A Pilot Study of RNA Sequencing to Improve the Diagnostic Yield of Bronchoalveolar Lavage Specimens in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Pulmonary complications often cause morbidity and mortality in pediatric allogeneic hematopoietic stem cell transplant (HSCT) recipients. While detection of infection and initiation of appropriate antimicrobial therapy improves survival, present techniques oftentimes do not detect infections in bronchoalveolar lavage (BAL) samples because of pretreatment with antimicrobial therapies and the need for a priori knowledge of likely viral pathogens, decreasing the yield of BAL. OBJECTIVE: We evaluated whether RNA-based massively parallel sequencing (MPS) would improve detection of infections in BAL fluid in pediatric allogeneic HSCT recipients. RESULTS: Nine patients underwent 10 BAL (1 patient underwent 2 BAL) and had sufficient BAL fluid for inclusion in this study. Clinical microbiological testing identified infections in 7 patients, and MPS identified infections in 5 patients, although some of these detected organisms were not detected by clinical testing. Results were fully concordant in 5 patients, fully discordant in 3 patients, and partially discordant in 2 patients. Bacterial, viral, and fungal infections were detected via both techniques. CONCLUSION: This suggests that MPS in conjunction with routine clinical testing increases the yield of detection of infectious organisms in the BAL fluid.

Transmitted Home Oximetry and Duration of Home Oxygen in Premature Infants.

OBJECTIVES: To determine if a home oxygen therapy (HOT) management strategy that includes analysis of recorded home oximetry (RHO) data, compared with standard monthly clinic visit assessments, reduces duration of HOT without harm in premature infants. METHODS: The RHO trial was an unmasked randomized clinical trial conducted in 9 US medical centers from November 2013 to December 2017, with follow-up to February 2019. Preterm infants with birth gestation ≤37 + 0/7 weeks, discharged on HOT, and attending their first pulmonary visit were enrolled. The intervention was an analysis of transmitted RHO between clinic visits (n = 97); the standard-care group received monthly clinic visits with in-clinic weaning attempts (n = 99). The primary outcomes were the duration of HOT and parent-reported quality of life. There were 2 prespecified secondary safety outcomes: change in weight and adverse events within 6 months of HOT discontinuation. RESULTS: Among 196 randomly assigned infants (mean birth gestational age: 26.9 weeks; SD: 2.6 weeks; 37.8% female), 166 (84.7%) completed the trial. In the RHO group, the mean time to discontinue HOT was 78.1 days (SE: 6.4), compared with 100.1 days (SE: 8.0) in the standard-care group (P = .03). The quality-of-life scores improved from baseline to 3 months after discontinuation of HOT in both groups (P = .002), but the degree of improvement did not differ significantly between groups (P = .75). CONCLUSIONS: RHO was effective in reducing the duration of HOT in premature infants. Parent quality of life improved after discontinuation. RHO allows physicians to determine which infants can be weaned and which need prolonged oxygen therapy between monthly visits.

The optimization of home oxygen weaning in premature infants trial: Design, rationale, methods, and lessons learned.

Improved survival among preterm infants has led to an increase in diagnosis of chronic lung disease and infants discharged home from the NICU on supplemental oxygen. Despite this increased prevalence, no clearly defined guidelines for the management of home oxygen therapy (HOT) exist. This lack of consensus leads to significant variability in the duration of home oxygen therapy and a general paucity of evidence-based practice. Our team has identified recorded home oxygen therapy (RHO) as a potential new resource to guide clinical decision making in the outpatient pulmonology clinic. By recording extended O2 saturation data during the weaning process, RHO has the potential to save cost and improve the processes of HOT management. Our team is currently supporting a prospective, multi-center, randomized, controlled trial of RHO guided HOT weaning with the aims of determining effect upon duration of HOT, perceived parent quality of life and effect upon growth and respiratory outcomes. We plan to randomize 196 infants into one of two study arms evaluating standard HOT management versus RHO guided oxygen weaning. Our primary outcomes are total HOT duration and parental quality of life. This trial represents an unprecedented opportunity to test a novel home monitoring intervention for weaning within a vulnerable yet quickly growing population. If effective, the use of RHO may provide clinicians a tool for safe weaning.

Polysomnographic values in children 2-9 years old: additional data and review of the literature.

The establishment of normal pediatric polysomnographic parameters is important for both clinical and research interests. Our objectives were to describe respiratory events, paradoxical breathing, periodic limb movements, and sleep architecture of children at the age of peak incidence of obstructive sleep apnea syndrome. We performed a retrospective cross-sectional analysis of a prospective cohort study of 66 children, 2-9 years old, at the Sleep Disorders Center at the Children's Hospital of Philadelphia. Subjects screened by questionnaire underwent a standard polysomnogram. The percent of total sleep time spent in sleep stages 1, 2, 3, 4, and rapid eye movement (REM) were 4 +/- 3%, 44 +/- 10%, 10 +/- 6%, 22 +/- 8%, and 21 +/- 6%, respectively. The arousal and awakening index was 11.2 +/- 4.3/hr. Respiratory events included a central apnea index of 0.08 +/- 0.14/hr, obstructive apnea index of 0.01 +/- 0.03/hr, and obstructive hypopnea index of 0.3 +/- 0.5/hr. The baseline arterial oxygen saturation (SpO2) was 97 +/- 1%, with a nadir of 92 +/- 3%. The index of periodic limb movements in sleep (PLMS) was 1.3 +/- 2.2/hr. Paradoxical breathing appeared significantly more frequent with piezo crystal effort belts (40 +/- 24% of epochs) than with respiratory inductive plethysmography (1.5 +/- 3% of epochs). We describe the occurrence of hypopneas during sleep, arousals and awakenings, and PLMS. We illustrate how different technologies can vary the apparent amount of paradoxical breathing. We also confirm previous data on the frequency distribution of sleep stages, SpO2, and relative rarity of respiratory events in this age group.

Relationship between sweat chloride, sodium, and age in clinically obtained samples.

BACKGROUND: The relationship between sweat electrolytes and age is uncertain, as is the value of measuring sodium or the chloride:sodium ratio. METHODS: 13,785 sweat tests performed over 23 years at one center through the Macroduct collection in clinically obtained samples were analyzed. RESULTS: Sweat chloride tended to decrease over the first year of life, slowly increase until the fourth decade, then either level off or slightly decrease. In children, sweat sodium overlapped between those with positive and negative sweat tests, but not in adults. If the sweat test was positive, there was a higher likelihood of having a chloride:sodium ratio >1, but most subjects with a ratio >1 did not have CF. CONCLUSIONS: Sweat chloride and sodium vary with age. Measurement of sweat sodium did not add discriminatory value. The proportion of subjects with a chloride:sodium ratio >1, with or without CF, varied greatly between age ranges.