Qualitative Evaluation of RADx-UP Projects Addressing COVID-19 Testing Disparities Among Underserved Populations.

In this article, we present findings from a May 2022 to March 2023 qualitative evaluation of Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) projects addressing COVID-19 testing disparities among underserved populations. Interviews with academic and community partners from 13 RADx-UP projects revealed that despite the pandemic, projects were able to build trust and relationships with underserved populations. By prioritizing community voices during a public health emergency, RADx-UP projects improved health equity and pandemic preparedness in these communities, successfully conducted community-engaged research, and built long-lasting community partnerships. (Am J Public Health. Published online ahead of print March 28, 2024:e1-e6. https://doi.org/10.2105/AJPH.2024.307632).

Gaps in Care Among Uncontrolled Severe Asthma Patients in the United States.

BACKGROUND: Understanding the implementation of key guideline recommendations is critical for managing severe asthma (SA) in the treatment of uncontrolled disease. OBJECTIVE: To assess specialist visits and medication escalation in US patients with SA after events indicating uncontrolled disease (EUD) and associations with health outcomes and social disparity indicators. METHODS: Patients with SA appearing in administrative claims data spanning 2015 to 2020 were indexed hierarchically on asthma-related EUD, including hospitalizations, emergency department visits with systemic corticosteroid treatment, or outpatient visits with systemic corticosteroid treatment. Patients with SA without EUD served as controls. Eligibility included age 12 or greater, 12 months enrollment before and after index, no biologic use, and no other major respiratory disease during the pre-period. Escalation of care in the form of specialist visits and medication escalation, health care resource use, costs, and disease exacerbations were assessed during follow-up. RESULTS: We identified 180,736 patients with SA (90,368 uncontrolled and 90,368 controls). Between 35% and 51% of patients with SA with an EUD had no specialist visit or medication escalation. Follow-up exacerbations ranged from 51% to 4% across EUD cohorts, compared with 13% in controls. Among uncontrolled patients with SA who were Black or Hispanic/Latino, 41% and 38%, respectively, had no specialist visit or medication escalation after EUD, compared with 33% of non-Hispanic White patients. CONCLUSIONS: A substantial proportion of uncontrolled patients with SA had no evidence of specialist visits or medication escalation after uncontrolled disease, and there was a clear relationship between uncontrolled disease and subsequent health care resource use and exacerbations. Findings highlight the need for improved guideline-based care delivery to patients with SA, particularly for those facing social disparities.

Environmental and Structural Factors Associated with Bacterial Diversity in Household Dust Across the Arizona-Sonora Border.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, and housing structure and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from US homes was enriched with Geodermatophilus, whereas dust from Mexican homes was enriched with Alishewanella and Chryseomicrobium. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Prenatal exposure to RSV season influences first-year risk of RSV lower respiratory illness and RSV-specific immune responses assessed at birth.

Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-γ and IL-4. The frequency of detectable IFN-γ (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-γ and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero.

Confirmatory factor analysis of the infant feeding styles questionnaire in infant and toddler child care teachers.

Early childhood is a critical time of development. Caregiver feeding style, including of child care providers, has been implicated in influencing children's food preferences and obesity. A better understanding of the determinants of child care providers' feeding styles is important as children increasingly receive daily care and nutrition in child care centers. Valid instruments to measure provider feeding styles specifically for infants are needed. This study's objective was to validate, for use with child care providers, the Infant Feeding Styles Questionnaire (IFSQ), an instrument originally designed for parents of infants and toddlers. Study data came from the Baby Nutrition and Physical Activity Self-Assessment for Child Care (Baby NAP SACC) study, a cluster randomized trial, designed to evaluate the efficacy of a six-month-long obesity prevention intervention in child care centers. The IFSQ was administered at baseline and follow-up to infant and toddler teacher participants (n = 244). Scores for baseline IFSQ teacher responses (n = 219) were calculated for the 13 sub-constructs across the five feeding styles. We tested reliability with Cronbach's alpha coefficients and performed confirmatory factor analysis to examine factor loadings and goodness of fit characteristics, modifying constructs to achieve best fit. Reliability coefficients ranged from 0.42 to 0.82 for all sub-constructs. Goodness of fit indices for the final model ranged from: root mean square error of approximation (RMSEA) 0.000-0.082; comparative fit index (CFI) 0.943-1.000; Tucker-Lewis index (TLI) 0.906-1.000; and standardized root mean squared error (SRMR) 0.006-0.130. In a sample of racially diverse infant and toddler child care teachers, final models of the laissez-faire, pressuring, and responsive constructs and the restrictive-diet quality sub-construct performed well. Overall model fit was poor for the indulgence construct, but good for solely its corresponding belief items.

Treating asthma in the time of COVID.

The Precision Interventions for Severe and/or Exacerbation-Prone Asthma clinical trials network is actively assessing novel treatments for severe asthma during the coronavirus disease (COVID-19) pandemic and has needed to adapt to various clinical dilemmas posed by the COVID-19 pandemic. Pharmacologic interactions between established asthma therapies and novel drug interventions for COVID-19 infection, including antivirals, biologics, and vaccines, have emerged as a critical and unanticipated issue in the clinical care of asthma. In particular, impaired metabolism of some long-acting beta-2 agonists by the cytochrome P4503A4 enzyme in the setting of antiviral treatment using ritonavir-boosted nirmatrelvir (NVM/r, brand name Paxlovid) may increase risk for adverse cardiovascular events. Although available data have documented the potential for such interactions, these issues are largely unappreciated by clinicians who treat asthma, or those dispensing COVID-19 interventions in patients who happen to have asthma. Because these drug-drug interactions have not previously been relevant to patient care, clinicians have had no guidance on management strategies to reduce potentially serious interactions between treatments for asthma and COVID-19. The Precision Interventions for Severe and/or Exacerbation-Prone Asthma network considered the available literature and product information, and herein share our considerations and plans for treating asthma within the context of these novel COVID-19-related therapies.

Nonallergic Rhinitis, Allergic Rhinitis, and Immunotherapy: Advances in the Last Decade.

Chronic rhinitis encompassing both allergic and nonallergic rhinitis affects a significant portion of the population worldwide, having a great impact on patient quality of life, and associated comorbid conditions, with an important societal economic burden. Allergists are often the first to evaluate and treat allergic and nonallergic rhinitis, addressing the individual triggers of the disease as well as the patient-specific responses to these triggers. This review focuses on the advances that have been made in the diagnosis, management, and treatment of nonallergic and allergic rhinitis over the past 10 years, including specific allergen immunotherapy, care pathways, and digital health.

Developing capacity for learning community systems: Experiences from the 100 Million Healthier Lives SCALE Initiative.

Introduction: This paper explores the capabilities that contribute to community transformation and the common pathways followed by communities in the 100 Million Healthier Lives SCALE (Spreading Community Accelerators through Learning and Evaluation) initiative in their transformation journeys towards a "Culture of Health". Methods: Funded by the Robert Wood Johnson Foundation (RWJF), from 2016 to 2020, between 18 to 24 community coalitions nationwide participated in SCALE, the goal of which was to co-design, implement, test, and scale up a model called the Community of Solutions (COS) Framework, that built community capacity around a set of skills and behaviors to advance culture change and create sustainable improvement in health, well-being, and equity. We adapted and applied two qualitative research techniques, meta-ethnography and participatory action synthesis, to evaluate SCALE initiative data. Results: Eight concepts emerged that represent the knowledge, capabilities and practices commonly acquired and utilized across the communities. Overall, these concepts emphasize individual and team leadership, quality improvement skills, an intentional focus on equity, and partnerships for spread and sustainment. Concepts were linked into lines of arguments which were unique storylines explaining the transformation pathways. Three stories of the transformation process emerged from the data. Causal Loop Diagrams (CLDs) were created to represent non-linear system relationships and visually capture some of the most important dynamics of the process of transformation. Even with vast heterogeneity among the SCALE communities and the diversity of activities that the communities undertook, our analysis showed there were a few basic principles that undergirded the process of building capability for transformation. Conclusions: The knowledge from our findings should be useful to expand further research and practice in community learning systems.

Immunotherapy for Asthma.

Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma.

Evaluation of Swab-Seq as a scalable, sensitive assay for community surveillance of SARS-CoV-2 infection.

The ongoing SARS-CoV-2 pandemic and subsequent demand for viral testing has led to issues in scaling diagnostic lab efforts and in securing basic supplies for collection and processing of samples. This has motivated efforts by the scientific community to establish improved protocols that are more scalable, less resource intensive, and less expensive. One such developmental effort has resulted in an assay called "Swab-Seq", so named because it was originally developed to work with dry nasal swab samples. The existing gold standard test consists of RNA extracted from a nasopharyngeal (NP) swab that is subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Swab-Seq adapts this method to a next-generation sequencing readout. By pairing this modification with extraction-free sampling techniques, Swab-Seq achieves high scalability, low cost per sample, and a reasonable turnaround time. We evaluated the effectiveness of this assay in a community surveillance setting by testing samples collected from both symptomatic and asymptomatic individuals using the traditional NP swab. In addition, we evaluated extraction-free sampling techniques (both saliva and saline mouth gargle samples). We found the assay to be as clinically sensitive as the qRT-PCR assay, adaptable to multiple sample types, and able to easily accommodate hundreds of samples at a time. We thus provide independent validation of Swab-Seq and extend its utility regarding sample type and sample stability. Assays of this type greatly expand the possibility of routine, noninvasive, repeated testing of asymptomatic individuals suitable for current and potential future needs.

Novel potential treatable traits in asthma: Where is the research taking us?

Asthma is a complex, heterogeneous disease in which the underlying mechanisms are not fully understood. Patients are often grouped into phenotypes (based on clinical, biologic, and physiologic characteristics) and endotypes (based on distinct genetic or molecular mechanisms). Recently, patients with asthma have been broadly split into 2 phenotypes based on their levels of type 2 inflammation: type 2 and non-type 2 asthma. However, this approach is likely oversimplified, and our understanding of the non-type 2 mechanisms in asthma remains extremely limited. A better understanding of asthma phenotypes and endotypes may assist in development of drugs for new therapeutic targets in asthma. One approach is to identify "treatable traits," which are specific patient characteristics related to phenotypes and endotypes that can be targeted by therapies. This review will focus on emerging treatable traits in asthma and aim to describe novel patient subgroups and endotypes that may represent the next step in the search for new therapeutic approaches.

High Insulin in Early Childhood Is Associated with Subsequent Asthma Risk Independent of Body Mass Index.

BACKGROUND: Asthma and obesity are major, interconnected public health challenges that usually have their origins in childhood, and for which the relationship is strengthened among those with insulin resistance. OBJECTIVE: To determine whether high insulin in early life confers increased longitudinal risk for asthma independent of body mass index. METHODS: The study used data from the Tucson Children's Respiratory Study (TCRS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Nonfasting insulin was measured in TCRS participants at age 6 years and fasting insulin in ALSPAC participants at age 8 years. Physician-diagnosed active asthma was determined at baseline and at subsequent assessments up to age 36 years in TCRS and 17 years in ALSPAC. RESULTS: In TCRS, high insulin (upper quartile) at age 6 years was associated with increased odds of having active asthma from ages 8 to 36 years compared with low insulin (odds ratio,1.98; 95% CI, 1.28-3.05; P = .002). Similarly, in ALSPAC, high insulin was associated with a significantly higher risk of active asthma from ages 11 to 17 years compared with low insulin (odds ratio, 1.59; 95% CI, 1.12-2.27; P = .009). These findings were independent of baseline body mass index in both cohorts, and were not related to other demographic and asthma risk factors nor other tested markers of systemic inflammation and metabolic syndrome. CONCLUSIONS: In 2 separate birth cohorts, higher blood insulin level in early childhood was associated with increased risk of active asthma through adolescence and adulthood, independent of body mass index. High insulin indicates a novel mechanism for asthma development, which may be a target for intervention.

The Role of IgE in Upper and Lower Airway Disease: More Than Just Allergy!

Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non-IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.