Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

Objectives: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown.

A Randomized Trial of a Composite T2-Biomarker Strategy Adjusting Corticosteroid Treatment in Severe Asthma: A Post Hoc Analysis by Sex.

Background: Approximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex.

Objective: To examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care.

Exacerbation Profile and Risk Factors in a Type-2-Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes.

The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2 and T2 at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation.

Kinetic characterization and thermostability of C. elegans cytoplasmic and mitochondrial malate dehydrogenases.

Malate dehydrogenase (MDH) catalyzes the conversion of NAD and malate to NADH and oxaloacetate in the citric acid cycle. Eukaryotes have one MDH isozyme that is imported into the mitochondria and one in the cytoplasm. We overexpressed and purified Caenorhabditis elegans cytoplasmic MDH-1 and mitochondrial MDH-2 in E.

Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma.

Background: Understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.

Methods: We reviewed patient choice to follow HCP advice to adjust asthma treatment in a UK-based randomised, controlled, single-blind (study participant), multicentre, parallel group 48-week clinical study comparing biomarker-directed treatment adjustment with standard care in severe asthma.

Results: Of 1572 treatment advisories (291 participants), instructions were followed in 1377 cases (87.

Sterile Compounding Knowledge, Skills, and Confidence Among Graduating Doctor of Pharmacy Students.

To determine whether the exposure to sterile compounding in the pharmacy curriculum produces Doctor of Pharmacy graduates who are both competent and confident in the area of sterile compounding, and to identify additional variables that may predict student performance. Participants were recruited from the fourth-year pharmacy class of 2018 at one university. The students were asked to complete a questionnaire assessing the following domains: demographics, confidence in compounding performance, prior experience, and theoretical knowledge.

The impact of demonstration plots on improved agricultural input purchase in Tanzania: Implications for policy and practice.

In this paper, the authors use survey data from over 800 households to examine the impact of demonstration plots and associated activities (distribution of small packs of agricultural inputs) on smallholder farmers' decisions to buy agricultural inputs in Tanzania. Using propensity score matching and inverse probability-weighted adjustment models, the authors estimated the effect of access to demonstration plots alone and demonstration plots combined with small packs of agricultural inputs on a household's decision to purchase improved inputs. The results indicate that access to demonstration plots and demonstration plots with small packs increased the probability of purchasing improved inputs by 13-17 percentage points.

Bacterial genome editing by coupling Cre-lox and CRISPR-Cas9 systems.

The past decade has been a golden age for microbiology, marked by the discovery of an unprecedented increase in the number of novel bacterial species. Yet gaining biological knowledge of those organisms has not kept pace with sequencing efforts. To unlock this genetic potential there is an urgent need for generic (i.

Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control).

Update on new biologics for intractable eosinophilic asthma: impact of reslizumab.

A small percentage of patients with asthma have uncontrolled symptoms and frequent exacerbations, despite treatment with inhaled corticosteroids and other agents. It has become clear that different subtypes of this severe, treatment-resistant group exist due to different mechanisms of the disease. All such patients require detailed assessment in specialist centers to characterize the disease and assess treatment adherence.

A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial.

Background: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy.

Omalizumab treats chronic rhinosinusitis with nasal polyps and asthma together-a real life study.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy.

Objective: To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP.

Methods: SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma.

Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast.

Background: BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors.

Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes.

Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro.

Mepolizumab for eosinophilic severe asthma: recent studies.

Introduction: In September 2014 two large clinical studies of the anti-IL-5 monoclonal antibody mepolizumab in severe asthma were published in the New England Journal of Medicine (MENSA and SIRIUS).

Areas Covered: Eosinophilic inflammation has long been recognised as a feature of asthma. Identification of IL-5 as a key cytokine specific for eosinophil development and survival lead to development of monoclonal antibody therapy targeting this pathway.

Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: a retrospective study of 2927 paediatric patients.

Background: Allergen immunotherapy (AIT) is effective treatment for allergic diseases, and subcutaneous use of depigmented polymerized extracts may allow rapid up-dosing and safe therapy. To date, there is little information on their safety and clinical effects for children and adolescents with allergic disease.

Methods: We performed a retrospective survey of patient notes of 2927 children and adolescents across 136 centres who had received subcutaneous AIT (SCIT) with depigmented polymerized extracts to pollen or mite allergens for at least 1 yr to collect documentation on safety and clinical symptoms.

Depigmented-polymerised allergoids favour regulatory over effector T cells: enhancement by 1α, 25-dihydroxyvitamin D3.

Background: Allergen immunotherapy (SIT) is the only treatment for allergic disease capable of modifying disease long term. To reduce the risk of anaphylaxis from SIT, allergen-extracts have been modified by polymerisation with glutaraldehyde to reduce IgE binding. It is suggested that these allergoid extracts also have reduced T cell activity, which could compromise clinical efficacy.