Michael Tracy, MD

Abstract

Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.The mean gestational age of the study population was 26.52.2 weeks and most subjects (69.1%) had severe BPD. The mean number of children in households (including the subject) was 2.11.3 children. Each additional child in the household was associated with a 13% increased risk for hospital admission, 13% increased risk for antibiotic use for respiratory illnesses, 10% increased risk for coughing/wheezing/shortness of breath, 14% increased risk for nighttime symptoms, and 18% increased risk for rescue medication use. Additional analyses found that the increased risks were most prominent when there were threeor more other children in the household.We observed that additional children in the household were a risk factor for adverse respiratory outcomes. We speculate that secondary person-to-person transmission of respiratory viral infections drives this finding. While this risk factor is not easily modified, measures do exist to mitigate this disease burden. Further studies are needed to define best practices for mitigating this risk associated with household viral transmission.

View details for DOI 10.1002/ppul.26747

View details for PubMedID 37937888

Abstract

To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation.Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests.There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P .001 for all events).There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

View details for DOI 10.1542/peds.2022-060651

View details for PubMedID 37122061

Abstract

Despite bronchopulmonary dysplasia (BPD) being a common morbidity of preterm birth, there is no validated objective tool to assess outpatient respiratory symptom control for clinical and research purposes.Data were obtained from 1049 preterm infants and children seen in outpatient BPD clinics of 13 U.S. tertiary care centers from 2018-2022. A new standardized instrument was modified from an asthma control test questionnaire and administered at the time of clinic visits. External measures of acute care use were also collected. The questionnaire for BPD control was validated in the entire population and selected subgroups using standard methodology for internal reliability, construct validity, and discriminative properties.Based on the scores from BPD control questionnaire, the majority of caregivers (86.2%) felt their child's symptoms were under control, which did not differ by BPD severity (p=0.30) or a history of pulmonary hypertension (p=0.42). Across the entire population and selected subgroups, the BPD control questionnaire was internally reliable, suggestive of construct validity (albeit correlation coefficients were -0.2 to -0.4.), and discriminated control well. Control categories (controlled, partially controlled, and uncontrolled) were also predictive of sick visits, emergency department visits, and hospital readmissions.Our study provides a tool for assessing respiratory control in children with BPD for clinical care and research studies. Further work is needed to identify modifiable predictors of disease control and link scores from the BPD control questionnaire to other measures of respiratory health such as lung function testing. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ppul.26358

View details for PubMedID 36793145

Abstract

Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers.We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains.Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge.Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD. Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. Benefits of interdisciplinary care for children have been observed in other chronic conditions.. Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..

View details for DOI 10.1055/s-0042-1755589

View details for PubMedID 36477715

Abstract

Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46-48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.

View details for DOI 10.3389/fped.2022.1012136

View details for PubMedCentralID PMC9615143

Abstract

To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater healthcare utilization for respiratory illnesses during the first three years of life.Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from nine BPD specialty clinics in the United States. All subjects were former preterm infants (<34 weeks) with BPD (71% severe) requiring outpatient follow-up between 0-3 years of age. Mixed logistic regression models were used to test for associations.Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to three years of age were also more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6-12 months chronological age.In this study, preterm children with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids and have chronic respiratory symptoms compared with children not in daycare indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.

View details for DOI 10.1016/j.jpeds.2022.06.037

View details for PubMedID 35803300

Abstract

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial NICU discharge.METHODS: Subjects were recruited from BPD clinics at ten tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart review. Surveys for clinical outcomes were administered to caregivers.RESULTS: Of the 470 subjects included in this study, 249 (53.0%) received employer-based insurance coverage and 221 (47.0%) received Medicaid as sole coverage at least once between 0-3 years of age. The Medicaid group was twice as likely to have sick visits (adjusted OR: 2.06; p=0.009) and emergency department visits (aOR: 2.09; p=0.028) and three times more likely to be admitted for respiratory reasons (aOR: 3.04; p=0.001) than those in the employer-based group. Additionally, those in the Medicaid group were more likely to have nighttime respiratory symptoms (aOR: 2.62; p=0.004).CONCLUSIONS: Children with BPD who received Medicaid coverage were more likely to utilize acute care and have nighttime respiratory symptoms during the first three years of life. More comprehensive studies are needed to determine why whether use of Medicaid represents a population with barriers to accessing care, lower socioeconomic status, and/or detrimental environmental exposures. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ppul.25933

View details for PubMedID 35437911

View details for DOI 10.1513/AnnalsATS.202201-007CME

View details for PubMedID 35239469

Abstract

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics.METHODS: Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up.RESULTS: A total of 413 preterm infants and children were recruited (mean age: 2.42.7 years) with a mean gestational age of 27.02.8 weeks and a mean birthweight of 951429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p=.001), home positive pressure ventilation (p=.003), diuretics (p<.001), inhaled corticosteroids (p<.001), and pulmonary vasodilators (p<.001) were found between centers, however no differences in acute care use were observed.DISCUSSION: This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.

View details for DOI 10.1002/ppul.25332

View details for PubMedID 33713587

Abstract

We performed a point prevalence study on infants with severe BPD collecting data on type and settings of ventilatory support; 187 infants were included from 15 centers, 51% who were on invasive positive pressure ventilation. We found significant center-specific variation in ventilator modes.

View details for DOI 10.1016/j.jpeds.2021.10.036

View details for PubMedID 34710394

Abstract

Bronchopulmonary dysplasia (BPD) has evolved considerably since its first description over 50 years ago. This review aims to provide a historical framework for conceptualizing BPD and a current understanding of the changing definition, epidemiology, pathophysiology, treatment, and outcomes of BPD. The transdisciplinary approach that led to the initial phenotypic description of BPD continues to hold promise today. Investigators are refining the definition of BPD in light of changes in clinical care and increasing survival rates of very preterm infants. Despite improvements in perinatal care the incidence of BPD continues to increase. There is growing recognition that antenatal risk factors play a key role in the development of BPD. Strategies designed to prevent or limit neonatal lung injury continue to evolve. Defining the phenotype of infants with BPD can meaningfully direct treatment. Infants with BPD benefit from an interdisciplinary approach to longitudinal care with a focus on growth and neurocognitive development. While the ultimate impact of BPD on long-term pulmonary morbidity remains an active area of investigation, current data indicate that most children and adolescents with a history of BPD have a quality of life comparable to that of other preterm infants.

View details for DOI 10.1089/ped.2020.1205

View details for PubMedID 35922031

View details for DOI 10.1089/ped.2020.1205

View details for DOI 10.1016/j.jpeds.2020.12.055

View details for PubMedID 33359301

View details for Web of Science ID 000556622800204

Abstract

Background: There is increasing interest in the pulmonary microbiome's bacterial and viral communities, particularly in the context of chronic airway infections in cystic fibrosis (CF). However, the isolation of microbial DNA from the sputum from patients with CF is technically challenging and the optimal protocols for the analysis of viral species, including bacteriophage, from clinical samples remains difficult. Materials and Methods: In this study, we evaluate a set of methods developed for processing and analyzing sputum from patients with CF with the goal of detecting Pf bacteriophage virion-derived nucleic acid. We evaluate the impact of bead beating, deoxyribonuclease digestion, and heating steps in these protocols focusing on the quantitative assessment of Pseudomonas aeruginosa and Pf bacteriophage in sputum. Results: Based on these comparative data, we describe an optimized protocol for processing sputum from patients with CF and isolating DNA for polymerase chain reaction or sequencing-based studies. Conclusion: These studies demonstrate the assessment of a specific bacteriophage and bacteria in sputum from patients with CF.

View details for DOI 10.1089/phage.2020.0003

View details for PubMedID 32626852

View details for PubMedCentralID PMC7327540

View details for Web of Science ID 000466776701222

View details for Web of Science ID 000466776701221

View details for DOI 10.1002/ppul.24126

View details for Web of Science ID 000446457700006

Abstract

Fungal infection in cystic fibrosis (CF) is a recognized challenge, with many areas requiring further investigation. Consensus definitions exist for allergic bronchopulmonary aspergillus in CF, but the full scope of clinically relevant non-allergic fungal disease in CF-asymptomatic colonization, transient or chronic infection localized to endobronchial mucus plugs or airway tissue, and invasive disease-is yet to be clearly defined. Recent advances in mycological culture and non-culture identification have expanded the list of both potential pathogens and community commensals in the lower respiratory tract. Here we aim to outline the current understanding of fungal presence in the CF respiratory tract, risk factors for acquiring fungi, host-pathogen interactions that influence the role of fungi from bystander to pathogen, advances in the diagnostic approaches to isolating and identifying fungi in CF respiratory samples, challenges of classifying clinical phenotypes of CF patients with fungi, and current treatment approaches. Development and validation of biomarkers characteristic of different fungal clinical phenotypes, and controlled trials of antifungal agents in well-characterized target populations, remain central challenges to surmount and goals to be achieved.

View details for PubMedID 29992775

Abstract

This review aims to provide clinicians engaged in the care of infants and children an update on the current understanding of the epidemiology, etiology, diagnostic evaluation, and clinical management of complicated pneumonia. The review provides timely information surrounding areas of consensus and ongoing research.The epidemiology and etiologies of complicated pneumonia continue to evolve over the past several decades in context of the introduction of new vaccines. We review uncommon and emerging pathogens. Immunocompromised patients are particularly at risk for complications. The 2011 clinical practice guidelines for pediatric community-acquired pneumonia from The Pediatric Infectious Diseases Society/Infectious Diseases Society of America and the British Thoracic Society are changing approaches to evaluation and management. The efficacy of new diagnostic laboratory studies, and imaging techniques, continues to be studied. Antibiotics are the mainstay of treatment, with several new options to consider. Techniques for the drainage of parapneumonic effusions continue to optimize.Although much is known about complicated pneumonia, it remains a significant burden. New diagnostic and therapeutic interventions hold much promise. This review seeks to provide clinicians with evidence that motivates a reasoned approach to the evaluation and management of complicated pneumonia.

View details for PubMedID 29528891

View details for Web of Science ID 000449980302106

Abstract

Bronchopulmonary dysplasia (BPD) or chronic lung disease of infancy BPD was originally described 50 years ago, in 1967 by Northway et al. This article possesses two fundamental objectives to provide: a brief historical perspective on BPD; and an update relative to current notions of epidemiology, pathophysiology, evaluation, and clinical management of BPD complicated by vascular disease. The review highlights areas of consensus and ongoing uncertainty.The clinical cause and presentation of infants with BPD has evolved over the past several decades. Considerable improvements in neonatal care, including surfactant replacement therapies, antenatal steroids, nutritional support, ventilator management, and attention to the potential of oxygen toxicity, underlie the evolution of BPD. Most children with BPD improve over time. However, in the presence of vascular disease, the morbidity and mortality associated with BPD increases considerably. Though recent recommendations include procuring an echocardiogram to screen for pulmonary hypertension in infants with established BPD, there is less agreement surrounding the additional diagnostic and putative treatment modalities for infants with BPD and pulmonary hypertension. The indications, rationale, potential benefits, and risks of vasodilator therapy in BPD are discussed.The pediatric community has 50 years of experience with BPD. Past experience should be used to inform present and future diagnostic and treatment strategies. This review seeks to arm the clinician with evidence that motivates a physiology-based approach to the management of infants with BPD and pulmonary hypertension.

View details for DOI 10.1097/MOP.0000000000000490

View details for Web of Science ID 000401074000011

View details for PubMedID 28338487

Abstract

Children with Tetralogy of Fallot, Pulmonary Atresia, and Major Aortopulmonary Collaterals (TOF/PA/MAPCAs) undergoing unifocalization surgery are at risk for developing more postoperative respiratory complications than children undergoing other types of congenital heart surgery. Bronchoscopy is used in the perioperative period for diagnostic and therapeutic purposes. In this study, we describe bronchoscopic findings and identify factors associated with selection for bronchoscopy.Retrospective case-control.All patients with TOF/PA/MAPCAs who underwent unifocalization surgery from September 2005 through March 2016 were included. Patients who underwent bronchoscopy in the perioperative period were compared to a randomly selected cohort of 172 control patients who underwent unifocalization without bronchoscopy during the study period.Forty-three children underwent perioperative bronchoscopy at a median of 9 days postoperatively. Baseline demographics were similar in bronchoscopy patients and controls. Patients who underwent bronchoscopy were more likely to have a chromosome 22q11 deletion and were more likely have undergone unifocalization surgery without intracardiac repair. These patients had a longer duration of mechanical ventilation, ICU duration, and length of hospitalization. Abnormalities were detected on bronchoscopy in 35 patients (81%), and 20 (35%) of bronchoscopy patients underwent a postoperative intervention related to abnormalities identified on bronchoscopy.Bronchoscopy is a useful therapeutic and diagnostic instrument for children undergoing unifocalization surgery, capable of identifying abnormalities leading to an additional intervention in over one third of patients. Special attention should be given to children with a 22q11 deletion to expedite diagnosis and intervention for possible airway complications.

View details for DOI 10.1002/ppul.23732

View details for PubMedID 28504356

View details for DOI 10.1542/hpeds.2017-0047

Abstract

Allergic bronchopulmonary aspergillosis (ABPA), a progressive fungal allergic lung disease, is a common complication of asthma or cystic fibrosis. Although ABPA has been recognized since the 1950s, recent research has underscored the importance of Th2 immune deviation and granulocyte activation in its pathogenesis. There is also strong evidence of widespread under-diagnosis due to the complexity and lack of standardization of diagnostic criteria. Treatment has long focused on downregulation of the inflammatory response with prolonged courses of oral glucocorticosteroids, but more recently concerns with steroid toxicity and availability of new treatment modalities has led to trials of oral azoles, inhaled amphotericin, pulse intravenous steroids, and subcutaneously-injected anti-IgE monoclonal antibody omalizumab, all of which show evidence of efficacy and reduced toxicity.

View details for DOI 10.3390/jof2020017

View details for PubMedID 29376934

View details for PubMedCentralID PMC5753079

View details for DOI 10.3390/jof2020017

View details for Web of Science ID 000390749606226

View details for Web of Science ID 000390749600791

View details for Web of Science ID 000390749607182

Abstract

Many pediatric lung diseases are characterized by infection. These infections are generally diagnosed, studied, and treated using standard culture methods to identify 'traditional pathogens'. Based on these techniques, healthy lungs have generally been thought to be sterile. However, recent advances in culture-independent microbiological techniques challenged this paradigm by identifying diverse microbes in respiratory specimens (respiratory microbiomes) from both healthy people and those with diverse lung diseases. In addition, growing evidence suggests a link between gastrointestinal microbiomes and inflammatory diseases of various mucosal surfaces, including airways.This article reviews the rapidly developing field of respiratory microbiome research, emphasizing recent progress made employing increasingly sophisticated technologies. Although many of the relevant studies have focused on adults with cystic fibrosis, recent research has included children and adults with other respiratory diseases, as well as healthy individuals. These studies suggest that even healthy children have airway microbiomes, and that both respiratory and gastrointestinal microbiomes often differ between healthy people and those with different types and severities of airway disease. The causal relationships between microbiomes, disease type and progression, and treatments such as antibiotics must now be defined.The advent of culture-independent microbiological techniques has transformed how we think about the relationship between microbes and airway disease. More research is required to translate these findings to improved therapies and preventive strategies.

View details for DOI 10.1097/MOP.0000000000000212

View details for Web of Science ID 000354214800014

View details for PubMedID 25888147

View details for PubMedCentralID PMC4443818

View details for Web of Science ID 000377582808179

View details for Web of Science ID 000209838206541