Medication Utilization and Lung Function Changes

Introduction This study aimed to describe the epidemiology and etiologies of critical respiratory diseases of ex-premature infants (EPIs) admitted to pediatric intensive care unit (PICU). In addition, we described the outcomes and resources used of EPIs and identified associated factors for mortality of these infants. Materials and Methods Infants ≤2 years old with acute respiratory illnesses admitted to PICU of Vietnam National Children’s Hospital from November 2019 to April 2021 were enrolled. We compared respiratory pathogens, outcomes, and PICU resources utilized between term infants and EPIs. Univariate followed by multivariable regression analysis were used to evaluate the association between risk factors and mortality. Results Among 1,183 patients aged ≤2 years were admitted for critical respiratory illness, 202 (17.1%) were EPIs. Respiratory viruses were detected in 53.5% and 38.2% among EPIs and term infants, respectively. Compared to term infants, a higher proportion of EPIs required mechanical ventilation (MV) (66.5 vs. 85.6%, p<0.005) and vasopressor support (10.7 vs. 37.6%, p<0.005). EPIs had a longer median duration of PICU stay (11.0 [IQR: 7; 22] vs. 6.0 days [IQR: 3; 11], p=0.09), hospital stay (21.5 [IQR: 13; 40] vs. 10.0 days [IQR: 5; 18], p<0.005) and case fatality rate (31.3% vs. 22.6%) compared to term infants. In EPIs, PIM3 score [ (aOR): 1.51; 95% (CI): 1.30-1.75] and PELOD2 score at admission (aOR: 1.41; 95% CI: 1.08-1.85) were associated with mortality. Conclusion EPIs with critical respiratory illnesses constituted a significant population in the PICU and required more PICU support and had worse clinical outcomes compared to term infants.

FEV 1/FVC normally decreases through childhood, increases briefly during early adolescence, and then declines throughout life. The physiology behind this temporary increase during early adolescence is not well understood. The objective of this study was to determine if this pattern also occurs in children with asthma. Design: Single-center, cross-sectional, retrospective analysis of pulmonary function tests (PFTs) obtained over a 5-year period in children 5 to 18 years of age with persistent asthma. Results: 1,793 patients satisfied all inclusion and exclusion criteria. Mean age (± SD) was 10.4 ± 3.8 years. 48% were female. Mean FEV 1 /FVC was 0.83 ± .09. FEV 1 /FVC in children with persistent asthma declined from age 5 to age 11 by 5.7 % compared to 7.3% in healthy girls, and 5.8% compared to 9.4% in healthy boys. FEV 1/FVC increased by 1.2% until age 16 in children with asthma, compared to 2.2% in healthy girls, and 2.5% compared to 2.3% in healthy boys. The ratio was lower in obese children with asthma at all ages but demonstrated the same curvilinear shape as in healthy children. In absolute terms, FEV 1 grew proportionately more than FVC during early adolescence, so the ratio of FEV 1/FVC increased during that period. The curvilinear shape of the curve remained in postbronchodilator testing, though significantly blunted. Conclusions: The “Shepherd’s Hook” pattern in the FEV 1/FVC curve is preserved in children with persistent asthma. This was also true in obese patients with asthma, although their FEV 1/FVC ratios were lower throughout all stages of childhood and adolescence.

Real-time ultrasound guided segmental bronchoscopic insufflation in a Tay-Sachs patient with atelectasisMatej Šapina, MD, PhD1,2,3*, Bojana Olujić, MD1,2, Tihana Nađ, MD1,2, Hrvoje Vinković, MD1,2, Zdravka Krivdić Dupan, MD1,2, Nikolina Hamidović, MD1, Mia Damašek, MD1,2, Krešimir Milas, MD1, Željko Zubčić, MD, PhD1,2, and Ivan Erić, MD, PhD1,21University hospital center Osijek, 31000 Osijek, Croatia2Medical faculty Osijek, 31000 Osijek, Croatia3Faculty of dental medicine and health Osijek, 31000 Osijek, Croatia*Corresponding author: [email protected]: +385 31 512 279Keywords: bronchoscopy, atelectasis, Tay-Sachs diseaseIntroductionTo the Editor,Atelectasis is the collapse of lung tissue and is a common problem in patients suffering from severe neurological diseases. Treatment depends on the underlying cause, and ranges from respiratory physiotherapy, mucus clearance methods, and in some cases bronchoscopic interventions. If left untreated recurrent infections may occur, along with impaired gas exchange and in the long run fibrosis of the affected area1.A female patient at the age of 3 years with Tay-Sachs disease and consequent severe global psychomotor delay and epilepsy was initially admitted due to a respiratory infection to the neuropediatric department, where she developed an epileptic status and desaturation, prompting a transfer to the Intensive Care Unit. The refractory epileptic status resolved only with several antiepileptics, which lead to intubation requiring invasive mechanical ventilation, after which the patient stabilized.An attempt to reduce sedation the next day resulted in repeated seizures. On the third day, inflammatory parameters increased, with a radiological finding suggestive of pneumonia and a large left atelectasis confirmed by ultrasound. Antibiotics were empirically started, and Moraxella catarrhalis and Adenovirus in the respiratory tract were obtained in the cultures.Lung ultrasound showed a large consolidation in the dorsal upper two thirds of the left hemithorax. Due to the size of the atelectasis, we decided to perform bedside bronchoscopy.A single use paediatric flexible bronchoscope (Ambu® aScope™ 5 Broncho) was introduced through the ETT. The tracheobronchial morphology did not show any obstructions. We applied our recently published modified segmental insufflation technique, however without the use of surfactant2.First, a bronchoalveolar lavage was performed for microbiological and cytological analysis, followed by ultrasound guided bronchoscopic treatment of the affected area. The patient was positioned on the right lateral decubitus position. As described previously, a cuff pressure manometer (AG Cuffill Cuff) and a 50 ml syringe were attached to a three-way stopcock connected to the bronchoscope’s working channel. Pressure controlled segmental insufflation of the lingula and upper lobe was performed directly observing an aeration of the atelectatic areas on the ultrasound with no complications.Subsequent ultrasound monitoring resulted in total expansion of the affected lung and resolution of inflammation, confirmed radiologically (Figure 1.). The patient could be safely extubated and transferred to the wards. No reoccurrence of atelectasis was observed.ConclusionThe treatment of pediatric atelectasis poses a challenge, with limited approaches available and a lack of evidence-based guidelines to guide clinical decision-making. A question that remains to be answered is not only the mode of treatment, but timing. Even with bronchoscopic treatment, different methods exist. In obstructive atelectasis, the approach is simple - to eliminate the obstruction, however, nonobstructive atelectasis remain challenging. Bronchoscopic lung insufflation technique has been explored in adults, with limited cases reported in children3. Several case reports utilized pressure-controlled insufflation with or without surfactant in long standing atelectasis as an add on treatment2; 4.We believe that patients with severe neurological diseases require special attention regarding their susceptibility for developing atelectasis5. Our approach is early bronchoscopic pressure-controlled insufflation in non-obstructive atelectasis. Depending on the duration, we additionally instill surfactant in long standing ones.Ultrasound is recently being used in lung recruitment maneuvers to monitor lung expansion, however, it was only recently reported to be utilized for segmental insufflation monitoring in a spinal muscular atrophy type I patient4. However, to our best knowledge, our case report is the first successful use on a Tay-Sachs patient using real time ultrasound monitoring during pressure-controlled segmental bronchoscopic insufflation. The benefits of ultrasound guidance is the direct visualisation of lung expansion reducing the need for fluoroscopic radiation exposure of visualisation and further monitoring. Besides it increases the safety of the procedure allowing for detection of development of pneumothorax.In conclusion, pressure controlled real-time ultrasound guided bronchoscopic segmental insufflation, with its low-cost, lightweight, and flexible setup, seems to be a safe and promising new modality for treatment of non-obstructive atelectasis, especially in children requiring complex care.FIGURESFigure 1. On the left a large left sided atelectasis can be seen causing the mediastinal shift. On the right complete regression of the atelectasis is observed before extubatingReferences1. Ogake S, Bellinger C. 2020. Role of bronchoscopy in atelectasis. Clinical Pulmonary Medicine. 27(1):30-32.2. Šapina M, Olujic B, Nađ T, Vinkovic H, Dupan ZK, Bartulovic I, Milas K, Kos M, Divkovic D, Zubčić Z. 2023. Bronchoscopic treatment of pediatric atelectasis: A modified segmental insufflation‐surfactant instillation technique. Pediatric Pulmonology.3. Abu‐Hasan MN, Chesrown SE, Jantz MA. 2013. Successful use of bronchoscopic lung insufflation to treat left lung atelectasis. Pediatric Pulmonology. 48(3):306-309.4. Esteban IA, Osona B, Ballestín AS, Rubio CC, de Mendiola JMFP, Gómez VA, López ME, Vicente JCDC. 2024. Bronchoscopic segmental alveolar recruitment in a patient with spinal muscular atrophy and massive atelectasis. Pediatric pulmonology.5. St‐Laurent A, Zysman‐Colman Z, Zielinski D. 2022. Respiratory prehabilitation in pediatric anesthesia in children with muscular and neurologic disease. Pediatric Anesthesia. 32(2):228-236.

Deterioration of lung diffusion capacity during childhood in sickle cell diseaseWord count: 1500To the Editor,The American Society of Hematology guidelines, 2019, recommended obtaining pulmonary function tests (PFTs) in patients with sickle cell disease (SCD) with various respiratory symptoms even if they are at their steady state.1 These guidelines acknowledged that the usefulness of routine PFT is unknown because of the lack of research. However, this society further suggested that if the PFTs are obtained, it should be a comprehensive study including lung volumes and lung-diffusing capacity for carbon monoxyde (DLCO), in addition to spirometry.1 A large study in adult patients (n=310) with SCD showed that pulmonary function is abnormal in 90% of adult patients with Hb-SS.2 Common abnormalities included restrictive physiology and decreased DLCO. In this study, decreased DLCO indicated more severe sickle vasculopathy characterized by impaired hepatic and renal function, and a negative linear correlation existed between DLCO and age, suggesting that in adults with Hb-SS, disruption of alveolar–capillary gas exchange progressively deteriorated with time.2 Two recent cross-sectional studies of children with SCD showed that pulmonary function, including DLCO, worsened with age and showed correlations with biological markers of inflammation (induced sputum IL‐6 levels or blood neutrophilia).3,4Overall, these studies highlight the potential interest of DLCO measurement in SCD. The DLCO is the product of KCO (carbon monoxide coefficient of transfer) and alveolar volume (VA) and these two latter indices need to be interpreted separately since the decrease in DLCO is often mitigated by a preserved KCO or even increased KCO in SCD. It has been demonstrated that when corrected for hemoglobin levels, the children with SCD compared to controls of similar age had elevated KCOcorrected. The determination of alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity for carbon monoxide (DLCO) or for nitric oxide (DLNO) has been done in SCD since the seventies, demonstrating an increase in Vc in SCD. KCO is mathematically linked to both Dm and Vc (1/KCO = VA/Dm + VA/θVc); thus, the increase in KCO is related to Vc increase, but since DLCO has been shown to worsen with age, the changes of DLCO, VA and KCO over time in children with SCD deserve to be studied.The objectives of our study were to describe the evolution of DLCO and its determinants, KCO and VA, and to further assess the initial risk factors of the decrease in DLCO in children/adolescents with SCD. To this end, we retrospectively recorded the routine follow-up PFTs of children with SCD who were included in a prospective cross-sectional study that included the measurement of both DLCO and DLNO with the calculation of Dm and Vc.5

Title: Major aortopulmonary collateral artery aneurysms- a rare cause of airway narrowing

Background and Aims: The long-term respiratory sequelae of COVID-19 infection in children remain poorly understood and may differ across countries. This study aims to investigate the respiratory sequelae, including residual respiratory symptoms and pulmonary function in Thai children. The secondary aim is to identify factors associated with the respiratory sequelae. Materials and Methods: This is an observational study involving 56 healthy children, aged between 7-18 years, who were diagnosed with COVID-19 infection from July 2021 to February 2023. Clinical data relating to COVID-19 infection and persistent symptoms after the infection were assessed after the infection up to six months. Spirometry was performed to assess pulmonary function. Results: Post COVID-19 symptoms were identified in 14 patients (25%), with fatigue, cough, and dyspnea being common symptoms (28-35%). A significant correlation was found between post COVID-19 symptoms and pneumonia (OR = 6.00, 95%CI [1.54,23.33], p=0.01). Abnormal pulmonary function was identified in 10 patients (17.8%) with obstructive impairment being the most common. However, there were no significant association between clinical factors and pulmonary function impairment. Conclusion: Prolonged respiratory symptoms and abnormal pulmonary function following COVID-19 infection are not uncommon in children. The post COVID-19 symptoms are possibly associated with COVID-19 pneumonia.

TITLE: CLINICAL EVIDENCE OF PANCREATIC RECOVERY IN CHILDREN WITH CYSTIC FIBROSIS ON IVACAFTORTo the Editor,Pediatric research has shown that young children with cystic fibrosis (CF) and treated with ivacaftor have seen improvements in pancreatic function. KIWI was a 24-week safety and efficacy trial of ivacaftor in children aged 2-5 years with CF (1). KLIMB was an 84-week open label extension of KIWI (2). Patients enrolled in KIWI revealed an average increase of 99.8 ug/g in fecal elastase (FE). Before beginning ivacaftor, 26 of 27 patients were pancreatic insufficient. After 24 weeks, 25% of these 26 patients had FE results demonstrating pancreatic sufficiency (>200 ug/g) (1). These improvements in FE were maintained during the 84-week KLIMB extension (2).In the ARRIVAL Study, a younger population was studied. Infants aged 12-24 months previously diagnosed with pancreatic insufficiency were assessed (3). After 24 weeks post ivacaftor initiation, six of nine, or 67%, of the infants had repeat FE values of >200 ug/g, consistent with pancreatic sufficiency, as well as evidence of decreased pancreatic inflammation noted with reduction in immunoreactive trypsinogen.Based on this data we instituted a new protocol for repeat FE monitoring in all patients with pancreatic insufficiency who started on ivacaftor by the age of two years. If FE is normal (>200 ug/g), discontinuation of pancreatic enzyme replacement therapy (PERT) is considered along with ongoing monitoring of clinical symptoms and adjustments to vitamin and diet recommendations as indicated.Below is a review of our cohort of pediatric patients who were currently, had been consistently treated with ivacaftor, and were assessed for current pancreatic function by repeat FE testing. All FE values were collected prior to initiation of elexacaftor/tezacaftor/ivacaftor (ETI) in those newly eligible. Nine patients at our CF center who were on PERT have started ivacaftor in the last 6 years with a mean current age of 4.9 years (SD 1.7). The median age of ivacaftor initiation was 1.1 years (range 0.4 - 2). The mean duration of treatment is 3.9 years (SD 1.3).Seven patients had a repeat FE result >200 ug/g. Six of the seven pancreatic insufficient patients presented as newly pancreatic sufficient as evidenced by a FE result of >200 ug/g compared to previous result of <200 ug/g. Patient I was included in this cohort as he was treated with PERT for clinical symptoms of pancreatic insufficiency even though his baseline FE values were above 200 ug/g.The six newly pancreatic sufficient patients started ivacaftor between 0.4 and 1.1 years of age. Our recovery data of 75% is close to the rate seen in the ARRIVAL study. We calculated binomial probability for pancreatic recovery in this small case control series using 0.67 factor based on previous data in ARRIVAL (4). This resulted in a 28% favorability of success.Unsurprisingly, the rate of recovery was higher in the younger age of initiation of ivacaftor than that seen in the older 2–5 year-old cohort in KIWI. A correlation between pancreatic recovery and younger age of initiation was also noted in a recently published multi-center retrospective study of all available CFTR modulators and PE recovery (5). In this study, of the 15 patients with FE results of 200 or greater, 10 had been treated with ivacaftor as their initial modulator therapy. Based on the demographic data, 62.5% of those treated with ivacaftor had pancreatic recovery, which is similar to our cohort data.We urge CF Centers to institute clinical protocols to recheck pancreatic elastase to assess for restoration of pancreatic function in all pediatric patients treated with PERT on ivacaftor. Subsequently, CF Centers should establish processes for discontinuing PERT, monitoring fat soluble vitamins, and adjusting diet as indicated. Resulting medication adjustments will significantly impact the treatment burden and cost for these children and their families. Those with pancreatic restoration should be monitored for symptoms of pancreatic insufficiency as well as growth trends at routine intervals and pursue repeat FE as indicated based on clinical assessment.This study was approved by the Oregon Health and Science University Institutional Review Board (IRB#26442).

Purpose: Predicting Bronchopulmonary dysplasia (BPD) to assess the risk-benefit of the therapy is necessary due to the side effects of medications. We developed and validated an instrument for predicting BDP and compared it with an instrument currently used in neonates born in a Brazilian hospital. Methods: Retrospective cohort of patients born between 2016 and 2020, with gestational ages (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of selection of component variables: stepwise, conditional inference tree, Fisher’s exact test and all the collected variables; 70% of the sample was randomly selected for the construction of risk prediction equations, and the remaining 30% were used for their validation, application and comparison with the National Institute of Child Health and Human Development (NICHD) instrument published in 2011, currently used in that institution. Sensitivity, specificity, and predictive values of the equations were calculated. Results: The equation that used variables whose p-value was lower than 5% in Fisher’s exact test (clinical chorioamnionitis, GA, birth weight, sex, need for surfactant, patent ductus arteriosus, late-onset sepsis, inspired fraction of oxygen, and respiratory support) presented the best results: specificity of 98% and positive predictive value of 93%. Our instrument allowed applying the prediction to small-for-gestational-age (SGA). The currently used calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to SGA patients. Conclusion: Our tool has a higher specificity and positive predictive value than the foreign instrument and is suited for SGA.

Introduction: Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in cystic fibrosis (CF) patients from Tasmania and Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report epidemic P. aeruginosa (AUST-03) strains in South African CF patients at a public academic hospital detected during a previous study and characterise the resistomes. Methods: The P. aeruginosa AUST-03 (ST242) strains were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multi-locus sequence typing and resistome characterisation was performed using public databases. Core single nucleotide polymorphism phylogenies were performed on P. aeruginosa ST242 strains from the study and from public databases. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. Results: A total of 11 P. aeruginosa AUST-03 strains were isolated from two children with CF who had pulmonary exacerbations. The majority of the P. aeruginosa AUST-03 strains (8/11) were multidrug resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the strains. The P. aeruginosa AUST-03 (ST242) study strains were most closely related to strains from Canada, China, Denmark and Slovenia. Conclusion: Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing patient segregation and infection control strategies to prevent further spread and outbreaks.

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.

Pediatric sleep-related breathing disorders, or sleep-disordered breathing (SDB), cover a range of conditions including obstructive sleep apnea (OSA), central sleep apnea (CSA), sleep-related hypoventilation disorders, and sleep-related hypoxemia disorder. Pediatric SDB is often underdiagnosed, potentially due to difficulties associated with performing the gold standard polysomnography (PSG) in children. This scoping review aims to: 1) provide an overview of the studies reporting on safe, noncontact monitoring of respiration in young children; 2) describe the accuracy of these techniques, and 3) highlight their respective advantages and limitations. PubMed and EMBASE were searched for studies researching techniques in children <12 years old. Both quantitative data and the quality of the studies were analyzed. The evaluation of study quality was conducted using the QUADAS-2 tool. A total of 17 studies were included. Techniques could be grouped into bed-based methods, ultra-wideband (UWB) radar, Doppler radar, video, infrared (IR) cameras, garment-embedded sensors, and sound analysis. Most either measured respiratory rate (RR) or detected apneas; five aimed to do both. Noncontact sleep monitoring techniques are safe, but accuracy data of these techniques is limited, and large heterogeneity exists regarding study quality and stage. Motion artifacts affect accuracies of apnea detection. Sleep respiration analysis could benefit from sleep stage classification and breathing sound analysis. Further research is crucial to facilitate easily accessible and safe non-contact methods for respiration monitoring in a home setting.

Background Cystic fibrosis (CF) related diabetes affects up to half of all adults with CF and is associated with higher morbidity and mortality. Our aim is to co-design an ideal model of care that integrates diabetes technology and better meets the needs of adults living with the condition to improve attendance, engagement, service satisfaction and clinical outcomes. Methods Using qualitative research methods, we evaluated disease perceptions, barriers and enablers to optimal CF-related diabetes management and service delivery. Integration of continuous glucose monitoring (CGM) was also explored. An initial broad purposive consumer survey was followed by focus groups with end-users. Grounded theory approach was utilized with major problem-areas identified then explored, coded and grouped into requisites for an ‘ideal model of care’ for adults living with CF-related diabetes. Results Two key themes emerged i) CGM was acceptable for use in adults with CF-related diabetes with many perceived benefits and should be integrated into the model of care, ii) an ideal model of care consisted of a dual-specialty service co-led by endocrinology and CF physicians and supported by diabetes nurse educator and CF dietitian with a goal to provide consistent and personalized diabetes management. Barriers to optimizing glycaemic control included diet, finger-prick testing, reduced access to CGM and pulmonary exacerbations. End-user feedback on CGM was overwhelmingly positive with regards to user operability. CGM was also identified as a tool that could be used to engage, educate and empower adults living with CF-related diabetes and facilitate constructive and personalized clinical decision-making by healthcare providers. Conclusion For adults living with CF, a diagnosis of diabetes is associated with increased treatment burden. End-users agreed CGM had many benefits and should be integrated into an ‘ideal model of care’ for CF-related diabetes that was co-led by endocrinology services integrated within a pre-existing CF service.

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.

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

Ventilator associated respiratory tract infections (VARTI) are among the most common indications for hospitalization among children with chronic respiratory failure requiring at-home ventilation. This review aims to provide an overview of the key clinical features, diagnostic approaches, and management strategies for home VARTIs while highlighting the challenges in diagnosis and management.

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.