Microinjection Molded Biopolymeric Airway Stent with Antibacterial and Anti-Hyperplastic Properties

Central airway stenosis is a condition that the diameter of the trachea or main bronchus shrinkage is caused by external compression or internal tissue hyperplasia, which can cause difficulty breathing, asphyxia, and even death. Airway stenting is an easy way to restore the patency of the central airway, but airway stents commonly used in clinical practice can lead to complications such as mucus plugging, bacterial infection, and granulation tissue hyperplasia. Moreover, the non-degradable characteristic makes it requires a second operation to remove, which has the potential to cause tissue damage. In this study, a biodegradable airway stent is fabricated by microinjection molding using the bioelastomer of poly (L-lactide-co-ε-caprolactone) as the matrix material. The airway stent has excellent mechanical properties and an appropriate degradation rate. The hydrophilic surface of the airway stent can inhibit mucus plugging. The loading of silver nanoparticles and cisplatin endows the stent with antibacterial and anti-hyperplastic functions. In vitro and in vivo experiments demonstrate that this study provides an antibacterial and anti-hyperplastic biodegradable airway stent with elastic properties to avoid secondary removal operation and reduce complications associated with mucus plugging, bacterial infection, and granulation tissue hyperplasia.     

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention

Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subsequently coupled to a carrier protein to form a neoglycoconjugate. The allergy-protective activity of arabinogalactan could be reproduced with the partial structure in subsequent in vivo experiments. This is the first example of a successful simplification of arabinogalactan with a single partial structure while retaining its allergy-preventive potential.     

Exhaled breath condensate: Determination of non-volatile compounds and their potential for clinical diagnosis and monitoring. A review

Exhaled breath condensate is a promising, non-invasive, diagnostic sample obtained by condensation of exhaled breath. Starting from a historical perspective of early attempts of breath testing towards the contemporary state-of-the-art breath analysis, this review article focuses mainly on the progress in determination of non-volatile compounds in exhaled breath condensate. The mechanisms by which the aerosols/droplets of non-volatile compounds are formed in the airways are discussed with methodological consequences for sampling. Dilution of respiratory droplets is a major problem for correct clinical interpretation of the measured data and there is an urgent need for standardization of EBC. This applies also for collection instrumentation and therefore various commercial and in-house built devices are described and compared with regard to their design, function and collection parameters. The analytical techniques and methods for determination of non-volatile compounds as potential markers of oxidative stress and lung inflammation are scrutinized with an emphasis on method suitability, sensitivity and appropriateness. The relevance of clinical findings for each group of possible non-volatile markers of selected pulmonary diseases and methodological recommendations with emphasis on interdisciplinary collaboration that is essential for future development into a fully validated clinical diagnostic tool are given.     

Tracking extended mucociliary transport activity of individual deposited particles: longitudinal synchrotron X‐ray imaging in live mice

To assess potential therapies for respiratory diseases in which mucociliary transit (MCT) is impaired, such as cystic fibrosis and primary ciliary dyskinesia, a novel and non‐invasive MCT quantification method has been developed in which the transit rate and behaviour of individual micrometre‐sized deposited particles are measured in live mice using synchrotron phase‐contrast X‐ray imaging. Particle clearance by MCT is known to be a two‐phase process that occurs over a period of minutes to days. Previous studies have assessed MCT in the fast‐clearance phase, ～20 min after marker particle dosing. The aim of this study was to non‐invasively image changes in particle presence and MCT during the slow‐clearance phase, and simultaneously determine whether repeat synchrotron X‐ray imaging of mice was feasible over periods of 3, 9 and 25 h. All mice tolerated the repeat imaging procedure with no adverse effects. Quantitative image analysis revealed that the particle MCT rate and the number of particles present in the airway both decreased with time. This study successfully demonstrated for the first time that longitudinal synchrotron X‐ray imaging studies are possible in live small animals, provided appropriate animal handling techniques are used and care is taken to reduce the delivered radiation dose.     

Numerical simulation of soft palate movement and airflow in human upper airway by fluid-structure interaction method

In this paper, the authors present airflow field characteristics of human upper airway and soft palate movement attitude during breathing. On the basis of the data taken from the spiral computerized tomography images of a healthy person and a patient with Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS), three-dimensional models of upper airway cavity and soft palate are reconstructed by the method of surface rendering. Numerical simulation is performed for airflow in the upper airway and displacement of soft palate by fluid-structure interaction analysis. The reconstructed three-dimensional models precisely preserve the original configuration of upper airways and soft palate. The results of the pressure and velocity distributions in the airflow field are quantitatively determined, and the displacement of soft palate is presented. Pressure gradients of airway are lower for the healthy person and the airflow distribution is quite uniform in the case of free breathing. However, the OSAHS patient remarkably escalates both the pressure and velocity in the upper airway, and causes higher displacement of the soft palate. The present study is useful in revealing pathogenesis and quantitative mutual relationship between configuration and function of the upper airway as well as in diagnosing diseases related to anatomical structure and function of the upper airway. The project supported by the National Natural Science Foundation of China (10672036, 10472025 and 10421002), the Natural Science Foundation of Liaoning Province (20032109). English text was polished by Yunming Chen.     

稳态条件下气溶胶粒子在口腔模型中的沉淀率

以实际人体解剖学数据为基础,利用流体力学软件构建了口腔模型。由于口腔形状不规则,流场中会有湍流产生,所以本文选用的是k-ω方程。在此基础上,假设吸入空气流量为一个常量,改变吸入气体、气溶胶粒子的物理参数,以调整St数的变化,模拟不同情况下气溶胶粒子运动情况。由模拟结果可知:气溶胶粒子在口腔中的沉淀率受粒子半径、密度、及流速的影响,并随这些量的增加而增加;沉淀率可以视作St数的函数,并随St数的增加而增加;气溶胶粒子在口腔中的沉淀分布受模型几何形状和湍流的影响,在喉部附近沉淀较为明显;粒子在口腔中将沿怎样的轨迹运动则取决于粒子在入口处的初始位置。     

Episodic paroxysmal laryngospasm: Voice and pulmonary function assessment and management

Episodic paroxysmal laryngospasm (EPL) is a sign of laryngeal dysfunction, often without a specific organic etiology, which can masquerade as asthma, vocal fold paralysis, or a functional voice disorder. The intermittent respiratory distress of EPL may precipitate an apparent upper airway obstructive emergency, resulting in unnecessary endotracheal intubation, cardiopulmonary resuscitation, or tracheostomy. During 27 months, seven women and three men, ages 30–76 years, were assessed by a high diagnostic index of suspicion, an intensive history including psychosocial factors, physical examination of the airways, provocative asthma testing, and swallowing studies. Videolaryngoscopy, stroboscopy, and pulmonary flow-volume loop testing were definitive. The classic appearance was paradoxic inspiratory adduction of the anterior vocal folds with a posterior diamond-shaped glottic gap. During an attack of stridor or wheezing, attenuation of the inspiratory flow rate as depicted by the flow-volume loop suggested partial extrathoracic upper airway obstruction. Swallowing evaluation by videolaryngoscopy and videoesophagography may uncover gastroesophageal reflux disease. Hallmarks of management include patient and family education by observation of laryngoscopic videos, a specific speech therapy program, psychotherapy, and medical treatment of associated disorders. Electromyography may become a valuable future adjunct. Unlike laryngeal dystonia, patients with EPL do not benefit from botulinum toxin type A.     

Alveolar macrophages modulate allergic inflammation in a murine model of asthma

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.     

Tissue-Specific stem cell differentiation in an in vitro airway model

The respiratory tract is the primary site of exposure to airborne compounds, with the bronchial epithelium providing one of the first lines of defence. A growing need exists for an accurate in vitro model of the bronchial epithelium. Here, normal human bronchial epithelial (NHBE) cells cultured at an air/liquid interface create a fully differentiated, in-vivo-like model of the human bronchial epithelium. Developmental characterisation includes (i) trans-epithelial electrical resistance, (ii) morphology and (iii) bronchial cell specific stains/markers. It is concluded that the basal/progenitor cells create a pseudo-stratified, mucociliary NHBE model containing basal, serous, Clara, goblet and ciliated cells, reflective of the normal human bronchial epithelium (days 24-33 ALI culture).     

Biseugenol Exhibited Anti-Inflammatory and Anti-Asthmatic Effects in an Asthma Mouse Model of Mixed-Granulocytic Asthma

In the present work, the anti-inflammatory and antiasthmatic potential of biseugenol, isolated as the main component from n-hexane extract from leaves of Nectandra leucantha and chemically prepared using oxidative coupling from eugenol, was evaluated in an experimental model of mixed-granulocytic asthma. Initially, in silico studies of biseugenol showed good predictions for drug-likeness, with adherence to Lipinski’s rules of five (RO5), good Absorption, Distribution, Metabolism and Excretion (ADME) properties and no alerts for Pan-Assay Interference Compounds (PAINS), indicating adequate adherence to perform in vivo assays. Biseugenol (20 mg·kg⁻¹) was thus administered intraperitoneally (four days of treatment) and resulted in a significant reduction in both eosinophils and neutrophils of bronchoalveolar lavage fluid in ovalbumin-sensitized mice with no statistical difference from dexamethasone (5 mg·kg⁻¹). As for lung function parameters, biseugenol (20 mg·kg⁻¹) significantly reduced airway and tissue damping in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with biseugenol but was inferior to dexamethasone in higher doses. In conclusion, biseugenol displayed antiasthmatic effects, as observed through the reduction of inflammation and airway hyperresponsiveness, with similar effects to dexamethasone, on mixed-granulocytic ovalbumin-sensitized mice.