Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10-9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10-16 and CPA3; p = 2.39 × 10-14) and wound healing (FN1; p = 7.63 × 10-9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora.

Pediatric Pulmonary Milestones 2.0: Development, Lessons Learned, and Future Directions.

Pediatric pulmonology fellowship training programs are required by the Accreditation Council for Graduate Medical Education to report Pediatric Subspecialty Milestones biannually to track fellow progress. However, several issues, such as lack of subspecialty-specific context and ambiguous language, have raised concerns about their validity and applicability to use for fellow assessment and curriculum development. In this Perspective, we briefly share the process of the Pediatric Pulmonology Milestones 2.0 Work Group in creating new specialty-specific Milestones and tailoring information on the Harmonized Milestones to pediatric pulmonologists, with the goal of improving the Milestones' utility for stakeholders, including pulmonology fellows, faculty, program directors, and accrediting bodies. In addition, we created a supplemental guide to better link the Milestones to pulmonary-specific scenarios to create a shared mental model between stakeholders and remove a potential detriment to validity. Through the process, a number of guiding principles were clarified, including: 1) every Milestone should be able to be assessed independently, without overlap with other Milestones; 2) there should be clear developmental progression from one Milestone to the next; 3) Milestones should be based on the unique skills expected of pediatric pulmonologists; and 4) health equity should be a core component to highlight as a top priority to all stakeholders. In this Perspective, we describe these principles that guided formulation of the Pediatric Pulmonary Milestones to help familiarize the pediatric pulmonary community with the new Milestones. In addition, we share lessons learned and challenges in our process to inform other specialties that may soon participate in this process.

The Latest National Asthma Education and Prevention Program Guidelines: A Review for the Busy Pediatrician.

Asthma is one of the most common chronic diseases affecting the pediatric population. The diagnosis and management of asthma is constantly evolving, and recently the National Heart, Lung, and Blood Institute published an updated guideline regarding various aspects of pediatric asthma. In this report, we review and summarize these guidelines and compare them with the Global Initiative for Asthma guidelines. [Pediatr Ann. 2023;52(4):e153-e158.].

Full-Term Neonatal Respiratory Distress and Chronic Lung Disease.

Respiratory distress occurs in 5% to 7% of live births at term gestation. Most cases are mild and transient and can be attributed to transient tachypnea of the newborn or "wet lung." Severe respiratory distress is often due to nonpulmonary causes such as sepsis or congenital heart disease. Occasionally, term neonatal respiratory distress is associated with an inherited primary lung disease such as primary ciliary dyskinesia or surfactant metabolism defects. These lung diseases have characteristic presentations in the neonatal period and are important to recognize, as they necessitate different management approaches and have lifelong implications. Suspicion for these diseases should prompt referral to a pediatric pulmonologist. [Pediatr Ann. 2019;48(4):e175-e181.].

Income is an independent risk factor for worse asthma outcomes.

BACKGROUND: Socioeconomic status (SES) is associated with asthma morbidity in observational studies, but the factors underlying this association are uncertain. OBJECTIVE: We investigated whether 3 SES correlates-low income, low education, and high perceived stress-were independent risk factors for treatment failure and asthma exacerbations in the context of a randomized controlled trial. METHODS: The effect of low SES (household income of <$50,000/y and household educational level of less than a Bachelor's degree) and high perceived stress (defined as a score of >20 on a perceived stress scale) on asthma morbidity was analyzed in 381 participants by using Poisson regression models. The primary outcome was treatment failure (defined in the trial protocol as a significant clinical or airflow deterioration), and the secondary outcome was asthma exacerbations requiring systemic corticosteroids. RESULTS: Fifty-four percent of participants had a low income, 40% had a low educational level, and 17% had high perceived stress levels. Even after adjusting for race and other important confounders, participants with lower income had higher rates of both treatment failures (rate ratio, 1.6; 95% CI, 1.1-2.3; P = .03) and exacerbations (rate ratio, 1.9; 95% CI, 1.1-3.3; P = .02). Adherence with inhaled corticosteroids was similarly high for both income categories. Education and perceived stress were not significantly associated with either outcome. CONCLUSIONS: In the context of a randomized controlled trial, participants with lower income were more likely to experience adverse asthma outcomes independent of education, perceived stress, race, and medication adherence.

Current Concepts of Transition of Care in Cystic Fibrosis.

Over the past 6 decades, advances in cystic fibrosis (CF) diagnosis and management have extended the life expectancy of patients far beyond childhood; therefore, all pediatric CF patients must prepare for transition to adult care. Readiness assessment, knowledge and skill education, and support structures are all elements of ideal transition. Transition should begin early in life with teaching skills and knowledge for disease care, and in adolescence the readiness to transition should be addressed. Transition is a gradual process of increasing responsibilities in self-care and disease management, an improvement in the understanding of CF, and an iterative process of self-assessment with knowledge acquisition. Communication and collaboration between pediatric and adult providers is necessary to ensure a smooth and successful transition with minimum effect on outcomes. Although there is increased knowledge of successful transition practices, this area presents many opportunities for advancement of care for the patient with CF. [Pediatr Ann. 2017;46(5):e188-e192.].

Hospital admissions for lower respiratory tract infections among infants in the Canadian Arctic: a cohort study.

BACKGROUND: It is unknown whether this burden of disease of lower respiratory tract infections is comparable across the Canadian Arctic. The objectives of this surveillance study were to compare the rates of hospital admission for lower respiratory tract infection and the severity of infection across Arctic Canada, and to describe the responsible viruses. METHODS: We performed a prospective multicentre surveillance study of infants less than 1 year of age admitted in 2009 with lower respiratory tract infection to all hospitals (5 regional, 4 tertiary) in the Northwest Territories, Nunavut and Nunavik to assess for regional differences. Nasopharyngeal aspirates were processed by means of a polymerase chain reaction respiratory viral panel, testing for 20 respiratory viruses and influenza A (H1N1). The role of coinfection was assessed by means of regression analysis for length of stay (short: < 7 d; long: > 14 d). Outcomes compared included rates of lower respiratory tract infection, respiratory syncytial virus infection, transfer to tertiary hospital and severe lower respiratory tract infection (respiratory failure, intubation and mechanical ventilation, and/or cardiopulmonary resuscitation). RESULTS: There were 348 admissions for lower respiratory tract infection in the population of interest in 2009. Rates of admission per 1000 live births varied significantly, from 39 in the Northwest Territories to 456 in Nunavik (p < 0.001). The rates of tertiary admissions and severe lower respiratory tract infection per 1000 live births in the Northwest Territories were 5.6 and 1.4, respectively, compared to 55.9 and 17.1, respectively, in Nunavut and 52.0 and 20.0, respectively, in Nunavik (p ≤ 0.001). Respiratory syncytial virus was the most common virus identified (124 cases [41.6% of those tested]), and coinfection was detected in 51 cases (41.1%) of infection with this virus. Longer length of stay was associated with coinfection (odds ratio [OR] 2.64) and underlying risk factors (OR 4.39). Length of stay decreased by 32.2% for every 30-day increase in age (OR 0.68). INTERPRETATION: Nunavut and Nunavik have very elevated rates of lower respiratory tract infection, with severe outcomes. Respiratory syncytial virus was the most common virus identified, and coinfection was associated with longer length of stay. Targeted public health interventions are required to reduce the burden of disease for infants residing in these Arctic regions.

Severe respiratory illness associated with enterovirus D68 - Missouri and Illinois, 2014.

On August 19, 2014, CDC was notified by Children's Mercy Hospital in Kansas City, Missouri, of an increase (relative to the same period in previous years) in patients examined and hospitalized with severe respiratory illness, including some admitted to the pediatric intensive care unit. An increase also was noted in detections of rhinovirus/enterovirus by a multiplex polymerase chain reaction assay in nasopharyngeal specimens obtained during August 5-19. On August 23, CDC was notified by the University of Chicago Medicine Comer Children's Hospital in Illinois of an increase in patients similar to those seen in Kansas City. To further characterize these two geographically distinct observations, nasopharyngeal specimens from most of the patients with recent onset of severe symptoms from both facilities were sequenced by the CDC Picornavirus Laboratory. Enterovirus D68 (EV-D68) was identified in 19 of 22 specimens from Kansas City and in 11 of 14 specimens from Chicago. Since these initial reports, admissions for severe respiratory illness have continued at both facilities at rates higher than expected for this time of year. Investigations into suspected clusters in other jurisdictions are ongoing.

The real-life effectiveness of palivizumab for reducing hospital admissions for respiratory syncytial virus in infants residing in Nunavut.

UNLABELLED: BACKGROUND/ OBJECTIVE: Nunavut has the highest hospitalization rates for respiratory syncytial virus (RSV) worldwide, with rates of 166 per 1000 live births per year <1 year of age. Palivizumab was implemented in Nunavut primarily for premature infants, or those with hemodynamically significant cardiac or chronic lung disease; however, the effectiveness of the program is unknown. The objective of the present multisite, hospital-based surveillance study was to estimate the effectiveness of palivizumab in infants <6 months of age in Nunavut for the 2009 and 2010 RSV seasons. METHODS: Infants identified as palivizumab candidates who were <6 months of age were compared with all admissions for lower respiratory tract infection through multisite, hospital-based surveillance documenting the adequacy of palivizumab prophylaxis, admission for lower respiratory tract infection and the results of RSV testing. The OR for RSV admission in unprophylaxed infants was compared with those who were prophylaxed, and the effectiveness of palivizumab was estimated. RESULTS: Within the study cohort (n=101) during the two RSV seasons, five of the 10 eligible infants who did not receive adequate prophylaxis were admitted with RSV while two of the 91 infants <6 months of age eligible for palivizumab who were adequately prophylaxed were hospitalized with RSV (OR 22.3 [95% CI 3.8 to 130]; P=0.0005). The estimated effectiveness of palivizumab for the cohort was as high as 96%. Eight eligible infants were missed by the program and did not receive prophylaxis. CONCLUSION: Palivizumab was highly effective in reducing hospitalizations due to RSV infection in Nunavut. Further efforts need to be made to ensure that all eligible infants are identified.