Health inequities in the modulator era.

PURPOSE OF REVIEW: To discuss the existing health inequities in people with cystic fibrosis (CF) and how the recent development of cystic fibrosis transmembrane regulator (CFTR) modulators may impact these inequities. RECENT FINDINGS: People with CF (pwCF) from low socioeconomic status (SES) have more pulmonary exacerbations, worse nutritional status, lower pulmonary function, and an increased mortality rate with less access to lung transplantation. pwCF who identify as racial and ethnic minorities have earlier mortality, lower lung function, are less likely to be detected on newborn screening resulting in a delayed diagnosis, are underrepresented in clinic trials, and less likely to be eligible for a CFTR modulator. Female sex is associated with more pulmonary exacerbations and earlier mortality. Sexual gender minorities are a vulnerable population with worse health outcomes, and more research is needed in CF. CFTR modulators are inaccessible to low to middle-income countries due to significant cost burden. SUMMARY: People with CF from low SES, racial and ethnic minorities, female sex, and sexual gender minorities face health inequities. CFTR modulator use will further widen existing health inequities given the unequal access to modulators based on nonqualifying genetics and exorbitant cost restricting use both on an individual and global level.

Management of chronic pulmonary disease in the time of coronavirus disease 2019.

PURPOSE OF REVIEW: The purpose of this review is to discuss the most recent data describing the impact of coronavirus disease 2019 (COVID-19) on the pediatric population with chronic pulmonary disease. We specifically focus on children with asthma, cystic fibrosis (CF), and lung transplant recipients. RECENT FINDINGS: Children with asthma, CF, and lung transplant recipients do not appear to have an increased risk of morbidity or mortality with COVID-19 infection compared to the general pediatric population. Data does not support the change or withdrawal of any asthma or CF maintenance medications; however, does advocate for the cessation of aerosolized medications whenever possible to minimize transmission risk. It may not be necessary to adjust immunosuppressive therapy when managing COVID-19 in pediatric lung transplant patients. Mechanisms of infection in airway epithelial cells in children may differ from adults, resulting in a milder phenotype. SUMMARY: Current data about pediatric patients with chronic lung disease infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is promising but remains scarce. Additional study is needed to definitively understand the complex interplay of the SARS-CoV-2 virus in the airway of children with chronic lung disease, how it differs from adults, and how best to manage the symptoms of acute infection.

Development of a miniaturized mechanoacoustic sensor for continuous, objective cough detection, characterization and physiologic monitoring in children with cystic fibrosis.

Cough is an important symptom in children with acute and chronic respiratory disease. Daily cough is common in Cystic Fibrosis (CF) and increased cough is a symptom of pulmonary exacerbation. To date, cough assessment is primarily subjective in clinical practice and research. Attempts to develop objective, automatic cough counting tools have faced reliability issues in noisy environments and practical barriers limiting long-term use. This single-center pilot study evaluated usability, acceptability and performance of a mechanoacoustic sensor (MAS), previously used for cough classification in adults, in 36 children with CF over brief and multi-day periods in four cohorts. Children whose health was at baseline and who had symptoms of pulmonary exacerbation were included. We trained, validated, and deployed custom deep learning algorithms for accurate cough detection and classification from other vocalization or artifacts with an overall area under the receiver-operator characteristic curve (AUROC) of 0.96 and average precision (AP) of 0.93. Child and parent feedback led to a redesign of the MAS towards a smaller, more discreet device acceptable for daily use in children. Additional improvements optimized power efficiency and data management. The MAS's ability to objectively measure cough and other physiologic signals across clinic, hospital, and home settings is demonstrated, particularly aided by an AUROC of 0.97 and AP of 0.96 for motion artifact rejection. Examples of cough frequency and physiologic parameter correlations with participant-reported outcomes and clinical measurements for individual patients are presented. The MAS is a promising tool in objective longitudinal evaluation of cough in children with CF.

Disparities and therapeutic advances in cystic fibrosis.

Cystic fibrosis (CF) has seen a multitude of therapeutic advances targeting its downstream effects. This has led to a steady increase in survival over the past few decades. The recent development of disease-modifying drugs targeting the underlying CFTR mutation has revolutionized treatment for CF. Despite these advances, individuals with CF who are racial and ethnic minorities, from low socioeconomic status, or female sex have worse clinical outcomes. The inequitable access to CFTR modulators from cost and/or genetic eligibility has the potential to further worsen the existing health disparities seen within the CF community.

The upper airway microbiome in Hispanic children with cystic fibrosis.

BACKGROUND: Hispanic people with cystic fibrosis (CF) have decreased life expectancy and earlier acquisition of Pseudomonas aeruginosa compared to non-Hispanic white individuals with CF. Racial and ethnic differences in the airway microbiome of CF may contribute to known health disparity, but have not been studied. The objective was to describe differences in the upper airway microbial community in Hispanic and non-Hispanic white children with CF. METHODS: This prospective, observational cohort study of 59 Hispanic and non-Hispanic white children with CF, ages 2-10 years old, was performed at Texas Children's Hospital (TCH) from February 2019 to January 2020. Oropharyngeal swabs were collected from the cohort during clinic visit. Swab samples underwent sequencing (16S V4 rRNA), diversity analysis, and taxonomic profiling. Key demographic and clinical data were collected from the electronic medical record and the CF Foundation Patient Registry (CFFPR). Statistical analysis compared sequencing, demographic, and clinical data. RESULTS: We found no significant difference in Shannon diversity or relative abundance of bacterial phyla between Hispanic and non-Hispanic children with CF. However, a low abundant taxa- "uncultured bacterium" belonging to the order Saccharimonadales was significantly higher in Hispanic children (mean relative abundance = 0.13%) compared to the non-Hispanic children (0.03%). Hispanic children had increased incidence of P. aeruginosa (p = 0.045) compared to non-Hispanic children. CONCLUSION: We did not find a significant difference in the airway microbial diversity between Hispanic and non-Hispanic white children with CF. However, we found a greater relative abundance of Saccharimonadales and higher incidence of P. aeruginosa in Hispanic children with CF.

Diversity, Equity, and Inclusion in the Pediatric Pulmonary Workforce: An Official American Thoracic Society Workshop Report.

Despite growing recognition of the need for increased diversity among students, trainees, and faculty in health care, the medical workforce still lacks adequate representation from groups historically underrepresented in medicine (URiM). The subspecialty field of pediatric pulmonology is no exception. Although there have been efforts to address issues of diversity, equity, and inclusion (DEI) in our own field, gaps persist. To address these gaps, the members of the Diversity, Equity, and Inclusion Advisory Group (DEI-AG) of the American Thoracic Society Pediatrics Assembly created and distributed a Needs Assessment Survey in the United States and Canada to better understand the racial and ethnic demographics of the pediatric pulmonary workforce and to learn more about successes, gaps, and opportunities to enhance how we recruit, train, and retain a diverse workforce. The DEI-AG leadership cochairs convened a workshop to review the findings of the DEI Needs Assessment Survey and to develop strategies to improve the recruitment and retention of URiM fellows and faculty. This Official ATS Workshop Report aims to identify barriers and opportunities for recruitment, training, and career development within the field of pediatric pulmonology. Additionally, we offer useful strategies and resources to improve the recruitment of URiM residents, the mentorship of trainees and junior faculty, and the career development of URiM faculty in academic centers. This Workshop Report is an important first deliverable by the DEI-AG. We hope that this work, originating from within the Pediatrics Assembly, will serve as a model for other Assemblies, disciplines across the ATS, and other fields in Pediatrics.

Congenital Lung Malformations.

Congenital lung malformations (CLM) comprise a spectrum of anatomical anomalies of the lungs and respiratory tree. The prenatal growth pattern of CLMs is unpredictable with larger lesions causing life-threatening complications, such as hydrops fetalis, and smaller lesions remaining asymptomatic and potentially regressing. The most common CLMs are congenital pulmonary adenomatoid malformations, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts. All these lesions have clinically similar presentations when symptomatic, but pathophysiologic differences that must be considered when evaluating and treating. This article reviews the most common CLMs, their pathophysiology, clinical presentation, diagnostic considerations, and current literature on the controversies surrounding CLM management. [Pediatr Ann. 2019;48(4):e169-e174.].

Paradoxical Vocal Cord Motion in Pediatric Patients.

Paradoxical vocal cord motion (PVCM), also termed vocal cord dysfunction, is a poorly understood disorder of episodic dyspnea characterized by inappropriate vocal cord adduction during inspiration and potentially during expiration. It can coexist or be confused with asthma, so appropriate diagnosis is key to optimizing treatment success. Although many patients with PVCM may have underlying psychologic issues, there is emerging evidence to suggest that this entity is not psychogenic in every patient. Both laryngeal irritants and exercise have been identified as additional contributing factors in PVCM. Diagnosis of PVCM requires awake laryngoscopic confirmation. However, many patients do not exhibit signs of PVCM during this examination, despite provocation during testing. Therefore, clinical history remains key in determining which patients should proceed with behavioral therapy under the guidance of a speech pathologist. In addition, treatment may include limiting patient exposure to potential sources of laryngeal irritation. Refractory patients may benefit from psychologic assessment and treatment. [Pediatr Ann. 2016;45(5):e184-e188.].

The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts.

It is well established that there is a dynamic relationship between the expanding tumor and the host surrounding tissue. Cancer-associated fibroblasts (CAFs), the most common cellular population found in the tumor microenvironment, supporting tumor growth and dissemination. Here, we set out to determine the factors that may be involved in dramatic alteration of gene expression pattern in CAFs, focusing on microRNA and transcriptional regulators. We established matched pairs of human CAFs isolated from endometrial cancer and normal endometrial fibroblasts. MicroRNA and mRNA analyses identified differential expression of 11 microRNAs, with miR-31 being the most downregulated microRNA in CAFs (p = 0.007). We examined several putative miR-31 target genes identified by microarray analysis and demonstrated that miR-31 directly targets the homeobox gene SATB2, which is responsible for chromatin remodeling and regulation of gene expression, and was significantly elevated in CAFs. The functional relevance of miR-31 and SATB2 were tested in in vitro models of endometrial cancer. Overexpression of miR-31 significantly impaired the ability of CAFs to stimulate tumor cell migration and invasion, without affecting tumor cell proliferation. Genetic manipulation of SATB2 levels in normal fibroblasts or CAFs showed that, reciprocally to miR-31, SATB2 increased tumor cell migration and invasion, while knockdown of endogenous SATB2 in CAFs reversed this phenotype. Introduction of SATB2 into normal fibroblasts stimulated expression of a number of genes involved in cell invasion, migration and scattering. These findings provide new insights into tumor-stroma interaction and document that miR-31 and its target gene SATB2, are involved in regulation of tumor cell motility.