5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.

Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.

Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown.

Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: A randomized controlled trial.

Background: Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses.

Objective: We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis.

Methods: We conducted a double-blind parallel design trial in patients with cat allergy.

Tailoring the Hybrid Magnetron Sputtering Process (HiPIMS and dcMS) to Manufacture Ceramic Multilayers: Powering Conditions, Target Materials, and Base Layers.

The mechanical and wear behavior of CrN/CrAlN multilayers were improved by tailoring the experimental conditions of a hybrid magnetron sputtering process based on a high-power impulse (HiPIMS) and two direct current magnetron sputtering (dcMS) power supplies. To this end, the influence of the base layer and of the combination of Cr and CrAl targets, which were switched to the dcMS and HiPIMS power supplies in different configurations, were investigated with respect to the growth of ceramic CrN/CrAlN multilayers onto commercial gas-nitrided diesel piston rings. The microstructure, grain morphology, and mechanical properties were evaluated by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and instrumented nanoindentation.

Role of Nitrogen and Yttrium Contents in Manufacturing (Cr, Y)N Film Nanostructures.

The high-power impulse magnetron sputtering (HiPIMS) technique was applied to deposit multilayer-like (Cr, Y)N coatings on AISI 304L stainless steel, using pendular substrate oscillation and a Cr-Y target and varying the nitrogen flow rate from 10 to 50 sccm. The microstructure, mechanical and tribological properties were investigated by scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, instrumented nano-hardness, and wear tests. The columnar grain structure became highly segmented and nanosized due to pendular substrate oscillation and the addition of yttrium.

Hybrid magnetron sputtering of ceramic superlattices for application in a next generation of combustion engines.

A hybrid magnetron sputtering process (dcMS/HiPIMS) was developed to manufacture nanostructured CrN/CrAlN multilayers, motivated by improving the low-emission efficiency when applied on gas-nitrided diesel piston rings of a next-generation of combustion engines. In order to improve the mechanical, tribological, and corrosion behavior of the multilayers, the hybrid dcMS/HiPIMS process was designed by selecting the optimal sputtering procedure applied to AISI 440 base steel. The effect of substrate bias and carousel rotational speed on the phase composition, crystallographic texture, residual stresses, surface roughness, coating periodicity and densification, instrumented hardness, elastic modulus, as well as wear and corrosion resistance was determined.

On Improving Wear Resistance of Cr-Al-N Coatings Using Dynamic Glancing Angle DC Magnetron Sputtering.

The development of alternatives for wear protection in surface engineering can be responsible for a significant decrease in energy waste as a large amount of the energy produced in the world is lost due to tribological contact. Dynamic Glancing Angle Deposition has been recently evaluated as a route to produce coatings with improved wear performance. In this technique, the substrate oscillates along with a determined range in front of the sputtering target during the growth of the film.

Nitrogen-Enriched CrAlN Multilayer-Like Coatings Manufactured by Dynamic Glancing Angle Direct Current Magnetron Sputtering.

Multilayer-like CrN and CrAlN coatings with different Al contents were deposited onto a stainless steel substrate using dynamic glancing angle deposition direct current magnetron sputtering (DGLAD dcMS) in a N rich atmosphere to understand the role of Al on the growth of the films and mechanical properties of the nitrides with a multilayer architecture. Chemical analysis by means of energy dispersive analysis (EDS) and glow discharge optical emission spectroscopy (GDOES) depth profiling revealed that while CrN samples were close to stoichiometric, the CrAlN coatings presented excess N between 70 and 80% at. An expressive change in texture was observed as the CrN coating changed its preferred orientation from (111) to (200) with the addition of Al, followed by a modification in morphology from grains with faceted pyramidal tops in CrN to dome-shaped grains in CrAlN coatings.

On manufacturing multilayer-like nanostructures using misorientation gradients in PVD films.

Due to their applicability for manufacturing dense, hard and stable coatings, Physical Vapor Deposition (PVD) techniques, such as High Power Impulse Magnetron Sputtering (HiPIMS), are currently used to deposit transition metal nitrides for tribological applications. Cr-Al-N is one of the most promising ceramic coating systems owing to its remarkable mechanical and tribological properties along with excellent corrosion resistance and high-temperature stability. This work explores the possibility of further improving Cr-Al-N coatings by modulation of its microstructure.

Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.

Background: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.

Acculturation is associated with asthma burden and pulmonary function in Latino youth: The GALA II study.

Background: Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures.

Objective: We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups.

A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.

Short-acting β-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma.

An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos.

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.

Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.

Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility.

Secondhand smoke exposure and asthma outcomes among African-American and Latino children with asthma.

Background: Secondhand smoke (SHS) exposures have been linked to asthma-related outcomes but quantitative dose-responses using biomarkers of exposure have not been widely reported.

Objectives: Assess dose-response relationships between plasma cotinine-determined SHS exposure and asthma outcomes in minority children, a vulnerable population exposed to higher levels of SHS and under-represented in the literature.

Methods: We performed analyses in 1172 Latino and African-American children with asthma from the mainland USA and Puerto Rico.

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.

Rationale: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response.

Objectives: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children.

A computable phenotype for asthma case identification in adult and pediatric patients: External validation in the Chicago Area Patient-Outcomes Research Network (CAPriCORN).

: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined.

Granulocyte colony-stimulating factor blockade enables dexamethasone to inhibit lipopolysaccharide-induced murine lung neutrophils.

Glucocorticoids promote neutrophilic inflammation, the mechanisms of which are poorly characterized. Using a lipopolysaccharide (LPS)-induced acute murine lung injury model, we determined the role of granulocyte colony-stimulating factor (G-CSF) in mouse lung neutrophil numbers in the absence and presence of dexamethasone, a potent glucocorticoid. G-CSF was blocked using a neutralizing antibody.

Identification of a novel locus associated with skin colour in African-admixed populations.

Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals.

Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease.

Background: Aspirin-exacerbated respiratory disease (AERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 (COX-1) enzyme. The prevalence of AERD remains unclear, and few studies have compared the clinical characteristics of patients with AERD to those with CRSwNP alone, asthma alone, or both CRSwNP and asthma.

Objective: To determine the prevalence of AERD within a tertiary care setting, and to identify unique clinical features that could distinguish these patients from those with both CRSwNP and asthma or with CRSwNP alone.

Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures.

Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data.

Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease.

Background: We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium.

Objective: We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease.

Breastfeeding associated with higher lung function in African American youths with asthma.

Objective: In the United States, Puerto Ricans and African Americans have lower prevalence of breastfeeding and worse clinical outcomes for asthma compared with other racial/ethnic groups. We hypothesize that the history of breastfeeding is associated with increased forced expiratory volume in 1 second (FEV) % predicted and reduced asthma exacerbations in Latino and African American youths with asthma.

Methods: As part of the Genes-environments & Admixture in Latino Americans (GALA II) Study and the Study of African Americans, asthma, Genes & Environments (SAGE II), we conducted case-only analyses in children and adolescents aged 8-21 years with asthma from four different racial/ethnic groups: African Americans (n = 426), Mexican Americans (n = 424), mixed/other Latinos (n = 255), and Puerto Ricans (n = 629).