiratory and gastrointestinal systems. Certain CFTR mutations, however, cause milder clinical phenotypes which may delay confirmatory diagnosis and treatment. Moreover, rare CFTR variants are not studied frequently or approved for genotype specific CFTR modulator therapies, creating further disadvantage. Herein, we describe a personalized medicine approach for a CF patient with three CFTR variants and mild clinical disease to aid in the diagnosis of CF and development of an optimized treatment plan. This strategy relied on the synergistic combination of advanced genetic analyses, patient-derived models of CFTR function and modulation, and personalized clinical care delivery. Whole Exome Sequencing revealed three compound heterozygous CFTR variants: c.2249C>T (p.P750L), c.1408G>A (p.V470M), and c.1251C>A (p.N417K). The CFTR channel function and nature of protein defects for both V470M and N417K mutations are not previously characterized. Patient-derived intestinal organoid models demonstrated residual CFTR channel activity, with improvement in channel function following treatment with the CFTR modulators. / n vitro studies in heterologous model system demonstrated that P750L has the features of Class II CFTR mutations, whereas V470M/N417K exhibited characteristics of Class II, III, and IV mutations, with all three variants responding to the combination modulator therapy of elexacaftor, tezacaftor, and ivacaftor (ETI) and showing functional rescue to near-wild-type CFTR levels. The laboratory data was then utilized to inform patient care, including off-label prescription of ETI. Following 18 months of ETI therapy, significant improvements were noted in key clinical outcomes, including sweat chloride, nutritional parameters, and respiratory and gastrointestinal symptoms. This study demonstrates a personalized medicine approach across clinical and laboratory domains used to care for CF patients with atypical symptoms and/or rare CFTR mutations.

Background and Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010-2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. Results: From 2010-2020, there were 8,765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7,591 children had a clinical diagnosis of CF and 1,174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1-9.1% after the first year of life. Conclusions: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Aim: Pulmonary near-infrared spectroscopy (NIRS) is a new and promising tool for diagnosis of neonatal respiratory diseases (RD). The study aimed to determine the role of pulmonary regional oxygen saturation (pRSO 2) values obtained by NIRS in the early distinction of neonatal pneumonia (NP) from transient tachypnea of the newborn (TTN). Methods: This prospective, observational, double-blind study was conducted in neonatal intensive care unit (NICU) between 2020-2021. Late preterm and term newborns hospitalized in the NICU due to the diagnosis of TTN and NP were included. Cerebral RSO2 and pRSO2 values were measured during the 1 st, 24 th, 48 th and 72 nd hours of hospitalization, using NIRS. Results: Of the eligible 40 infants, 65% (n:26) were diagnosed as TTN and 35% (n:16) as NP. The pRSO 2 values were significantly higher in the TTN group than the NP group for both apexes (75.3±8.7 vs. 69±5.4, p:0,018, respectively) and lateral lung (77.8±6 vs. 72.7±6.2, p:0,016, respectively) in the 1 st hour of hospitalization. There were significant differences in pRSO 2apex and pRSO 2lateral values between the 1 st and 24 th hours of hospitalization and the 24 th and 48 th hours in the NP group (p 2: 0.001 for both). The optimal pRSO 2apex cut-off value was >72% to predict the diagnosis of NP with a sensitivity of 78.6% and a specificity of 69.2%. Conclusion: Pulmonary NIRS may be considered as a feasible and promising diagnostic tool in late preterm and term infants with RD. It may also be helpful for the early differentiation of NP from TTN and the courses of these diseases.

BACKGROUND & OBJECTIVES: Porcine surfactant (200 mg/kg initial dose) seems to be superior over bovine surfactants (100 mg/kg) in respiratory distress syndrome (RDS). There is limited data on choice of surfactant from the developing world. Logically using higher doses of porcine surfactant comes with additional burden of cost. We decided to evaluate the clinical effect of different types of surfactants. METHODS: A retrospective analysis was conducted from August 2019 to December 2022 in 6 tertiary centres. Neonates 24-34 weeks of gestation with RDS requiring either porcine (200 mg/kg) or bovine surfactant (100 mg/kg) were enrolled. The proportion of combined outcomes of death and or CLD, redosing and other morbidities in either group were analysed. The subgroup of preterm >28 weeks and outcomes between different surfactants were analysed. RESULTS: Out of 1149 eligible babies, 302 (26%) received surfactant after stabilisation with CPAP. 158 received porcine and 144 received bovine surfactant via INSURE technique. There was a higher combined outcome of death or CLD in porcine compared to the bovine group [48 (30%) vs 20 (13%), OR:2.7; 95% CI:1.5-4.8; p=0.001] and similar combined outcomes in >28 weeks sub-group. Redosing [27 (17%) Vs 18 (12%), OR:1.4; 95% CI:0.7-2.7; p=0.2] was similar. Other morbidities like air leak, invasive ventilation, CPAP duration were similar between both the groups and different types of surfactants. CONCLUSION: Porcine surfactant at 200mg/kg had similar combined outcomes of death/ CLD and redosing compared to bovine surfactant in preterm >28 weeks. Considering the cost burden in the developing world, the efficacy needs evaluation in randomised clinical trials.

In conclusion, we present this case in order to complement CFTR gene mutations data of Chinese children with cystic fibrosis and improve clinicians' understanding of this disease in China. Besides, with the development of molecular biology technology, gene detection was expected to play an important role in the early diagnosis, early treatment, and prognosis improvement of the disease.