bronchial asthma Introduction Bronchial asthma is a chronic inflammatory condition involving a variety of cells including eosinophils, mast cells, T lymphocytes, neutrophils, and epithelial cells of the airway, as well as cellular elements ，which gives rise to the increase of airway hyper-reactivity. Extensive changeable and reversible ventilation restriction is common and can cause recurrent tachypnea, feeling of out of breath, and coughing. The symptoms are more usually present and aggravated at night or early in the morning. Remission might be achieved spontaneously or following treatment. etiology The pathogenesis of asthma is complicated and is affected by genetics and the environment. It is a multigene disoder and closely related to atopy. Most patients have prior history of eczema, allergic rhinitis, food or drug allergy, and quite a few patients have family history. The formation and attack of asthma is also a consequence of the function of multiple environmental factors such as inhalation of allergens, respiratory tract infection, and coldness. epidemiology 160 million patients in the word prevalence ：1%--5% ，1% in china Prevalence in male is similar to that in female The onset is before 12 years of age in the majority Family history could be found in 20% patients Related to allergic rhinitis, eczema and nasal polyp etiology １．Genetic factors: multigene inheritance heritability 70-80% ２．Predisposing factors: air pollution 1 ）inhalants ：dust mites 、pollen 2 ）infections 3 ）food 4 ）change of weather 5 ）mental factors 6 ）exercise 运动7 ）drugs 8 ）menstruation, pregnacy Pathogenic mechanism Asthma is Characteristic of hyper-reactivity of the airway Chronic （allergic ）inflammation is the basic lesion of asthma Allergic inflammation Is divided into 3 subtypes according to the different cytokines secreted by CD4 Th cell: Th0 、Th1 and Th2 。Investigations have shown that allergic reactions like asthma are mediated by Th2 cells. There is an increase or predominance of Th2 or its cytokines. The resulting airway inflammation could be classified into the following two types: 1. IgE mediated and T lymphocyte dependent pthway 2.NonIgE mediated and T lymphocyte dependent pathway Immunologic factorsthe role of IgE mediation The combination of allergen with specific IgE triggers the degranulation of the mast cells and eosinophils, resulting in release of mediators including leukotrienes C,D,E, and the subsequent smooth muscle contraction, edema of the mucosa, increase of secretion, and finally stenosis of the bronchioles ,which all contribute to asthma. Total serum IgE or specific serum IgE titer increase is seen in patients with asthma , indicating type I allergic reactions might be present. nonIgE mediated, T lymphocyte dependent pathway In delayed type allergic reaction, Th2 cell directly initiates imflammatory response by activation and agglutination of various inflammatory cells via the release of multiple cytokines(IL-4 、IL-13 、IL-3 、IL-5 ）Neuromental factors The complicated autonomic innervation of the bronchiopulmonary sysytem includes cholinergic, adrenergic ,nonadrenergic and noncholinergic nerves. -adrenergic receptor malfunction and the increased tone of the vagus, or with simultaneous increase of -adrenergic reactivity,would promote contraction of the smooth muscle and secretion of the glands, resulting in attack of asthma Neuromental factors The inhibitory system of NANC is the major nervous system that relaxes the smooth muscle of the airway. Substance P, the transmitter of the stimulative nervous system of NANC, is present in the class C chemosensitive afferent fibers of the vagus.when the class C afferent nerve ending is exposed due to injury of the airway, local lesion might be aggravated. Abrupt change of emotion might induce asthma attack, especially in those with refractory asthma. Endocrine factors Asthma disappears in puberty in some patients; aggravated in menstruation period , during pregnancy, and when there is hyperthyroidism Pathogenic mechanism 　　　　　IgE 、mast cell smooth muscle contraction of the bronchiole allergen allergen histamine 、ECF immediate asthma reaction AAI ventilation disorder 　　　　　　　PAF 　ECF 　airway obstruction by exudation Late asthma reaction 　LTS 　　microvascular transudation （LAR ）congestion and edema of the mucosa 　　　BHR 　　　PGS 　　　　　　　　　　　injury and exfoliation of the epithelial cells 　　　　　　　　　　　　exposure of nerve ending neuropeptide 、substance P 　　　　inflammatory cells 　　　（macrophage 、eosinophils and neutrophils ）Hyper-reactivity of the airway Bronchial reactivity refers to the contractive reaction of the airway to various stimuli including those chemical, physical or pharmacologic in nature. Airway hyper-reactivity (AHR) is defined as the excessive bronchial contraction in response to the stumuli which do not elicit response or only cause minor response under normal conditions. AHR is one of the important characteristics of asthma, whilie airway imflammation is one of the most important mechanisms that contribute to AHR Pathology The basic pathology of bronchial asthma includes imflammation and remodeling of the airway. The basic pathological change of the inflammmation includes infiltration of mast cells, macrophages, eosinophils, lymphocytes and neutrophils; edema of the submucosa, increase of the permeability of the microvasculature, retention of the secretion within the bronchioles, spasm of the bronchial smooth muscle, detachment of the cilated epithelium, exposure of the basal membrane, poliferation of goblet cells and increase of bronchial secretion, which contribute to form the chronic 剥脱性eosinophilic bronchitis Clinical manifestation The typical onset of asthma is accompanied by sneezing, nasal secretion, coughing and out of breath. If timely treatment is not given, the bronchial narrowing might get worse and cause dsypnea. In severe cases, the patient is obliged to take the sitting position which is refered to as othopnea, coughing with or without large amount of whitish foamy sputum, or even with cyanosis. Clinical manifestation Physical examination: Increased anteroposterior diameter of the chest, over-resonance on percussion, wheezing all over the chest; when severe dyspnea exists, both breathing sounds and wheezing could be reduced or absent. No symptoms and sighns might be present during the interval of attack, in some cases, wheezing could be noted on exersion Clincal manifestation Symptoms are more severe at night, and could be relieved after medication or spontaneously. When severe acute asthma attack could not be mitigated within 24 hours by appropriate use of adrenomimetics, the patient is in the state of persistent asthma. The patient might be struggling due to dyspnea before he becomes weak and unable to cough. Blood pressure might decline , cyanosis might appear, and the patient might even die from acute respiratory failure. Lab Peripheral blood ：eosinophils increase. A false white cell count increase might occur if adrenaline is used. X-ray ：over-inflation of the lung; increased lung markings; small area shadow might appear along the bronhchioles if there is bronchial pneumonitis or atelectasis Lab Lung function test ：decrease of airflow rate and tidal volume, increase of reserve volume. Blood gas test shows a decrease in PaO2; an initial PaCO2 decline may be noted and an elevation follows with progression. pH decreases in the late stage.during the interval of attack, lung function is usually normal except the reserve volume is increased. Daily test of PEF and its variance is helpful for the judgement of the existence of subclinical asthma. Lab The suspected antigen is used for skin test so as to find out the allergen. The skin prick test is quite reliable diagnosis Diagnostic criteria for asthma Criteria for cough variant asthma Diagnotic criteria 1.recurrent breathlessness,wheezing,coughing,and tightness in the chest. Usually related to contact of allergen,cold air,physical or chemical stimuli,upper respiratory tract infection with virus,and exercise,ect. 反复2.diffuse or