Late Development of Pneumatoceles in Necrotizing PneumoniaSila Y. Kocer 1, Nathan C. Hull MD2, D. Dean Potter, Jr. MD 3, Theresa Madigan MD 4, Jennifer M. Boland MD5 and Nadir Demirel MD 61Ondokuz Mayis University School of Medicine, Samsun, Turkey2Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Pulmonology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] : Sila Y. Kocer, Ondokuz Mayis University School of Medicine, Körfez, 55270 Samsun, Turkey. Email address: [email protected]. Tel.: +905514571963Conflict of interest: The authors declare no conflict of interest.Author contributions : Sila Y. Kocer: Writing – original draft. Nathan C. Hull: Writing – review and editing.D. Dean Potter Jr.: Writing – review and editing.Theresa Madigan: Writing – review and editing.Jennifer M. Boland: Writing – review and editing.Nadir Demirel: Writing – review and editing.Keywords : Lung cysts; complicated pneumonia; lobectomy; imaging; childrenTo the editor,Community-acquired pneumonia (CAP) is one of the most common serious infections in children, although it usually has a good prognosis1. Necrotizing pneumonia (NP), a rare but severe complication of CAP, consists of the destruction of the consolidated lung parenchyma, potentially leading to the formation of thin-walled cavities known as pneumatoceles 2. While they often resolve spontaneously without sequalae, progressively enlarging pneumatoceles have been reported 5. We report a pediatric case with an unusual course of pneumatocele development.A 3-year-old female with history of congenital hypothyroidism and mild asthma presented to her primary care physician for evaluation of intermittent fever for the past 6 days, with a maximum temperature of 38.8°C. She had a worsening wet cough and complained of chest pain while coughing. Lung examination was normal except for mild tachypnea. Based on the patient’s presentation, empiric oral amoxicillin 90 mg/kg/day was started for possible CAP. The patient presented to the clinic on day 6 of her antibiotic treatment with persistent low-grade fever and ongoing cough. She had normal vital signs, and there were no signs of respiratory distress. The lung examination revealed crackles at right lung fields. A chest X-ray (CXR) showed a large consolidation and an airspace with an air-fluid level in the right upper lobe (RUL) (Figure 1A). There was no pleural effusion. The patient was diagnosed with complicated pneumonia and was referred to our hospital.A chest computed tomography (CT) without intravenous (IV) contrast showed a large consolidation in the RUL with scattered internal cystic areas containing air-fluid levels (Figure 1B, C). These findings raised concern for NP, abscess, or congenital pulmonary airway malformation with superimposed pneumonia. Laboratory test results showed mild anemia (hemoglobin concentration of 10 g/dl), leukocytosis (white blood cell count of 14.1 x 109/L), thrombocytosis (platelet count of 752 x 109/L), and high C-reactive protein (CRP) (80 mg/L, normal: <5 mg/L). She was admitted and started on IV ceftriaxone and IV vancomycin. She remained afebrile during admission and was clinically well appearing. A nasal swab culture for Methicillin-resistant Staphylococcus aureus was negative, therefore, on day 2 of admission, IV vancomycin was discontinued. AStreptococcus pneumoniae urine antigen test was positive. Serologic testing for endemic fungi was negative. A QuantiFERON-TB Gold was indeterminate due to inadequate mitogen response. On day 3 of admission, in preparation for discharge, IV ceftriaxone was switched to oral cefdinir 14 mg/kg/day to complete a 4-week course. She remained afebrile and well after an additional 24-hour period of observation and was subsequently discharged.Towards the conclusion of her antibiotic course, a follow-up CXR showed near resolution of the RUL consolidative opacity with a few small residual lucencies in the RUL, presumed to be residual pneumatoceles (Figure 1D). She was asymptomatic without a cough, and her lung examination was normal. Inflammatory markers, including CRP and sedimentation rate, as well as white blood cell count and platelet count, were in the normal range. One month later, while the patient remained asymptomatic, a follow-up CXR revealed an enlarged pneumatocele (Figure 2A, B). A chest CT with IV contrast demonstrated a 7.2 x 5.3 x 7.6 cm air-filled cavity in the RUL (Figure 2C, D). No definite connection to the adjacent airways was seen on the chest CT. The patient then underwent a thoracoscopic right upper lobectomy. The procedure was challenging due to adhesions and bleeding (Figure 2E). The pathology examination of the resected lung tissue showed a simple fibrous-walled cyst devoid of epithelial lining, consistent with pneumatocele (Figure 2F). Gram stain, fungal smear, bacterial culture and fungal culture of the explanted lung tissue were negative. The patient made a full recovery, both radiologically and clinically.Patients with NP usually present with symptoms of CAP, unresponsiveness to initial outpatient treatment, such as high fever, cough, tachypnea, and general unwell appearance 1. The initial treatment of NP consists of IV antibiotics covering the most common etiologic agents of NP, which are known to be S. pneumoniae , Group AStreptococci and S. aureus . The optimal duration of antimicrobial therapy is not clearly defined; however, usually prolonged with a median duration of 4 weeks reported in the literature2, which aligns with guideline suggestions for therapy of empyema and parapneumonic effusion 3. Improvement in clinical and laboratory parameters usually allows for IV to oral antibiotic transition, which was accomplished relatively early for our patient, due to her less severe initial presentation and rapid clinical improvement. Pneumatoceles, air-filled cysts that can arise as a complication of NP, typically regress over weeks to months when NP is treated, but might require segmental or lobar resection if they become tense (exceeding more than 50% of the involved lobe), infected, or rupture 1. In our patient, many of the small pneumatoceles decreased in size after antibiotic treatment, with subsequent delayed and marked enlargement of one of them. A report on giant lung cysts emerging after NP suggested that, when patients remain clinically stable, treatment of pneumatoceles should be conservative with antibiotics alone regardless of the size of the cysts, as interventional procedures carry a risk of complications such as bronchopleural fistula 4. However, a study that proposed a treatment algorithm for pneumatoceles, recommended surgical resection for those that remained unresolved despite a conservative approach and gradually grew in size and wall thickness5. Our patient had no symptoms related to the pneumatocele. Nevertheless, it can be challenging to anticipate the progression of pneumatoceles, as they can enlarge enough to compromise respiration. The unusual expansion within a span of 1 month in our case, led to the decision of surgical resection.To summarize, we present a 3-year-old otherwise healthy girl with NP. After 4 weeks of antibiotic therapy, the right lung consolidations resolved and pneumatoceles decreased in size. However, one month later, while she remained clinically asymptomatic, a follow-up CXR revealed the progressive enlargement of a pneumatocele which eventually required surgical resection. Based on this experience, we suggest a close radiological follow-up of patients with post-infectious pneumatoceles, regardless of symptoms, until complete radiologic resolution is demonstrated.References1. de Benedictis FM, Kerem E, Chang AB, Colin AA, Zar HJ, Bush A. Complicated pneumonia in children. Lancet. 2020;396(10253):786–798. doi:https://doi.org/10.1016/s0140-6736(20)31550-62. Masters IB, Isles AF, Grimwood K. Necrotizing pneumonia: an emerging problem in children? Pneumonia (Nathan). 2017;9(1). doi:https://doi.org/10.1186/s41479-017-0035-03. Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, Kaplan SL, Mace SE, McCracken GH, Moore MR, et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25–e76. doi:https://doi.org/10.1093/cid/cir5314. Gross I, Gordon O, Cohen‐Cymberknoh M, Reiter J, Tsabari R, Gileles‐Hillel A, Erlichman I, Hevroni A, Shoseyov D, Kerem E. Giant lung cysts following necrotizing pneumonia: Resolution with conservative treatment. Pediatr Pulmonol. 2019;54(6):901–906. doi:https://doi.org/10.1002/ppul.243215. Imamoğlu M, Cay A, Koşucu P, Ozdemir O, Cobanoğlu U, Orhan F, Akyol A, Sarihan H. Pneumatoceles in postpneumonic empyema: an algorithmic approach. J Pediatr Surg. 2005;40(7):1111–1117. doi:https://doi.org/10.1016/j.jpedsurg.2005.03.048Authors and affiliations : Sila Y. Kocer 1, Nathan C. Hull MD 2, D. Dean Potter, Jr. MD3, Theresa Madigan MD 4, Jennifer M. Boland MD 5 and Nadir Demirel MD 61Ondokuz Mayis University School of Medicine, Samsun, Turkey2Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of Pediatric Pulmonology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA. Email address: [email protected] of interest: The authors declare no conflict of interest.

Title: Determinants of school absences due to respiratory tract infections among children during COVID-19 pandemic: a cross-sectional study of the Sentinel Schools Network.Antoni Soriano-Arandes1,●,○, Andreu Colom-Cadena2,3,●, Anna Bordas2,3, Fabiana Ganem2,3,4, Lucia Alonso3,5, Marcos Montoro2,3, Mireia Gascon6,7,8, Maria Subirana6,7,8, Ariadna Mas9, Jordi Sunyer6,7,8, Pere Soler-Palacin1, Jordi Casabona2,3,4,8 ; on behalf of Sentinel School Network of Catalonia*Paediatric Infectious Diseases and Immunodeficiencies Unit. Children’s Hospital. Vall d’Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.Centre d’Estudis Epidemiològics sobre les ITS i Sida de Catalunya (CEEISCAT). Badalona, Spain.Institut d’Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.Departament de Pediatria, d’Obstetrícia i Ginecologia i de Medicina Preventiva i de Salut Publica, Universitat Autònoma de Barcelona, Bellaterra, Spain.Fundació Lluita contra les infeccions, Badalona, Spain.ISGlobal, Barcelona. Spain.Universitat Pompeu Fabra (UPF), Barcelona, SpainCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Instituto de Salud Carlos III, Madrid, Spain.Direcció Assistencial d’Atenció Primària i Comunitària, Institut Català de la Salut, Barcelona, Catalonia, Spain● Contributed equally to this work with: Antoni Soriano-Arandes, Andreu Colom-Cadena○ Corresponding author: Antoni Soriano-Arandes,[email protected]. ORCID: 0000-0001-9613-7228Keywords: COVID-19, respiratory infections, ventilation, school, CO2, Indoor air qualityTo the editor:Different public health measures were implemented during the COVID-19 pandemic to maintain the schools open1,2. Regarding COVID-19 vaccination, at the beginning of this study, more than 92% and 40% of population older than 12 years and children aged 5-11 years in Spain was fully vaccinated against COVID-19, respectively3.Ventilation was proposed as one of the main strategies to reduce aerosol transmission for SARS-CoV-2 during the pandemic. A study from Germany assessed the efficiency of air purifiers in reducing aerosols in high-school classrooms4. However, no clinical endpoints were investigated and, therefore, a very low certainty of evidence was graded by a Cochrane review5. In an Italian study, the authors concluded that ventilation reduced the likelihood of SARS-CoV-2 infection in classrooms by 80%6. Moreover, a survey study from the US reported that elementary schools with face masks and ventilation strategies in place had lower SARS-CoV-2 incidence rates7. In a Lancet Task Force Commission review8, the authors concluded that improving building ventilation systems may carry benefits beyond protection from COVID-19. However, there is scarce evidence that demonstrate the association of epidemiological and environmental risk factors, including CO2 concentrations, with the incidence of respiratory tract infections (RTI) in children who are attending schools.The present study is part of COVID-19 Sentinel Schools Network of Catalonia (CSSNC), a project including 23 schools and 5687 students, teachers and other school staff with the aim to monitor SARS-CoV-2 and other respiratory viruses, their determinants and preventive measures in Catalonia9. The objectives of this study are to assess the potential association of demographic and epidemiological factors, including the indoor environmental conditions (CO2levels) in the classrooms, with students’ school absence due to RTI.We conducted a cross-sectional study in two different periods, the first from April 19 to June 21, 2022, and the second from November 8 to December 21, 2022. The main outcome of the study was the absence of the child from attending the school in person due to RTI or other non-respiratory medical causes. The study population was composed of 253 students (4-11 years) belonging to 20 classrooms, 11 in spring 2022 and 9 in autumn 2022, attending 4 and 16 classrooms of preschool (4 to 5 years-old) and primary school (6 to 11 years-old) stages, respectively. A written informed consent was previously obtained from parents or guardians of children.Absences from school attendance were notified by the tutor/teacher to the study researchers. We proceed to collect epidemiological and clinical/diagnostic data within the first 48 hours through a case report form deposited on the digital platform REDCap©. All the absences (cases) were followed-up through telephone calls made by health professionals until their return to the school. RTI was registered according to the symptoms described during the telephonic interview and confirmed through the computerised health record programme of the Health Ministry (eCAP).Sensors to monitor the CO2 concentrations (DIOXCARE DX700 PDF, Smartcare Services, Spain) were installed in classrooms, recording data every 10 minutes. For the analysis we only used the measurements taken during the time in which the students were in the classroom. We obtained a median [IQR] of CO2 levels which was used to conduct our analyses. All the participating schools received an operational protocol to install the sensor correctly and download data weekly.We calculated the RTI incidence per week and for the total study period. We performed a descriptive analysis of all survey variables, stratifying them by respiratory-related absence or absence due to other causes. Additionally, we ran a univariate logistic model to study the association between the type of absence and each described variable to obtain the corresponding odds ratios, 95% confidence intervals and p-values.Furthermore, we conducted a Latent Class Analysis (LCA) to explore potential groups of students with similar symptomatology. We started exploring the optimal number of latent classes, trying two to five classes, and we selected the best model using the entropy criterion, which indicates the accuracy of the latent classes, combined with other goodness of fit criteria such as BIC, cAIC and likelihood ratio. All these measures suggested that the optimal number of classes was two. However, we also examined the rest of number of classes to see if their classification had more clinical significance. All statistical analyses were performed in R (version 4.2.2).We registered one-hundred and five school absences during the study, 43 in the first study period (spring 2022), and 62 in the last one (autumn 2022) (Figure 1S ). Among these, we could obtain data related to the diagnosis in 98 (93%) cases, the rest of them were lost during the follow-up of the absence. Seventy-one absences were respiratory-related and 27 were due to other causes, mainly with gastrointestinal symptoms (66.7%). Among the absences due to RTI, the most were upper RTI (56/71, 78.9%), and only six (8.5%) were confirmed infections, 2 caused by influenza virus and 4 due to SARS-CoV-2 infection. These results represent a RTI incidence of 15.9 and 33.1 cases per 100 population in the first and second study period, respectively. The maximum weekly RTI incidence was of 10.2 cases per 100 population in December 12-18, 2022.The clinical, epidemiological and environmental characteristics of study sample are summarized in table 1 , categorized by type of absence (respiratory versus non-respiratory). We found a statistically significant association with absences due to RTI when someone else at home had respiratory symptoms (OR=9.12, CI 95%=2.54-33.39). We found a positive association between higher median levels of CO2at class and respiratory-related absences (OR=1.2, CI 95%=0.98-1.46). Moreover, there were more respiratory absences in autumn (OR=2.4, CI 95%=0.97-5.94). However, these last two associations did not reach statistical significance at a level of 0.05; although their p-values were lower than 0.1.No other epidemiological risk factors were associated with RTI incidence, such as household floor level, number of people living at home, living with smokers, having any comorbidity or being vaccinated against COVID-19.Finally, in Figure 1 , we present the symptomatology of absences belonging to each of the two latent classes. We can see that in the first cluster, the most frequent symptoms were cough, nasal congestion and fever, whereas in the second one, fever, gastrointestinal symptoms, and fatigue predominated.Our findings confirm that the RTI incidence during the study period was very high in children attending in the CNSSC schools, and the main medical cause of school absence. Although differences on school absence due to RTI were observed between spring and autumn, they were not statistically significant and in any case they may be due to the respiratory viruses’ seasonal pattern. In fact, the most important and significantly associated risk factor for RTI was the presence of someone else at home with respiratory symptoms, suggesting that households could be the main setting for initiating of the transmission of RTI.We observed a slightly association between RTI and median of CO2 levels in classrooms (p=0.07), which is an indicator of the degree of ventilation. However, we cannot exclude other potential factors such as rainfall, ambient temperature, or air pollutants (e.g. PM2.5, NO2, etc.) influencing on this outcome, as suggested by other authors10. To our knowledge, previous studies assessed the CO2concentration as a proxy of ventilation to evaluate the risk transmission of SARS-CoV-2 in schools11,12, but they did not analyse the association between CO2 median values and RTI incidence.Finally, we studied the symptomatology associated with the school absences through a LCA. The best approach to differentiate RTI from other causes was using two latent classes, and the most frequent symptoms were cough, nasal congestion and fever.The major strength of this study is our extensive data collection on clinical, epidemiological and environmental factors related to the school and also to the households of the participants. However, there were limitations such as possible incomplete reporting of RTI or insufficient sample size to determine small effect sizes. CO2 concentration was only measured in a selection of classrooms per school, so it may not be representative for the entire study period and school.In conclusion, RTI incidence was very high during the study period being the most important and significantly associated factor with RTI to have anyone else at home with respiratory symptoms. This suggests that households and not schools could be the key epidemiological factor for initiating the transmission of RTI to the children. Improving household preventive measures could reduce childhood RTI. In the LCA, the most frequent symptoms associated with RTI were cough, nasal congestion and fever. Although we found a slightly association between RTI and reduced ventilation we cannot exclude other potential factors influencing on this outcome. The study has been crucial to assess the feasibility and potential utility of collecting both school absence and morbidity data for further developing a systematic monitoring system.

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

Paediatric home invasive mechanical ventilation patients are a small but resource intensive cohort, requiring close monitoring and multidisciplinary care. Patients are often dependent on their ventilator for life support, with any significant complications such as equipment failure, tracheostomy blockage, or accidental decannulation becoming potentially life threatening, if not identified quickly. This review discusses the indications and variations in practice worldwide, in terms of models of care, including home care provision, choice of equipment and monitoring. With advances in technology, optimal monitoring strategies for home, continue to be debated: In-built ventilator alarms are often inadequately sensitive for paediatric patients, necessitating additional external monitoring devices to minimise risk. Pulse oximetry has been the preferred monitoring modality at home, though in some special circumstances such as congenital central hypoventilation syndrome, home carbon dioxide monitoring may be important to consider. Children should be under regular follow up at specialist respiratory centres where clinical evaluation, nocturnal oximetry and capnography monitoring and/or poly(somno)graphy and analysis of ventilator download data can be performed regularly to monitor progress. Recent exciting advances in technology, particularly in telemonitoring, which have potential to hugely benefit this complex group of patients are also discussed.

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.

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.

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 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.

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.