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.

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.

Background: Bronchiolitis is a viral respiratory illness most commonly caused by respiratory syncytial virus (RSV). COVID-19 disrupted typical patterns of viral transmission. Our study aimed to compare low value care for bronchiolitis in a tertiary emergency department (ED) in the United States over the previous five years. Methods: This was a descriptive cohort study through a retrospective chart review from 2017-2022 analyzing ED visits for bronchiolitis including disposition, disease severity, chest radiographs, albuterol, and high flow nasal cannula. A year was a 12 month period from March to February. Results: In the three years prior to the pandemic, there were over 2000 ED visits for bronchiolitis per year (3.1% of all ED visits), which decreased to 450 visits for bronchiolitis (1% of all visits) in 2020. Human rhino/enterovirus was the most common virus detected (92%). Admission rates, albuterol use, high flow nasal cannula use, and chest radiographs were all higher during the first year of the pandemic. The summer of 2021 had the highest visits across the 5 study years (2743, 4.0% of all visits) with a return to previous rates of resource utilization. Conclusions: During the early pandemic, measures to halt the spread of COVID-19 also altered the transmission of RSV and emergency visits for bronchiolitis. There was an increase in lower value care while the volume was low and rhinovirus was the dominant virus detected. As restrictions lifted in 2021, there was a large resurgence of RSV in the atypical summer months with a return of previous rates of resource utilization.

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.

Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome as well as aplasia of lacrimal and salivary glands (ALSG). Previous studies indicate that pathogenic variants in FGF10 can cause lethal human developmental disorders of the lung, but reports on diffuse lung disease caused by pathogenic variants in the FGF10 gene are lacking. We describe four children with postnatal onset of severe diffuse lung disease and heterozygous variants in FGF10, each detected by whole exome or whole genome sequencing. All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years and one patient is alive at age of six years, but still symptomatic. One patient presented signs of severe dental caries suggestive for ALSG or LADD-syndrome. Histopathological analysis of lung biopies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to diffuse developmental disorders of the lung and early onset lung fibrosis. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints.

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.

Huiyong Hu1#, Xiaoping Jing2#, Xiuhua Duan3, Leiping Zhou4, Yunfeng Xu1*1 Department of the Ultrasonography, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;2 Department of Traditional Chinese Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;3 Department of Radiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;4 Department of Radiology, International Peace Maternity & Child Health Hospital of China welfare institute, Shanghai Jiao Tong University, school of medicine, Shanghai 200030, China;# These authors contributed equally to this work.* Corresponding author: Yunfeng Xu, Department of the Ultrasonography, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine;Address: 1400 West Beijing Road, Shanghai, China Lane 24 Zip Code 200040;Phone: 18917128478E-mail: xuyunfeng65@163. com (F X).During a prenatal ultrasonography examination late in the second trimester, a fetus was found to have a right diaphragmatic hernia (Figure S1). Multidepartment dynamic monitoring was instituted, and the fetus was later successfully delivered by cesarean section after fetal distress became evident. After intubation, the infant was stabilized and transferred to the Department of Neonatology at our hospital.The enhanced computed tomography of the chest and stomach displayed multiple air-filled intestinal shadows in the right chest cavity, the widest being about 20.0 mm. The right lung, mediastinum, and heart were compressed and displaced, and most of the lung tissue in the right lung was consolidated. Atelectasis is evident in the irregular enhancement shadow at the right upper abdomen, about 43.5 × 32.0 mm in size. The boundary between some sections and the posterior margin of the right lobe of the liver was unclear, but the blood supply (hepatic artery and portal vein branches) was visible (Figure). Blood gases, routine bloodwork, liver and kidney function, and myocardial enzymes were essentially normal.At 40 + 4 weeks, with the infant under total anesthesia, hernia repair was performed. The liver and intestines in the thoracic cavity were brought back into the abdominal cavity; the tissues around the hernia ring in the diaphragm were carefully dissociated; and patch repair and suturing were performed (Figures S2–S4). After the operation, the infant’s vital signs were stable and their condition remained good during follow-up.Congenital diaphragmatic hernia (CDH) is a potentially fatal birth defect[1-3]. In China today, all pregnant women undergo ultrasonography to uncover pregnancy- related conditions[4]. A “green channel” – that is, a multidepartment collaborative for the emergency treatment of perioperative pulmonary hypertension, pulmonary dysplasia, and other complications in newborns with CDH – has been established, helping to assure the best prognosis for those infants.

Introduction: During the COVID-19 pandemic, pediatric visits due to acute lower respiratory infections (ALRIs) decreased, but most reports are from hospitalized patients. There is little information on this phenomenon in outpatients, who are the majority in IRABs. We evaluated the impact of the COVID-19 pandemic on ALRIs related outpatient visits in the City of Buenos Aires. Methods: Observational study including all outpatient visits of children under 2 years of age to the public health system of the City of Buenos Aires, between Jan 01, 2018 and Dec 31, 2022. We estimated the total number visits and the ALRIs-related visits, and their distribution throughout the study period. Results: A total of 704,426 visits were registered, 7.38% of them due to ALRIs. ALRIs-related visits decreased from the implementation of a national lockdown (2020) and increased again as the restriction measures decreased, particularly the return to full school attendance (2021). In general, the proportion of ALRIs-related vists was significantly higher in the cold months than in the warm ones (9.8% vs. 5.5%; OR: 1.76, 95%CI: 1.73-1.79; p<0.001). This difference was observed before (2018, 2019) and after the pandemic (2022), but not in 2020-2021. The peak of ALRIs-related visits occurred in the cold months in pre-pandemic years (2018-2019), did not appear in 2020, reappeared delayed in 2021 and recovered seasonality in 2022. Conclusion: Outpatient ALRIs-related visits decreased significantly in the city of Buenos Aires during the COVID-19 pandemic and currently seem to have recovered their magnitude and seasonality.

Introduction: This study aimed to determine if a respiratory therapist (RT)-driven high flow nasal cannula (HFNC) protocol could decrease duration of HFNC use, pediatric intensive care unit (PICU) and hospital length of stay (LOS), and duration of continuous albuterol use in pediatric patients with critical asthma. Methods: This was a quality improvement project performed at a quaternary academic PICU. Patients admitted to the PICU between 2 and 18 years of age with a diagnosis of asthma requiring continuous albuterol and HFNC were included. Implementation of a RT-driven HFNC protocol [Plan-Do-Study-Act (PDSA) 1] occurred in October 2017. Additional interventions included weaning continuous albuterol and HFNC simultaneously (PDSA 2; March 2019), adjusting HFNC wean rate (PDSA 3; July 2020), and a HFNC holiday (PDSA 4; October 2021). HFNC duration was the primary outcome. Secondary outcomes included LOS data and continuous albuterol duration. Noninvasive ventilation (NIV), invasive mechanical ventilation (IMV), and 7-day PICU and hospital readmission rates were balancing measures. Results: 410 patients were included. Patient demographics and adjunct therapy use did not differ among the groups. HFNC duration decreased from 26.8 to 18.1 hours, both PICU and hospital LOS were decreased (41 to 31.8 hours, and 86.5 to 68 hours respectively) after PDSA 2. These outcomes remained stable during PDSA 3 and 4. Continuous albuterol duration and NIV use remained stable, while IMV use decreased throughout the study. Conclusions: An RT-driven HFNC protocol led to an improvement in clinical outcomes for pediatric patients with critical asthma without an increase in adverse events.

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)

Background: Small air filled peripheral subpleural cysts are a well described feature of pulmonary anatomy at computerised tomographic (CAT) scan in children with Trisomy 21, yet only anecdotally described in association with other pathologies. The significance of these cysts is unknown. Objective: To investigate and explore the pathogenesis of these subpleural cysts in children. Materials and Methods: A retrospective review of 16 cases with subpleural cysts diagnosed on CT chest was performed. The distribution, location and ancillary CT findings were recorded. Hospital charts were reviewed for clinical details, especially cardiac abnormalities, pulmonary artery hypertension (PAH) and genetic associations. Histopathological and clinical correlative data were recorded. Results: 11/16 children (69%) were found to have an underlying chromosomal or genetic abnormality, six of whom had Trisomy 21. The remaining 5/16 cases (21%) had miscellaneous disorders without an identifiable genetic basis. The most common co-morbidities were cardiac abnormalities (81%) and PAH (62.5%). Regardless of their underlying etiologies, the cysts were present bilaterally in most cases (14/16, 88%). We observed both the postnatal development and the progression of cysts in our cohort . On long term follow-up, there were five deaths (31%) and six cases (38%) requiring maintenance oxygen therapy due to chronic hypoxia. Two cases (12.5%) became completely asymptomatic after correction of their underlying abnormalities. Conclusion: Subpleural cysts are not exclusive to Trisomy 21 and may be seen in other inherited or acquired causes, likely due to altered alveolar growth. We suspect these cysts are a sign of an underlying developmental disorder with variable clinical effect, especially in children with congenital cardiac disease.

Background: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. Objective: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years post-tracheostomy placement in children with BPD and tracheostomies. Methods: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and >1 respiratory culture obtained in 36 months post-tracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years post-tracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. Results: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased risk of decannulation (aRR 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. Conclusion: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.