Pulmonary outcomes of congenital diaphragmatic hernia patients based on defect size (CDH Study Group Stage).

Background: Congenital diaphragmatic hernia (CDH) is associated with significant pulmonary morbidity. Previous investigation has shown that postnatal inpatient morbidity is linked to diaphragmatic defect size. The objective of this study was to evaluate long-term pulmonary outcomes by CDH study group defect size. Methods: A retrospective analysis was conducted for CDH patients (n=133) managed in a neonatal intensive care unit (NICU) at a single children's hospital within an adult hospital system and subsequently followed up at a comprehensive multidisciplinary CDH clinic (n=102) from January 2012 to April 2022. CDH patients were stratified according to Congenital Diaphragmatic Hernia Study Group (CDHSG) Stage, and then categorized as low-risk (LR), defect size A and B, or high-risk (HR), defect size C and D. Inpatient data, including the presence of pulmonary hypertension, extracorporeal life support (ECLS) utilization, and mechanical ventilation days, were collected. Post-discharge data including the prevalence of asthma, pulmonary hypertension, emergency department visits, the total number of hospitalizations, and average rehospitalization days were collected. Frequentist analysis was used. Results: The outcomes for 133 NICU patients were analyzed (HR: n=54, LR: n=79). During NICU stay, the prevalence of pulmonary hypertension [HR: 16/54 (30%) vs. LR: 9/79 (12%), P=0.009], ECLS utilization [HR: 19/54 (35%) vs. LR: 4/79 (5%), P<0.001], and the average number of mechanical ventilation days [HR: 17 days (IQR: 12-27) vs. LR: 5 days (IQR: 2-9), P<0.001] were significantly higher in the HR CDH group. Post NICU discharge, the prevalence of asthma [HR: 20/54 (37%), vs. LR: 17/79 (22%), P=0.050)] and the total days of rehospitalization [HR: 9 (IQR: 2-27) vs. LR: 4 (IQR: 1-8), P=0.035] were significantly higher in HR group. Of the patients seen in the comprehensive multidisciplinary CDH clinic, obstructive lung disease measured by impulse oscillometry was increased in the HR CDH population compared to the reference group [median R5Hz was 12.95 kPa/(L/s) in CDH vs. 9.8 kPa/(L/s) (P=0.010)]. Conclusions: HR CDHSG Stage is associated with worse inpatient and long-term pulmonary outcomes.

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2.

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.

Cardiac arrhythmias associated with volume-assured pressure support mode in a patient with autonomic dysfunction and mitochondrial disease.

NONE: A 15-year-old boy with autonomic dysfunction and mitochondrial disease was diagnosed with sleep-related hypoventilation at 6 years of age and treated with bilevel positive airway pressure therapy. At 12 years of age, treatment was transitioned to volume-assured pressure support (VAPS) due to clinical evidence of respiratory muscle weakness. Subsequent titration polysomnogram revealed the emergence of cardiac arrhythmia (isolated premature ventricular contractions, bigeminy, and trigeminy) while on VAPS mode that improved after transition to bilevel positive airway pressure therapy. During the titration study, higher tidal volumes correlated with increased pressures and the presence of arrhythmia. Prior to initiation of VAPS therapy, the patient had normal electrocardiogram evaluations. This case highlights the potential relationship between VAPS therapy and cardiac arrhythmias, especially in patients with underlying conditions with associated cardiac abnormalities, such as autonomic dysfunction and mitochondrial disease. While using VAPS mode, patients should be closely monitored for cardiac rhythm abnormalities.

The Effect of Comprehensive Medical Care on the Long-Term Outcomes of Children Discharged from the NICU with Tracheostomy.

BACKGROUND: Survival of infants with complex care has led to a growing population of technology-dependent children. Medical technology introduces additional complexity to patient care. Outcomes after NICU discharge comparing Usual Care (UC) with Comprehensive Care (CC) remain elusive. OBJECTIVE: To compare the outcomes of technology-dependent infants discharged from NICU with tracheostomy following UC versus CC. METHODS: A single site retrospective study evaluated forty-three (N=43) technology-dependent infants discharged from NICU with tracheostomy over 5½ years (2011-2017). CC provided 24-hour accessible healthcare-providers using an enhanced medical home. Mortality, total hospital admissions, 30-days readmission rate, time-to-mechanical ventilation liberation, and time-to-decannulation were compared between groups. RESULTS: CC group showed significantly lower mortality (3.4%) versus UC (35.7%), RR, 0.09 [95%CI, 0.12-0.75], P=0.025. CC reduced total hospital admissions to 78 per 100 child-years versus 162 for UC; RR, 0.48 [95% CI, 0.25-0.93], P=0.03. The 30-day readmission rate was 21% compared to 36% in UC; RR, 0.58 [95% CI, 0.21-1.58], P=0.29). In competing-risk regression analysis (treating death as a competing-risk), hazard of having mechanical ventilation removal in CC was two times higher than UC; SHR, 2.19 [95% CI, 0.70-6.84]. There was no difference in time-to-decannulation between groups; SHR, 1.09 [95% CI, 0.37-3.15]. CONCLUSION: CC significantly decreased mortality, total number of hospital admissions and length of time-to-mechanical ventilation liberation.

Characteristics and Outcomes of Children with Clinical History of Atopic Versus Non-atopic Asthma Admitted to a Tertiary Pediatric Intensive Care Unit.

BACKGROUND: Children admitted to the Pediatric Intensive Care Unit (PICU) with status asthmaticus have variable clinical courses, and predicting their outcomes is challenging. Identifying characteristics in these patients that may require more intense intervention is important for clinical decision-making. OBJECTIVE: This study sought to determine the characteristics and outcomes, specifically length of stay and mortality, of atopic versus non-atopic asthmatics admitted to a PICU with status asthmaticus. METHODS: A retrospective study was conducted at a children's hospital from November 1, 2008 to October 31, 2013. A total of 90 children admitted to the PICU were included in the analysis. Patients were divided into two groups based on the presence of specific historical data indicative of a clinical history of atopy. Children were considered to be atopic if they had a parental history of asthma, a personal history of eczema, or a combined history of wheezing (apart from colds) and allergic rhinitis (diagnosed by a medical provider). The median hospital Length Of Stay (LOS), PICU LOS, cardiopulmonary arrest, and mortality were compared between atopic and non-atopic asthma groups. Regression models were used to estimate the LOS stratified by atopic or non-atopic and by history of intubation in present hospitalization. RESULTS: Median hospital LOS for atopic children was 5.9 days (IQR of 3.8-8.7) and 3.5 days (IQR of 2.2-5.5) for non-atopic asthmatics (z = 2.9, p = 0.0042). The median PICU LOS was 2.5 days (IQR 1.4-6.1) for atopic asthmatics and 1.6 days (IQR 1.1-2.4) for non-atopic asthmatics (z = 2.5, p = 0.0141). The median LOS was significantly higher for atopic intubated patients compared to non-atopic intubated patients (p=0.021). Although there was an increased tendency towards intubation in the atopic group, the difference was not significant. There was no significant difference in cardiopulmonary arrest or mortality. CONCLUSION: A clinical history of atopic asthma in children admitted to the PICU with status asthmaticus was associated with longer length of stays The longest LOS was observed when atopic patients required intubation.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of morbidity and mortality in vulnerable populations. Macrolides have received considerable attention for their anti-inflammatory actions beyond their antibacterial effect. We hypothesize that prophylactic azithromycin will be effective in reducing the severity of RSV infection in a mouse model. METHODS: Four groups of BALB/c mice were studied for 8 days: Control (C), RSV-infected (R), early prophylaxis with daily azithromycin from days 1 to 8, (E), and late prophylaxis with daily azithromycin from days 4 to 8 (L). Mice were infected with RSV on day 4, except for the control group. All groups were followed for a total of 8 days when bronchoalveolar lavage cell count and cytokines levels were measured. Mouse weight, histopathology, and mortality data were obtained. RESULTS: Prophylactic azithromycin significantly attenuated post-viral weight loss between group R and both groups E and L (P = 0.0236, 0.0179, respectively). IL-6, IL-5, and Interferon-Gamma were significantly lower in group L (P = 0.0294, 0.0131, and 0.0056, respectively) compared with group R. The total cell count was significantly lower for group L as compared with group R (P < 0.05). Mortality was only observed in group R (8%). Lung histology in the prophylactic groups showed diminished inflammatory infiltrates and cellularity when compared with group R. CONCLUSION: Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

Use of Nasal Non-Invasive Ventilation with a RAM Cannula in the Outpatient Home Setting.

BACKGROUND: Nasal non-invasive-ventilation (Nasal NIV) is a mode of ventilatory support providing positive pressure to patients via a nasal interface. The RAM Cannula is an oxygen delivery device that can be used as an alternative approach to deliver positive pressure. Together they have been successfully used to provide respiratory support in neonatal in-patient settings. OBJECTIVE: To describe the outpatient use of Nasal NIV/RAM Cannula as a feasible alternative for home respiratory support in children with chronic respiratory failure. METHODS: We performed a retrospective case series of 18 children (4 months to 19 years old) using the Nasal NIV/RAM Cannula in the Pediatric Pulmonary Clinic at the McGovern Medical School, UTHealth (2014-16). Consideration for Nasal NIV/RAM Cannula utilization included: inability to wean-off in-patient respiratory support, comfort for dyspnea, intolerability of conventional mask interfaces and tracheostomy avoidance. RESULTS: Average age was 7 years. 50% were Caucasian, 38% African-American and 11% Hispanics. Pulmonary disorders included: chest wall weakness (38%), central control abnormalities (33%), obstructive lung disease (16%) and restrictive lung disease (11%). Indications for Nasal NIV/RAM Cannula initiation included: CPAP/BPAP masks intolerability (11%), dyspnea secondary to chest wall weakness (38%) and tracheostomy avoidance (50%). Average length of use of Nasal NIV/RAM Cannula was 8.4 months. Successful implementation of Nasal NIV/Ram Cannula was 94%. One patient required a tracheostomy following the use of Nasal NIV/RAM Cannula. Significant decrease in arterial PaCO2 pre and post Nasal NIV/RAM cannula initiation was notable (p=0.001). CONCLUSION: Outpatient use of Nasal NIV/RAM Cannula may prove to be a feasible and save treatment alternative for children with chronic respiratory failure, chest wall weakness, dyspnea and traditional nasal/face mask intolerance to avoid tracheostomy.

Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial.

INTRODUCTION: Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade. METHODS AND ANALYSIS: A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3-6 months during two respiratory syncytial virus (RSV) seasons (2015-2016 and 2016-2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach. DISCUSSION: We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters. ETHICS AND DISSEMINATION: This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published. TRIAL REGISTRATION NUMBER: NCT02544984.