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.

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.

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.

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.

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