bronchial asthma

1. bronchial asthma

2. 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.

3. 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.

4. 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

5. 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

6. Pathogenic mechanism • Asthma is Characteristic of hyper-reactivity of the airway • Chronic （allergic） inflammation is the basic lesion of asthma

7. 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

8. 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.

9. 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）

10. 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

11. 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.

12. Endocrine factors Asthma disappears in puberty in some patients; aggravated in menstruation period , during pregnancy, and when there is hyperthyroidism

13. 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 LTSmicrovascular 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）

14. 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

15. 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

16. 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.

17. 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

18. 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.

19. 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

20. 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.

21. Lab The suspected antigen is used for skin test so as to find out the allergen. The skin prick test is quite reliable

22. diagnosis Diagnostic criteria for asthma Criteria for cough variant asthma

23. 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 scattered expiratory wheezing could be heard during the attack, the expiratory phase is lengthened. 3.the abve symptoms and signs might be remitted after treatment or spontaneously. 4.other causes of wheezing, short of breath,coughing and tightness in the chest are excluded. 5.at least one of the following tests is positive,if the clinincal picture is （eg no wheezing or signs）：①positive bronchial or exercise challenge test②positive bronchodilatator test［FEV1 increase by more than 15%，and the increase of absolute FEV1 volume>200ml］；③daily PEF variance or 24 hour fluctuation≥20%。 when1~4or4、5 are met，bronchial asthma is diagnosed。

24. Differential diagnosis • 1.Cardiac asthma Aminophylline, morphine, epinephrine • 2.喘息性慢性支气管炎 • 3. Bronchiogenic lung cancer • 4. eosinophilic lung diseases

25. Staging • Asthma could be classified into the following 3 stages according to its clinical picture: exacerbation phase, persistent phase, and remission phase.

26. Criteria for cough variant asthma • Also named allergic coughing, which is a potential insidious form of asthma and occurs at all age group. Its exclusive symptom is chronic coughing with no positive signs. Therefore it might be misdiagnosed as bronchitis. However it is believed by most physicians that its mechanism of pathogenesis is identical to that of asthma, and treatment is effective when medications for asthma are indicated.

27. Criteria for cough variant asthma Recurrent or persistent coughing for more than 2 months without much sputum, which occurs at night or in the early morning, and got worse after exercise. No infection is present or long term use of antibiotics proves not effective. Bronchodilatators could reduce coughing（basic criterium） History of allergy or familial allergy，airway is high responsive, positive allergen skin prick test

28. Evaluation of non-exacerbation phase severe： frequent attack of symptoms,limited capability,bad sleeping,PEF or FEV≤60％ of predicted,PEF varience>30％ moderate：daily attacked,sleeping and ability compromised,nocturnal asthma>once a week, PEF or FEV1≤50％，<80％of predicted，PEFR>30％

29. Evaluation of non-exacerbation phase minor：symptoms≥once a week，but less than once a day.ability and sleeping might be affected.nocturnal asthma>twice a month，PEF or FEV1≥80％，PEFR 20～30％ intermittent：symptoms appear intermittently,<once a week,short duration of attack（hours～days）, nocturnal asthma≤twice amonth，pulmonary function is normal，PEF or FEV1≥80％，PEFR<20％

30. Evaluation of the severity for acute attack Clinical feature minormoderate severe acute sleep apnea breathlessness walking moving rest position supine sitting bending forward speech sentence phrases words unable to speak irritation possible often often sleepiness confusion sweating yes yes significant

31. Evaluation of the severity for acute attack Clinical feature minormoderate severe acute sleep apnea Breath rate somewhat quickened markedly apnea Motion of accessory respiatory no frequent frequent paradoxical muscles and movement of the three depressions chest and abdomen Sign Wheezing sound scattered diffuse diffuse weakened or absent Pulse rate <100 100—120 >120 >120 or pulse rate （>12岁） slowed，irregular

32. Evaluation of the severity for acute attack Clinical feature minormoderate severe acute sleep apneaPaCO2 <6 ≤6>6possible respiratory failure （kPa） SaO2 >95 91—95 ≤90 (％) pH decline

33. Goal of management for asthma ⑴to effectively control acute attack and maintain minimal symtoms or no symptoms ⑵to prevent aggravation； ⑶to keep lung function around normal level； ⑷maintain the ability to exercice； ⑸avoid the adverse reaction of the medications for asthma.

34. Standards for asthma control • ⑴minimal (or no) chronic symptoms,including symptoms at night. • ⑵minimal times of asthma attack； • ⑶no emergency room visit due to asthma • ⑷minimal use of ß2 antagnists； • ⑸no limitation of ability(including exercise). • （6）24 hour PEF variance<20％； • (7)PEF noraml or almost normal； • (8)minimal adverse reactions of medications

35. Elimination of etiology Avoid allergen, appropriate treatment of infection, eradicate exposure to the predisposing factors(smoking, paint, icecream, abrupt change of weather)

36. Asthma: Prevention • Stop smoking • Decrease ETS exposure • Reduce exposure to biological dust • Reduce exposure to pollution • Reduce risk to respiratory viruses • Dietary: Increase antioxidants and Omega 3s • Decrease exposure to cow’s milk, dairy, nuts, soy, wheat in infancy

37. Asthma: Treatment • Remove the allergen • Drug Therapy • Bronchodilators (For acute responses) • Adrenocorticol hormone: dangerous side effects if used long term • Psychosocial Techniques • Stress Management • Social Support

38. What’s New for Treating Asthma? • Medications: • long term or controller medications • quick relief medications • Stepped therapy: start high, back down • Asthma monitoring and action plans • Environmental controls

39. Overview of Medications • Controller medications • control inflammation • long duration bronchodilation • multiple new medications • Quick relief medications • for intermittent or breakthrough symptoms • Controversy: Use worsens asthma? Marker of worsening asthma?

40. Controller Agents • Inhaled corticosteroids • Systemic corticosteroids • Long acting 2 agonists • Cromolyn and derivatives • Methylxanthines • Leukotriene Modifiers

41. Inhaled Corticosteroids • Control airway inflammation locally • Ideal: control asthma (high local potency); no side effects (low systemic effects) • fluticasone, budesonide **** • beclomethasone * • (triamcinolone, flunisolide)

42. Systemic Corticosteroids • May be needed initially • Side effect profile well known • Step down therapy • Alternatives: high dose inhaled corticosteroids; methotrexate; other immunosuppressive drugs

43. Long acting ß2 Agonists • Salmeterol • prolonged

44. Quick Relief Medications • ß2 Agonists • Anticholinergics • Systemic corticosteroids

45. Managing Asthma Long term • Prevent symptoms • Maintain normal pulmonary function • Maintain normal activity levels • Prevent exacerbations, emergencies • Optimize medical therapy • Patient satisfaction (compliance)

46. B-agonists Corticosteroids Oxygen Intubation & Mechanical Ventilation Methylxanthines Ipratropium Bromide BiPAP Heliox MgSO4 Infusion Mucolytics Chest Physical Therapy Aggressive Hydration Antibiotics Inhalational Anesthetics ECMO Inhalational Furosemide Inhalational MgSO4 Potential Treatments for Acute Asthma

47. Methylxanthines (Theophylline) • Used for over 50 years to treat asthma • Poorly understood mechanism of action • Physiologic effects thought to include bronchodilation, stimulation of diaphragmatic contractility, mucocilliary clearance, and possibly some anti-inflammatory effect. • Dose related toxicities include nausea, vomiting, headache, CNS stimulation, seizure, hematemasis, hyperglycemia, and hypokalemia

48. Ipratropium Bromide • A synthetic anticholinergic compound • Anticholinergic compounds are known to cause bronchodilation • Atropine has been used, but often limited due to side effects such as tachycardia, dry mouth, disturbances of visual accommodation, etc. • Ipratropium thought to be relatively free of side effects, but with preservation of bronchodilatory properties