Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity.

People with obesity often have severe, difficult-to-control asthma. There is a need to develop better treatments for this population. One potential treatment is roflumilast, a phosphodiesterase 4 inhibitor, as it is reported to have efficacy for the treatment of asthma and can promote weight loss.

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.

Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity.

CC16 is a protein mainly produced by nonciliated bronchial epithelial cells (BECs) that participates in host defense. Reduced CC16 protein concentrations in BAL and serum are associated with asthma susceptibility. Few studies have investigated the relationship between CC16 and asthma progression, and none has focused on BECs.

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life.

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n=50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC=0.724).

Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study.

Background: Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study.

Creatine Kinase Is Decreased in Childhood Asthma.

The identification of novel molecules associated with asthma may provide insights into the mechanisms of disease and their potential clinical implications. To conduct a screening of circulating proteins in childhood asthma and to study proteins that emerged from human studies in a mouse model of asthma. We included 2,264 children from eight birth cohorts from the Mechanisms of the Development of ALLergy project and the Tucson Children's Respiratory Study.

Small Peptide Derivatives Within the Carbohydrate Recognition Domain of SP-A2 Modulate Asthma Outcomes in Mouse Models and Human Cells.

Surfactant Protein-A (SP-A) is an innate immune modulator that regulates a variety of pulmonary host defense functions. We have shown that SP-A is dysfunctional in asthma, which could be partly due to genetic heterogeneity. In mouse models and primary bronchial epithelial cells from asthmatic participants, we evaluated the functional significance of a particular single nucleotide polymorphism of SP-A2, which results in an amino acid substitution at position 223 from glutamine (Q) to lysine (K) within the carbohydrate recognition domain (CRD).

Maternal prenatal immunity, neonatal trained immunity, and early airway microbiota shape childhood asthma development.

Background: The path to childhood asthma is thought to initiate in utero and be further promoted by postnatal exposures. However, the underlying mechanisms remain underexplored. We hypothesized that prenatal maternal immune dysfunction associated with increased childhood asthma risk (revealed by low IFN-γ:IL-13 secretion during the third trimester of pregnancy) alters neonatal immune training through epigenetic mechanisms and promotes early-life airway colonization by asthmagenic microbiota.

Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.

People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling.

β-Arrestin-biased proteinase-activated receptor-2 antagonist C781 limits allergen-induced airway hyperresponsiveness and inflammation.

Background And Purpose: Asthma is a heterogenous disease strongly associated with inflammation that has many different causes and triggers. Current asthma treatments target symptoms such as bronchoconstriction and airway inflammation. Despite recent advances in biological therapies, there remains a need for new classes of therapeutic agents with novel, upstream targets.

Multiplex Detection of Antibody Landscapes to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Influenza/Common Human Coronaviruses Following Vaccination or Infection With SARS-CoV-2 and Influenza.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to co-circulate, representing 2 major public health threats from respiratory infections with similar clinical presentations. SARS-CoV-2 and influenza vaccines can also now be co-administered. However, data on antibody responses to SARS-CoV-2 and influenza coinfection and vaccine co-administration remain limited.

COVID-19 on the Navajo Nation: experiences of Diné families of children with asthma.

Objective: The first case of COVID-19 on the Navajo Nation (NN) was found on March 17, 2020. Even with strong public health efforts, NN saw the highest per capita infection rate in the US during May of 2020 with 2450/100,000. To determine the impact of COVID-19 on families of children with asthma on the NN, families participating in the NHLBI funded Community Asthma Program were contacted to see if they would share their experiences.

School-supervised Asthma Therapy is Associated with Improved Long-Term Asthma Outcomes for Underrepresented Minority Children.

Asthma morbidity disproportionately impacts children from low-income and racial/ethnic minority communities. School-supervised asthma therapy improves asthma outcomes for up to 15 months for underrepresented minority children, but little is known about whether these benefits are sustained over time. We examined the frequency of emergency department (ED) visits and hospital admissions for 83 children enrolled in Asthma Link, a school nurse-supervised asthma therapy program serving predominantly underrepresented minority children.

BASH-GN: a new machine learning-derived questionnaire for screening obstructive sleep apnea.

Purpose: This study aimed to develop a machine learning-based questionnaire (BASH-GN) to classify obstructive sleep apnea (OSA) risk by considering risk factor subtypes.

Methods: Participants who met study inclusion criteria were selected from the Sleep Heart Health Study Visit 1 (SHHS 1) database. Other participants from the Wisconsin Sleep Cohort (WSC) served as an independent test dataset.

Club cell secretory protein and lung function in children with cystic fibrosis.

Background: Club cell secretory protein (CC16) exerts anti-inflammatory functions in lung disease. We sought to determine the relation of serum CC16 deficits and genetic variants that control serum CC16 to lung function among children with cystic fibrosis (CF).

Methods: We used longitudinal data from CF children (EPIC Study) with no positive cultures for Pseudomonas aeruginosa prior to enrollment.

CENTER-IT: a novel methodology for adapting multi-level interventions using the Consolidated Framework for Implementation Research-a case example of a school-supervised asthma intervention.

Background: Implementation science frameworks advise the engagement of multi-level partners (at the patient, provider, and systems level) to adapt and increase the uptake of evidence-based practices (EBPs). However, there is little guidance to ensure that systems-level adaptations reflect the voices of providers who deliver and patients/caregivers who receive EBPs.

Methods: We present a novel methodology, grounded in the Consolidated Framework for Implementation Research (CFIR), which anchors the engagement of multi-level partners to the voices of individuals who deliver and receive EBPs.

Sampling Low Air Pollution Concentrations at a Neighborhood Scale in a Desert U.S. Metropolis with Volatile Weather Patterns.

Background: Neighborhood-scale air pollution sampling methods have been used in a range of settings but not in low air pollution airsheds with extreme weather events such as volatile precipitation patterns and extreme summer heat and aridity-all of which will become increasingly common with climate change. The desert U.S.

,-Dimethyldithiocarbamate Elicits Pneumococcal Hypersensitivity to Copper and Macrophage-Mediated Clearance.

Streptococcus pneumoniae is a Gram-positive, encapsulated bacterium that is a significant cause of disease burden in pediatric and elderly populations. The rise in unencapsulated disease-causing strains and antimicrobial resistance in S. pneumoniae has increased the need for developing new antimicrobial strategies.

An Online Weight Loss Intervention for People With Obesity and Poorly Controlled Asthma.

Background: Weight loss might improve asthma control in people with obesity. However, people with asthma might have particular challenges losing weight and the amount of weight loss needed to improve asthma control is not clear.

Objectives: To pilot-test an online weight loss intervention and to estimate the impact of weight loss on asthma control.

Extensive evaluation of ATAC-seq protocols for native or formaldehyde-fixed nuclei.

Background: The "Assay for Transposase Accessible Chromatin sequencing" (ATAC-seq) is an efficient and easy to implement protocol to measure chromatin accessibility that has been widely used in multiple applications studying gene regulation. While several modifications or variants of the protocol have been published since it was first described, there has not yet been an extensive evaluation of the effects of specific protocol choices head-to-head in a consistent experimental setting. In this study, we tested multiple protocol options for major ATAC-seq components (including three reaction buffers, two reaction temperatures, two enzyme sources, and the use of either native or fixed nuclei) in a well-characterized cell line.