Introduction: Infants and children diagnosed with BPD have a higher likelihood of recurrent hospitalizations and asthma-like symptoms. Socio-environmental factors that influence frequency and severity of pulmonary symptoms in these children during the pre-school age are poorly under-stood. In this study, we used the Area Deprivation Index (ADI) to evaluate the relationship between the socio-environmental exposures in children with BPD and respiratory outcomes during the first few years of life. Methods: A registry of subjects recruited from outpatient BPD clinics at Johns Hopkins University (n=909) and the Children’s Hospital of Philadelphia (n=125) between January 2008 and October 2021 was used. Subjects were separated into tertiles by ADI scores aggregated to ZIP codes. Care-giver questionnaires were used to assess the frequency of respiratory morbidities and acute care usage for respiratory symptoms. Results: The mean gestational age of subjects was 26.8±2.6 weeks with a mean birthweight of 909±404 grams. The highest tertile (most deprived) of ADI was significantly associated with emer-gency department visits (aOR 1.72; p=0.009), hospital readmissions (aOR 1.66; p=0.030), and activi-ty limitations (aOR 1.55; p=0.048) compared to the lowest tertile. No association was seen with steroid, antibiotic or rescue medication use, trouble breathing, or nighttime symptoms. Conclusion: In this study, children with BPD who lived in neighborhoods of higher deprivation were more likely to be re-hospitalized and have ED visits for respiratory reasons. Identifying socio-environmental factors that contribute to adverse pulmonary outcomes in children with BPD may provide opportunities for earlier interventions to improve long-term pulmonary outcomes.

The diagnosis of primary ciliary dyskinesia (PCD) is made through a combination of clinical features supported by a panel of diagnostic tests. Our cases highlight the similarities in the clinical presentation of patients with the specific immunodeficiency activated phosphatidylinositol 3-kinase delta syndrome 1 (APDS1 or PIK3CD) and PCD. We highlight the importance of repeating nasal nitric oxide testing (nNO) when PCD has not been confirmed by genetic or ciliary electron micrograph (EM) analysis in the setting of an expanded suppurative lung disease differential that includes considerations for immunodeficiency as well as PCD.

Pediatric Pulmonology , LetterElevated serum TARC/CCL17 levels are associated with childhood interstitial lung disease in patients with SFTPC gene mutationYuto Otsubo MD1; Yuji Fujita MD1; Yusuke Ando MD, PhD1; George Imataka MD, PhD1; Shigemi Yoshihara MD, PhD11Department of Pediatrics, Dokkyo Medical University, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0207, JapanCorresponding author:Yuto OtsuboDepartment of Pediatrics, Dokkyo Medical University, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, JapanTel: +81-0282-86-1111Fax: +81-0282-86-7152E-mail: [email protected]:Childhood interstitial lung disease; TARC/CCL17; SFTPCRunning head:Childhood ILD and increased TARC/CCL17 levelTo the Editor,Childhood interstitial lung disease (ILD) is a serious and often life-threatening disease that causes interstitial lung lesion formation during childhood. Several causative genes of childhood ILD, such asSFTPC , SFTPB , and ABCA3 , have been identified in some children. The pathogenesis of ILD caused by SFTPC mutations may include the accumulation of surfactant protein C (SP-C) in vesicles, inhibition of pulmonary surfactant reuptake, and decreased secretion of SP-C, but this remains to be confirmed.1Thymus and activation-regulated chemokine/C-C motif chemokine ligand 17 (TARC/CCL17) is a known disease marker of atopic dermatitis. Recently, an association between idiopathic pulmonary fibrosis, a representative disease with pulmonary interstitial lesions, and TARC/CCL17 has been reported,2 but none between childhood ILD and TARC/CCL17.Here we report our experience of a case of childhood ILD in which the patient had an SFTPC mutation and an elevated TARC/CCL17 level at disease onset that decreased as the patient improved with treatment. TARC/CCL17 may be involved in the pathogenesis of ILD in children withSFTPC mutation, which is different from the pathogenesis of atopic dermatitis.An otherwise healthy 15-month-old girl was admitted to our hospital with fever, difficulty breathing, and poor oral intake. Nine days prior to the visit, nasal discharge and cough appeared and gradually worsened; subsequently, poor oral intake appeared. No fine crackles were noted. The patient required supplemental oxygen and was admitted to the hospital. She had no history of respiratory impairment at birth, but she had a family history of ILD in her maternal grandmother. Informed consent was obtained from the patient’s guardians for the publication of this case report.Laboratory tests showed a white blood cell count of 941 × 109/L, neutrophil count of 58%, C-reactive protein level of 0.01 mg/dL, lactate dehydrogenase level of 929 IU/L, Krebs von den Lungen-6 (KL-6) level of 909 U/mL (normal range < 500 U/mL), surfactant protein A level of 2770 ng/mL (normal <43.8 ng/mL), and surfactant protein D level of 319 ng/mL (normal <43 ng/mL), which were suspicious findings for ILD (Table 1). ß-D-glucan level was 7.9 pg/mL (normal <20 pg/mL) and cytomegalovirus antibodies were negative for both IgG and IgM. Chest radiography showed bilateral frosted shadows (Fig. 1), and a chest computed tomography scan showed bilateral diffuse frosted shadows (Fig. 2), leading to ILD diagnosis.Although prednisolone was started on the 2nd day of admission, the patient’s respiratory status did not sufficiently improve, and oxygen supplementation was required. Therefore, methylprednisolone (30 mg/kg/day) was administered twice for 3 consecutive days on days 13-15 and 19-21; however, the respiratory status remained poor. Hydroxychloroquine (10 mg/kg/day) was then started on day 21, and azithromycin (10 mg/kg/day) three times a week was started on day 56, following which the respiratory status gradually improved. On drinking cold water, the patient often coughed and sometimes vomited. When the water was warmed from 4°C to approximately 20°C, coughing and cough-induced vomiting drastically decreased. On day 66 of hospitalization, the patient was discharged with home-based oxygen. Respiratory status, oxygenation, and laboratory data for ILD markers such as KL-6 gradually improved (Table 1).Genetic analysis of SFTPB , SFTPC , ABCA3 ,CSF2RA , and CSF2RB showed SFTPC mutation and p.I73T (c.218T>C), and the ILD was determined to be caused by theSFTPC mutation.Additional examination revealed elevated TARC/CCL17 level at 10,270 pg/mL (normal <998 pg/mL), but IgE (24.2 IU/mL; normal <173 IU/mL) and IL-4 (2.7 pg/mL; normal <6 pg/mL) levels were not elevated in the early stages of treatment. TARC/CCL17 level decreased to 2,122 pg/mL on day 131 after the admission. Granulocyte-macrophage colony-stimulating factor (GM-CSF) level was measured twice on days 11 and 83, and on both, the GM-CSF level was under 5 pg/mL without significant elevation. Anti-GM-CSF antibody (0.3 U/mL; normal <1.7 U/mL) was negative.It has been hypothesized that many of these effector cell populations are recruited by TARC/CCL17 and act profibrogenically, but the details remain largely unknown.3) SFTPC mutations increase the number of abnormal alveolar type 2 epithelial cells (AT2) due to impaired metabolism of SP-C. A knock-in mouse model capable of regulating the expression of an isoleucine-to-threonine substitution at codon 73 (p.I73T) in SFTPC, at the same site as in the present case, showed persistently elevated TARC/CCL17 level in the bronchoalveolar lavage fluid (BALF). Furthermore, the same study also reported that TARC/CCL17 is specifically released by AT2.3 In ILD caused by SFTPC mutations, its pathogenesis involves AT2 hyperplasia. The decrease in TARC/CCL17 level in our patient suggests that either AT2 itself or TARC/CCL17 production from AT2 itself decreased with treatment. In this case, we report, for the first time, elevated serum TARC/CCL17 level in a patient with SFTPC mutation, which decreased with treatment.Our patient showed no symptoms of atopic dermatitis, and she had no skin condition, and no elevation of IgE and IL-4 levels. In the SFTPC p.I73T mouse model mentioned above, no significant level of IL-4 or IL-13 was detected in BALF, and no involvement of the Th2 response was observed.This high TARC/CCL17 level was not considered to be a result of the GM-CSF cascade. TARC/CCL17 is released from macrophages as a product of the GM-CSF cascade.4) GM-CSF is also known to be produced by AT2.5) However, in this case, serum GM-CSF levels were normal and not elevated, both at the beginning of treatment and after improvement.The limitation of this case is that bronchoalveolar lavage was not performed; therefore, the evaluation was based on serum level rather than local lung findings.This case suggests that TARC/CCL17 is involved in ILD pathogenesis. Further elucidation of the chemokine and receptor signaling cascade may lead to the targeting of some stages for therapy, which may be an important issue for future medical treatment. Therefore, elucidation of this pathogenesis is desirable.References1) Beers MF, Mulugeta S. Surfactant protein C biosynthesis and its emerging role in conformational lung disease. Annu Rev Physiol 2005;67:663-696.2) Sivakumar P, Ammar R, Thompson JR, Luo Y, Streltsov D, Porteous M, McCoubrey C, Ill EC, Beers MF, Jarai G, et al. Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis. Respir Res 2021;22;273:1-13.3) Nureki SI, Tomer Y, Venosa A, Katzen J, Russo SJ, Jamil S, Barrett M, Nguyen V, Kopp M, Mulugeta S, et al. Expression of mutant Sftpc in murine alveolar epithelia drives spontaneous lung fibrosis. J Clin Invest 2018;128:4008-4024.4) Hamilton JA. GM-CSF-dependent inflammatory pathways. Front Immunol 2019;10;2055:1-8.5) Woo YD, Jeong D, Chung DH. Development and functions of alveolar macrophages. Mol Cells 2021;44:292-300.Conflicts of interest:The authors disclose no conflicts.Contributors:YO cared for the patient, conceived the concept of the case report, and drafted the initial manuscript. YF, YA, GI, and SY critically reviewed the manuscript for intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.Acknowledgment:We would like to thank Editage (www.editage.com) for English language editing.We thank Dr. Goro Koinuma, Division of Pulmonology, National Center for Child Health and Development, Tokyo, Japan, for his invaluable expert opinion regarding the diagnosis and treatment of the patients.Sources of funding:No funding was obtained for this study.

Background: Children should be weaned from the ventilator once their clinical condition improves. Extubation failure is associated with poorer clinical outcomes in children. Predictive indicators of successful extubation are needed. This study aims to evaluate the predictive value of ultrasonographic diaphragm imaging could help predict weaning success. Methods: In this prospective, observational study conducted between March and December 2021, children between 1 month and 10 years of age who were mechanically ventilated for more than 48 hours were included. Diaphragm ultrasound (DUS) examinations were performed at the end of 2-hour extubation readiness test (ERT). The end-inspiratory thickness, end-expiratory thickness, diaphragmatic thickening fraction, diaphragmatic excursion, inspiratory slope and expiratory slope were evaluated. Results: Twenty-four (60%) patients were successfully extubated, while 16 (40%) required invasive or non-invasive mechanical ventilation support which were classified as failed extubation group. Three of the sixteen patients in the failed extubation group required re-intubation. Diaphragm thickening fraction was significantly greater in the successful weaning group (55,05 ± 23,75% vs. 30,9 ± 10,38%) (p<0,001). Diaphragm excursion was significantly greater in the SW group (14 ± 4,4 mm vs 11,05 ± 3,25 mm) (p<0,001). DTF and DE were found to have a sensitivity and specificity of 91.67 %, 87.50 %, and 83.33 %, 81.25 %, respectively. Conclusion: Diaphragm ultrasound is a feasible and promising tool to guide physicians during weaning from IMV. Among all DUS measurements, the DE and DTF indexes showed better performance in extubation failure than other diaphragmatic parameters.

Background Children with tracheostomies are at an increased risk of bacterial respiratory tract infections. Infections caused by multidrug-resistant organisms (MDROs) are more difficult to treat and can result in severe complications. We investigated the risk factors and sequelae of MDRO positivity in tracheostomy and chronic ventilator-dependent children. Methods We performed a retrospective chart review of 75 tracheostomy and chronic ventilator-dependent children at St. Louis Children’s Hospital. Data on demographics, respiratory cultures, hospitalizations, emergency department (ED) visits, and antibiotic usage were collected. We determined the frequency of MDRO positivity and compared the number of hospitalizations, number of ED visits, and antibiotic usage in patients with and without MDRO-positive cultures. Patient clinical variables were analyzed before and after MDRO acquisition. Results We found 75.7% (56/74) of our participants had an MDRO-positive culture, with methicillin-resistant Staphylococcus aureus (MRSA, n=36, 64%) and Pseudomonas aeruginosa (n=8, 14%) being the most commonly detected organisms. Patients with MDRO-positive cultures had a greater number of annual non-pulmonary admissions [OR=1.99, 95% CI (1.21-3.29), P= 0.008], inpatient antibiotic courses [OR=1.27, 95% CI (1.07-1.50), P=0.006], total antibiotic courses [OR=1.26, 95% CI (1.08-1.48), P= 0.004], and chronic antibiotic use [OR=2.31, 95% CI (1.12-4.74), P=0.03] compared to MDRO-negative participants. Patients that acquired MDROs during the study period subsequently required increased outpatient antibiotics [P= 0.006] but did not have increased pulmonary admissions or ED visits. Conclusion Frequent antibiotic usage and hospitalizations increase the risk of MDRO acquisition in children with tracheostomies and ventilator-dependence. Further antibiotic stewardship may help prevent resistant infections in technology-dependent children.

Introduction: There is evidence for increased risk of eating disorders in individuals with diet-treated chronic illnesses, however, data in patients with Cystic Fibrosis (CF) is less clear. No studies have evaluated avoidant/restrictive food intake disorder (ARFID) in the CF population. We investigated the prevalence of disordered eating, including ARFID, in adolescents and young adults with CF. Methods: Patients with CF aged 14-35 years were recruited to complete three validated surveys: (1)Eating Disorder Examination Questionnaire (EDE-Q), (2)Nine-Item Avoidant/Restrictive Food Intake Disorder Scale (NIAS), and (3)Cystic Fibrosis Questionnaire-Revised (CFQ-R). Univariate linear regression analysis identified baseline risk factors associated with these survey scores. Variables with univariate p<0.20 were considered for inclusion in a multivariable linear regression model. Backwards stepwise linear regression was used to identify the final model. Results: A total of 52 patients enrolled. The prevalence of eating disorder measured on the EDE-Q was 9.6%, and on the NIAS was 13.5%. The CFQ-R eating and weight subscales were associated with scores on the EDE-Q, and CFQ-R eating subscale and being dF508 homozygous were correlated with the NIAS total score. Discussion: A clinically significant number of participants screened positive for disordered eating on the EDE-Q and NIAS. Scores on the eating and weight scales of the CFQ-R were associated with the scores on these surveys. Further work is needed to better understand the optimal way to use such tools to screen and treat for eating disorders in individuals with CF.

Background: Cystic fibrosis is a common cause of pancreatic exocrine insufficiency. Clinically pancreatic insufficiency is treated as a permanent problem. However, new cystic fibrosis transmembrane conductance regulator (CFTR) protein modulator therapies, like ivacaftor, can change pancreatic function in children. Also, children with residual CFTR function mutations may be pancreatic insufficient in infancy and spontaneously become pancreatic sufficient. Aims: To evaluate the benefit of reviewing pancreatic function, testing and diagnosis, of a cohort and repeat testing to patients with the potential to change function. Methods: all children with cystic fibrosis managed at Perth Children’s Hospital at the end of 2019 were reviewed for pancreatic function testing at diagnosis, genotype and current modulator and pancreatic enzyme replacement therapy use. Children with the potential to change pancreatic function were offered repeat testing. Results: 204 children were included. 11 children were prescribed ivacaftor and four of these became pancreatic sufficient. Five children with a residual CFTR function mutation were pancreatic insufficient at diagnosis. Four became pancreatic sufficient. Conclusion: there is benefit in re-evaluating pancreatic function in children with cystic fibrosis regularly, especially if on ivacaftor or pancreatic insufficient with a residual CFTR function mutation.

Background: Pediatric bronchoscopy is an important tool in pediatric pulmonology. However, the practices involved in the procedure are variable. Objective: To evaluate prevalent practice and variations in pediatric flexible bronchoscopy in India. Methods: An online survey conducted between September 2018 to March 2019 via Google forms. The survey was sent to members of the Respiratory Chapter of IAP, personal contacts, and members of Indian Chest Society. Physicians performing flexible bronchoscopy in children were asked to respond. Survey had 95 questions in seven domains including patient preparation, sedation, procedural aspects, monitoring, bronchoscope cleaning, and complications. Results: The survey received 24 (14 in private sector) complete responses from 14 cities. Pediatric bronchoscopy was mainly done for diagnostic purposes. Conscious sedation was used by most (19, 79%). Midazolam plus fentanyl 9 (37.5%) was the preferred sedation regimen. Routine atropine was used by 4 (16%). For topical anaesthesia- nebulized only, both nebulized and spray as go, and spray as go lignocaine only was used by 1 (4.2%), 6 (25%), and 17 (71%) centres, respectively. The methods of providing oxygen during bronchoscopy were free flow (9,37.5%), nasal prongs (8,33.3%), mask (6,25%), and LMA (1,4.2%). Therapeutic procedures included removal of mucus plugs (17, 71%), bronchoscopic intubation (11, 45%) and foreign body removal (10, 41%). The suction for BAL included wall mounted suction in maximum (15, 62.5%). The number of aliquots for BAL varied from 2-6 and volume for each aliquot also varied (1-2 ml/kg or 5-10 ml). The complications rate of less than 5 % was reported by almost all. Conclusion: There is large variation in pediatric flexible bronchoscopy practices across the country highlighting the need to develop a uniform guideline.

Background: In this pilot study, we investigated whether induced sputum (IS) could serve as a viable alternative to bronchoalveolar lavage (BAL) and yield robust inflammatory biomarkers in toddlers with cystic fibrosis (CF) featuring minimal structural lung disease. Methods: We collected IS, BAL (right middle lobe and lingula) and blood, and performed chest computed tomography (CT) scans from 2-year-olds with CF (N=11), all within a single visit. Inflammatory biomarkers included 20 soluble immune mediators and neutrophil elastase (NE), as well as frequency and phenotype of T cells, monocytes / macrophages and neutrophils. Results: At the molecular level, nine mediators showed similar levels in IS and BAL (CXCL1, CXCL8, IL-1, IL-1RA, IL-6, CCL2, CXCL10, M-CSF, VEGF-A), four were higher in IS than in BAL (CXCL5, IL-1, CXCL11, TNFSF10) and two were present in IS but undetectable in BAL (IL-10, IFN-). Meanwhile, soluble NE had lower activity in IS than in BAL. At the cellular level, T-cell frequency was lower in IS than in BAL. Monocytes / macrophages were dominant in IS and BAL with similar frequencies but differing expression of CD16 (lower in IS), CD115 and surface-associated NE (higher in IS). Neutrophil frequency and phenotype did not differ between IS and BAL. Conclusions: IS collected from 2-year-olds with CF yields biomarkers of early airway inflammation with good agreement with BAL notably with regards to molecular and cellular outcomes related to neutrophils and monocytes/macrophages.

Successful Extubation in Preterm InfantsTo the Editor,I read with great interest the article by O’Connor et al1 describing factors that lower the likelihood of successful extubation by day 14 in mechanically ventilated neonates with or at risk of developing bronchopulmonary dysplasia (BPD), born at <30week gestational age (GA). These factors were younger GA at birth, and at the time of commencing steroids had higher MAPs and had higher oxygen requirements. They studied 287 neonates and noted that each additional week of GA at birth led to a 1.53 increase in the odds of successful extubation. Higher average fraction of inspired oxygen (FiO2) requirements in the preceding 24 h resulted in a 0.94 decrease in the odds of successful extubation and higher mean airway pressure (MAP) resulted in 0.76 decrease in odds of successful extubation.I have been using the probability of successful extubation calculator (http://extubation.net/), which incorporates the same factors as described by Connor et al 1. The calculator was described earlier by Gupta et al 2. They incorporated GA, MAP and FiO2 in the calculation, same as Connor et al 1. The only difference was the inclusion of the respiratory severity score (RSS), which is nothing but a product of MAP and FiO2 [(RSS= mean airway pressure (cm H2O) x FiO2 (0.21-1.00)].Although, we have a probability score model for successful extubation among preterm infants, as described by Gupta et al 2, I do agree with Connor et al 1 that we need to develop prognostic scoring model for intubated preterm infants.References:O’Connor K, Hurst C, Llewellyn S, Davies M. Factors associated with successful extubation following the first course of systemic dexamethasone in ventilator-dependent preterm infants with or at risk of developing bronchopulmonary dysplasia [published online ahead of print, 2022 Jan 7]. Pediatr Pulmonol . 2022;10.1002/ppul.25821. doi:10.1002/ppul.25821Gupta D, Greenberg RG, Sharma A, et al. A predictive model for extubation readiness in extremely preterm infants. J Perinatol . 2019;39(12):1663-1669. doi:10.1038/s41372-019-0475-xAuthor:Shabih Manzar, MDLouisiana State University Health Sciences CenterDepartment of Pediatrics1501 Kings HighwayShreveport, LA 71103Phone: 318-626-1623Fax: 318-675-6059Email: [email protected] contribution: Dr. Manzar wrote the draft.Funding and financial support: NoneConflict of interest: None

Introduction: A number of measures were began due to coronavirus 2019 disease (Covid-19) pandemic in many countries worldwide. A lockdown was applied for aged <18 years, education was continued online, and wearing a mask became mandatory in public places, which created an unprecedented period for children. Real-life data is limited showing how children with asthma are affected due to major changes. This study reveal how asthmatic children are affected by pandemic conditions based on real-life data. Methods: Patients with asthma aged 6–18 years who were followed up in March, April, and May 2019—before the Covid-19 pandemic—were included in the study. Data from March-April-May 2020 and 2019 were compared to reveal the effects of the pandemic-related lifestyle changes on symptoms, frequency of exacerbations, and drug use in asthmatic children. Results: A total of 86 children with asthma aged 6–18 years were included in this study. Time spent inside the home was significantly higher in 2020 than in 2019. Need for rescue medications and emergency department visits were significantly lower in 2020 compared to 2019 (p<0.001). The number of well controlled patients with asthma was higher in 2020 than in 2019 (p < 0.0001). Number of patients using prophylactic drugs within the last 3 months was lower in 2020 compared to 2019 (p = 0.007). Conclusion: The present study provides valuable insights into the condition of children over the age of 6 years during the Covid-19 pandemic based on real-life data. During the pandemic period, the number of asthmatic exacerbations, rescue drug use and asthma control were positively affected in school aged children with asthma.

Introduction: Point of care ultrasound (POCUS) is a useful tool to determine endotracheal tube placement; however, few studies have compared it with standard methods of confirmation. We evaluated the diagnostic accuracy of POCUS and time-to-interpretation for correct identification of tracheal versus esophageal intubations compared to a composite of standard-of-care methods in neonates. Methods: A cross-sectional study was conducted in the Neonatal Intensive Care Unit (NICU) at Aga Khan University Hospital Karachi Pakistan. All required intubations were performed as per NICU guidelines. The ETT placement was determined using standard-of-care methods (auscultation, colorimetric capnography, and chest X-ray) by a clinical team, and simultaneously by POCUS. Timings were recorded for each method by independent study staff. Results: A total of 348 neonates were enrolled in the study. More than half (58%) of intubations were in an emergency scenario. Using an expert as the reference standard, POCUS user interpretation showed 100% sensitivity and 94% specificity. We found a 99.4% agreement (Kappa: 0.96; p<0.001) between the POCUS user and expert. Diagnostic accuracy of POCUS compared with at least two standard-of-care methods demonstrated 99.7% sensitivity, 91% specificity, and 98.9% agreement (Kappa:0.93; p<0.001). The median time required for POCUS interpretation was 3.0 (IQR 3.0 -4.0) seconds for tracheal intubation. The time recorded for auscultation and capnography was 6.0 (IQR 5.0 -7.0) and 3.0 (IQR 3.0-4.0) respectively. Conclusion: POCUS is a rapid and reliable method of identifying ETT placement in neonates. Early and correct identification of airway management is critical to save lives and prevent mortality and morbidity.

Introduction: The reliability of breath sound analysis using an improved method in infants has been reported. Objective: Breath sounds of infants with respiratory syncytial virus (RSV)-induced acute bronchiolitis were analyzed to evaluate their specificity and examine their relationship with the severity. Subjects and methods: We evaluated the inspiratory and expiratory breath sound parameters of 33 infants (median age=2 months old) diagnosed with RSV-induced acute bronchiolitis. The sound powers of inspiration and expiration and the spectrum curve indices (ratio of the third and fourth area to the total area under the curve and ratio of the power and frequency at 50% and 75% of the highest frequency were evaluated at the acute phase and recovery phase. Furthermore, the relationship between the breath sound parameters and the clinical severity of acute bronchiolitis was examined. Results: Analyses of the breath sound spectrogram showed that the power of expiration at the acute phase was large, and was the expiration-to-inspiration sound power ratio in a mid-frequency range (E/I MF), with values decreased in the recovery phase. Data of the inspiratory sound spectrum curve showed the improvement of airway stenosis during the recovery period. Furthermore, there were significant relationships between the E/I MF and SpO2 and the severity score of acute bronchiolitis. Conclusion: In RSV-induced acute bronchiolitis, specificity of breath sounds was observed in the expiration sound and the reversible airway stenosis was evaluated. Breath sound analyses are expected to be useful for the diagnosis and clinical evaluation of the severity of acute bronchiolitis.

Nutritional support is essential in the critical care of the very preterm infant, however, study of the potential role of nutrition in the multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) is limited. Achievement of full enteral feeding faster has not been shown to be harmful and may be of benefit in extremely preterm infants. This commentary discusses the studied risk and potential benefits of more rapid enteral feeding advancement in extremely preterm infants.

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000–100,000 in Europe. As its onset usually occurs in adulthood, data from paediatric patients are limited. We present here a very rare practical EGPA clinical case involving a paediatric patient. Presently, data on mepolizumab usage in paediatric patients are limited, with only a few case reports published.

Background: Since the outbreak of the Coronavirus disease 2019 (COVID-19) pandemic, there has been a decline in pediatric emergency department visits. Our aim was to assess the pattern of pediatric foreign body aspiration (FBA) during the first year of the COVID-19, in comparison to the prior years. Methods: In this retrospective multicenter study, we compared the number of children that presented with FBA during the COVID-19 year (March 1st, 2020 to February 28, 2021), to the annual average of the years 2016-2019. We also compared the lockdown periods to the post-lockdown periods and the percentage of missed FBA, proven FBA, and flexible bronchoscopy as the removal procedure. Results: 345 children with FBA from six centers were included, 276 in the pre-COVID-19 years (average 69 per year) and 69 in the COVID-19 year. There was no difference in the prevalence of FBA between the COVID-19 year and any of the prior four years. Examining the lockdown effect, the monthly incidence of FBA dropped from a pre-COVID-19 average of 5.75 cases to 5.1 cases during lockdown periods and increased to 6.3 cases in post-lockdown periods. No difference in the percentage of missed FB or proven FB was observed. There was a significant rise in the usage of flexible bronchoscopy as the removal procedure (Average of 15.4% vs 30.4%, p=0.001) Conclusion: There was no difference in the prevalence of FBA during the COVID-19 year. However, there were fewer cases during lockdown periods, compared to post-lockdown periods, presumably related to better parental supervision.

Introduction Spirometry plays an important role in the assessment of possible respiratory failure in children with neuromuscular disorders (NMDs). However, obtaining reliable spirometry results is a major challenge. We studied the relation between Forced Oscillation Technique (FOT) and spirometry results. FOT is an easy, non-invasive method to measure respiratory mechanics, i.e. respiratory resistance R and respiratory reactance X. We hypothesized an increased resistance R and reduced reactance X in patients with more reduced lung function. Methods In this prospective single center study we included all children with NMDs able to perform spirometry. We consecutively measured respiratory resistance R and reactance X at 5, 11 and 19 Hz and (Forced) Vital Capacity, Peak Expiratory Flow. Spearman correlation coefficients were calculated and regression curves were estimated. Results We included 148 patients, with a median age of 13 years (IQR 8-16). All correlation coefficients were statistically significant with p = 0.000. A negative correlation was found between resistance R and spirometry outcomes (spearman correlation coefficient (ρ) between -0.5 and -0.6). A positive correlation was found between reactance X (i.e. less negative outcomes) and spirometry outcomes (ρ between 0.4 and 0.6). Highest correlation was found at lower frequencies. Regression analysis showed a non-linear relation between FOT and spirometry results. Conclusion We found a non-linear relation between FOT and spirometry results with increased resistance R and reduced reactance X in patients with more restrictive lung function decline. Given the difficulties with performing spirometry, FOT may be a promising surrogate measure of lung function.

Pilot Study of Nuclear Scintigraphy To Assess Cough Clearance in DMDTo the Editor:Respiratory muscle weakness as a consequence of neuromuscular disease results in ineffective cough, atelectasis, and pneumonia. Augmented airway clearance treatments such as mechanical in-exsufflation and high frequency chest compression have been shown to decrease morbidity and mortality in children with neuromuscular disease, although the evidence supporting these therapies in clearance of airway secretions is indirect.We sought to pilot the use of nuclear imaging of the clearance of pulmonary secretions before and after voluntary coughing and airway clearance treatment to explore the role of measures of pulmonary function to predict airway clearance. This technique has been used for some time in patients with cystic fibrosis but has not been applied to patients with neuromuscular disease or to assess the utility of airway clearance devices. To this end, we recruited 7 outpatient subjects (7.8-21 years of age) with Duchenne Muscular Dystrophy when clinically well and categorized as “Early Ambulatory” (requiring minimal assistive devices, n=4); “Early Non-ambulatory” (using wheelchair some of time, n=2); and “Late Non-Ambulatory” (always using wheelchair, n=1). This study was approved by local Institutional Review Board.Spirometry was performed according to ATS specifications and normalized using Global Lung Initiative equations. Peak cough flow was measured from total lung capacity (TLC) and data was normalized with previously published equations[1]. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured at the mouth using a hand-held pressure manometer and maximal pressure from FRC was also be measured at the nares (SNIP) during a sniff maneuver[2] using a small nasal occluder and handheld transducer Maximal static pressures and SNIP pressures were normalized using previously published data.For imaging of mucus clearance, 4 mCi of Technetium [Tc-99m] sulfur-colloid particles in 2 ml of normal saline were delivered by nebulizer using a defined breathing pattern for 2 minutes [3]. During continuous imaging, subjects were asked to voluntarily cough every 10 seconds for 1 minute using guidance from a metronome, and this sequence was repeated 3 times. The subject then received an airway clearance treatment for 30 minutes using a high frequency chest compression device with pressure adjusted between 80-100% of maximum, and compression frequencies cycled between 5Hz-15Hz. The device was paused every 10 minutes at which time the patient was asked to cough every 10 seconds over 1 minute.Image analysis was performed according to previously published methods. Measurements of radioactivity in the right lung were corrected for background and radioactive decay and normalized by starting radioactive counts. A single retention curve was generated from the initial cough clearance period and the period during which the high frequency chest compression device was operated. Cough clearance (CC) represents the percent of total deposited radioactivity cleared during the associated period. We designated the percentage cleared by 18 voluntary coughs over 3 minutes as CCvol, and the percentage cleared during three 10 min periods of HFCC and 18 voluntary coughs over 3 minutes as CCHFCC. CCvol and CCHFCCwere correlated with physiologic measures including peak cough flow (PCF), MIP/MEP, and SNIP using Spearman’s correlation.Pulmonary function was overall well preserved (FVC 92% ± 35%). Respiratory muscle strength (in cmH2O) decreased with disease severity (e.g. MIP EA 73.5 ± 26, ENA 62.5 ± 14.8, LNA 47). Peak cough flow (% predicted) decreased with severity (EA 94±11, ENA 79±9, LNA 46). Complete details are provided in the online supplement.Representative imaging of two subjects is shown (Figure 1). Significant intra-subject differences were seen in clearance with voluntary cough and with cough augmented with HFCC vest (Figure 2). Voluntary cough was responsible for 46-96% of the total clearance and HFCC-augmented clearance for 3-53% of total clearance. For most patients, the kinetics of clearance with HFCC-augmented cough did not appear very different than for voluntary cough.Statistical comparisons between disease stages were hampered by the small sample size in each group. Nonetheless, while there appeared to be a trend for decreasing CCvol with stage of disease (Figure 2), age, and PCF, we found no statistically significant correlations between voluntary cough clearance and measures of pulmonary function (FVC, r=0.39), respiratory muscle strength (PCF, r=-0.63; SNIP r=-0.12, MIP r=0.43, MEP r=0.29), age (r=-0.57), height (r=-0.49), weight (r=-0.37). Additionally, we did not find statistically significant correlations between augmented cough clearance and measures of pulmonary function (FVC, r=0.40), respiratory muscle strength (PCF, r=-0.08; SNIP r=-.02, MIP r=-0.07, MEP r=0.05), age (r=-0.39), height (r=-0.75), weight (r=-0.03).This study is the first we are aware of to directly examine cough clearance of secretions using nuclear scintigraphy in patients with DMD. Importantly, the measurements were well tolerated by subjects. We did not find a relationship between CPF, respiratory muscle strength, or spirometry and voluntary cough clearance. However, these results must be qualified based on the small number of enrolled subjects. We do note that many of the patients had good cough clearance. Additionally, HFCC did not consistently alter the rate of secretion clearance above noted with voluntary cough.While Bach et al[4] showed that PCF >160 L/min was a predictor of successful tracheal decannulation in adults with neuromuscular disease, Airen et al[5] found that the majority of healthy children <13 years old generated PCFs < 270 l/min despite having the ability to generate MEP > 60 cmH2O. This suggests that PCF may change with age and that an absolute threshold cannot be used across the age span. There are no studies specifically examining use of HFCC in patients with DMD. As patients with DMD are expected to have impairment in cough, mechanical in-exsufflation would be expected to assist with airway clearance by replacing the function of weak respiratory muscles in a way that HFCC does not. Lechtzin et al[6] showed that in adults with neuromuscular diseases, HFCC decreased inpatient costs and costs for treating pneumonia compared to the year prior to initiating HFCC. Measures of pulmonary function, including PCF, were not assessed. It would be of interest to examine secretion removal with in-exsufflation using this nuclear imaging method.While we were not able to demonstrate a relationship between cough clearance and measures of respiratory muscle strength, peak cough flow, or FVC, it is possible that this relationship exists and would be demonstrated in a larger population. However, the longstanding assumption that PCF is a reliable indicator of need for airway clearance, especially in children, is not supported by these data. The biggest limitation of our pilot study is the small sample size. We suspect enrollment was limited due to preference for interventional studies. Another limitation is that for our population, the impairment of respiratory muscle strength was mild for most subjects. Additional subjects with more advanced weakness may have helped clarify the relationship between respiratory muscle strength and airway clearance. Finally, there can be day-to-day variations of clearance.There are now a number of airway clearance technologies being proposed for patients with neuromuscular and airway diseases (e.g. cystic fibrosis, ciliary dyskinesia). These include high frequency chest compression vests, battery-powered vests, in-exsufflation devices (with or without oscillation), intrapulmonary percussive ventilation devices, and handheld oscillating positive expiratory pressure devices. We propose that the imaging methodology used in this study could be utilized to compare these different techniques, some of which are costly and with limited or no comparison data. In addition, there are patients that will be unable to cooperate with pulmonary function measurements and an imaging assessment of airway clearance may be useful to determine optimal strategies.In conclusion, we demonstrated that use of nuclear scintigraphy is a feasible technique to examine airway clearance for patients with respiratory muscle weakness, as it has been used for patients with cystic fibrosis. Additional studies will be needed to further examine the relationship between pulmonary function measures and secretion removal.Daniel J. Weiner MD1,Hoda Abdel Hamid MD2,Timothy E. Corcoran PhD3Divisions of Pediatric Pulmonology1 and Neurology2, Department of PediatricsUPMC Children’s Hospital of PittsburghDivision of Pulmonary, Allergy and Critical Care Medicine3, Department of MedicineUniversity of Pittsburgh School of Medicine