Education and implementation of home spirometry in an adolescent cystic fibrosis population.

BACKGROUND: Lung function in individuals with cystic fibrosis (CF) is closely monitored as an objective marker of clinical status. The COVID-19 pandemic shifted our ability to assess individuals from in-person to remote monitoring using telehealth. As part of efforts to monitor individuals remotely during this time, this study describes the process of education and implementation of home spirometry in an adolescent CF population at Nemours Children's Hospital in Wilmington, Delaware, USA. In addition, this study reviews the ability of adolescents with CF to produce reliable, consistent, and accurate results using home spirometry. METHODS: This was a quality-improvement study over a 9-month period at a single CF center. Home spirometers were supplied by the CF Foundation to 40 adolescents with CF. An educational curriculum was used for initial training on the device by a dedicated CF respiratory therapist. After training, participants reported spirometry results weekly until reliable technique was established. Once reliable technique was achieved, participants reported results monthly. Results were retrospectively reviewed to determine accuracy and consistency. The percentages of patients who were able to achieve reliable, consistent, and accurate results were recorded as well as the need for additional training or other reasons for inability to produce ongoing results. RESULTS: Home spirometers were distributed to 40 adolescents. Out of these 40 participants, 35 (88%) completed initial training; 29 (83%) sent at least one set of results, and 24 (60%) established reliable technique after an average of 5 weekly attempts. When home spirometer results were retrospectively reviewed, 83% (20/24) were deemed accurate in comparison to spirometry completed in clinic, and 83% (20/24) showed consistency between efforts sent. CONCLUSION: Home spirometry, when properly implemented with structured education and active participant engagement, has potential to provide meaningful data and feedback to CF care teams. Implementation of this process requires substantial resources and active participation from an adolescent population who are at higher risk for non-adherence. Future studies are needed to determine the impact of home spirometry on clinical outcomes and reliability over time and to address barriers to consistent and enduring engagement in the adolescent population.

Daytime Sleepiness in Children With Asthma: Examining Respiratory and Non-respiratory Factors.

Objective Daytime sleepiness is common in youth with asthma (YWA). Treatments designed to mitigate daytime sleepiness in YWA require an understanding of the primary causes of this problem. We examined respiratory- and non-respiratory-related factors associated with daytime sleepiness in YWA. Methods One hundred YWA (eight to 17 years old) were included in a cross-sectional study. Daytime sleepiness, quality of life, anxiety, bedtime cellphone use, and respiratory symptoms were self-reported. Asthma severity, lung function, and the number of prescribed medications were obtained from electronic medical records. Multivariable regression models identifying variables associated with daytime sleepiness were generated. Results Participants were 54% male and 45% Black, with a mean age of 12.1 years. The multivariable regression model showed decreased quality of life (b = -0.328, p = 0.004) and increased bedtime cellphone use (b = 0.300, p = 0.004)were significantly related to daytime sleepiness, while anxiety (b = 0.213, p = 0.05), prescribed asthma medications (b = 0.173, p = 0.05), and worse lung function (b = -0.173, p = 0.05)were marginally related to daytime sleepiness. Conclusions In addition to optimizing asthma control, strategies targeting anxiety, quality of life, and nocturnal cellphone use are important to mitigate daytime sleepiness in YWA.

Acceptability and feasibility of a brief behavioral sleep intervention for youth with CF.

Youth with CF are at increased risk for physiological and behavioral sleep difficulties due to disease-specific symptoms and more general pediatric sleep challenges. Despite evidence suggesting that behavioral sleep interventions are effective for improving common sleep difficulties, no interventions exist for youth with CF. SLEEP-CF was designed to fill this gap by providing tailored, flexible behavioral sleep support to youth with CF. Results suggest that SLEEP-CF is an acceptable and feasible behavioral sleep intervention, even in a population with normative sleep habits. There may be benefit in terms of improving sleep knowledge and sleep hygiene. Technology use during and after bedtime is prevalent. CF care team members are encouraged to assess sleep as part of routine CF care, and to provide support as indicated.

Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in an adolescent with homozygous G85E cystic fibrosis.

Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) is a triple combination drug therapy approved for individuals with cystic fibrosis (CF) who possess at least one copy of the F508del cystic fibrosis transmembrane conductance regulator (CFTR) variant. ELX/TEZ/IVA improves lung function and decreases the frequency of CF exacerbations in clinical studies, which has led to investigation of this therapy on rare CFTR variants. Rare mutations have limited research publications; therefore, reporting outcomes is critical to expanding knowledge and understanding of therapeutic efficacy. This case highlights a CF adolescent homozygous for the G85E CFTR variant who had resolution of chronic respiratory symptoms after initiating ELX/TEZ/IVA.

Adolescent E-cigarette or Vaping Use-Associated Lung Injury in the Delaware Valley: A Review of Hospital-Based Presentation, Management, and Outcomes.

E-cigarette or vaping use-associated lung injury (EVALI) remains a major concern due to ongoing use of nicotine and/or cannabis-containing products and resulting acute lung injury. There are few published reports describing the clinical features, comorbidities, severity of disease, and outcomes of treatment in adolescents. This report describes the experience of a single tertiary care children's hospital in the Delaware Valley and reviews data from all patients diagnosed with EVALI in the emergency department and inpatient setting from July 2019 to June 2021 at the Nemours Children's Hospital in Wilmington, Delaware. Demographic, clinical, therapeutic, diagnostic features, and outcomes are presented. Abstinence and steroids improved outcomes in our population. Obtaining a vaping history, negative infectious testing, elevated inflammatory markers, and characteristic computed tomography findings were key to making the diagnosis of EVALI.

A Qualitative Exploration of Sleep Habits and Intervention Needs Among Youth with Cystic Fibrosis.

Evidence suggests that individuals with Cystic Fibrosis (CF) experience difficulties with sleep architecture and hygiene, although research is limited. There are currently no behavioral sleep interventions for youth with CF. The current study used qualitative methods to understand sleep needs and concerns among youth with CF, as well as to obtain feedback about potentially useful behavioral sleep intervention strategies. Semi-structured interviews were conducted with youth with CF between the ages of 11-17 and their parents. Themes were extracted from the data and will be used to inform the development of a brief behavioral sleep intervention for youth with CF. Youth and their parents described several CF-specific sleep concerns, often related to respiratory symptoms, and a number of strategies used to manage these concerns. They also described concerns that apply to the general population, including pervasive use of technology around bedtime. Many evidence-based behavioral sleep intervention strategies are acceptable to youth with CF, although modifications are appropriate to reduce time burden and address CF-specific needs. Youth with CF experience a number of disease-specific and more generalized sleep concerns which are likely amenable to behavioral intervention. Results from this study will be used to inform the development of a brief behavioral sleep intervention for youth with CF.

Polysomnographic characteristics and treatment modalities in a referred population of children with trisomy 21.

Background: Children with Trisomy 21 (T21) are at an increased risk of sleep-disordered breathing (SDB), which can impact daily functioning and cause other health complications. Accordingly, it is imperative to diagnose and treat SDB in this population. Current guidelines recommend screening polysomnogram by age 4 or sooner if clinically indicated. There are limited published studies describing characteristics of SDB in children with T21, particularly in infants and young children. Objective: The objective of this study is to characterize SDB and treatment modalities in infants and young children with T21. Methods: This is a retrospective review of a cohort of children (≤60 months of age) with T21 who completed a polysomnogram (PSG) between 2015 and 2020 at a pediatric referral center. Demographic information, relevant medical history, polysomnography parameters, and treatment details of these children were collected from EMR. Descriptive and comparative statistics were calculated for the cohort; additional subgroup analysis was completed by age 0-35 months and 36-60 months. Results: Most of the cohort met criteria for sleep apnea (84.1%), and airway surgery was the most common treatment modality (71.4%). The mean AHI was high (21.4 events/hour) with a trend towards hypoventilation (mean EtCO2 = 55.9 mmHg; mean percentage of TST with EtCO2 > 50 mmHg 20.8%). Mean arousal index was elevated (32 events/hour). There were no significant differences in SDB by age when we compared children 0-35 months and 36-60 months. Conclusions: This cohort of referred children with T21 showed high prevalence of SDB with a trend towards hypoventilation and disrupted sleep quality with no significant differences by age. These data highlight the importance of maintaining a high index of suspicion for SDB in young patients with T21 and obtaining PSG testing to characterize sleep and breathing.

Newborn Screening for Cystic Fibrosis: Infant and Laboratory Factors Affecting Successful Sweat Test Completion.

Newborn screening (NBS) for Cystic Fibrosis (CF) has revolutionized the diagnosis of this inherited disease. CF NBS goals are to identify, diagnose, and initiate early CF treatment to attain better health outcomes. Abnormal CF NBS infants require diagnostic analysis via sweat chloride testing (ST). During ST, insufficient sweat volume collection causes a "quantity not sufficient" (QNS) test result and may delay CF diagnosis. The CF Foundation recommends QNS rates <10% for infants <3 months, but many CF Centers experience difficulties meeting this standard. Our quality improvement (QI) study assessed infant and laboratory factors contributing to ST success and QNS rates from 2017-2019. Infants' day of life (DOL) at successful ST completion was analyzed according to infant factors (birth weight (BW), gestational age, ethnicity, and sex). Laboratory factors and procedures affecting ST outcomes were also reviewed. At our institution, BW and gestational age were the infant factors found to significantly affect DOL at ST completion. ST education, reduced number of laboratory technicians, and direct observation during ST completion also improved ST success rates. This study supports QI measures and partnerships between CF centers and laboratory staff to identify and improve ST QNS rates while sustaining practices to ensure timely CF diagnostic testing.

Abnormal pulmonary lymphatic flow in patients with paediatric pulmonary lymphatic disorders: Diagnosis and treatment.

Pulmonary lymphatic disorders are characterized by the presence of the abnormal lymphatic tissues in the thoracic cavity, presenting clinically as chylothorax, chylopericardium, chyloptysis, interstitial lung disease and plastic bronchitis. These conditions include: neonatal chylothorax, cardiac and non-cardiac plastic bronchitis, non-traumatic chylothorax, post congenital cardiac surgery chylothorax and complex lymphatic malformations. Recently developed lymphatic imaging techniques, such as intranodal lymphangiography and dynamic contrast enhanced magnetic resonance lymphangiography demonstrated abnormal pulmonary lymphatic flow from thoracic duct into pulmonary parenchyma as a pathophysiological mechanism of these diseases. Novel minimally invasive lymphatic interventions, such as thoracic duct embolization, interstitial lymphatic embolization and surgical lympho-venous anastomosis, provide an effective treatment of these conditions.

Status asthmaticus requiring extracorporeal membrane oxygenation associated with rhinovirus infection.

Objective: Evolving research links human rhinovirus (HRV) with status asthmaticus (SA) as well as severe respiratory illness in patients with atopy and asthma. This case series reviews five episodes of HRV-associated SA that required extracorporeal membrane oxygenation (ECMO). Methods: Charts of four patients, five total episodes of ECMO, with SA secondary to HRV were reviewed in this IRB-approved case series. Outcomes included demographic information, past medical history, clinical parameters and spirometry. Results: Patients (three male, one female), mean age 9 years (range 7-12 years) at the time of admission, were African American, on Medicaid, carried a diagnosis of persistent asthma, and had documented non-adherence to prescribed, daily controller medications. One patient had passive smoke exposure. All patients had a mean IgE of 734 (range 12-2497) with seasonal allergic rhinitis was diagnosed in three patients. Cases occurred in spring (3/5) and fall (2/5). Venous/venous ECMO (4/5) or venous/arterial ECMO (1/5) was continued for a mean duration of 4.2 days (range 3-7 days). Spirometry after hospitalization had a mean FEV1 of 1.59 L (81% predicted, range 69%-91%), and an FEF25%-75% 1.13 L (47.5% predicted, range 41%-65%) at an average of 16.7 weeks post ECMO. Conclusions: This case series highlights the association between persistent, poorly controlled asthma and severe SA with HRV infection resulting in ECMO. Despite life-threatening illness, these patients did not demonstrate significant large-airway obstruction following infection. However, patients showed persistently abnormal small airway function, which could be a risk factor or early evidence of vulnerability to infection.

Costello syndrome: Clinical phenotype, genotype, and management guidelines.

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

Quantitative Analysis of Thoracoabdominal Asynchrony in Pediatric Polysomnography.

STUDY OBJECTIVES: Objective measurements of thoracoabdominal asynchrony (TAA), such as average phase angle (θavg), can quantify airway obstruction. This study demonstrates and evaluates use of θavg for predicting obstructive sleep apnea (OSA) in pediatric polysomnography (PSG). METHODS: This prospective observational study recruited otherwise healthy 3- to 8-year-old children presenting for PSG due to snoring, behavioral problems, difficulty sleeping, and/or enlarged tonsils. Respiratory inductance plethysmography (RIP) was directly monitored and data were collected during each PSG. θavg and average labored breathing index (LBIavg) were calculated for earliest acceptable 5-minute periods of stage N3 sleep and stage R sleep. Associations between θavg and obstructive apnea index (OAI) and obstructive apnea-hypopnea index (OAHI), as well as between LBIavg and OAI and OAHI, were examined. RESULTS: Forty patients undergoing PSG were analyzed. Thirty percent of patients had OSA, 57.5% had enlarged tonsils, and 17.5% were obese. θavg during stage N3 sleep and stage R sleep had significant positive correlations with OAI (Spearman r = .35 [P = .03] and .40 [P = .01], respectively) and θavg during stage N3 sleep with OAHI (r = .35 [P = .03]). LBIavg showed lower correlations. Median θavg during stage R sleep (33.1) was significantly greater than during stage N3 sleep (13.7, P = .0005). CONCLUSIONS: Association of θavg with OAI and OAHI shows that θavg reflects airway obstruction and has potential use as a quantitative indicator of OSA. RIP provides valuable information that is readily available in PSG. The significant difference between θavg in stage N3 sleep and stage R sleep confirms the clinical observation that there is more asynchrony during rapid eye movement sleep than non-rapid eye movement sleep.

Risk factor analysis for mortality among infants requiring tracheostomy.

INTRODUCTION: An increasing number of tracheostomies are performed in infants with complex comorbidities including bronchopulmonary dysplasia (BPD) and congenital heart disease (CHD). With this shift in indications, there is an urgent need to characterize outcomes in this population. METHODS: This 5-year retrospective chart review assessed rates of 12-month mortality in infants who were ≤12 months of age at the time of tracheostomy at a tertiary care pediatric hospital and risk factors associated with death. Patient characteristics evaluated included chronologic age and post-menstrual age at tracheostomy placement, gestational age and weight, sex, ethnicity, indication for tracheostomy, and comorbidities including BPD, CHD, subglottic stenosis (SGS), craniofacial syndromes, and chromosomal trisomy syndromes. Subgroup analysis was performed in infants with CHD. RESULTS: One hundred thirty-two tracheostomies were performed during the study period with an overall 12-month mortality of 14.4% (19/132). Mortality was increased in patients with CHD (35%) and decreased in patients with SGS (3.7%). No other patient characteristics were associated with differences in mortality. There was a trend towards improved mortality outcomes among patients born at earlier gestational ages. CONCLUSIONS: Among infants with tracheostomy in this cohort, overall mortality rates were relatively low but not insignificant. CHD was associated with increased mortality; however, children with SGS showed more favorable outcomes. Other patient characteristics were not associated with differences in mortality. These data clarify outcomes in a group of infants with tracheostomy.

Management of Congenital Heart Disease Associated with Ellis-van Creveld Short-rib Thoracic Dysplasia.

OBJECTIVE: To evaluate clinical outcome of patients with Ellis-van Creveld syndrome (EVC) in whom congenital heart disease (CHD) repair was delayed intentionally to reduce the risk of postoperative respiratory morbidity and mortality. STUDY DESIGN: This retrospective review of 51 EVC c.1886+5G>T homozygotes born between 2005 and 2014 focused on 18 subjects who underwent surgery for CHD, subdivided into early (mean, 1.3 months) vs delayed (mean, 50.1 months) repair. RESULTS: Growth trajectories differed between control subjects and patients with EVC, and CHD was associated with slower weight gain. Relative to controls, infants with EVC had a 40%-75% higher respiratory rates (independent of CHD) accompanied by signs of compensated respiratory acidosis. Blood gases and respiratory rates approached normal values by age 4 years. Hemodynamically significant CHD was present in 23 children, 18 (78%) of whom underwent surgical repair. Surgery was performed at 1.3 ± 1.3 months for children born between 2005 and 2009 (n = 9) and 50.1 ± 40.2 months (P = .009) for children born between 2010 and 2014 (n = 9). The latter had shorter postoperative mechanical ventilation (1.1 ± 2.4 days vs 49.6 ± 57.1 days; P = .075), shorter intensive care duration of stay (16 ± 24 days vs 48.6 ± 44.2 days; P = .155), and no postoperative tracheostomies (vs 60%; P = .028) or deaths (vs 44%; P = .082). CONCLUSION: Among children with EVC and possibly other short-rib thoracic dysplasias, delayed surgical repair of CHD reduces postoperative morbidity and improves survival. Respiratory rate serves as a simple indicator for optimal timing of surgical repair.

Pseudomonas eradication and clinical effectivness of Ivacaftor in four Hispanic patients with S549N.

Ivacaftor was approved for rarer class-III CFTR mutations including S549N in 2014. Since these mutations are uncommon, ongoing reports of patient experiences with Ivacaftor and these mutations are important. This case series describes the clinical effectiveness (including airway infection status, lung function, and growth) of Ivacaftor therapy in four pediatric Hispanic patients with S549N and F508del over 24 months. In these patients, Ivacaftor was highly efficacious with no further Pseudomonas-positive cultures despite prior chronic colonization in three patients as well as notable improvements in lung function and growth. The remarkable improvements in lung function and growth were similar to G551D patients with more striking changes in airway infection status. Pediatr Pulmonol 2017;52:E37-E39. © 2017 Wiley Periodicals, Inc.

The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells.

Humidification of inspired gas is important for patients receiving respiratory support. High-flow nasal cannula (HFNC) effectively provides temperature and humidity-controlled gas to the airway. We hypothesized that various levels of gas humidification would have differential effects on airway epithelial monolayers. Calu-3 monolayers were placed in environmental chambers at 37°C with relative humidity (RH) < 20% (dry), 69% (noninterventional comparator), and >90% (HFNC) for 4 and 8 hours with 10 L/min of room air. At 4 and 8 hours, cell viability and transepithelial resistance measurements were performed, apical surface fluid was collected and assayed for indices of cell inflammation and function, and cells were harvested for histology (n = 6/condition). Transepithelial resistance and cell viability decreased over time (P < 0.001) between HFNC and dry groups (P < 0.001). Total protein secretion increased at 8 hours in the dry group (P < 0.001). Secretion of interleukin (IL)-6 and IL-8 in the dry group was greater than the other groups at 8 hours (P < 0.001). Histological analysis showed increasing injury over time for the dry group. These data demonstrate that exposure to low humidity results in reduced epithelial cell function and increased inflammation.

Respiratory mechanics in an infant with perinatal lethal hypophosphatasia treated with human recombinant enzyme replacement therapy.

Hypophosphatasia is a rare autosomal recessive disorder caused by deficient activity of tissue nonspecific alkaline phosphatase (TNSALP) and characterized by defective bone mineralization. In the perinatal lethal form, respiratory complications due to rachitic deformities of the thoracic cage and associated hypoplastic lungs are present. ENB-0040 is a bone-targeted human recombinant TNSALP fusion protein that aims to restore skeletal mineralization. The goal of this study was to characterize pulmonary and thoracic cage mechanics in an infant with the perinatal lethal form of hypophosphatasia under enzyme replacement therapy. Pulmonary function testing was performed on a preterm, 8-week-old patient with hypophosphatasia who was mechanically ventilated since birth because of severe chest wall insufficiency. The measurements consisted of respiratory impulse oscillation measurements (resistance and reactance), ventilatory mechanics (compliance and resistance), and thoracoabdominal motion (TAM) analysis. At baseline, chest wall compliance was 50% of normal, and the TAM indicated predominantly abdominal displacement. After 12 weeks of treatment, a consistent decrease in ventilator requirements and improvement in lung function and chest wall mechanics were observed and correlated with thoracic cage radiologic findings. Measurable changes in chest wall dynamics and respiratory mechanics using noninvasive technology were useful for respiratory management and therapeutic guidance of ENB-0040 treatment in this patient.

Cultured human airway epithelial cells (calu-3): a model of human respiratory function, structure, and inflammatory responses.

This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury.