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Polymeric structures fabricated using fused filament fabrication (FFF) have limited use in engineering applications as a result of their poor inter-laminar bonding. In this study, we utilize a dual-material print head to encase a low glass transition temperature (Tg) polymer (acrylonitrile butadiene styrene) within a high-Tg shell (polycarbonate). The resulting structure, if annealed at a temperature between the core and shell polymer Tg values, creates a tough interior with high inter-laminar strength while retaining the as-printed three-dimensional geometry of the part. Fracture toughness of annealed, shelled parts was evaluated using single edge notch bend (SENB) fracture specimens and reached values more than 1800% higher than unannealed specimens. Importantly, the annealed specimens exhibited consistent ductile failure and plastic deformation, unlike the as-printed parts which exhibited brittle inter-laminar fracture. Parts with complex geometries are presented to demonstrate geometric stability during annealing and a practical load bearing application.

Eosinophilic granulomatosis with polyangiitis (EGPA), a rare vasculitis with substantial morbidity, is characterized by asthma, eosinophilia, sinusitis, pulmonary infiltrates, neuropathy, positivity for antineutrophil cytoplasmic antibody, and multiorgan vasculitis. Although treatment options previously included corticosteroids and immunosuppressants, anti-interleukin 5 therapies have gained interest in EGPA treatment. Mepolizumab was approved for and recently benralizumab was found to have safety and efficacy in EGPA.To determine the safety and efficacy of reslizumab in EGPA.In this open-label, pilot study, we evaluated the safety and efficacy of intravenous reslizumab (3 mg/kg) in EGPA in 10 subjects. Oral corticosteroid dose, adverse events, exacerbations, symptom control, disease activity, blood markers, and lung function were evaluated before, during, and after 7 monthly reslizumab treatments.Reslizumab was tolerated and resulted in a significant reduction in daily oral corticosteroid (P.05). Of the 10 subjects, 3 experienced an EGPA exacerbation during the treatment. One had a severe adverse event, requiring removal from the study.Yielding similar results to other anti-interleukin 5 biologic medications, reslizumab is generally a safe and effective treatment for EGPA that warrants further study.ClinicalTrials.gov Identifier: NCT02947945.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis associated with significant morbidity and mortality that has historically been treated with systemic corticosteroids and immunosuppressants. The IL-5 antagonist mepolizumab was Food and Drug Administration approved in 2017 after demonstrating safety and efficacy in EGPA. We hypothesized that benralizumab, an IL-5 receptor antagonist approved for eosinophilic asthma, would demonstrate safety and efficacy in EGPA. Objectives To determine the safety and efficacy of benralizumab in EGPA as measured by reduction in oral corticosteroid dose and EGPA exacerbations. Methods We conducted a prospective 40-week open-label pilot study of benralizumab 30 mg administered subcutaneously in 10 patients with EGPA. Adverse events, oral corticosteroid dosing, exacerbations, and lung function were evaluated before, during, and after benralizumab treatment. Paired tests and tests derived from longitudinal models were used to compare outcome variables between phases or visits. Results Benralizumab was well tolerated and resulted in reduction of median corticosteroid dose from 15 mg at the start to 2 mg at the end of treatment. Geometric mean corticosteroid dose was reduced from 11.6 mg during pretreatment to 6.3 mg during treatment phase. Five patients were able to achieve a dose of 0 mg. Mean annualized exacerbation rate was lowest during the treatment (1.5) compared with the pre- and posttreatment phases (4.6, P = .008 for treatment vs pre- and postphases combined). Conclusions Benralizumab was well tolerated, facilitated oral corticosteroid reduction, and reduced exacerbations in EGPA. Larger controlled trials are warranted to further evaluate the role of benralizumab in EGPA.

Polymeric structures fabricated using Fused Filament Fabrication (FFF) suffer from poor inter-laminar fracture toughness. As a result, these materials exhibit only a fraction of the mechanical performance of those manufactured through more traditional means. Here we show that thermal annealing of confined structures manufactured using the FFF technique dramatically increases their inter-laminar toughness. Single Edge Notch Bend (SENB) fracture specimens made from acrylonitrile-butadiene-styrene (ABS) feedstock were isothermally heated in a supporting fixture, post-manufacture, across a range of times and temperatures. Fracture testing was then used to quantify the changes in inter-laminar toughness offered by annealing through measurements of the Mode I critical elastic-plastic strain energy release rate, JIc. Under the most aggressive annealing conditions, the inter-laminar toughness increased by more than 2700% over the non-annealed baseline material. Void migration and aggregation during the annealing process was analyzed using X-ray tomography and provides insight into the toughening mechanisms. Time-scales of reptation and polymer mobility at the interface during annealing are also modeled and agree with fracture experiments.

Polymeric components manufactured via freeform fabrication (FFF) typically have poor inter-laminar toughness resulting from incomplete bonding across layers during production. Here we study the effect of printing and post-processing on the inter-laminar toughness of additively manufactured semi-crystalline (poly-lactide (PLA)) structures. Specimens were subject to post-print thermal annealing to promote inter-laminar bonding, while post-annealing quenching rates were chosen to vary the induced degree of crystallinity in the final structure, as characterized via dynamic scanning calorimetry (DSC). Critical elastic-plastic strain energy release rates (JIc) of annealed samples were evaluated using the single edge notched bend (SENB) geometry and post-testing fractography. The results show that as-printed PLA adopts an amorphous character with good inter-laminar toughness and ductility. Post-print annealing can double the toughness via increased interfacial wetting, but only if the material is quenched rapidly to preserve the amorphous character. In contrast, post-print annealing followed by slow cooling results in a semi-crystalline state (≈25% crystallinity) with low fracture toughness and brittle fracture behavior.

Age and sex are associated with differences in asthma prevalence and morbidity.To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma.We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003.A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088).Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.

Asthma remains one of the most common diseases worldwide and results in significant societal health care costs and in morbidity and mortality to those afflicted. Despite currently available medications, 5-10% of patients with asthma have severe disease with debilitating symptoms and/or life-threatening exacerbations. Bronchial thermoplasty is a device-based therapy with proven efficacy in this subgroup of patients. Thus far, bronchial thermoplasty has been shown to reduce exacerbations and to improve important measures of asthma control. The purpose of this article is to review the pathophysiology of severe asthma, including the role of airway smooth muscle cells and the procedural aspects of bronchial thermoplasty, and to review the evidence behind this important therapy.

Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis, and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be underdiagnosed and undertreated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (ie, corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population.

Recent statistics have shown that asthma deaths and hospitalizations are decreasing, but there are unmet challenges in the management of severe asthma in children. Current asthma management is focused on achieving asthma control through an effort to minimize asthma impairment via specifically addressing factors that affect day-to-day symptoms, and minimizing the risk of future asthma-related events, such as asthma exacerbations, disease progression, and adverse effects to medications. New targeted medications have been developed for which therapeutic responses have been correlated with specific biomarkers; for example, sputum or blood eosinophil count with anti-IL-5 therapy and serum periostin with anti-IL-13 therapy. These drugs hold great promise, but will likely be expensive alternatives to traditional asthma therapy. There is a growing need to address the age-specific challenges in the management of subjects with asthma from the young to the very old. In the future, it will be important to develop strategies to prevent the development of asthma and, in children with the disease, to maximize the appropriate use of, and adherence to, the available medications before considering more expensive alternatives. To do this, we will need to standardize and harmonize medical care, while improving communication and setting up systems of collaboration. If executed effectively, this effort should have a marked impact on reducing the prevalence of asthma in the future and the consequent burden of asthma on society.