Introduction: Pediatric pulmonary embolism (PE) is rare but associated with adverse outcomes. We aimed to characterize PE cases admitted in a tertiary hospital and to evaluate sensitivity of PE diagnostic prediction tools. Methods: Retrospective, descriptive study of PE cases admitted from 2008 to 2020. Data was collected from hospital records. Patients were grouped according to PE severity and setting (outpatients, inpatients). Associations with demographic characteristics, risk factors, clinical presentation, management and outcomes were analyzed. PE diagnostic prediction tools were applied. Results: 29 PE episodes occurred in 27 patients, 62.9% female, mean age 14.1 years. Most PE were central and massive or submassive. One was diagnosed in autopsy. Outpatients (n=20), admitted for classic PE symptoms, were adolescents; in half the diagnosis had been missed previously. Risk factors included contraceptives (65%), thrombophilia (35%), obesity (20%) and auto-immunity (20%). Inpatients´ PE (n=8), diagnosed during cardiorespiratory deterioration (n=5) or through incidental radiological findings (n=3), were younger and had immobilization (87.5%), complex chronic diseases (75%), infections (75%) and central venous catheter (62.5%) as risk factors. Retrospectively, D-dimer testing and adults’ scores performed better than pediatrics’ scores (sensitivity 92.9-96% vs 85.7- 92.9%). Both pediatrics’ scores missed a case with a positive family history. Discussion: Pediatric PE diagnosis is often delayed or missed. To improve it, the development of pediatric prediction tools as from validated adult scores merits to be explored. We propose that clinical presentation and risk factors may be different in inpatients and outpatients. Family history should be included.

Background and objective: The number of children with complex physical and developmental pathologies, including chronic respiratory insufficiency, surviving and growing beyond early childhood continues to rise. No study has examined the clinical pathway of children on invasive LTMV in an Irish setting. Our data over a 10-year period was reviewed to see if our demographics and outcomes are in line with global trends. Methods: Children’s Health Ireland (CHI) at Crumlin, Dublin is Ireland’s largest tertiary paediatric hospital. A retrospective review analysed data from children in our centre commenced on LTMV via a tracheostomy over 10 years (2009 – 2018). This data was subdivided into two epochs for statistical analysis of longitudinal trends. Results: Forty-six children were commenced on LTMV from 2009 to 2018. Many had complex medical diagnoses with associated co-morbidities. Far less children, 30.4% (n=14) commenced on LTMV in the latter half of the 10-year period, they also fared better in all aspects of their treatment course. Focusing solely on children who have needed LTMV over this timeframe has enabled us to isolate trends specific to this cohort. Less patients commenced LTMV on a year on year basis, and for those that require tracheostomy and LTMV, their journey to decannulation tends to be shorter. Conclusion: Over the period reviewed, less patients over time necessitated long-term invasive therapy and those patients are being weaned and decannulated with ever more success. This has implications in terms of predicting numbers transitioning to adult services and allocation of hospital and community care resources.

Objective: To determine whether viral coinfection is a risk for severe lower respiratory tract infection (LRTI). Working Hypothesis: Children with viral coinfection had a higher risk for admission to the intensive care unit (ICU) than those with a single virus infection. Study Design: Retrospective, observational study for ten years. Patient-Subject Selection: Children between 1-60 months of age hospitalized with LRTI. Methodology: We defined severe LRTI as admission to the ICU for high-flow nasal cannula oxygen/bilevel positive airway pressure/invasive ventilation and assessed demographic and laboratory data with potential risk factors from the patients’ medical records. Results: Of 2115 children hospitalized with LRTI, 562 had severe, and 1553 had mild disease. Viral coinfection was present in 28.3% of all patients, and those with viral coinfection were at a higher risk of severe LRTI than those with a single virus infection (43.8% vs. 22.7%; aOR, 3.44; 95% CI, 2.74-4.53). Respiratory syncytial virus (RSV) and rhinovirus (except for between 25-60 months) coinfections were associated with severe LRTI in all ages, whereas parainfluenza virus-3 (PIV3; 7-24 months) and bocavirus (7-12 months) coinfections led to severe LRTI in early childhood. Moreover, influenza-A coinfection caused severe LRTI in children between 7-12 and 25-60 months. Other risk factors included young age, prematurity, history of atopy, exposure to tobacco smoke, underlying condition, neutrophilia, lymphopenia, and high CRP value. Conclusion: Children with viral coinfection, particularly with rhinovirus, RSV, influenza-A, PIV3, and bocavirus, may be followed closely regarding the clinical changes.

Introduction: COVID-19 emerged in China leading to worldwide morbidity and mortality, including depression and anxiety. As the pandemic spread throughout Italy and Europe, mental health concerns emerged for people with cystic fibrosis (pwCF), who are at increased risk. This led to development of a Telehealth Psychological Support Intervention to help adolescents/young adults with CF and caregivers cope with the stress and emotional challenges of the lockdown which began in Italy in March 2020. Methods: This intervention utilized cognitive behavioral skills (e.g., relaxation training, cognitive reframing). Participants included 16 adolescents/adults and 14 parents, who completed 4 individual video sessions with a psychologist. Stress ratings, PHQ-8 and GAD-7 were completed electronically. Feasibility and Satisfaction were rated. Results: Ratings of stress significantly decreased from pre to post-testing for both pwCF (paired t=-4.06 (14), p<.01) and parents (paired t=-5.2, p< 001). Most participants reported clinically elevated depression and anxiety at the pre-test, with statistically significant reductions in depression for pwCF (pre: M=8.0 to post M=4.7; paired t (14)=2.8, p <.05) but not anxiety (pre: M=6.9 to post: M=5.6, t (14)=1.2, p=NS). Reductions in depression were found for parents (pre: M=6.4 to post: M 5.1, (14) t=-2.5, p<.05) but not anxiety (pre: M=8.1 to post: M=7.9, t (14)=-0.2, p=ns). Positive ratings of Feasibility and Satisfaction were documented. Conclusion: This brief telehealth intervention yielded significant reductions in stress and depression for participants. Anxiety was not reduced, possibly because COVID was ongoing. This intervention was effective for improving mental health and was highly feasible and satisfactory.

Abstract Continuous intravenous (IV) sildenafil may avoid the acute systemic vasodilatory effects of bolus dosing in infants with pulmonary hypertension (PH). We aimed to examine the tolerability of different methods of IV sildenafil administration. Methods: We retrospectively evaluated subjects less than 12 months old with PH, who had been started on IV sildenafil. Vital signs, oxygen requirement, and vasoactive-inotropic score (VIS) before and after sildenafil initiation were noted, as was the need for discontinuation due to side effects. Results: Forty-three subjects were identified (23 continuous, 20 intermittent dosing). There were no statistically significant differences between groups in gender or gestational age, but higher baseline inspired oxygen (FiO2) and VIS in the continuous group suggested a higher baseline severity of illness (p=0.012). After sildenafil initiation, there were no significant differences in the change in blood pressure, oxygen saturation, FiO2, or VIS between groups, and no difference in the number of subjects requiring discontinuation due to side effects (4 in the continuous group, 1 intermittent, p=0.35). Eight subjects (34.8%) in the continuous group and 3 (15%) in the intermittent group died (p=0.024). Conclusions: In this small cohort of infants with PH treated with continuous or intermittent IV sildenafil, there were no statistically significant differences between groups in the change in vital signs, VIS, and oxygen requirement, or the need for discontinuation of therapy due to side effects. A higher mortality rate in the continuous infusion group may be explained by higher baseline illness severity.

Background: Cystic fibrosis (CF) pulmonary exacerbations (PEx) are associated with significant drop in pulmonary function. The clinical value of measuring bronchodilator (BD) responsiveness during treatment for PEx to monitor or predict recovery of lung function is unclear. Methods: A retrospective analysis of spirometry with BD response testing obtained during hospital admissions for PEx in pediatric CF patients. Repeated events were included for patients with BD testing during multiple admissions. Results: 249 spirometries with BD testing in 102 patients were completed around day 7 (day 4-10) of hospital admission for treatment of CF PEx. Median (IQR) forced expiratory volume in one second (FEV1) was 70.6% predicted (58.1, 84.6) prior to the PEx event (best FEV1 in 6 months prior to admission), 54.4% (41.5, 66.9) at admission, 62.3% (48.4, 74.7) around day 7 of admission and 67.1% predicted (53.8, 78.2) at end of treatment. BD response around day 7 correlated poorly with FEV1 prior to PEx (r=-0.16, p=0.02), and did not correlate with recovery to baseline FEV1 at end of treatment (r=0.08, p=0.22). Only 23/249 (9%) patients had a BD response of ≥12 % and 200 ml. BD response was not related to age or severity of lung disease and led to an immediate change in clinical management in only 4 cases. CONCLUSIONS: BD response in CF patients treated for PEx is poorly correlated with baseline pulmonary function and does not correlate with recovery of FEV1 with treatment. These data suggest that routine testing for BD response is not indicated during PEx.

An Association of the Arginase 1 Gene with Preschool Wheezing PhenotypesHartmut Grasemann and Fernando HolguinArginases are enzymes that metabolize L-arginine to form urea and L-ornithine. The two arginase isoforms, arginase I and arginase II, which are encoded by two different genes (ARG1 and ARG 2), are expressed in various cell types throughout the human body, including the lungs and airways. Arginase competes with nitric oxide synthase (NOS) for L-arginine as substrate, and increased arginase expression and activity in asthma reduces nitric oxide (NO) bioavailability, causing airways obstruction and contributing to reactive oxygen species production (1). Arginase also plays a role in allergen-induced airway remodeling in chronic asthma, presumably due to increased formation of L-ornithine, the precursor of L-proline and the polyamines (2). Proline is further metabolized to collagen and the polyamines putrescine, spermidine and spermine, which among other functions, also inhibit NOS. Increased production of endogenous NOS inhibitors including the polyamines as well as asymmetric dimethylarginine (ADMA), further contribute to the imbalance of NOS and arginases in asthma (figure 1).Previous studies of genetic variations or single nucleotide polymorphisms (SNPs) in arginase genes had shown associations with atopy and asthma. For example, SNPs in both arginase genes were associated with atopy and asthma in children and with risk for asthma in adults (3,4,5). Interestingly, ARG1 and ARG2 were also found to be associated with bronchodilator response in children and adults with asthma, and ARG1 with long term outcome on inhaled corticosteroid (ICS) therapy in adult asthma (5,6,7,8,9).Preschool wheeze is a common phenomenon, usually benign and mostly self-limited (10,11). Different phenotypes of preschool wheeze have been described, including early transient wheeze, late onset wheeze and persistent wheeze (12). A more recent classifications distinguishes multiple trigger wheeze (MTW) from episodic wheeze (EW), which is mainly caused by viral respiratory tract infections. The clinical usefulness of phenotype driven classifications has been questioned for a number of reasons including the longitudinal instability of phenotypes. However, some evidence suggests that MTW may be linked to later onset allergic asthma and MTW may therefore be more likely to respond to asthma treatment as compared to EW (13,14,15,16,17,18). Interestingly, a more recent analysis of the natural history of MTW and EW in two large independent birth cohorts demonstrated that phenotypes may track over time (19), suggesting that the two indeed represent different disease entities and not just differences in severity of the same disease.In a study by Gokmirza Ozdemir et al., published in this issue of theJournal , the authors report an association between arginase 1 gene polymorphisms and preschool wheezing phenotypes (20). In a cohort of 83 well characterized preschool wheezers with either multi trigger wheeze (MTW) or episodic wheeze (EW) phenotype of Turkish origin and matched controls, there was a difference in homozygous frequency of the ARG1 rs2781667T>C SNP between wheezing phenotypes and between patients with vs without allergic rhinitis. The homozygous frequency of this SNP in ARG1 was significantly higher in MTW vs EW, and in allergic rhinitis vs no allergic rhinitis. There were no associations of other tested SNPs in either ARG1 or ARG2 with preschool wheezing, allergic rhinitis, presence of aeroallergen sensitivity or tobacco exposure. Further analyses also showed significant differences in a number of haplotype frequencies in ARG1 between all wheezers and controls, and also between wheezing phenotypes. No associations were found with ARG2 in this study (20). Thus, these results show that in the population studied, variants in ARG1 but not ARG2 were associated with wheezing phenotypes in pre-school age.This observation is exiting as the genotype-phenotype association implies that arginase I could be involved in the development of preschool wheeze and wheezing phenotypes, possibly through an effect on L-arginine availability for nitric oxide synthase (NOS) or by affecting airway remodelling. However, the population studied here was relatively small and the findings have not yet been confirmed by others. Therefore, the results need to be interpreted with caution and additional studies are needed for confirmation. Similarly, it is unclear at this point, whether the SNPs and haplotypes found to be different in frequency between groups, alter arginase expression or activity, and what the biological or molecular explanation could be for the observed associations. Nevertheless, these observations by Gokmirza Ozdemir et al. are promising, and once confirmed in larger and independent cohorts, also have the potential to help develop a genetic test for wheezing pre-schoolers that may predict future asthma risk and response to asthma therapies.References1) North ML, Grasemann H, Khanna N, Inman MD, Gauvreau GM, Scott JA. Increased ornithine-derived polyamines cause airway hyperresponsiveness in a mouse model of asthma. Am J Respir Cell Mol Biol. 2013 Jun;48(6):694-702.2) Maarsingh H, Dekkers BG, Zuidhof AB, Bos IS, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H. Increased arginase activity contributes to airway remodelling in chronic allergic asthma. Eur Respir J. 2011 Aug;38(2):318-28.3) Donthi S, Neela VSK, Gaddam S, Mohammed HH, Ansari SS, Valluri VL, Sivasai KSR. Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I. Indian J Med Res. 2018 Aug;148(2):159-168.4) Li H, Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Estela Del Rio-Navarro B, Kistner EO, Gjessing HK, Lara-Sanchez Idel C, Chiu GY, London SJ. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. J Allergy Clin Immunol. 2006 Jan;117(1):119-26.5) Vonk JM, Postma DS, Maarsingh H, Bruinenberg M, Koppelman GH, Meurs H. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta2 agonist and steroid response. Pharmacogenet Genomics. 2010 Mar;20(3):179-86.6) Duan QL, Gaume BR, Hawkins GA, Himes BE, Bleecker ER, Klanderman B, Irvin CG, Peters SP, Meyers DA, Hanrahan JP, Lima JJ, Litonjua AA, Tantisira KG, Liggett SB. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011 Feb 15;183(4):449-54.7) Litonjua AA, Lasky-Su J, Schneiter K, Tantisira KG, Lazarus R, Klanderman B, Lima JJ, Irvin CG, Peters SP, Hanrahan JP, Liggett SB, Hawkins GA, Meyers DA, Bleecker ER, Lange C, Weiss ST. ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts. Am J Respir Crit Care Med. 2008 Oct 1;178(7):688-94.8) Sy HY, Ko FW, Chu HY, Chan IH, Wong GW, Hui DS, Leung TF. Asthma and bronchodilator responsiveness are associated with polymorphic markers of ARG1, CRHR2 and chromosome 17q21. Pharmacogenet Genomics. 2012 Jul;22(7):517-24.9) Scaparrotta A, Franzago M, Marcovecchio ML, Di Pillo S, Chiarelli F, Mohn A, Stuppia L. Role of THRB, ARG1, and ADRB2 genetic variants on bronchodilators response in asthmatic children. J Aerosol Med Pulm Drug Deliv. 2019 Jun;32(3):164-173.10) Kurukulaaratchy RJ, Matthews S, Holgate ST, Arshad SH. Predicting persistent disease among children who wheeze during early life. Eur Respir J. 2003 Nov;22(5):767-71.11) Caudri D, Wijga A, A Schipper CM, Hoekstra M, Postma DS, Koppelman GH, Brunekreef B, Smit HA, de Jongste JC. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age. J Allergy Clin Immunol. 2009 Nov;124(5):903-10.e1-7.12) Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8.13) Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souëf PN, Brand PL. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr. 2010 Jan;99(1):56-60.14) Sonnappa S, Bastardo CM, Wade A, Saglani S, McKenzie SA, Bush A, Aurora P. Symptom-pattern phenotype and pulmonary function in preschool wheezers. J Allergy Clin Immunol. 2010 Sep;126(3):519-26.e1-7.15) Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, de Blic J, de Jongste JC, Eber E, Everard ML, Frey U, Gappa M, Garcia-Marcos L, Grigg J, Lenney W, Le Souëf P, McKenzie S, Merkus PJ, Midulla F, Paton JY, Piacentini G, Pohunek P, Rossi GA, Seddon P, Silverman M, Sly PD, Stick S, Valiulis A, van Aalderen WM, Wildhaber JH, Wennergren G, Wilson N, Zivkovic Z, Bush A. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008 Oct;32(4):1096-110.16) Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J, Kuehni CE, Merkus PJ, Pedersen S, Valiulis A, Wennergren G, Bush A. Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J. 2014 Apr;43(4):1172-7.17) Garcia-Marcos L, Martinez FD. Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity markers? J Allergy Clin Immunol. 2010 Sep;126(3):489-90.18) van Wonderen KE, Geskus RB, van Aalderen WM, Mohrs J, Bindels PJ, van der Mark LB, Ter Riet G.Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers. Clin Exp Allergy. 2016 Jun;46(6):837-47.19) Spycher BD, Cochrane C, Granell R, Sterne JAC, Silverman M, Pedersen E, Gaillard EA, Henderson J, Kuehni CE. Temporal stability of multitrigger and episodic viral wheeze in early childhood. Eur Respir J. 2017 Nov 2;50(5):1700014.20) Gokmirza Ozdemir, P, Eker D, Celik V, Beken B, Gurkan H, Yazicioglu M, Sut N. The relationship between arginase genes polymorphisms and preschool wheezing phenotypes. Pediatr Pulmonol. 2020 ….

We aimed to test the hypothesis that a lung ultrasound severity score (LUS) and assessment of left ventricular eccentricity index of the interventricular septum (LVEI) by focused heart ultrasound can predict extubation success in mechanically ventilated infants. We conducted a prospective study on premature infants <34 weeks’ of gestation. LUS was performed on postnatal days 3 and 7 by an investigator who was masked to infants’ ventilator parameters. LVEI and pulmonary artery pressure (PAP) were measured at postnatal day 3. A receiver operator curve was constructed to assess the ability to predict extubation success. Spearman correlation was performed between LVEI and PAP. A total of 104 studies were performed to 66 infants; of them 39 had mild and 65 had moderate-severe lung disease. LUS predicted extubation success with a sensitivity and a specificity of 91% and 69%, respectively. Area under the curve was 0.83 (CI: 0.75-0.91). LVEI did not differ between infants that succeeded and failed extubation. It correlated with PAP during systole (r=0.66). We conclude that LUS predicts extubation success in mechanically ventilated preterm infants whereas LVEI correlates with high PAP.

OBJECTIVES: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24) versus maximum concentration (Cmax) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. METHODS: A retrospective review was conducted in patients aged at least one month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019 . Patients were excluded if they had no growth of PsA on sputum culture or if two post-dose tobramycin levels were not obtained following a dose adjustment of ≥20%. RESULTS: A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n=91), 75.8% had an AUC24 ≥80 and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration (MIC). There was a significant correlation between AUC24 and Cmax (r2 = 0.727; p<0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 hours (50% versus 28.7%; p=0.047). CONCLUSIONS: The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multi-daily dosing of IV tobramycin should be used only in select pediatric and adult patients with CF.

The pandemic has had a dramatic and negative impact on opportunities for training in pediatric airway endoscopy. This commentary discusses ways in which training programs can address this issue.

Abstract Background Lung ultrasound (LUS) has been used to diagnose neonatal respiratory diseases. However, few simple method has been reported to predict respiratory support needs(RSN). Our aim was to determine the diagnostic accuracy of a semiquantitative LUS assessment method predicting respiratory support need. Methods We conducted a prospective diagnostic accuracy study following the STARD (Standards for the Reporting of Diagnostic Accuracy Studies) guidelines at a tertiary level academic hospital between 2019 and 2020. After birth, infants were transferred to a monitoring room to determine NICU treatment need. 310 late preterm and term infants with respiratory symptoms enrolled. The LUS assessment was performed for each participant at one of the following times: 0.5 h, 1 h, 2 h, 4 h, and 6 h after birth. Reliability was tested by ROC analysis. Surfactant administration and other RSNs were based on the 2019 European guidelines as well as the infant’s clinical condition. Results 74 have RSN, and 236 were healthy according to a 3-day follow-up confirmation. Six LUS imaging patterns were found. Two “high-risk” patterns were highly correlated with RSN(area under the curve (AUC) = 0.95; 95% CI, 0.92-0.98, p<0.001). This accuracy is supported by the AUC of “low-risk” patterns (0.89, 95% CI, 0.85-0.93, p<0.001). The predictive value of LUS is greater than that of only using respiratory symptoms (e.g., respiratory rate) (AUC of LUS vs AUC of respiratory rate, p<0.01). Conclusions LUS is a useful tool to predict RSN and is more reliable than assessments based on respiratory symptoms alone.

Fetal lung fluid: Not the same as amniotic fluidAuthor: Hemananda Muniraman MBBS, FAAP, FRCPCHAffiliations:Creighton University School of Medicine, Phoenix Campus, Arizona, USCorresponding Author: Hemananda Muniraman, MBBS, FAAP, FRCPCHAssistant Professor of Pediatrics Affiliate, Creighton University School of MedicinePhoenix Campus, 350 W Thomas Rd, Phoenix, AZ, US 85013Email; [email protected], Phone: +16022564628 Fax: +16026276325Conflict of Interest Disclosure: I have no conflicts of interest relevant to this article to disclose. Funding/Support.No funding to be reportedKey words: Extreme preterm, neonates, pneumatocele, fetal lung fluidDear Dr MurphyEditor in chief, Pediatric PulmonologyI read with interest the recently published article “Pulmonary pneumatoceles in neonates” by Dr Rocha. [1] It is a well written comprehensive review of pulmonary pneumatoceles in neonates and an important resource for the clinicians in decision making, that I found to be very insightful whilst recently managing an extreme preterm with a large pneumatocele.However, I wanted to bring attention to a statement in the introduction where the author states that the “preterm infants’ lungs are filled with amniotic fluid”. This is not accurate and appears to be a common misconception, particularly among medical students and junior residents despite recognition of fetal lung fluid as being a separate entity from the amniotic fluid as originally described in 1948 by Jost and Policard. [2] I believe this is an important knowledge gap that needs to be addressed. Understanding of metabolism and role of fetal lung fluid in lung development and postnatal transition is essential to clinicians involved in the care of newborns and infants.Though a comprehensive review of fetal lung fluid is beyond the scope of this letter, I provide a brief basic overview of fetal lung fluid with references for more comprehensive reading.Fetal lung fluid is a chloride rich acidic fluid produced with in the fetal lungs by secretion of chloride across the distal lung epithelial cells and is a major determinant for fetal lung growth and development. The fluid lung volume is maintained by transglottic pressure gradient with periodic egress of excess fluid during fetal breathing. Decreased lung fluid volume is associated with pulmonary hypoplasia and conversely, upper airway lesions obstructing the egress of lung fluid leads to increase in fetal lung fluid and volume, a principle used in fetal interventions such as endoluminal tracheal occlusion to enhance pulmonary growth in conditions namely congenital diaphragmatic hernia. [2,3,4]As important the fetal lung fluid is for lung development, clearance of lung fluid is crucial for normal postnatal transition and establishment of air filled lungs for effective gas exchange. Clearance of lung fluid is a complex and coordinated process that starts before the process of birth itself. The rate of lung fluid secretion diminishes before labor at term gestation. Catecholamines namely epinephrine released during labor upregulates the epithelial sodium channels (ENaC) promoting influx of sodium and fluid from lumen into pulmonary interstitial space thereby reversing the direction of fluid movement in the perinatal period. Lung fluid is decreased to about 35% following active labor and birth which are further cleared with neonatal cry and breathing and inflow of air after birth. The fluid from the interstitial space is cleared over the next few hours via pulmonary circulation and lymphatic drainage. However this process is impaired in infants delivered by elective cesarean sections leading to increased retained lung fluid after birth and resulting in transient respiratory distress and tachypnea of newborn (TTN). In preterm infants, catecholamine induced fluid reabsorption via ENaC is limited and may contribute to respiratory distress after birth. Prenatal maternal steroids and triiodothyronine administration is known to induce expression of messenger RNA for ENaC subunits in the fetal lungs and may facilitate lung fluid clearance. [2,4]Lastly, amniotic fluid aspiration into fetal lungs, with and without meconium contamination, has been reported to be the cause of respiratory distress with case reports of massive amniotic fluid aspiration noted on postmortem histological examination of newborn lungs. [5]References:Rocha G. Pulmonary pneumatoceles in neonates. Pediatr Pulmonol. 2020 Jul 21. doi: 10.1002/ppul.24969. Epub ahead of print. PMID: 32691976.Katz C, Bentur L, Elias N. Clinical implication of lung fluid balance in the perinatal period. J Perinatol. 2011 Apr;31(4):230-5. doi: 10.1038/jp.2010.134. PMID: 21448181.Hooper SB, Harding R. Fetal lung liquid: a major determinant of the growth and functional development of the fetal lung. Clin Exp Pharmacol Physiol. 1995 Apr;22(4):235-47. doi: 10.1111/j.1440-1681.1995.tb01988.x. PMID: 7671435Kallapur S, Jobe A; Fetal Lung fluid. Richard J. Martin, Avroy A. Fanaroff, Michele C. Walsh. Fanaroff And Martin’s Neonatal-Perinatal Medicine : Diseases of the Fetus and Infant, 10th edition. Philadelphia, PA :Elsevier/Saunders, 2015Lavezzi AM, Poloniato A, Rovelli R, Lorioli L, Iasi GA, Pusiol T et al. Massive Amniotic Fluid Aspiration in a Case of Sudden Neonatal Death With Severe Hypoplasia of the Retrotrapezoid/Parafacial Respiratory Group. Front Pediatr. 2019 Apr 4;7:116. doi: 10.3389/fped.2019.00116. PMID: 31019904

Pulmonary hypertension represents an increasingly important group of pediatric patients which commonly come to the attention, if not the primary care of pediatric pulmonologists around the world. There have been major advances in diagnosis and therapy over the past 25 years. To address potential gaps in knowledge, the authors were invited by the Editor of Pediatric Pulmonology to organize a series of manuscripts in a special supplement of the journal. Our authors include pulmonologists, pharmacists, intensivists, mid-level practitioners, neonatologists and cardiologists. We believe that this issue will be of great interest to most of the readership community that the Journal addresses.

Infants born before 32 weeks post-menstrual age (PMA) and receiving respiratory support at 36 weeks PMA are diagnosed with bronchopulmonary dysplasia. This label suggests that their need for supplemental oxygen is primarily due to acquired dysplasia of airways and airspaces, and that the supplemental oxygen (O2) is treating residual parenchymal lung disease. However, current approaches to ventilatory support in the first days of life, including artificial surfactant use and lower ventilating pressures have changed the pathology of chronic lung disease, and emerging evidence suggests that immature ventilatory control may also contribute to the need for supplemental oxygen at 36 weeks PMA. In all newborns, maturation of ventilatory control continues ex utero and is a plastic process. Supplemental O2 mitigates the hypoxemic effects of delayed maturation of ventilatory control, as well as reduces the duration and frequency of periodic breathing events. Prematurity is associated with altered and occasionally aberrant maturation of ventilatory control. Infants born prematurely, with or without a diagnosis of BPD, are more prone to long-lasting effects of dysfunctional ventilatory control. Awareness of the interaction between parenchymal lung disease and delayed maturation of ventilatory control is essential to understanding why a given premature infant requires and is benefitting from supplemental O2 at 36 weeks PMA.

Necrotising pneumonia complicated by mycotic pseudoaneurysm has been reported very rarely in infancy. Here we present a five month old girl who had an acute life-threatening presentation of cavitatory pneumonia.

We describe the demographic, clinical, and laboratory characteristics of children with COVID 19 in comparison with those of not-laboratory-confirmed cases. We conducted a cross-sectional study on the epidemiological, clinical, radiological, and laboratory characteristics, and outcome of 422 children (aged 0–18 years) with suspected and confirmed COVID 19 admitted to the pediatric emergency department from March 23rd to July 23rd, 2020. Of the 422 children with suspected COVID-19 included in this study, COVID-19 was PCR-confirmed in 78 (18.4%). Fever (51.2%) and cough (43.5%) were the most prominent symptoms in children with confirmed cases. The clinical status of the patients with confirmed COVID-19 was significantly milder than that of those with suspected COVID-19. The proportion of COVID-19 pneumonia cases was 44.4%, 5.5%, 18.7%, and 8.5% for the age groups of ≤ 1, 2–6, 7–12, and ≥ 12 years, respectively. Of the 422 children, 128 (30.3%) underwent nasopharyngeal PCR testing for other respiratory viral pathogens; 21 (16.4%) were infected with viral pathogens other than severe acute respiratory syndrome-related coronavirus-2. Only one patient (4.7%) with confirmed COVID-19 had coinfection with respiratory syncytial virus and rhinovirus. The areas under the receiver-operating characteristics curves were 0.812 for WBCs, 0.752 for neutrophils, 0.717 for lactate dehydrogenase, and 0.708 for lymphocyte for predicting COVID-19 (p ≤ 0.001). Fever and cough or other clinical symptoms or signs should not be considered hallmarks of COVID 19. In this study, the WBC, neutrophil, and lymphocyte counts were predictive of COVID-19 positivity.

Background and objectives: Shared decision making (SDM) prior to non-urgent tracheostomy in a child with chronic respiratory failure (CRF) is recognized as the standard of care, but has proven challenging to implement in practice. We hypothesize that utilization of the microsystem model for analysis of the complex ecosystem in which SDM occurs will yield insights that enable formation of a reproducible, measurable SDM process. Methods: Retrospective chart review of a case series of children with CRF in whom a SDM process was pursued. The process included a palliative care consult, a validated decision aid and 12 key questions designed to elucidate information integral to an informed decision. Investigators reviewed a single hospital admission for each child, focusing on the 3 core elements of a medical microsystem- the patient, the providers, and information. Results: 29 patients who met inclusion criteria ranged in age from 0 to 19 years (median 1.7) and remained in the hospital from 10 to 316 days (median 38). Patients were medically complex with multiple and varied respiratory diagnoses, multiple and varied comorbidities, and varying psychosocial environments. 14/29 children received tracheostomies. Each child encountered a mean of 6.2 medical specialties, 1.9 surgical specialties and 8.5 non-physician led services. Answers to 12 key questions were not documented systematically and often not found. Conclusion: A unique SDM microsystem is formed around each child but not optimally utilized. Explicit recognition of these microsystems would enable team formation and an SDM process comprised of measurable steps and communication patterns.

Objective: Τo investigate the association of serum vitamin D and nasal secretion antimicrobial peptides (AMPs) levels with the severity of acute bronchiolitis. Study design: We conducted a prospective single pediatric tertiary care center cohort study of inpatients aged 0-18 months with a first episode of acute bronchiolitis from November 1st 2014 to April 30th 2017. Disease severity was determined by the length of hospitalization and supplemental hospital data. Qualitative measurements included serum 25(OH)D and nasal secretion LL-37 and β-defensin-2 levels. Correlations were examined with the Mann-Whitney and Kruskal-Wallis criteria for qualitative and the correlation coefficient Spearman’s rho for quantitative factors. Multiple linear and logarithmic regression were performed in order to adjust for confounding factors. Results: The study population consisted of 153 infants and toddlers with mean age 3.6 months (SD: +2.8). The median level of serum 25(OH)D was 51.4 nmol/L (IQR: 29.7-72.2). No association was found between serum 25(OH)D and AMPs nasal secretions levels. Serum 25(OH)D and nasal secretion β-defensin-2 levels were not associated with the severity of bronchiolitis. In contrast, LL-37 levels were inversely associated with the length of hospitalization (rho = -0.340, p = 0.001) and the need for medication use (p = 0.001) and this association remained significant after adjustment for potential confounders. Conclusion: A significant association between LL-37 nasal secretions levels with the severity of acute bronchiolitis was found in hospitalized infants and toddlers. The role of LL-37 in the pathogenesis of bronchiolitis merits further investigation.