Bronchial asthma

1
Bronchial asthma

• Department of respiration
• Kong Lingfei

2
Asthmahuman killer!
3
Background of asthma

• Prevalence in the world 1.6 hundred million
• in China 13
• in Shenyang 1.24 (1999)
• GINA Global Initiative for Asthma(1994)
• WHO/HLBI
• Bronchial asthmatic diagnosis guideline (1997)
• Chinese Medical Academy

4
Definitions of asthma

• Chronic airway inflammation
• Broncho-hyperresponsiveness, BHR
• Airflow limitation

5
Mechanism allergy theory

• antigen antigen
• ?
  ?again
• atopy?IgE antibody?mast cells,
  basophils
• 
  ? histamine
• inflammatory
  media LTs
• 
  ? PAF
• 
  ECP
• immediate asthmatic
  reaction, IAR
• 
  ?
• bronchial smooth
  muscle spasm
• airway
  narrow

6
Mechanism never-receptor disorder theory

• adrenergic and cholinergic nerous systems, AC
• non-adrenergic and non-cholinergic nerous
  systems, NANC
• AC a1-receptor?M1-?M3-receptors
  excitement
• NANCPS-receptor
  ?
• bronchial smooth muscle
  contraction
• AC ß-receptor?M2-receptor
  excitement
• NANC VIP receptor
  ?
• bronchial smooth muscle
  dilation
• asthmatic airway a1?M1?M3?PS?/ ß ?M2?VIP?

7
Mechanism airway inflammation theory

• antigen
• ?
• allergic airway inflammation, AAI
  ECP
• ?
  MBP
• inflammatory cells ?inflammatory media LTs
• EOS ?
  PAF
• neutrophils late asthmatic
  reaction, LAR
• T lymphocyte(Th1/Th2?)
• ?
• Th2 cytokine IL-3?4?5,GM-CSF ?IgE?

8
Differ mechanisms in acute and chronic asthma
inflammation cells ? epithelium injury
bronchial contraction mucous edema airway
secretion?
cell proliferation excellular base?
airway narrow
airway reversibility?
BHR?
exacerbation
symptoms
9
Other mechanisms induced factors

• Allergen pollen, acarus
• infection virus or mycoplasmal infection
• climate and physical and chemical factors
• drugs aspirin induced asthma, AIA
• ß-receptor inhibitor
• heredity
• Gastroesophageal reflux disease, GERD
• Psychological, incretion factors, sports

10
Diagnosis standards of asthma

• symptoms
• signs
• recovered ways
• except other cardiac and pulmonary diseases
• lung function examination?untypical asthma

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Untypical asthma

• Cough variant asthma, CAV
• Asthma with gastroesphgeal reflux
• Exercise induced asthma, EIA
• Drug induced asthma, DIA
• Occupational asthma, OA

12
Lung functions diagnosis of asthma

• Obstructive ventilation insufficiency
• and reversibility of airway obstruction
• Variance rate of peak expired flow (PEF)
• in 24 hours 20
• Bronchial challenge is positive

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Lung functions diagnosis of asthma(1)

• FEV1 lt 80 pre, FEV1/FVC lt 70
• bronchial dilation test is positive
• Post FEV1 - Pre FEV1
• FEV1improved rate 100
• Pre FEV1
• determinant standardFEV1 improved rate15()
• FEV1 improved rate200ml

14
Lung functions diagnosis of asthma(2)
PEF meter PEF predicted
value
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Lung functions diagnosis of asthma(2)

• PEF lt 80pre and PEF variance rate 20
• PEF max PEF min
• PEF variance rate 100
• 1/2( PEF max PEF min )
• Determinant standardPEF variance rate(24h) 20
  ()

16
Lung functions diagnosis of asthma(3)

• Bronchial challenge is positive
• therapeutic properties
• forbid properties
• methods drug induce methocholiner
• 
  histamine
• exercise induce

17
The steps of chronic persistent asthma

• ?? ?? ???? ???? ???? FEV1
  PEF???
• 
  ?PEF
• 1 ???? lt1?/w 2?/m ???
  80 lt20
• ???? 1?/w gt2?/m ????? gt80
  lt20
• lt1?/d
• 3 ???? ????? gt1?/w ????? 6080
  2030
• 4 ???? ???? ?? ??
  lt60 gt30
  

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The steps of acute exacerbation asthma
???? ?? ??
?? ??? ??
??,??? ??? ??? ??
??? ??? ??? ???? ????
?? ?? ???? ????
??? ????? ????? ??,???? ??
? ?
???? ???? ???? ??
gt30?/? ??? ?? ??
?? ?????? ??? ??????
???? ???? ???? ??
lt100?/? 100200?/? gt120?/? lt120?/?,??? ??
?,lt10mmHg ?,10-25mmHg ??,gt25mmHg
?,?? ?ß2?PEF gt70 5070
lt50?lt100L/min
PaO2 ?? 6080mmHg
lt60mmHg PaCO2 lt40mmHg 45mmHg
gt45mmHg SaO2 gt95 9195
90 pH
??

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Distinguishing diagnosis of asthma

• Cardiac asthma
• COPD
• Upper airway obstruction (lung cancer)
• Pulmonary eosiniphil infiltration

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Correlation between asthma and COPD
21
Discrimination between asthma and COPD
Asthma
COPD ?? ?? ??? ????(?????) ????(??
??) ?? ?? ?? ?? ???????? ?????? ??? ??
?? ????? ??? ???? ???? ???? ?? ???? ??? ???
?? ??????
22
Drugs for treating asthma

• Glucocorticosteroid -anti-inflammation
• ß 2-agonist
• theophylline bronchodilators
• anticholinergic drug
• non-steroid anti-inflammations

23
Steroids with vein injection
steroid dose dose character
dose/d (mg) (mg)
(mg)
methylprednisonlone 40 4
11-hydroxide 40320 Hydrocortison
100 20 11-ketone 1001000 dexamethas
on 5 0.75 11-ketone
1030
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Inhaled steroids

• Baclomethason dipropionate ???(BDP) 50ug200
  
• Budesonide
  ???(BUD) 100ug 100
• 
  ??? ??
• 
  ????? 1mg/2ml
• Fluticasone propionate ???(FP)
  125ug 100
• Fluticasone Salmeterol ???
  100/50ug60
• 
  250/50ug60

25
Using principles of inhaler steroid

• ????????????????
• ??????
• ??????????????
• ??????ß2-?????
• ?????????

26
Inhaled ß2- agonists

• Salbutamol ???
  200ug200
• ???????
  0.05 20ml
• Terbutaline ???
  250ug200
• ??????
  250ug100
• ????????
  5mg/ml
• Salmeterol ???
  50ug200
• ???
  50ug48
• Formoterol ?????
  4.5ug60

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Oralß2- agonists

• Terbutaline ???? 2.5mg
• Procaterol ??? 50ug
• Formoterol ??? 40ug
• Salbutemol ??? 8mg
• Bambuterol ?? 4mg

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Classification of ß2-agonsts (Politiek)
????
????
4? ??? ????? ??????? ???????
1? ??? ????? ???????
?
????
3? ??? ????? ??????? ??????? ???????
2? ???? ????? ??????? ???????
?
Politiek, et al. Eur Respir J 1999, 13 988
? ? ??????
29
Using principles ofß2-agonist

• ?????????????
• ??????????????
• ???????,????lt4?/?
• ?????????????
• ??????????

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Theophylline

• ivaminophylline 0.25
• doxofylline 0.1
• po aminophylline 0.1 short action
• AEA
• ??? 0.1 long
  action
• ??? 0.4

31
Using principles of theophylline

• ????????????
• ??????????????????
• ?????????
• ??????????????????
• ?????????(??? 1020ug/ml)
• ?????????(??? 510ug/ml)
• ??????????

32
Anti-cholinergic drug

• Ipratropium bromide ??? 20ug200
• ??????
  20ml
• Ipratropium bromide ??? 20ug200
• Salbutamol ??? 2ml

33
Using principles of anti-cholinergic drug

• ???COPD????
• ???????????????
• ???????
• ?????????????????
• ??????????????????

34
Non-steroid anti-inflammation drugs

• Anti-histamine inhaler???? 5mg200
• oral
  ????????
• 
  ????????
• LTs receptor inhibitor ??? 10mg5
  

35
Using principles of other anti-inflammation

• ??????????Atopy ??
• ???????????????
• ????????????????
• ????????????????
• ???????????????

36
Drug therapy of asthma ??????
??????

• ????ß 2-???
• ??????
• ????ß 2-???
• ????????
• ????

• ????????
• ????ß 2-???
• ????????
• ????
• ??????
• ?????
• ???

37
long therapy projects of asthma
GINA 2002
??? Step1 ????
?????? ????
??????
38
long therapy projects of asthma
GINA 2002
??? Step2 ????
?????? ????(200-500?gBDP????)
?????? ????,?????,???????
39
long therapy projects of asthma
GINA 2002
??? Step3 ????
???? ????(200-1000?g BDP????) ????????2-?????
?????? ????(500-1000?g BDP????)???????????(500-10
00?g BDP????)???????2-?????????????(gt1000?g
BDP????)?????(500-1000?g BDP????)????????
40
long therapy projects of asthma
GINA 2002
??? Step4 ????

• ????
• ????(gt1000?g BDP????)????????2-?????
• ??????,???????????
• ????
• ??????
• ?????2-?????
• ????

??????
41
Combined therapy
Low dose inhaler steroid (400 µg /d)
?
exacerbation
inhaler steroid of double dose
Barnes, Nice 2001