Lung transplantation is a recognised therapy for end stage respiratory failure in children and young people. It is only available in selected countries, and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear that data from studies in adults, and from studies in other solid organ transplants in children, that systemic iniquities exist in this field. While data relating specifically to paediatric lung transplantation are relatively sparse, professionals should be aware of the risk that health care systems may result in disparities in access and outcomes following lung transplantation in children.

Background: In preschoolers, performing an acceptable spirometry and measuring bronchodilator response (BDR) is challenging; impulse oscillometry (IOS) may be an alternative to spirometry. However, there is still no consensus in standardization of BDR for IOS in young children. Objective: The objective of the study was to identify optimal thresholds to define a positive BDR test with IOS. Methods: Young infants aged 3 to 6 years with suspected asthma were evaluated in a real life setting with both IOS and spirometry pre- and post-BDR. The BDR was defined as positive when the change of FEV1 was ≥12% and/or ≥200 mL. Results: Among 72 patients (age 4.98 ± 0.94 years; 64% boys), 36 (age 5.15 ± 0.99 years; 64% boys) were selected for the subsequent analysis according to ATS / ERS quality criteria of measurements. The spirometric BDR was found positive in seven subjects (19.4%). In IOS, the mean decrease in R5 and AX was 19.86% ± 10.04 and 44% ± 22.10, and the mean increase in X5 was 23.28% ± 17.82, respectively. A decrease in R5 of 25.7% (AUC 0.77, p = 0.03) and an increase in X5 of 25.7% (AUC 0.75, p = 0.04) showed the best combination of sensitivity and specificity to detect an increase of FEV1 ≥12% and/or ≥200 mL. Conclusion: The IOS may present a valid alternative to spirometry to measure BDR in preschool children. We are considering a decrease of 26% in R5 and an increase of 26% in X5 as diagnostic threshold for BDR.

Objective: To determine levels of moral distress in a pediatric unit caring for patients with tracheostomy/ventilator dependence. Hypothesis: Moral distress will be significant in a dedicated pediatric trach/vent unit. Methods: The Moral Distress Survey-Revised (MDS-R) is a 21-question survey measuring moral distress in pediatrics. The MDS-R was anonymously distributed to MD/DOs, advanced practice practitioners (APPs), RNs and RTs in a unit caring for tracheostomy/ventilator dependent patients. Descriptive statistics, bivariate and multivariate analysis were performed. Results: Response rate was 48% (61/127). Mean MDS-R score was 83 (range 43-119), which is comparable to reported levels in the pediatric intensive care unit. APPs had the highest median rate of moral distress (112, IQR 72-138), while MD/DOs had the lowest median score (49, IQR 43-77). RNs and RTs had MDS-R scores between these two groups (Medians of 91 and 84 respectively). Conclusions: Moral distress levels in a unit caring for long term tracheostomy and ventilator dependent patients are high, comparable to levels in pediatric ICUs. APPs had higher levels of distress compared to other groups. This may be attributable to the constant stressors of being the primary provider for complex patients, especially in a high-volume inpatient setting.

Combination therapy with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) corrector lumacaftor and the CFTR potentiator ivacaftor has demonstrated significant impact on clinical parameters in Phe508del homozygous people with CF. Whether these changes under treatment are correlated to serum levels of both drugs had yet to be investigated. We therefore analyzed data from our previous study (OrkambiFacts, ClinicalTrials.gov Identifier: NCT02807415). In summary, we did not find statistically significant correlations between serum drug levels and changes in clinical parameters and biomarkers of CFTR function such as FEV1, BMI, sweat chloride, nasal potential difference (NPD) and intestinal current measurement (ICM). Absolute blood levels of lumacaftor or ivacaftor do not seem to be informative biomarkers to predict clinical improvement or the attenuation of the basic defect.

Objective: To identify the pathogens and compare the clinical characteristics between different type pathogen infection among children with community-acquired pneumonia (CAP) requiring bronchoalveolar lavage. Study design: Children <14 years old hospitalized with CAP requiring bronchoalveolar lavage were enrolled between February 2019 to January 2020. Multiplex reverse transcription polymerase chain reaction (mRT-PCR) and loop-mediated isothermal amplification (LAMP) were used for pathogen detection. The demographic and clinical characteristics were compared between different type pathogen infection groups. Results: Among 1166 children studied, ≥1 pathogen was detected in 1084 (93.0%) children and co-infection was detected in 215 (18.4%) children. Mycoplasma pneumoniae, Streptococcus pneumoniae and adenovirus were the most frequently detected pathogens. Children infected with atypical bacteria alone were older and more likely to display a fever, cough, decreased breath sounds, consolidation, single lobar infiltration, mucosal erosion and/or necrosis and plastic bronchitis. Children with virus-atypical bacteria co-infection were more prone to manifest fatigue, chest pain, tachypnea, chest indrawing, and mucosal erosion and/or necrosis. Those infected with virus alone or co-infected with ≥3 pathogens were liable to display changes in bronchial morphology. Conclusions: Pathogens were detected in 93.0% of enrolled children. M. pneumoniae infection might be the greatest pediatric disease burden due to CAP in North China. Keywords: Children; community-acquired pneumonia; bronchoalveolar lavage fluid; etiology; co-infection.

Objectives: The objective of this study is to compare the Dinakara and Cotes equations in their ability to predict post hematopoietic stem cell transplant (HSCT) pulmonary complications and mortality. Hypothesis We hypothesize the pre-transplant diffusing capacity adjusted for hemoglobin (DLCOHgb) by the Cotes equation in pediatric patients undergoing HSCT will predict morbidity and mortality more accurately than the Dinakara equation. Study-Design: Data was collected retrospectively from chart review of patients who underwent their first HSCT at Riley Hospital for Children using a database maintained by the Pediatric Stem Cell Transplant Program. Patient-Subject Selection: Patients who performed pre-transplant diffusing capacity for carbon monoxide (DLCO) that met ATS criteria, and a hemoglobin recorded within 7 days of their pulmonary function testing were included. Methodology: Paired t-tests and ANOVA models were used to define any differences between the two equations at baseline and when stratifying by hemoglobin level. Logistic regression models were used to determine associations between the Dinakara and Cotes equation with mortality at one- and three-years post-transplant. Results: 90 patients underwent HSCT during the study period, and 69 patients met inclusion criteria. Odds ratios for mortality using DLCO corrected for the Dinakara (1.08 SD 0.98-1.19) and Cotes (1.09 SD 0.97-1.22) were similar (p-value > 0.05). Neither Dinakara or Cotes corrective equation was superior at predicting pulmonary complications. (p-values 0.1388 and 0.5246 respectively) Conclusions: The Dinakara and Cotes equations differed in their calculation of DLCOHgb at lower Hb levels, their ability to predict mortality and pulmonary complications after HSCT was not different.

We hereby present a case report of an extremely preterm newborn with bronchopulmonary dysplasia (BPD), spending more than 4 months of his early life in the newborn intensive care unit (NICU). The uniqueness of this case report is the difference in the algorithm used for the treatment of BPD with regards to the family’s preference and its successful outcome.

A document by Ian Sinha. Click on the document to view its contents.

Persistent Pulmonary Hypertension of the Newborn (PPHN) is defined as a failure of the normal circulatory transition after birth. PPHN manifests as a progressive and potentially fatal hypoxemic respiratory failure. The condition is associated with a persistent increase in pulmonary vascular resistance and reduced blood flow in the pulmonary vessels without an accompanying congenital heart defect. The abnormalities in pulmonary circulation lead to right-to-left shunting through the foramen ovale and usually also through the ductus arteriosus, with resultant hypoxemia, which manifests clinically as cyanosis. Management options in PPHN include optimal lung inflation, oxygenation, prevention of acidosis, stabilization of blood pressure, sedation and pulmonary vasodilator therapy. While inhaled nitric oxide (iNO) is the most commonly used treatment option, alternative methods can be used whenever is unavailable or contraindicated. We report three cases of severe PPHN, in which due to the lack of adequate response to intravenous MgSO4, the patients were switched to milrinone.

Paediatric multisystem inflammatory syndrome: temporally associated with SARS-COV-2 (PIMS-TS) is a well described rare but severe COVID-19 related syndrome. PIMS-TS have been reported in children from geographical areas of high COVID-19 infection. Most children with PIMS-TS require management in an intensive care unit with variable respiratory involvement. Adults recovering from COVID-19 infection have been reported to suffer from respiratory morbidity but such outcomes are unknown in children. We present the first report of normal short term respiratory outcomes as measured by spirometry in children with SARS-COV-2 antibody positive, PIMS-TS syndrome managed at a specialist children’s hospital in the UK.

Bronchopulmonary dysplasia (BPD) was first described by Northway et al in 1967. This article describes the evolution of our understanding of the pathophysiology of BPD and the approaches to treatments of this illness developed over the past fifty years. These interventions had their roots in the understanding of the principles of the surface tension present at air- liquid interfaces, which were developed over 150 years before BPD’s initial description. Improving outcomes in neonatal care have led to greater survival of preterm and very preterm infants, and to an evolution of the pathogenesis and pathology of BPD, from an illness caused primarily by barotrauma and oxygen toxicity to one of interruption of lung development. While the incidence of BPD has remained about the same in recent decades, this is because survival of infants born at lower gestational ages is increasing. Understanding of molecular, genetic and physiologic mechanisms has led to newer treatments that have mitigated some of the harmful effects of prolonged mechanical ventilation. Recognition of BPD as a chronic multi-system disease has resulted in further improvements in care after discharge from neonatal intensive care. Since many of the origins of chronic obstructive lung disease in adults are based in childhood respiratory illnesses, improving outcomes of BPD in infancy and childhood will undoubtedly lead to improved respiratory outcomes in the adults that these children will become.

Background: Asthmatic children present variable degrees of airway inflammation, remodeling and resistance, which correlates with disease control and severity. Chronic inflammatory process of the airways triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. This study has investigated for the first time, whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present correlation with the resistance of respiratory system and of proximal and distal airways. Methods: 24 asthmatic children (persistent mild and moderate) and 24 non-asthmatic children (both between 6-13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, pulmonary and systemic immune response. Results: Asthmatic children showed an increased number of blood eosinophils (p<0.04), basophils (p<0.04), monocytes (p<0.002) and lymphocytes (p<0.03). In addition, asthmatic children showed an impaired lung function, as demonstrated by FEV1%pred. (p<0.0005) and FEV1/FVC (p<0.004), decreased total resistance of respiratory system (R5Hz; p<0.009), increased resistance of proximal airways (R20Hz; p<0.02), increased elastance (Z5Hz; p<0.02) and increased reactance (X5Hz; p<0.002). Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p<0.0001) and in the serum (p<0.0001); TGF-beta in the BC (p<0.0001) and in the serum (p<0.004); IL-5 in the BC (p<0.02) and in the serum (p<0.01); IL-4 in the serum (p<0.0002). Conclusions: Impulse oscillometry is a sensitive method to detect airway resistance in asthmatic children, reflecting airway remodeling, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

Macrolides and corticosteroid resistant have been reported in mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult even by sensitive antibiotics in severe MPP (SMPP). SMPP children might develop into airway remodeling even bronchiolitis/bronchitis obliterans. There is an urgent need to identify serum biomarkers indicating the progress of MPP and to discover new target drugs for the treatment of SMPP. In this study, we collected serum samples from general MPP (GMPP) and SMPP patients to perform proteomics profiling. Total 130 differentially expressed proteins with 61 up-regulated in GMPP and 69 up-regulated in SMPP were identified. Among these, FCGBP was one of the most altered protein with highest fold change. Biological enrichment analysis indicated an uncontrolled inflammation catastrophe in SMPP. In addition, complement, coagulation cascades, collagen-containing extracellular matrix and platelet degranulation pathway were enriched in both groups. KEGG analysis indicated an enriched platelet activation in SMPP. ELISA was then performed to verify the dynamic serum FCGBP expression level between other GMPP and SMPP patients. FCGBP level in SMPP was significantly higher than that in GMPP. FCGBP level in GMPP exhibited a decreased trend while SMPP showed the opposite trend during the disease course. Our study demonstrates the first proteomics characteristic of GMPP and SMPP and provides FCGBP as a new serum biomarker indicating the progress of SMPP. Further CMap analysis identified 25 drugs target for the treatment of SMPP. Among them, MTOR inhibitor, a macrolide compound and cell proliferation inhibitor, is the most promising drug targeting for the treatment of SMPP.

An adolescent female with ventilator-dependent spinal muscular atrophy type 1 (SMA-1) and megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome had been struggling with recurrent small to large volume hemoptysis for years secondary to complex arteriovenous malformations (AVMs) in her lungs. Despite numerous embolizations, she continued to experience hemoptysis from new AVMs. She was then started on sirolimus (rapamycin) and remains hemoptysis-free for over 12 months. To our knowledge, there are no known cases of SMA-1 with MCAP syndrome and related complex vascular malformations successfully treated with sirolimus.