Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.

To the editor, Chronic eosinophilic pneumonia (CEP) is an idiopathic disease rarely reported in children1,2. It typically occurs in non-smoking, middle age females and the diagnosis requires exclusion of systemic or primary eosinophilic lung diseases1,2. The triad of pulmonary symptoms (usually for >2 weeks), abnormal chest radiographic findings and eosinophilia in the blood and/or pulmonary tissue in the absence of an alternative etiology is highly suggestive of CEP. Patients may present with cough (90-93%) dyspnea (50-90%), fever (77-87%), night sweats (23%), weight loss (57-75%), rhinitis or sinusitis (6-24%), chest pain (8-16%), hemoptysis (8-10%), and weakness/fatigue1,2. An asthma phenotype is present in roughly a third to 3/4 of patients. Bilateral peripheral consolidative infiltrates are seen on chest radiograph (CXR) with computed tomography (CT) showing peripheral airspace disease and reactive hilar adenopathy1,2. Peripheral eosinophilia is almost universal with cell counts routinely higher than 1000/mm3 and more than half of patients also have an elevated IgE2. Eosinophilia on the bronchoalveolar lavage (BAL) ranges from 12 to 95% with a mean of 58%2. The triad of pulmonary symptoms, radiographic findings and eosinophilia in CEP typically respond to prednisone within a few days2. Initial doses range from 0.5 to 1mg/kg/day and may be tapered after clinical/radiographic improvement. Duration of therapy depends on the response and is highly variable, with a mean of 19 months but a range of 0.5 to 96 months1. Relapse is common, occurring in up 50% of patients2. While the pathogenesis of CEP is not fully understood, the underlying mechanism undoubtedly involves eosinophils and likely shares inflammatory pathways with asthma, which is why it may be amenable to treatment with novel biologic therapies approved for asthma. Although there are case reports of patients with CEP who were treated with either omalizumab or mepolizumab, there are no reports of treatment with dupilumab3.  However, there is a report of a patient possibly experiencing CEP as a consequence of dupilumab4.             We present the case of an 11-year-old, previously healthy, African American female who presented with fever, cough, dyspnea, chest pain and decreased appetite of 3 months duration. Her past medical history was significant for pneumonia three months prior that failed to resolve with antibiotics.  She was subsequently prescribed albuterol and treated as an outpatient with a working diagnosis of asthma. Her symptoms persisted and she was ultimately hospitalized with chronic pneumonia of unclear etiology.  Her family and social histories were unremarkable.  She strongly denied vaping or inhalant abuse. Her physical exam was remarkable for bilateral coarse crackles, signs of respiratory distress and reproducible chest pain. Her CXR showed bilateral consolidative opacities and her CT demonstrated bilateral lymphadenopathy and multilobar consolidation (see Figures 1 &2). Her initial lab work was remarkable for a white blood cell count of 10,000/µL (3.84-9.84/µL) with 10% (0-4%) peripheral eosinophilia, erythrocyte sedimentation rate of 103 mm/hr (0-15mm/hr), and C reactive protein of 7mg/dL (0.00-0.50mg/dL). She was treated with 14 days of antibiotics without clinical improvement. During the course of follow up her FEV1 declined > 35% and she developed a severe persistent asthma phenotype.  She was evaluated for tuberculosis, allergic bronchopulmonary aspergillosis, helminth infection, eosinophilic granulomatosis with polyangitis, sarcoidosis, and immunodeficiency however her work up was negative. She underwent bronchoscopy, which demonstrated significant bilateral lower airway casts that were 93% eosinophilic. She was treated with high dose prednisone for 4 weeks and improved for a few months, however her symptoms returned. She continued oral prednisone intermittently for approximately 22 months without improvement and was deemed refractory to therapy.  Repeat imaging during that time demonstrated persistent opacities and she developed bronchiectasis.  Repeat bronchoscopies revealed return of mucoid impactions. Throughout her course, she continued to have eosinophilia in the blood (ranging from 0.4 to 13%) and on BAL (ranging from 9-93%).  She was then treated with pulse methylprednisolone and daily cyclosporine in an attempt to gain clinical remission which resulted in modest improvement of symptoms. She continued daily cyclosporine with the addition of dupilumab every 2 weeks for 6 months. Following the addition of dupilumab significant clinical and radiographic improvement were noted within 2 weeks.   Her cyclosporine was subsequently weaned without recurrence of symptoms and she remains symptom free with marked improvement in her Chest X-ray findings for over 12 months on subcutaneous dupilumab injections q 2 weeks. Dupilumab is an injectable humanized IgG4 monoclonal antibody, approved for home use in patients with eosinophilic or steroid dependent asthma, which targets IL-4α receptors and inhibits IL-4 and IL-13 binding. It has been shown to reduce the frequency of asthma exacerbations, improve FEV1 and reduce oral steroid use in patients with severe asthma5.  This is the first report of dupilumab as a therapy to treat CEP and the first report of monoclonal antibody therapy to treat CEP in a pediatric patient. Dupilumab may be an alternative for CEP that is refractory to corticosteroids or that requires prolonged therapy. It may also be a more convenient therapy compared to other monoclonal antibodies available to patients because it can be administered at home.  References1. Jederlinic PJ, Sicilian L, Gaensler EA. 1988. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore). 67(3):154-162.2. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF. 1998. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The groupe d'etudes et de recherche sur les maladies "orphelines" pulmonaires (germ"o"p). Medicine (Baltimore). 77(5):299-312.3. Lin RY, Santiago TP, Patel NM. 2019. Favorable response to asthma-dosed subcutaneous mepolizumab in eosinophilic pneumonia. J Asthma. 56(11):1193-1197.4. Menzella F, Montanari G, Patricelli G, Cavazza A, Galeone C, Ruggiero P, Bagnasco D, Facciolongo N. 2019. A case of chronic eosinophilic pneumonia in a patient treated with dupilumab. Ther Clin Risk Manag. 15:869-875.5. Castro M, Rabe KF, Corren J, Pavord ID, Katelaris CH, Tohda Y, Zhang B, Rice MS, Maroni J, Rowe P et al. 2020. Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Res. 6(1).

We read the letter to the editor “B-lines score: artifacts as a sign of neonatal specific disease?” by Quarato et al. and we are pleased by the interest aroused by our article “Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study” published on your journal. This study included preterm neonates with respiratory distress syndrome (RDS), requiring non-invasive ventilation and surfactant. The aim of our citated study was to asses changes of a validated neonatal lung ultrasonography score (nLUS) after surfactant treatment. Our data demonstrate a lowering of the nLUS 2h and 12h after surfactant treatment. In their letter to the editor Quarato et al. expressed criticism about the nLUS score validation and about the utility of the Lung Ultrasound (LUS) as a diagnostic tool. They conclude that “LUS can be used only for diagnosing minimal pleural effusion and, at least, as complementary imaging, in addiction to chest radiographs (CR), for monitoring the reduction of subpleural pneumonitic consolidations under therapy”. Our citated study hasn’t focused on validation of the nLUS score or on LUS as a diagnostic tool for neonatal RDS, so we don’t get how Quarato’s concerns can be addressed to our paper. Nevertheless, finding the debate about nLUS or LUS in the neonatal field an occasion to promote an improving in the care of the preterm babies, we will discuss objections raised in Quadrato’s work, point by point.

Objectives: To evaluate the risk factors of recurrent pulmonary exacerbation and poor prognosis in children with idiopathic pulmonary hemosiderosis (IPH).  Methods: In this multicenter study, 54 patinets with diagnosis of IPH included. Medical records were retrospectively reviewed from three tertiary care hospitals between 1979 and 2019. Also, current information and the long-term progress of patients was determined by contacting the families by telephone. Results: A total of 54 children were included. The median age of onset of symptoms was 4.5 ± 3.8 years. The median time from onset to diagnosis was 0.9 years ± 2.2. The mean number of recurrent episodes per child in the recurrence-positive group was 3.55 (1-15). Univariate analysis demonstrated that patients presenting with hypoxia or requiring transfusion at the time of presentation had significantly more recurrence episodes (P=0.002). Multivariate analysis showed that the presence of hypoxia at the time of initial presentation was a significant independent predictor of recurrent episodes (P=0.027). The median follow-up was 3.3 ± 4.8 years (0.75 months-27 years). There was a significant relationship between the presence of hypoxia, transfusion history, ANA positivity, and elevated transaminases at the time of initial evaluation and treatment response. Conclusions: The present study provides important information on the clinical course and outcome of pediatric IPH, and substantial information regarding factors that affect recurrent exacerbations and prognosis. Demonstrating of hypoxia as an independent risk factor in recurrence episodes could be guide physicians in the planning of treatment strategies.

Background: Lung ultrasound (LUS) has been successfully used in the diagnosis of different pulmonary diseases. Present study design to determine the diagnostic value of LUS in the evaluation of children with COVID-19, and to compare chest X-ray and LUS results with tomography (CT).   Method and objectives: In this prospective multi-center study, 40 children with confirmed COVID-19 were included. LUS was performed to all patients at admission. The chest X‐ray and CT were performed according to the decision of the primary physicians. LUS results were compared with chest X-ray and CT. The sensitivity and specificity and diagnostic performance was determined. Results: Of the 40 children median (range) was 10.5 (0.4-17.8) years. Chest X-ray and LUS were performed on all and chest CT was performed on 28 (70%) patients at the time of diagnosis. Sixteen (40%) patients had no apparent chest CT abnormalities suggestive of COVID-19, whereas 12 (30%) had abnormalities. LUS confirmed the diagnosis of pulmonary involvement in 10 out of 12 patients with positive CT findings. LUS demonstrated normal lung patterns among 15 patients out of 16 who had normal CT features. The sensitivity identified by the chest X-ray and LUS tests was comparedand statistically significantly different (p=0.016). Chest X-ray displayed false-negative results for pulmonary involvement in 75% whereas for LUS it was 16.7%. Conclusions: LUS might be a useful tool in the diagnostic steps of children with COVID-19. A reduction in chest CT assessments may be possible when LUS is used in the initial diagnostic steps for these children.

Objective: In this study, we aimed to determine the prevalence and clinical importance of vitamin D deficiency in children and adolescent patients who were hospitalized with the diagnosis of COVID-19. Material and Methods: 40 patients who were diagnosed to have COVID-19 and hospitalized with the real-time reverse transcription polymerase chain reaction (RT-PCR) method were included. The control group consisted of 45 healthy patients with normal vitamin D levels. The age of admission, clinical and laboratory data, and 25-hydroxycholecalciferol (25-OHD) and parathormone (PTH) levels were recorded. Those with vitamin D levels which are below 20 ng/ml were determined as Group 1 and those with ≥20 ng/ml as Group 2. Results: The median levels of vitamin D level were 13.14 (4.19-69.28) in the group of patients with COVID-19 and 34.81(3.8-77.42) in the control group. Compared to the control group, there was a statistically significantly lower vitamin D level (p <0.001) in the COVID-19 patient group. At admission, the symptom of fever was significantly higher in Group 1 than in Group 2 (p =0.038). The distribution of disease severity according to vitamin D levels was not found significantly different. In conclusion; our study is the first to evaluate vitamin D levels and its relationship with clinical findings in pediatric patients diagnosed with COVID-19. There are significantly lower levels of vitamin D in children with COVID-19 than those in the control group. This shows that vitamin D, which is effective in the immunological mechanism, also has an effect in the physiopathology of the disease.

Background: Elevated Pre-discharge capillary blood gas partial pressure of carbon dioxide (pCO2) has been associated with increased adverse events including readmission. This study aimed to determine if pre-discharge pCO2 or 36-week pCO2 was associated with increased respiratory readmissions or other pulmonary healthcare utilization in the year after NICU discharge for infants with BPD discharged with home oxygen, using a standardized outpatient oxygen weaning protocol. Methods: This was a secondary cohort analysis of infants born <32 weeks gestational age with BPD, referred to our Pulmonary clinic for home oxygen therapy either from our level IV NICU or local level III NICUs between 2015-17. Infants with major non-respiratory comorbidities were excluded. Subject information was obtained from electronic health records. Results: Of 125 infants, 120 had complete 1-year follow-up. Twenty three percent of infants experienced a respiratory readmission after NICU discharge. There was no significant association between pre-discharge or 36-week pCO2 and respiratory readmissions, emergency room visits, new or increased bronchodilators or diuretics. Higher 36-week pCO2 was associated with a later corrected age when oxygen was discontinued (<6 months, median 54 mm Hg, Interquartile range (IQR) 51-61; 6-11 months, median 62 mm Hg IQR 57-65; ≥12 months, median 66 mm Hg, IQR 58-73; p=0.006). Conclusions: Neither pre-discharge pCO2 nor 36-week pCO2 was associated with one-year respiratory readmissions. Higher pCO2 at 36 weeks was associated with longer duration of home oxygen. Neonatal illness measures like 36-week pCO2 may be useful in communicating expectations for home oxygen therapy to families.

Periodic breathing is indicative of immaturity of respiratory control and is well recognized within the normal limits in both full term and premature infants but unusual beyond infancy and at high altitude. We would like to focus on the importance of recognizing and scoring the pattern of periodic breathing in older children both clinically and in the sleep laboratory as an abnormal breathing pattern that should draw the attention of the treating physician into the possibility of hindbrain malformation or other significant pathology. Despite that sleep disordered breathing including central and obstructive apneas with or without hypoventilation are well reported as a manifestation of Chiari type I malformation, scoring periodic breathing pattern beyond infancy has not been an area of focus.

Objectives: Although albuterol, the most frequently used bronchodilator, has been traditionally and generally delivered via nebulization (NEB) with compressed air/oxygen, the benefits of metered‐dose inhalers with a spacer (MDI+S) have been widely recognized as an alternative method for albuterol administration. The aim of this systematic review was to compare the response to albuterol delivered through NEB with albuterol delivered through MDI+S in pediatric patients with asthma exacerbations. Methods: We conducted an electronic search in MEDLINE/PubMed, EMBASE, Ovid and ClinicalTrials. To be included in the review, a study had to a randomized clinical trial comparing albuterol delivered via NEB versus MDI+S; and had to report the rate of hospital admission (primary outcome), or any of the following secondary outcomes: oxygen arterial saturation, heart rate (HR), respiratory rate, the pulmonary index score (PIS), adverse effects, and need for additional treatment. Results: Fifteen studies (n=2057) met inclusion criteria. No significant differences were found between the two albuterol delivery methods in terms of hospital admission (RR 0.89; 95% CI 0.55 to 1.46; I2=32%; p=0.65). There was a significant reduction in the PIS score (MD -0.63; 95% CI -0.91 to -0.35; I2=0%; p < 0.00001), and a significantly smaller increase in HR (better) (MD -6.47; 95% CI -11.69 to -1.25; I2=0%; p=0.02) when albuterol was delivered through MDI+S than when it was delivered through NEB. Conclusions: This review showed a significant reduction in the PIS and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB.

The difference in morbidity and mortality between adult and pediatric COVID-19 infections is dramatic. Understanding pediatric-specific acute and delayed immune responses to SARS-CoV-2 is critical for the development of vaccination strategies, immune-targeted therapies, and treatment and prevention of MIS-C. The goal of this review is to highlight research developments in understanding of the immune responses to SARS-CoV-2 infections, with a specific focus on age-related immune responses.

To the editor,Following the online podcast recorded the 31 March 2020 by the International Committee of the American Thoracic Society Pediatrics Assembly and recently published in Pediatric Pulmonology1, we have interesting discussion with my international colleagues about the likelihood of acute bronchiolitis caused by SARS-CoV-2 infection in absence of RSV co-infection. Here, we report 2 cases of COVID-19 in infants < 3 months old admitted to our paediatric unit. The infants presented fever and neurological symptoms and after a short period, acute bronchiolitis.Case 1 : A term-born boy with unremarkable history was admitted to the emergency department with poorly tolerated high fever (38.8°C) and rhinitis. The parents, who had no history of asthma or allergy, showed clinical signs suggesting SARS-CoV-2 infection. RT-PCR for SARS-CoV-2 on a nasopharyngeal swab was positive for the father and the grandfather, who was hospitalized in the intensive care unit. Neurologic examination of the infant revealed lethargy and hypotonia with a bulging anterior fontanelle. The respiratory condition and clinical examination findings including hemodynamics were normal.The first blood test showed isolated lymphopenia (lymphocyte count 1.56 x109/L; normally 4-6x109/L) without modification of biological inflammatory parameters, as assessed by normal levels of C-reactive protein (CRP) and procalcitonin (PCT). Spinal fluid analysis, cytobacteriological urine analysis and blood culture were negative. RT-PCR of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for respiratory syncytial virus (RSV) and influenza virus (IV). The patient received fluid volume expansion(20 ml/Kg of 0.9% sodium chloride solution) together with antibiotic treatment (cefotaxime, amoxicillin and gentamicin at meningeal doses) for 24 hr, that was stopped with a positive RT-PCR test for SARS-CoV-2 and negative blood culture. Favourable clinical outcome was obtained shortly thereafter, allowing the infant to return home 2 days later.Ten days later, the child returned with acute bronchiolitis. Respiratory symptoms included polypnea, shortness of breath, wheezing and hypoxia (SpO2< 92 %). Lung ultrasonography revealed signs of interstitial syndrome with thickened and irregular pleural line associated with confluent B lines and small multifocal subpleural consolidations. RT-PCR for RSV and IV remained negative. Treatment associated supplemental oxygen and enteral nutrition for 6 days. A second episode of acute bronchiolitis occurred 1 month later, but a RT-PCR test for SARS-CoV-2 was negative. The chest X-ray was normal. The child remained hospitalized for 5 days with enteral nutrition support but did not require oxygen supplementation. Long-term treatment with inhaled daily corticosteroids (fluticasone) was introduced.Case 2 : A term-born eutrophic male with otherwise unremarkable neonatal history was referred for poorly tolerated high fever at age 2 months. Both parents had clinical signs of COVID-19 but were not tested (a member of the family had a positive test). The neurologic examination revealed lethargia and hypotonia in the child; the respiratory condition and clinical examination findings including hemodynamics were normal. The first blood test showed lymphopenia (lymphocyte count: 1.86 x109/L; normally 4-6x109/L)without modification of biological inflammatory parameters. Cytobacteriological examination of urine and blood culture were negative and spinal fluid analysis was not performed. RT-PCR testing of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for RSV and IV. The patient did not receive any antibiotics. On day 3 after admission, the respiratory condition progressively worsened, with retraction, wheezing, increased respiratory rate at 80/min and hypoxia (SpO2 < 92%) requiring supplemental oxygen together with enteral nutrition for 3 days. The chest X-ray was normal, and no lung ultrasonography was performed. The infant was returned to the emergency department 2 weeks later with a non-severe wheezing episode and was discharged at home.These 2 cases of COVID-19 in infants hospitalized for poorly tolerated high fever and neurological symptoms in whom acute bronchiolitis developed at a delay of 2 to 8 days suggest that SARS-CoV-2 infection may cause acute bronchiolitis in absence of viral co-infection such as RSV. Pneumonia is the most common diagnosis among symptomatic children with COVID-191. High-resolution CT scan usually shows ground-glass opacities or bilateral lung consolidations, especially in the periphery, and lung ultrasonography, as in our case 1, reveals signs of lung involvement. In contrast, to the best of our knowledge, acute bronchiolitis due to SARS-CoV-2 infection has never been reported. The wheezing episodes described in our patients were likely due to SARS-CoV-2 infection for the following reasons: first, RT-PCR tests for RSV and IV were always negative in both children, and second, the epidemic season for both viruses was over and the lockdown in France was still active at the time of the cases. Finally, previous study of virus repartition in positive respiratory samples from infants with acute bronchiolitis detected close to a 5% frequency of coronaviruses OC43 and 229E2. Moreover, a recent experimental model of COVID-19 in ferrets showed lung lesions compatible with bronchiolitis3. Our patients showed bronchiolitis symptoms several days after those of COVID-19, which may explain the lack of wheezing episodes reported in the literature. Case 2 was diagnosed with recurrent wheezing presumably due to SARS-CoV-2 infection. RSV as well as rhinovirus bronchiolitis is a risk factor for recurrent wheezing and asthma4,5,but little is known about the long-term impact of SARS-CoV-2 infection in lung function trajectory, which emphasizes the need to follow these children. Whether the infection in symptomatic or asymptomatic infants may predispose to recurrent wheezing or asthma remains to be determined.

A document by Andres Perez-Lopez. Click on the document to view its contents.

Long isolation period for suspected child cases was proposed based in one case. New evidence suggests that children are not as dangerous as they seemed, as a vehicle for this infection. We must be cautious when making recommendations for a disease that affects millions of people, based on just one case.

Objective: Multi-dose dexamethasone pretreatment prevents postextubation airway obstruction (PEAO), however, its optimal dose in children is not known. We planned to compare effect of 24h pretreatment of low dose (LD) (0.25mg/kg/dose) versus high dose (HD) (0.5mg/kg/dose) dexamethasone for prevention of PEAO. Design: Stratified (for age and intubation duration) randomized open-label non-inferiority trial. Setting: 15-bed Pediatric Intensive Care Unit in a tertiary care teaching hospital of a lower-middle income country. Patients: Children (3mo-12yrs) intubated for ≥48h and planned for first extubation over 26 months (Feb’17 to Mar’19). Children with preexisting upper airway conditions, chronic respiratory diseases, steroid or IVIG therapy in last 7 days, gastrointestinal bleeding, hypertension and hyperglycemia were excluded. Interventions: Low dose (n=144) or high dose (n=143) dexamethasone (q6h) for 6 doses. Extubation was planned after 5th dose. Measurements and Main Results: Patients were monitored for PEAO (Westley’s Croup Score >4) for 24 hours. 238 patients were included in per-protocol analysis. 78 patients (33%) developed PEAO; both groups were similar (LD, 41/121, 34% vs HD, 37/117, 32% p=0.71). Risk difference of LD vs HD touches the non-inferiority margin of 0.12 and hence the overall result is non-significant. Incidence of reintubation was also similar (LD, 10/121, 8.3% vs HD, 9/117, 7.7%; p=0.87). Intubation for more than 7 days was an independent risk factor for development of PEAO. Conclusions: Multi-dose 24-hour pretreatment with low dose dexamethasone is not inferior to high dose in preventing PEAO and reintubation among unselected patients in the studied clinical setting. Multi-centric trials with larger sample size among children at high risk of developing PEAO are needed.

Objectives: To compare the efficacy of different non-invasive respiratory support modes for primary respiratory support of preterm infants with Respiratory Distress Syndrome (RDS). Design: Systematic review and network meta-analysis using the Bayesian random effects approach. MEDLINE, EMBASE and CENTRAL were searched. Interventions : HFNC (High Flow Nasal Cannula), CPAP (Continuous Positive Airway Pressure), BiPAP (Bilevel CPAP), NIPPV (Non Invasive Positive Pressure Ventilation). Main outcome measures: Requirement of invasive mechanical ventilation, any treatment failure. Results: 34 studies including 3994 patients were included. NIPPV was more effective in decreasing the requirement of mechanical ventilation than CPAP {RR [95% Credible Interval (CrI)] - 0.60 (0.44, 0.79)}and HFNC [0.66 (0.43, 0.99)]. Surface under the cumulative ranking curve (SUCRA) for NIPPV, BiPAP, HFNC and CPAP were 0.94, 0.59, 0.32 and 0.13. For the outcome of treatment failure, both NIPPV and BiPAP were more efficacious compared to CPAP and HFNC {0.56 (0.44, 0.71) [NIPPV vs CPAP], 0.69 (0.51, 0.93) [BiPAP vs CPAP], 0.42 (0.30, 0.63) [NIPPV vs HFNC], 0.53 (0.35, 0.81) [BiPAP vs HFNC]}. The SUCRA for NIPPV, BiPAP, CPAP and HFNC were 0.96, 0.70, 0.32 and 0.01. NIPPV was associated with a reduced risk of air leak compared to BiPAP and CPAP [0.36 (0.16, 0.73); 0.54(0.30, 0.87), respectively]. NIPPV resulted in lesser incidence of BPD or mortality when compared to CPAP [0.74 (0.52, 0.98)]. Nasal injury was lesser with HFNC compared to CPAP [0.15 (0.01, 0.60)]. Conclusions: Most effective primary mode of non-invasive respiratory support in preterm neonates with RDS was NIPPV.

Tracheoesophageal fistula (TEF) with esophageal atresia (EA) is a common congenital anomaly that is associated with significant respiratory morbidity throughout life. The objective of this document is to provide a framework for the diagnosis and management of the respiratory complications that are associated with the condition. As there are no randomized controlled studies on the subject, a group of experts used a modification of the Rand Appropriateness Method to describe the various aspects of the condition in terms of their relative importance, and to rate the available diagnostic methods and therapeutic interventions on the basis of their appropriateness and necessity. Specific recommendations were formulated and reported as Level A, B, C based on whether they were based on “strong”, “moderate” or “weak” agreement. The tracheomalacia that exists in the site of the fistula was considered the main abnormality that predisposes to all other respiratory complications due to airway collapse and impaired clearance of secretions. Aspiration due to impaired airway protection reflexes is the main underlying contributing mechanism. Flexible bronchoscopy is the main diagnostic modality, aided by imaging modalities, especially CT scans of the chest. Non-invasive positive airway pressure support, surgical techniques such as tracheopexy and rarely tracheostomy are required for the management of severe tracheomalacia. Regular long-term follow-up by a multidisciplinary team was considered imperative. Specific templates outlining the elements of the clinical respiratory evaluation according to the patients’ age were also developed.

Background: Diagnostic sweat testing is required for infants with positive newborn screening (NBS) tests for cystic fibrosis (CF). Infants have “quantity not sufficient” (QNS) sweat volumes more often than older children. A comprehensive study of QNS sweat volumes in infants has not previously been reported. Methods: We surveyed US CF Centers to obtain QNS rates in all infants who had sweat testing at < 14 days and < 3 months of age. We then calculated QNS rates reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) 2010-2018 in 10-day increments from 1 to 60 days of life. We compared QNS sweat tests rates in preterm (< 37 weeks gestational age) versus term infants. We assessed age at sweat test and proportion of infants who did not have a sweat test reported by 60 days of age. Results: Thirty-nine of 144 (27%) of CF Centers reported a mean QNS rate of 10.5 % (range, 0-100) in infants < 14 days old. CFFPR data showed highest QNS rates in the youngest infants and in those born < 37 weeks gestation. The median age at sweat testing decreased over time, but > 22% of infants did not have a sweat test reported by 60 days. Conclusion: Higher QNS rates are seen in the youngest infants with CF, but > 80% of infants < 2 weeks of age have adequate sweat volumes. Sweat testing should not be delayed in infants with a positive CF NBS test.

Despite significant successes in treating children with pulmonary hypertension, many still die from their disease. Death most often results from right ventricular failure. Bilateral lung transplantation has historically been the ultimate palliation for children who develop heart failure despite maximal medical therapy. Creating an atrial level shunt has been advocated as a pre-transplant intervention to help reduce symptoms and perhaps serve as a bridge to transplant. More recently, the utilization of a pulmonary-to-systemic anastomosis, i.e., Potts shunt, has demonstrated efficacy in ameliorating symptoms in children with severe, progressive disease. This improvement is often coincident with a reduction in expensive and onerous pulmonary hypertension specific medications. Improvement has been sustained over years in some children, delaying the need for transplant consideration. Research is ongoing to determine more specific risk/benefits of using the Potts shunt in children with pulmonary hypertension both in the short term and long.