Numerical simulation of particle deposition in obstructive human airways

To investigate airflow pattern and its impact on particle deposition, finite-volume based computational fluid dynamics （CFD） simulations were conducted in the diseased triple-bifitrcation airways. Computations were carried out for twenty Reynolds numbers ranging from 100 to 2 000 in the step of 100. Particles in the size range of 1-10 μm were conducted. Two particle deposition mechanisms （gravitational sedimentation and inertial impaction） were considered. The results indicate that there are strong relationship between airflow structures and particle deposition patterns. Deposition efficiency is different for different particles in the whole range of the respiratory rates. Particles in different sizes can deposit at different sites. Smaller particles can be uniformly deposited at the inside wall of the considered model. Larger particles can be mainly deposited in the proximal bifurcations. Deposition fraction varies a lot for different inlet Reynolds numbers. For lower Reynolds numbers, deposition fraction is relatively small and varies a little with varying the diameters. For Reynolds number to target the aerosols at the specific site. higher Reynolds numbers, there is a most efficient diameter for each

Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells： potential roles in airway inflammation

Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in E/f3 （homologous to human ESE-1） knockout mice, the expression of the inflammatory cytokine interleukin-6 （IL-6） is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.

Potential Role of Interleukin-25/Interleukin-33/Thymic Stromal Lymphopoietin-Fibrocyte Axis in the Pathogenesis of Allergic Airway Diseases

Objective： Allergic airway diseases （AADs） are a group of heterogeneous disease mediated by T-helper type 2 （Th2） immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources： Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection： We had done a literature search using the following terms ＂allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte＂. Related original or review articles were included and carefully analyzed. Results： It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin （IL）-25, IL-33, and thymic stromal lymphopoietin （TSLP）, are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions： In view of the redundancy ofcytokines and ＂united airway＂ theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.

Inflammatory airway features and hypothalamic-pituitary- adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

Background Bronchial asthma （BA） and chronic obstructive pulmonary disease （COPD） are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal （HPA） axis function in asthmatic rats combined with COPD. Methods Brown Norway （BN） rats were used to model These three models were compared and evaluated with the inflammatory airway diseases of BA, COPD and COPD＋BA. respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness （AHR）, inflammatory cytokines and HPA axis function. Results The inflammatory airway features and HPA axis function in rats in the COPD＋BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group （P 〈0.05）. Conclusions BN rat can be used as an animal model of COPD＋BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

Teaching chronic obstructive airway disease patients using a metered-dose inhaler

Asthma and chronic obstructive airway disease ,（COAD） are chronic inflammatory disorders of the airways which are usually associated with widespread airway obstruction that is often relieved by treatment. β2-adrenoreceptor agonists and corticosteriods are the mainstay of the management of this disease. The preferred route of administration of these agents is by inhalation. This allows the drug to be delivered directly to the airway with more rapid relief and fewer side effects than systemic route. The main disadvantage of metered-dose inhaler （MDI） use is that the correct use requires good technique;

The relationship between the expression of transient receptor potential vanilloid 1 and the airway remodeling in elderly patients with chronic obstructive pulmonary disease

Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(COPD).Methods According to airflow obstruction severity,totally 100 cases of elderly patients with

Interventional pulmonology for chronic inflammatory airway diseases

Chronic inflammatory airway diseases,such as chronic bronchitis,chronic obstructive pulmonary disease,emphysema,and bronchial asthma,pose significant healthcare challenges.Interventional treatments offer promise as valuable complements to the optimal medical therapy recommended by the Global Initiative for Chronic Obstructive Lung Disease guideline and the Global Initiative for Asthma guideline.By directly accessing the airways,these minimally invasive procedures enable precise interventions.They encompass a wide range of techniques including bronchial thermoplasty and targeted lung denervation for both chronic obstructive pulmonary disease and severe asthma,bronchoscopic lung volume reduction(including the use of endobronchial valves,coils,and bronchoscopic thermal vapor ablation),airway bypass and peripheral stent placement for emphysema,bronchial rheoplasty and spray cryotherapy for chronic bronchitis,and other emerging methods.These interventional treatments aim to improve patients’symptoms by reducing lung volume,alleviating hyperinflation,eliminating vagal innervation,disrupting hyperplastic goblet cells and thus reducing excessive mucus secretion,and weakening submucosal smooth muscles.This review highlights the potential advantages of interventional treatments for chronic inflammatory airway diseases and discusses relevant techniques tailored to specific disease subtypes.The overall aim is to assist interventional pulmonologists in selecting the most appropriate techniques for individual patients.

Re-epithelializaiton by epithelial inoculation with recipient phenotype in heterotopically transplanted rat allografts

Background Re-epithelialization has remained a major obstacle in both tracheal and lung transplantations.This study examines the realization of re-epithelialization by epithelial inoculation in a rat heterotopic tracheal transplantation model.Methods The original epithelia of tracheas from donor Wistar rats were removed and the tracheas were then inoculated with 106/ml in vitro cultured epithelial cells of the Spraque-Dawley （SD） rat phenotype.These allo-tracheas were then heterotopically transplanted into SD rats.After 28 days,the allo-trachea tissues were recovered and assessed for epithelial morphology and cellular differentiation using immunohistochemical analysis.An additional experimental group was used to compare the outcomes of re-epithelialization in immunosuppressed animals.Results Histological examination showed that allografts with epithelial inoculation maintained patent tracheal lumens,which were obliterated in controls.Recipient immunosuppression facilitated the formation of an integrated ciliated epithelial layer,further demonstrated by the presence of a dense cilia population,a well-developed plasma membrane,and readily recognizable intercellular junctions.Epithelial cellular differentiation markers such as cytokeratin 14 and 18,and cystic fibrosis transmembrane conductance regulator （CFTR） were all positive in allografts under immunosuppression.Conclusion Concurrent recipient-derived epithelial inoculation with immunosuppression can result in complete reepithelialization with the recipient phenotype and suppress the luminal obliteration process in heterotopic transplantations.

Neural Mechanisms Underlying the Coughing Reflex

Breathing is an intrinsic natural behavior and physiological process that maintains life.The rhythmic exchange of gases regulates the delicate balance of chemical constituents within an organism throughout its lifespan.However,chronic airway diseases,including asthma and chronic obstructive pulmonary disease,affect millions of people worldwide.Pathological airway conditions can disrupt respiration,causing asphyxia,cardiac arrest,and potential death.The innervation of the respiratory tract and the action of the immune system confer robust airway surveillance and protection against environmental irritants and pathogens.However,aberrant activation of the immune system or sensitization of the nervous system can contribute to the development of autoimmune airway disorders.Transient receptor potential ion channels and voltage-gated Na+channels play critical roles in sensing noxious stimuli within the respiratory tract and interacting with the immune system to generate neurogenic inflammation and airway hypersensitivity.Although recent studies have revealed the involvement of nociceptor neurons in airway diseases,the further neural circuitry underlying airway protection remains elusive.Unraveling the mechanism underpinning neural circuit regulation in the airway may provide precise therapeutic strategies and valuable insights into the management of airway diseases.