Improving Asthma Control Test completion rates across a multi-site pediatric pulmonary clinic network: a quality improvement initiative.

Objective: Assessing asthma control is an essential part of the outpatient management of children with asthma and can be performed through validated questionnaires such as the Asthma Control Test (ACT). Systematic approaches to incorporating the ACT in outpatient visits are often lacking, contributing to inconsistent completion rates. We conducted a quality improvement initiative to increase the proportion of visits where the ACT is completed for children with asthma in our multi-site pediatric pulmonary clinic network.Methods: We developed an intervention of sending the ACT questionnaire to patients and caregivers through the electronic patient portal to complete prior to their visits. This strategy was first piloted at one clinic beginning in July 2020 and then expanded to 5 other clinics in the network in October 2020. Our outcome measure was average monthly proportion of visits with a completed ACT, tracked using statistical process control charts. The process measure was method of ACT completion tracked using run charts.Results: At the pilot clinic, average monthly completion rate rose within 3 months of the intervention from 27% to 72% and was sustained more than 22 months. Completion across all clinics increased from 57% pre-intervention to 76% post-intervention. Importantly, the intervention did not rely on clinic staff to administer the questionnaire and did not interfere with existing clinic flow.Conclusion: An intervention of delivering the ACT electronically to patients and caregivers for completion prior to visits led to a rapid and sustained improvement in ACT completion rates across a large, pediatric pulmonary clinic network.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Clinical and radiological characteristics of e-cigarette or vaping product use associated lung injury.

PURPOSE: E-cigarette or vaping product use associated lung injury (EVALI) has received national attention as an epidemic resulting in cases of significant morbidity and mortality. We aim to present the clinical and imaging findings in adolescents with pulmonary symptoms from suspected EVALI. METHODS: Chest radiographs and CTs of adolescents (< 19 years) with acute pulmonary symptoms and history of vaping were reviewed by two radiologists in consensus. Clinical presentation and laboratory data were derived from the electronic medical records including pulmonary function tests (PFTs). RESULTS: Eleven patients were identified (9 male, mean 16.6 years). The most common presentation was progressive, subacute respiratory distress with abdominal pain. All but one of the patients tested positive for tetrahydrocannabinol. Chest radiograph features were notable for interstitial pattern of opacities (91%) and basilar abnormalities (82%). CT features were notable for ground-glass opacities (89%), interstitial opacities (78%), and subpleural sparing (67%). Eight patients underwent PFTs. Six had diffusing capacity measurement, which demonstrated impaired diffusion in 3 (50%). All patients received supportive treatment with supplemental oxygen and corticosteroids. CONCLUSION: Adolescents with suspected EVALI commonly present with subacute respiratory distress with abdominal pain. Imaging findings include ground-glass opacities, subpleural sparing, and basilar opacities, most consistent with organizing pneumonia or hypersensitivity pneumonitis. Recognition of the common imaging findings may have significant patient management implications, especially if the diagnosis is not suspected clinically. The lung function effects of vaping are consistent with mildly reduced airflow, which improves on follow-up testing, and reduced diffusion capacity, which, concerningly, does not improve.

Clinical and molecular spectrum of CHOPS syndrome.

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.

Hypoxemia in sickle cell disease: significance and management.

Hypoxemia is common in SCD and likely exacerbates SCD vasculopathy. Pulse oximeter correlation with arterial oxygen tension in patients with SCD may at times be poor and arterial blood gas confirmation is required in hypoxic patients. Supplemental oxygen should be administered for the correction of hypoxemia, which if untreated creates a risk of multi-organ failure. Transfusion and hydroxyurea can improve oxygen delivery to tissues and organs. The role of supplemental oxygen therapy in preventing or reversing SCD vasculopathy is controversial. Nitric oxide therapy for VOC pain has not fulfilled promise to date. On the other hand, lung distension (CPAP, incentive spirometry, PEP therapy) are promising treatments requiring further study.

Respiratory muscle force and lung volume changes in a population of children with sickle cell disease.

Sickle cell disease (SCD) is a disorder known to impact the respiratory system. We sought to identify respiratory muscle force and lung volume relationships in a paediatric SCD population. Thirty-four SCD-SS subjects underwent pulmonary function testing. Height, weight, age, and gender-adjusted percent predicted maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values were compared to spirometry and lung volumes. Statistical analyses were performed using Pearson's correlation coefficient and paired two-tailed t-test. The mean ± standard deviation (SD) MIP and MEP was 69·6 ± 31·6 cm H2 O and 66·9 ± 22·9 cm H2 O, respectively, and mean ± SD percent predicted MIP (101·3 ± 45·9) exceeded MEP (72·1 ± 26·0) (P = 0·002). MIP correlated with forced vital capacity (FVC; r = 0·51, P = 0·001) and TLC (r = 0·54, P < 0·0001). MEP also correlated with FVC (r = 0·43, P = 0·011) and total lung capacity (TLC; r = 0·42, P = 0·013). Pearson's correlation coefficient testing yielded relationships between MIP and MEP (r = 0·64, P < 0·0001). SCD-SS patients showed correlations between respiratory muscle force and lung volume, and reduced percent predicted expiratory muscle force compared to inspiratory muscle force. Respiratory muscle strength may affect lung volumes in these patients, and expiratory muscles may be more susceptible than the diaphragm to SCD-induced vaso-occlusive damage.

Variants of DENND1B associated with asthma in children.

BACKGROUND: Asthma is a complex disease that has genetic and environmental causes. The genetic factors associated with susceptibility to asthma remain largely unknown. METHODS: We carried out a genomewide association study involving children with asthma. The sample included 793 North American children of European ancestry with persistent asthma who required daily inhaled glucocorticoid therapy and 1988 matched controls (the discovery set). We also tested for genomewide association in an independent cohort of 917 persons of European ancestry who had asthma and 1546 matched controls (the replication set). Finally, we tested for an association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31 and asthma in 1667 North American children of African ancestry who had asthma and 2045 ancestrally matched controls. RESULTS: In our meta-analysis of all samples from persons of European ancestry, we observed an association, with genomewide significance, between asthma and SNPs at the previously reported locus on 17q21 and an additional eight SNPs at a novel locus on 1q31. The SNP most strongly associated with asthma was rs2786098 (P=8.55x10(-9)). We observed replication of the association of asthma with SNP rs2786098 in the independent series of persons of European ancestry (combined P=9.3x10(-11)). The alternative allele of each of the eight SNPs on chromosome 1q31 was strongly associated with asthma in the children of African ancestry (P=1.6x10(-13) for the comparison across all samples). The 1q31 locus contains the 1q31 locus contains DENND1B, a gene expressed by natural killer cells and dendritic cells. DENND1B protein is predicted to interact with the tumor necrosis factor α receptor [corrected]. CONCLUSIONS: We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma.

The impact of obstructive sleep apnea in children with sickle cell disease and asthma.

INTRODUCTION: Asthma and obstructive sleep apnea (OSA) are chronic diseases that disproportionately affect children with sickle cell disease (SCD). The literature describes the negative impact that both conditions have on children with SCD separately; however, the effect of OSA on asthmatic children with OSA is less specific. We hypothesized that the presence of OSA in children with SCD and asthma is associated with specific hematologic markers, worse clinical outcomes, and greater healthcare utilization. METHODS: We retrospectively evaluated children with both SCD and asthma who underwent polysomnography (PSG). We assessed their demographic information, PSG data, hematologic indices, and healthcare utilization based on the concurrent presence of OSA. RESULTS: Fifty-nine percent of the cohort had OSA with a lower oxygen saturation (SpO2 ) nadir (87% vs. 93%, p < 0.001) and a lower median daytime SpO2 (96.5% vs. 98.5%, p < 0.05); those with OSA were more likely to have the hemoglobin SS genotype (86% vs. 46.5%, p = 0.03). Additionally, those with OSA had a higher mean corpuscular volume (87 vs. 77.2 fL, p = 0.03) and reticulocyte count (10.1% vs. 5.5%, p < 0.01). There was no difference in asthma severity or healthcare utilization between those with OSA and those without OSA. DISCUSSION: Overall, children with SCD and asthma might be at increased risk for developing OSA, and screening for sleep-disordered breathing should be incorporated as part of their routine care.

High prevalence of aquagenic wrinkling of the palms in patients with cystic fibrosis and association with measurable increases in transepidermal water loss.

Aquagenic wrinkling of the palms (AWP) is a cutaneous phenomenon marked by the transient formation of edematous, translucent papules and plaques on the palms and fingertips within minutes of water exposure. AWP is anecdotally reported in patients with cystic fibrosis (CF) and several studies have recently confirmed this association. The primary aim of this study was to determine the prevalence of aquagenic wrinkling of the palms in subjects with cystic fibrosis (CF) compared to controls, and secondarily to evaluate for genotype-phenotype correlations among CF subjects found to have AWP. Fifty-one children with CF and 25 control children who were being treated for asthma underwent a 5-minute hand immersion in lukewarm water. The test for AWP was positive if subjects demonstrated >30% wrinkling over the palm. Secondary analyses explored associations with genotype, pancreatic and pulmonary function, body mass index (BMI), and sweat chloride levels. Palmar transepidermal water loss (TEWL) was also measured for all subjects with and without AWP. Forty-three of the subjects (84%) with CF demonstrated aquagenic wrinkling, in contrast to none (0%) of the controls. These results remained statistically significant when stratified for by age and race. TEWL was significantly higher in CF subjects with AWP compared to CF subjects without AWP and controls. No genotype-phenotype correlations were detected in patients with AWP, nor were there associations of AWP with other phenotypic features of CF, although these analyses were likely underpowered. Aquagenic wrinkling of the palms is prevalent in children with CF and is associated with increased TEWL.

Benefit of pulmonary subspecialty care for children with sickle cell disease and asthma.

OBJECTIVE: Asthma is a recognized comorbidity in children with sickle cell disease (SCD). It increases the risk of acute chest syndrome (ACS), vaso-occlusive episodes, and early mortality. We aim to determine whether evaluation and management of children with SCD and asthma by a pulmonologist reduce rate of asthma exacerbation and ACS. METHODS: The study included 192 patients with SCD (0-21 years) followed at Children's Hospital of Philadelphia Hematology between January 1, 2015, and December 31, 2018, with a diagnosis of asthma, wheeze, or cough. Patients were placed in two groups: those evaluated by a pulmonologist (SCD-A-P) and those not (SCD-A). Rates of emergency department (ED) visits and hospitalizations for asthma exacerbation and ACS were compared between groups and over time. RESULTS: SCD-A-P patients (n = 70) were predominantly SCD type SS with lower hemoglobin and hematocrit compared to SCD-A patients (n = 122). SCD-A-P started with a higher average rate of hospital visits for asthma exacerbation and ACS per year (2.69 [1.02-4.37]) compared to SCD-A (0.43 [0.24-0.63]), (p < 0.001). For SCD-A-P patients with at least one hospital visit (n = 48), the average rate decreased from 3.93 (1.57-6.29) to 0.85 (0.48-1.23) following pulmonary consultation (p = 0.014) and was comparable to the SCD-A rate by study end. CONCLUSION: SCD-A-P was mainly SCD type SS and had higher ED/hospitalization rates for asthma exacerbation and ACS compared to SCD-A, but the rates significantly decreased following pulmonology consultation. These findings support the pulmonologist's role in the multidisciplinary care of SCD patients and highlight the need for evidence-based asthma guidelines for children with SCD.

Pediatric Simulation of Intrinsic PEEP and Patient-Ventilator Trigger Asynchrony During Mechanical Ventilation.

BACKGROUND: Intrinsic PEEP during mechanical ventilation occurs when there is insufficient time for expiration to functional residual capacity before the next inspiration, resulting in air trapping. Increased expiratory resistance (RE), too rapid of a patient or ventilator breathing rate, or a longer inspiratory to expiratory time ratio (TI/TE) can all be causes of intrinsic PEEP. Intrinsic PEEP can result in increased work of breathing and patient-ventilator asynchrony (PVA) during patient-triggered breaths. We hypothesized that the difference between intrinsic PEEP and ventilator PEEP acts as an inspiratory load resulting in trigger asynchrony that needs to be overcome by increased respiratory muscle pressure (Pmus). METHODS: Using a Servo lung model (ASL 5000) and LTV 1200 ventilator in pressure control mode, we developed a passive model demonstrating how elevated RE increases intrinsic PEEP above ventilator PEEP. We also developed an active model investigating the effects of RE and intrinsic PEEP on trigger asynchrony (expressed as percentage of patient-initiated breaths that failed to trigger). We then studied if trigger asynchrony could be reduced by increased Pmus. RESULTS: Intrinsic PEEP increased significantly with increasing RE (r = 0.97, P = .006). Multivariate logistic regression analysis showed that both RE and negative Pmus levels affect trigger asynchrony (P < .001). CONCLUSIONS: A passive lung model describes the development of increasing intrinsic PEEP with increasing RE at a given ventilator breathing rate. An active lung model shows how this can lead to trigger asynchrony since the Pmus needed to trigger a breath is greater with increased RE, as the inspiratory muscles must overcome intrinsic PEEP. This model will lend itself to the study of intrinsic PEEP engendered by a higher ventilator breathing rate, as well as higher TI/TE, and will be useful in ventilator simulation scenarios of PVA. The model also suggests that increasing ventilator PEEP to match intrinsic PEEP can improve trigger asynchrony through a reduction in RE.

Bronchopulmonary dysplasia-A historical perspective.

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.

Stakeholder Involvement in Evaluation: Does it Affect Observers' Perceptions of an Evaluation? And Which Stakeholder Group(s) Do People Think Should to Participate?

BACKGROUND: Stakeholders are often involved in evaluation, such as in the selection of specific research questions and the interpretation of results. Except for the topic of whether stakeholder involvement increases use, a paucity of research exists to guide practice regarding stakeholders. OBJECTIVES: We address two questions: (1) If a third-party observer knows stakeholders were involved in an evaluation, does that affect the perceived credibility, fairness, and relevance of the evaluation? (2) Among individuals with a possible stake in an evaluation, which stakeholder group(s) do they want to see participate; in particular, do they prefer that multiple stakeholder groups, rather than a single group, participate? RESEARCH DESIGN: Six studies are reported. All studies address the former question, while Studies 3 to 5 also focus on the latter question. To study effects of stakeholder involvement on third-party views, participants read summaries of ostensible evaluations, with stakeholder involvement noted or not. To examine a priori preferences among potential stakeholders, participants completed a survey about alternative stakeholder group involvement in an evaluation in which they would likely have an interest. RESULTS AND CONCLUSIONS: Across studies, effects of reported stakeholder participation on third-parties' views were not robust; however, small effects on perceived fairness sometimes, but not always, occurred after stakeholder involvement and its rationales had been made salient. All surveys showed a large preference for the involvement of multiple, rather than single stakeholder groups. We discuss implications for research and practice regarding stakeholder involvement, and for research on evaluation more generally.

Pulmonary complications of neuromuscular disease: a respiratory mechanics perspective.

Paediatric neuromuscular disease compromises both the gas exchange and pump functions of the respiratory system. This can have profound implications for both growth and development of the respiratory system, as well as morbidity and mortality. Aspiration lung disease is common, and leads to increasingly restrictive pulmonary physiology over time. Abnormal lung and chest wall mechanics, and weak respiratory muscles, can combine to cause respiratory failure. Improving the balance between the work of breathing (by decreasing the respiratory load) and the respiratory pump (by improving respiratory muscle strength and decreasing respiratory muscle fatigue) can help prevent the onset of respiratory failure. Airway clearance techniques and non-invasive ventilation are two important tools in this effort. Better ways of assessing the respiratory pump, mechanical function, control and fatigue are needed especially in children.

Airway function throughout the lifespan: Pediatric origins of adult respiratory disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death of adults in the USA and worldwide. While environmental factors such as smoking and air pollution are major contributors to COPD, pediatric respiratory disease and more specifically early childhood wheezing are frequent predisposing factors. It is therefore possible that aggressive prevention and treatment of childhood respiratory illness may modify adult COPD risk. This article reviews some of the physiological factors that may explain the pediatric origins of childhood lung disease. One such factor is the "tracking" of normal lung function which occurs with growth. The maximal expiratory flow volume (MEFV) curve is an ideally suited tool to monitor tracking of airway function over the lifespan, as its relative effort independence makes it highly reliable. Study of the MEFV curve has demonstrated that individuals with similar lung volumes can have large differences in maximal flows, reflecting a disconnection between airway and lung growth ("dysanapsis"). Less than average airway size due to dysanaptic airway growth or airway remodeling may be independent risk factors for the development of COPD and the asthma/COPD overlap syndrome in adult life. There are intriguing early data suggesting that perhaps at least some of this risk is modifiable by improving asthma control with inhaled corticosteroids and minimizing asthma exacerbations.

"Reactance inversion" at low frequencies in a child undergoing treatment of a cystic fibrosis exacerbation.

INTRODUCTION: Impulse oscillometry (IOS) employs high frequency sinusoidal or impulse pressure and flow waveforms to interrogate the mechanical properties of the respiratory system. It has special applications to preschool and younger children who may have difficulty performing the repetitive forced expiratory maneuvers required for spirometry. CASE PRESENTATION: We present a case illustrating improvements of respiratory system mechanics measured by IOS in a 6-year-old child with cystic fibrosis (CF) who demonstrated clinical and radiological improvement after a course of therapy with hospitalization and intravenous antibiotics, and initiation of a cystic fibrosis transmembrane regulator (CFTR) protein corrector/potentiator agent. We also report a new finding: observed lower than expected reactance at low compared to high frequencies ("reactance inversion"). CONCLUSION: Reactance inversion may reflect parallel pathway inhomogeneities in resistance and elastance or intrabreath airway inertance changes in young children with CF. Further study is needed in children with airway obstruction due to asthma, cystic fibrosis, and chronic lung disease of infancy to demonstrate the prevalence of this finding and whether it is specific to a measurement device.

Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.

Background: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions. Participants were divided into four subcommittees on the basis of expertise: 1) acute chest syndrome, 2) lower airways disease and pulmonary function, 3) sleep-disordered breathing and hypoxia, and 4) pulmonary vascular complications of SCD. Before the workshop, a comprehensive literature review of each subtopic was conducted. Clinically important questions were developed after literature review and were finalized by group discussion and consensus.Results: Current knowledge is based on small, predominantly observational studies, few multicenter longitudinal studies, and even fewer high-quality interventional trials specifically targeting the pulmonary complications of SCD. Each subcommittee identified the three or four most important unanswered questions in their topic area for researchers to direct the next steps of clinical investigation.Conclusions: Important and clinically relevant questions regarding sickle cell lung disease remain unanswered. High-quality, multicenter, longitudinal studies and randomized clinical trials designed and implemented by teams of multidisciplinary clinician-investigators are needed to improve the care of individuals with SCD.