Pediatric interventional bronchoscopy: from early limitations to achievable opportunities.

PURPOSE OF REVIEW: The rapid evolution of bronchoscopy equipment and technologies, from the introduction of the 1.1 mm flexible cryoprobe to the use of navigational and robotic bronchoscopy, has afforded unprecedented opportunities for pediatric advanced diagnostic and interventional bronchoscopy. While there is growing interest among pediatric pulmonologists to incorporate these new techniques into their practice, the current pediatric landscape is characterized by few practicing interventional bronchoscopists, scant published literature, and no formal training programs. RECENT FINDINGS: While the majority of the published literature consists of case reports and small case series, the increased application of new techniques is starting to yield larger and more structured studies that will be able to provide more objective commentary on the proposed indications, safety, and efficacy of such techniques in the pediatric population. SUMMARY: For many decades, progress in pediatric advanced diagnostic and interventional bronchoscopy was slow and deliberate, limited by the lack of appropriately sized equipment and experienced interventional bronchoscopists. The current opportunities afforded require equal, or perhaps even more, vigilance as pediatric pulmonologists employ new equipment and technologies and define new practices and standards of care. Importantly, this review is meant to serve as a general conspectus of pediatric advanced diagnostic and interventional bronchoscopy and not a consensus guideline for the performance of advanced or even routine bronchoscopy in the pediatric population. For technical standards of pediatric bronchoscopy, refer to existing guidelines [1,2] .

Center-level self-study identifies opportunities to advance equity in cystic fibrosis clinical trial participation.

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

Single-Cell RNA Sequencing Reveals New Basic and Translational Insights in the Cystic Fibrosis Lung.

Cystic fibrosis (CF) is a multisystemic, autosomal recessive disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, with the majority of morbidity and mortality extending from lung disease. Single-cell RNA sequencing (scRNA-seq) has been leveraged in the lung and elsewhere in the body to articulate discrete cell populations, describing cell types, states, and lineages as well as their roles in health and disease. In this translational review, we provide an overview of the current applications of scRNA-seq to the study of the normal and CF lungs, allowing the beginning of a new cellular and molecular narrative of CF lung disease, and we highlight some of the future opportunities to further leverage scRNA-seq and complementary single-cell technologies in the study of CF as we bridge from scientific understanding to clinical application.

The CFTR variant profile of Hispanic patients with cystic fibrosis: Impact on access to effective screening, diagnosis, and personalized medicine.

Hispanic patients comprise an appreciable and increasing proportion of patients with cystic fibrosis (CF) in the United States (US). Hispanic patients with CF are known to have increased morbidity and mortality compared to non-Hispanic white patients with CF, and ongoing investigations are underway to identify contributing factors amenable to intervention in order to address the disparate health outcomes. One contributing factor is the different CF transmembrane conductance regulator (CFTR) variant profile observed in Hispanic patients with CF. The most common CFTR variant, p.Phe508del (legacy name F508del), is proportionally underrepresented in Hispanic patients with CF. This difference has implications for prenatal screening, newborn screening (NBS), and CFTR variant-specific therapeutic options. In particular, the recent approval of a highly effective CFTR modulator for patients carrying at least one copy of F508del, elexacaftor/tezacaftor/ivacaftor triple combination therapy, underscores the potential for unequal access to personalized treatment for Hispanic patients with CF. We report the CFTR variant profiles of Hispanic patients with CF and non-CF Hispanic infants with a false-positive New York State CF NBS at a single center in New York City over a 5-year study period, as an opportunity to address the racial and ethnic disparities that currently exist in CF screening, diagnosis, and treatment. In addition to the previously documented disparate prevalence of the CFTR variant F508del in Hispanic patients, we observed two CFTR variants, p.His609Arg (legacy name H609R) and p.Thr1036Asn (legacy name T1036N), frequently identified in our Hispanic patients of Ecuadorian and Mexican ancestry, respectively, that are not well-described in the US population. The presence of population-specific and individually rare CFTR variants in Hispanic patients with CF further accentuates the disparity in health outcomes, as these CFTR variants are often absent from prenatal and NBS CFTR variant panels, potentially delaying diagnosis, and without an approved CFTR variant-specific therapy.

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

For children with severe asthma, guideline-based management focuses on the escalation of anti-inflammatory and bronchodilatory medications while addressing comorbid conditions. Bronchoscopy, in this context, has been relegated to ruling out asthma mimickers. More recently, however, there have been questions surrounding the clinical utility of bronchoscopy in severe childhood asthma. In this solicited lecture summary, we discuss the past, present, and potential future applications of bronchoscopy in severe childhood asthma.