嗜酸性粒细胞

上皮细胞
1. 作为物理屏障，参与粘液纤毛的清除和有害 物质的去除；
上皮细胞
2. 释放类花生四烯酸类物质、肽酶、基质蛋白、 前炎症性细胞因子、趋化因子和氧化氮；
3. 表达主要组织相容性复合体II(人白细胞抗原
DR)而起抗原呈递功能。
气道平滑肌细胞、纤维母细胞
气道平滑肌细胞 纤维母细胞
可活化成产生与哮喘发病机制有关 的前炎症性细胞因子的细胞
轻度稳定的哮喘
极早期变化：存在网状基底膜的增厚，肥大 细胞、Th细胞和激活的嗜酸性 粒细胞的粘膜炎症。 调节性细胞因子IL-4和IL-5的产 生和释放是变应性哮喘的特征。
一、哮喘的炎症反应
气道上皮脱落，基底膜下纤维化，气道平滑
肌肥大，粘液过度分泌和包括激活的肥大细胞、 嗜酸性粒细胞、中性粒细胞、巨噬细胞、嗜碱性 粒细胞和淋巴细胞参与的多细胞性炎症。 炎症细胞对气道炎症和气道狭窄起主要作用， 相互联系。
气道炎症与气道重建
炎症：有血管的组织对损伤的一种反应。急性 炎症通过短暂重建的修复过程来保护 机体，使组织恢复正常，此期有一过性 重建反应。
2000
Risk Factors for Asthma

Host factors: predispose individuals to, or protect them from, developing asthma

Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist
Developed economies might expect to spend 1-2 percent of total health care expenditures on asthma. Developing economies likely to face increased demand
T 淋巴细胞
机制 结果 分泌IL-2、干扰素
TH1
TH2
和TNF-
介导迟发型变态反应
T淋巴细胞
分泌IL-4、IL-5、IL-13 介导过敏性炎症反应
IL-4、IL-13诱导、促进IgE的合成
IL-13粘液的高分泌、上皮下的纤维化和嗜酸性粒细胞 趋化物、嗜酸性粒细胞活化趋化因子的增高
IL-5、GM-CSF诱导嗜酸性粒细胞的趋化、分化和激活， 并延长嗜酸性粒细胞的存活。
Taking your breath away. Left: A normal lung is clear . Right: the molecule IL-13 may trigger mucus production and airway tightening, as shown in a patient who died of an asthma attack. CREDITS: (LEFT) WARNOCK ET AL., PRACTICAL PATHOLOGY OF CHEST DISEASE, 1996; (RIGHT) MARTHA WARNOCK
哮喘的定义
• 哮喘是由多种细胞包括气道的炎性细胞和结构细胞 （如嗜酸粒细胞、肥大细胞、T淋巴细胞、中性粒细胞、 平滑肌细胞、气道上皮细胞等）和细胞组分参与的气 道慢性炎症性疾病。这种慢性炎症导致气道高反应性， 通常出现广泛多变的可逆性气流受限，并引起反复发 作性的喘息、气急、胸闷或咳嗽等症状，常在夜间和 （或）清晨发作、加剧，多数患者可自行缓解或经治 疗缓解。 • 这个定义实际上包含了哮喘的慢性和急性两种特点：
Risk Factors that Lead to Asthma Development
Host Factors
Genetic predisposition Atopy Airway hyperresponsiveness Gender Race/Ethnicity
Environmental Factors
50
30 20
85 86 87 88 89 90 91 Year 92 93 94 95 96
Hospitalization Rates for Asthma
by Age, U.S., 1974 - 1997
Rate/100,000 Persons 40 35 30 25 20 15 10 5 0 74 76 78 80 82 84 86 Year 88 90 92 94 96 <15 15-44 45-64 65+
Sweden
(Aberg et al)
Japan
(Nakagomi et al)
Scotlwenku.baidu.comnd
(Rona et al)
UK
(Omran et al)
USA
(NHIS)
New Zealand
(Shaw et al)
Australia
(Peat et al)
{ 1966 1989 { 1979 1991 { 1982 1992 { 1982 1992 { 1989 1994 { 1982 1992 { 1975 1989 { 1982 1992

MODERN VIEW OF ASTHMA
Allergen
Macrophage/ Dendritic cell Th2 cell Mast cell
Multiple Mediators Mucus (>100) plug
Neutrophil
Eosinophil Nerve activation Epithelial shedding
正常人 哮喘病人
Figure 1. Specimen of Bronchial Mucosa from a Subject without Asthma (Panel A) and a Patient with Mild Asthma (Panel B) (Hematoxylin and Eosin, x40). In the subject without asthma, the epithelium is intact; there is no thickening of the sub-basement membrane, and there is no cellular infiltrate. In contrast, in the patient with mild asthma, there is evidence of goblet-cell hyperplasia in the epithelial-cell lining. The sub-basement membrane is thickened, with collagen deposition in the submucosal area, and there is a cellular infiltrate. Photographs courtesy of Nizar N. Jarjour, M.D., University of Wisconsin.
Death Rates for Asthma
By Race, Sex, U.S., 1980-1998
Rate/100,000 Persons 5 Black Female 4 3 White Female Black Male
2
1 White Male
0 1980
1985
1990 Year
1995
潜在的慢性炎症,反复出现的急性症状
支气管哮喘防治指南。中华结核和呼吸杂志2008; 31(3): 177-185
Epidemiology
Burden of Asthma

Asthma is one of the most common chronic diseases worldwide

Prevalence increasing in many countries, especially in children

Poorly controlled asthma is expensive; investment in prevention medication likely to yield cost savings in emergency care
Worldwide Variation in Prevalence of Asthma Symptoms
气道炎症
气道高反应性
嗜酸性粒细胞
机制 释放毒性介质(碱性蛋白、 嗜酸性粒细胞阳离子蛋 白、嗜酸性粒细胞过氧化 物酶和嗜酸性粒细胞衍生 的神经毒素) 结果
嗜酸性粒 细胞
气道反应性增高、气 道上皮破坏
活性氧 白三烯 前炎症性细胞因子(GMCSF、IL-3、IL-4、IL-5)
IT Eos
Lungs
Shen HH, J I 2003
International Study of Asthma and Allergies in Children (ISAAC)
Lancet 1998;351:1225
Increasing Prevalence of Asthma in Children/Adolescents
Finland
(Haahtela et al)
Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections Parasitic infections Socioeconomic factors Family size Diet and drugs Obesity
Asthma
Huahao Shen, M.D, Ph.D, FCCP,FCSRD
www.googlehuxi.cn
Second Hospital, Zhejiang University Institute of Respiratory Diseases Zhejiang University
气管镜下的哮喘本质：气道炎症
重建：是在生长时或对损伤和(或)炎症的反应 中组织结构发生的大小、质量或数量的改 变。
肥大细胞
机制 结果 增加气道平滑肌张 力，气流阻塞
抗原
结合 IgE释放组胺引 起 CysLTs 合成 释放蛋白酶(胰酶、 stromolysin、糜蛋白酶)
肥大细胞
前炎症细胞因子(TNF-、 GM-CSF、IL-3、 IL-4、 IL-5、IL-13) 趋化因子
Factors that Exacerbate Asthma

Allergens Air Pollutants


Respiratory infections
Exercise and hyperventilation
Weather changes
Sulfur dioxide Food, additives, drugs
0 5 10 15 20 25 30 35
Prevalence (%)
Trends in Prevalence of Asthma By Age, U.S., 1985-1996
80 70 60 Rate/1,000 Persons Age (years) <18 18-44 45-64 65+ Total (All Ages) 40
A major cause of school/work absence An overall increase in severity of asthma increases the pool of patients at risk for death

Burden of Asthma


Health care expenditures very high
Plasma leak Oedema
Subepithelia fibrosis Sensory nerve activation Cholinergic reflex Bronchoconstriction Hypertrophy/hyperplasia
Mucus Vasodilatation hypersecretion New vessels hyperplasia