1. Asthma
Review of Pathophysiology and
Treatment

2. Definition

It is a chronic inflamatory disorder due
to hyperresponsiveness of airways
characterized by dysponea,
cough,wheezing and chest tightness
with variable airway obstruction.

3. Types
Early onset asthma Late onsetasthma
 Nocturnal asthma
Brittle asthma
 Cardiac asthma
Catamenial asthma
 Cough variant asthma
 Aspirin sensitive asthma
 Occupational asthma


4. Child-onset asthma
– Associated with atopy
– IgE directed against common
environmental antigens (house-dust
mites, animal proteins, fungi
– Viral wheezing Infants/children,
allergy/allergy history associated with
continuing asthma through childhood

5. Adult-onset asthma
– Many situations
– Allergens important
– Non-IgE asthma have nasal polyps,
sinusitis, aspirin sensitivity or NSAID
sensitivity
– Idiosyncratic asthma less understood

6. Adult-onset asthma
– Occupational exposure
 animal
products, biological enzymes, plastic
resin, wood dusts, metal
 removal from workplace may improve
symptoms although symptoms persist in some

7. Pathophysiology
Airway limitation usually reversible
 Airway hyperreactivity
 Airway inflamation


With increased severity and chronicity
remodelling,fibrosis and fixed narrowing of airways
and decreased response to drugs.

8. Airway Inflammation
More often triggered by infections and chronic allergies.
IgE mediated triggering mast cell release.
Causes “fixed” obstruction not responsive to albuterol and
more often has an inspiratory component.
Strong genetic contribution.
Needs steroids.

9. Airway hyperresponsiveness
Primarily smooth muscle mediated.
Can occur at any age.
Reversible with albuterol. Primarily expiratory wheezes.
Results in air trapping / obstruction (can be quantified on
PFT’s).
Variable throughout lungs. May cause atelectasis on xray.
Primary process for wheezing due to cold air, exercise,
pet allergens.

10. Airflow limitation
– Acute bronchoconstriction
IgE -dependent mediator release from mast
cell (leukotrienes, histamine, tryptase,
prostaglandins)
 aspirin /NSAID
 non-IgE response (cold air, exercise, irritants)


11. 
Airflow limitation
– Chronic mucus plug formation
 secretions
& inspissated plugs
 persistent airflow limitation in severe intractable
asthma
– Airway remodeling
 irreversible
component of airflow limitation
secondary to structural airway matrix changes

12. A Closer Look

13. Etiology

Environmental(hygeine hypothesis)

Genetical

14. Common Triggers
Infections: viral respiratory illness
(rhinovirus, influenza, RSV, parainfluenz
a, human metapneumovirus), sinus
infections
Allergens: seasonal allergens, indoor
allergens, pets
Irritants: cigarette smoke, wood
smoke, other pollutants, weather
changes

15. Diagnosis
Compatible history plus either/or
 FEV more than15% following
bronchodilator therapy.
 More than 20% diurnal variation on
PEFR diary for 3 days a week for 2
weeks.
 FEV more than 15% decrease after 6
minutes of exercise.


16. Differential Diagnosis
Upper RTI
 Lower RTI
 Systemic


17. Asthma Classification

Mild
intermittent
Day symptoms < 2/week,
Night symptoms < 2/month
Normal FEV , FEV/FVC normal
Mild
persistent
Day symptoms >2 per week but not daily,
Night symptoms> 3-4/month
Normal FEVFEV/FVC normal
Moderate
persistent
Daily symptoms, affect activity,
night symptoms > 1/weekFEV60-80%
FEV/FVC reduced < 5%
Continuous symptoms, limited activity,
Severe
persistent
FEV <60%FEV/FVC reduced >5%.

18. Investigation
Lab investigations
 Radiology
 Spirometry
 PEFR recording


19. Pharmacologic Therapy
Long-term control medications
 (Controllers)
 Short term control medications
 (Relievers)

– corticosteroids
 inhaled
form
 systemic steroids used to gain prompt control
of disease when initiating inhaled tx
– cromolyn sodium or nedocromil
 mild-to-moderate
anti-inflammatory medications

20. Management
AccordingtoGINA,NAEPP3,WHO,NHI,
 NHLBI guidelines management should
be in 4 steps.
 Assess and monitor asthma severity
and control
 Patient education
 Environmental control
 Medical therapy


21. Pharmacologic Therapy

Long-term control medications
– corticosteroids
 inhaled
form
 systemic steroids used to gain prompt control
of disease when initiating inhaled tx
– cromolyn sodium or nedocromil
 mild-to-moderate
anti-inflammatory medications
(may be used initially in children)
 preventive tx. prior to exercise or unavoidable
exposure to known allergens

22. Relievers
Beta adrenergic agonists.
 Anticholinergic agents
 Phosphodiesterase inhibitors
 Corticosteroids
 Antimicrobials


23. Controllers
Anti inflamatory agents (steroids)
 Long acting bronchodilators




Mediator inhibitors
Beta adrenergic agonists
Phosphodiesterase inhibitors
Leukotrienes modifiers
 Desensitization drugs
 Vaccinations
 Miscellaneous agents


24. Long-term control medications
– Long-acting beta2-agonists
 used
concomitantly with anti-inflammatory
meds for long-term symptom control especially
nocturnal symptoms
 prevents exercise-induced bronchospasm
– Methylxanthines
 sustained-release
theophylline used as
adjuvant to inhaled steroids for prevention of
nocturnal symptoms

25. Long-term control medications
– Leukotriene modifiers
 zafirlukast
- leukotriene receptor antagonist
 zileuton - 5-lipoxygenase inhibitor is alternative
therapy to low doses of inhaled
steroids/nedocromil/cromolyn
 alternative tx to low dose inhaled
steroids/cromolyn/nedocromil
 recommended for >12yrs with mild persistent
asthma.

26. Quick relief medications
– Short acting beta2-agonists - relief of acute
symptoms
– Anticholinergics - may provide additive benefit
to beta2 drugs in severe exacerbation. May be
alternative to beta2-agonists
– Systemic steroids - moderate-to-severe
persistent asthma in acute exacerbations or to
prevent recurrence of exacerbations

27. Treatment/Long Term Control

Corticosteroids
– Most potent and effective
– Reduction in symptoms, improvement in
PEF and spirometry, diminished airway
hyperresponsiveness, prevention of
exacerbations, possible prevention of
airway wall remodeling
– Suppresses: cytosine production, airway
eosinophilic recruitment, chemical mediators

28. LABA

Long-acting beta-2 agonists
– Relax airway smooth muscle
– Duration of action >12 hrs
– Not used in acute exacerbations
– Adjunct to anti-inflammatory tx for longterm symptom control especially nocturnal
symptoms

29. Methylxanthines
– Provides mild-moderate bronchodilation
– Low dose has mild anti-inflammatory action
– Sustained release form used as alternative
but not preferred to long-acting beta2
agonists to control nocturnal symptoms
– Use may be necessary because of cost or
patient compliance

30. Leukotriene modifiers
– Leukotrienes are potent biochemical
mediators released from mast cells,
eosinophils, and basophils that:
 contract
bronchial smooth muscle
 increase vascular permeability
 increase mucus secretions
 attract & activate inflammatory cells in airways

31. Leukotriene modifiers
– Zafirlukast & zileuton (oral tabs)
 improves
lung fx and diminishes symptoms &
need for short-acting beta2 agonists
– Studies in mild-moderate asthma showing
modest improvements
– Alternative to low-dose inhaled steroids for
pts. with mild persistent asthma
– Further study in of other groups needed

32. Asthma Treatment/Quick Relief

Short-acting beta2 agonists
– Relax airway smooth muscle and increase
in airflow in <30 minutes
– Drug of choice for treating symptoms and
exacerbations and EIB
– Use of >1 canister/mo indicates
inadequate control and indicates need to
intensify anti-inflammatory tx
– Regularly scheduled use NOT
recommended

33. Anticholinergics
– Cholinergic innervation important in
regulation of airway smooth muscle tone
– Ipratropium bromide (quaternary derivative
of atropine without its’ side effects)
– Additive benefit with inhaled beta 2agonists in severe asthma exacerbations
– Effectiveness in long-term management
not demonstrated

34. 
Systemic steroids
– speed resolution of airflow obstruction
– reduce rate of relapse

Medications to reduce oral steroid
dependence
– Troleandomycin, cyclosporin, gold,
methotrexate, IV immunoglobulin,
dapsone, hydroxychloroquine

35. Intermittent Asthma

Step 1
– Short-acting inhaled beta 2 agonists PRN
 IF
NEEDED >2 X/wk PATIENT SHOULD BE
MOVED TO THE NEXT STEP OF CARE
(exception is EIB or viral infections)
– Viral infections
 mild
symptoms - beta 2 agonist Q 4-6 hr
 moderate-to-severe symptoms - short course of
systemic steroids recommended plus above

36. Persistent Asthma

Mild, moderate or severe
– Daily long-term control recommended

Mild persistent asthma (step 2 care)
– Daily anti-inflammatory meds - inhaled
steroids (low dose) or cromolyn or
nedocromil
– Sustained release theophylline alternative
but not preferred

37. 
Moderate persistent asthma (step 3
care)
– Increase inhaled steroids to medium dose
OR
– Add long-acting bronchodilator to a lowmedium dose of inhaled steroids
OR
– Increase to medium dose steroid then
lower dose & add nedocromil (+/-)

38. 
Moderate persistent asthma (if not
adequately controlled)
– Increase to high dose inhaled steroids &
add long-acting bronchodilator (serevent or
theophylline)

39. 
Severe persistent asthma (step 4)
– If not controlled on high dose of inhaled
steroids and long-acting bronchodilator
ADD oral systemic steroids on a
regularly scheduled, long-term basis
 use
lowest dose
 monitor closely
 attempt to reduce or take off when control
established

40. Complications
Due to drugs
 Due to disease


41. 