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Dr M. Dikgang
   Chronic inflammatory disease of airways
   Increased responsiveness of tracheobronchial
    tree
   Multiplicity of stimuli
   Episodic disease
   Narrowing of airways (acutely and gradually),
    relieved spontaneously or after therapy.
Risk Factors
             (for development of asthma)



                INFLAMMATION

Airway
Hyperresponsiveness                    Airflow Obstruction



                    Risk Factors       Symptoms
                 (for exacerbations)
   Asthma is one of the most common chronic
    diseases worldwide —160 million patients suffer
    from asthma
   Prevalence increasing in many countries,
    especially in children — 1~4% in adult, 3~5% in
    children in China
   A major cause of school/work absence
   An overall increase in severity of asthma
    increases the pool of patients at risk for death
Worldwide Variation in Prevalence of
Asthma Symptoms



International Study of
Asthma and Allergies in
Children (ISAAC)




Lancet 1998;351:1225
Environmental
 Genetic factors                        factors

                       Mixed
Atopic                 factors            Non-
asthma                                    atopic/idiosyncratic
                                          asthma


         Early onset
                                 Late onset
Stimuli:
 Allergens (mites, fur, feathers,molds etc)

 Pharmacological (NSAIDS, B-blockers etc)

 Environmental (NO2, sulphur dioxide)

 Occupational (wood/vegetable
   dust,pharmaceuticals etc)
 Infections (viruses-RSV, para-influenza)

 Exercise

 Emotional stress (vagal efferent activity,
   endorphins)
   Gross overdistention of lungs, non-collapsible
   Gelatinous plugs of exudate in bronchial
    branches, down to terminal bronchioles
   Hypertrophy of bronchial smooth muscle
   Hyperplasia of mucosal & submucosal blood
    vessels
   Mucosal oedema
   Thickening of basement membrane
   Eosinophilic infiltrates in the bronchial walls
   History and patterns of symptoms
   Physical examination
   Measurements of lung function
   Measurements of allergic status to identify risk
    factors
   Recurrent episodes of wheezing
   Troublesome cough at night
   Cough or wheeze after exercise
   Cough, wheeze or chest tightness after
    exposure to airborne allergens or pollutants
   Colds ―go to the chest‖ or take more than 10
    days to clear
   Lung function tests- FEV1/FVC ratio (<70%or
    normal), PEFR
   Bronchodilator test- reversibility (>15%
    improvement in FEV1)
   CXR
   Sputum (thick, with eosinophils + Charcots-
    Leyden crystals), blood (IgE levels,
    eosinophilia)
   Allergy tests- skin, inhalants, catecholamines
    etc.
Asthma                  COPD

cannot be fully prevented can be prevented
  can be fully controlled
                        cannot be fully reversed
    does not progress        is progressive
COPD and Asthma are different
         diseases!
  Asthma           COPD
      Allergic
                                  Small airway
  inflammation of
                    COPD           narrowing
       airways
                      &                &
                    Asthma       Bronchospasm
       Hyper-        (15%)             &
   responsiveness
                                 Airway collapse
   Bronchospasm
                                 Maintain
 Control inflammation
                             bronchodilatation
       with ICS
                                with regular
Minimal bronchodilator
                              bronchodilator
History         COPD            Asthma
Smoker or ex-   Nearly always   Variable
smoker
Onset          Usually > 40     Most < 30 years
               years
Breathlessness Gradual and      Paroxysmal
               progressive
Chronic cough Common            Infrequent
with sputum
Investigation COPD               Asthma
s
FEV1              Always reduced Variable

Daily variation in Minimal       ―Morning dip‖
PEF                              + day-to-day
Reversibility     <15%           >15%
To effectively controll asthma by…

A. Suppressing and reversing
   inflammation
B. Treating bronchoconstriction
    and related symptoms
   Life-threatening medical emergencies

   Treatment is often most safely undertaken in a
    hospital or hospital-based emergency
    department
Initial Assessment
                 History, Physical Examination, PEF or FEV1

                             Initial Therapy
                       Bronchodilators; O2 if needed
Good Response
                        Incomplete/Poor Response              Respiratory Failure

Observe for at       Add Systemic Glucocorticosteroids
 least 1 hour
                   Good Response         Poor Response
  If Stable,
 Discharge to         Discharge        Admit to Hospital        Admit to ICU
    Home
Goals of Long-term Management

   Achieve and maintain control of symptoms
   Prevent asthma episodes or attacks
   Maintain pulmonary function as close to normal levels
    as possible
   Maintain normal activity levels, including exercise
   Avoid adverse effects from asthma medications
   Prevent development of irreversible airflow limitation
   Prevent asthma mortality
Uncontrolled
                        Controlled (mild          Partly controlled         (moderate-
  Characteristic         intermittent)            (mild persistent)         severe
                       (All of the following)   (Any present in any week)
                                                                            persistent)
                       None (2 or less /             More than
Daytime symptoms
                       week)                        twice / week
   Limitations of                                                            3 or more
                               None                       Any                features of
     activities
                                                                             partly
     Nocturnal                                                               controlled
    symptoms /                 None                       Any                asthma
    awakening                                                                present in
 Need for rescue /     None (2 or less /             More than               any week
“reliever” treatment   week)                        twice / week
                                                < 80% predicted or
  Lung function
                              Normal             personal best (if
  (PEF or FEV1)
                                                known) on any day

   Exacerbation                None             One or more / year          1 in any week
   Preventers - anti-inflammatory

   Relievers   - short acting bronchodilators
                          that provide rapid relief of
                          symptoms
   Controllers - sustained bronchodilator
                     action with unproven or mild
                          anti-inflammatory action
Classification of drugs used in the
  maintenance treatment of asthma
 PREVENTERS            CONTROLLERS                 RELIEVERS
 Anti-inflammatory    Sustained broncho-           For quick relief of
  action to prevent   dilator action but weak     symptoms and use in
   asthma attacks     or unproven anti-           acute attacks as p.r.n.
                      inflammatory effect               dose only
Inhaled               Long-acting ß2            Short-acting ß2
corticosteroids       agonists                  agonists
 Beclomethasone         Salmeterol               Salbutamol
 Budesonide             Formoterol               Fenoterol
 Fluticasone          Methylxanthines            Terbutaline
 Flunisolide                                     Hexoprenaline
 Triamcinolone
                        Sustained-release        Orciprenaline
                        theophyllines
Oral                                            Anti-cholinergics
corticosteroids       Leukotriene                Ipratropium
Prednisone            receptor                  Short-acting
Prednisolone          antagonists**                 theophyllines
Methylprednisolone      Montelukast
                        Zafirlukast
       ** Provisional categorisation pending further data
MILD
                               Increasing Severity                                      SEVERE
INTERMITTENT


                                                                                   Inhaled
                                                                               corticosteroids
                                                                                > 1000 µg/day
                                                              Inhaled               (BDP
                                                          corticosteroids        equivalent)
                                                             500 - 1000               +/-
                                           Inhaled             µg/day
                                       corticosteroids                               Oral
                                                                (BDP           corticosteroids
                                      200 - 500 µg/day      equivalent)
                                     (BDP equivalent)                                 +/-
                                                                  +            Long-acting ß2
                                              +
                                       Long-acting ß2     Long-acting ß2           agonist
                                    agonist (preferred)       agonist                 +/-
                                    or SR theophyllines     (preferred)               SR
                       Inhaled                                and/or
                                              or                                theophyllines
                   corticosteroids                               SR
                                           Inhaled
                   200 - 500 µg/day                        theophyllines
                                    corticosteroids 500
                         (BDP
                                    - 1000 µg/day (BDP
                     equivalent)
                                         equivalent)
                                                                            Refer pulmonologist
 ß2 agonists prn   ß2 agonists prn    ß2 agonists prn     ß2 agonists prn    ß2 agonists prn may be
                                                                               required 4-6 x/day


                     LTRA?                                    LTRA
   A convenient and reliable
    multi-dose device
   New propellant is HFA
    (ozone-friendly)
   Rapidly moving, short-
    duration plume
   Impaction of spray in
    oropharynx likely
   Evaporating spray feels
    cold
   70% of dose lodges in
    pharynx and much may be
    swallowed, 15 -20% in
    lung
   Remove mouthpiece
    cap
   Shake inhaler
    (suspensions only)
   Breathe out
   Place actuator
    mouthpiece between lips
   Fire while breathing in
    slowly and deeply
   Continue to inhale
   Hold breath (for 10 sec)
       CRUCIAL ERRORS
       Firing device at or after end of inhalation
       Stopping inhalation / inhaling through nose (―cold
        Freon‖ effect)
       Bizarre errors (e.g. not removing mouthpiece cap)
       NON-CRUCIAL ERRORS
       Firing device before start of inhalation
       Fast inhalation
       No breath-hold / short breath-hold
       Failure to shake inhaler (suspensions only)
   Useful for small children (used with
    snug-fitting face mask)
   Useful in improving inhaled steroid
    deposition in those with difficulty co-
    ordinating firing of pMDI during or
    before inhalation
   Shake inhaler (suspensions only)
   Insert pMDI into spacer
   Breathe out
   Fire while (or before) breathing in
    slowly and deeply
   Continue to inhale
   Hold breath (for 10 sec)
   Repeat with second puff
   Remove cover (device-specific)
   Prepare device / load dose (device-specific)
   Pierce capsule (single-dose devices only)
   Breathe out gently
   Place mouthpiece between lips
   Inhale deeply and quickly*
   Breath-hold (device-specific)
   Replace cover and store in dry cool environment
Montelukast - Singulair
Zafirlukast - Accolate
Advantages:
• Unique mode of action
• Anti-inflammatory – no bronchodilator effect
• Very simple dosing: taken by mouth; single dose strength for children, another for
adults
• Safe
• Use:
    – Add to inhaled corticosteroids
    – Monotherapy in mild allergic asthma   (children)

Disadvantages:
• Poor efficacy (not better than theophylline for most endpoints especially in adults
( More useful in children)
• Expensive !
DISADVANTAGES
ADVANTAGES                    Bulky, inconvenient
 Easy to use correctly once Electricity supply usually needed
  prepared: relaxed tidal     Preparation and assembly a problem,
  breathing                    especially for the elderly?
 Convenient way of           Long treatment times
  delivering high doses
 Patients find them          Cleaning / contamination issues
  reassuring                  Expensive
 Dose control possible in  Patients rely on them instead of using
  sophisticated devices        controller medications
 No propellants needed       Their use can delay patients presenting to
                               emergency departments and lead to
                               asthma deaths (false sense of security)
                              They are air and not oxygen-driven, so do
                               not correct hypoxia
Reasons for poor
patient adherence to treatment
    Misunderstanding about need for both
     long-term preventive and quick-relief
     medications
    Difficulty with inhaler devices
    Fear of side effects or addiction
    Cost of medication
    Dislike of medication
Follow-up

At regular visits (every one to six months):
 Monitor asthma control
  – Review symptoms
   – Measure lung function
   – Assess compliance
 Modify the treatment plan
  – Reinforce compliance
   – Adjust medications
   Kasper et-al. Harrison’s Principles of Internal
    Medicine, 16th edition: 2005; McGraw-Hill, New York,
    USA: pp1508-1516

   Zhiwen Zhu. Pulmonary & Critical Care Medicine, 1st Affiliated
    Hospital of Sun Yat-Sen University, China

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Asthma presentation2011

  • 2. Chronic inflammatory disease of airways  Increased responsiveness of tracheobronchial tree  Multiplicity of stimuli  Episodic disease  Narrowing of airways (acutely and gradually), relieved spontaneously or after therapy.
  • 3. Risk Factors (for development of asthma) INFLAMMATION Airway Hyperresponsiveness Airflow Obstruction Risk Factors Symptoms (for exacerbations)
  • 4. Asthma is one of the most common chronic diseases worldwide —160 million patients suffer from asthma  Prevalence increasing in many countries, especially in children — 1~4% in adult, 3~5% in children in China  A major cause of school/work absence  An overall increase in severity of asthma increases the pool of patients at risk for death
  • 5. Worldwide Variation in Prevalence of Asthma Symptoms International Study of Asthma and Allergies in Children (ISAAC) Lancet 1998;351:1225
  • 6. Environmental Genetic factors factors Mixed Atopic factors Non- asthma atopic/idiosyncratic asthma Early onset Late onset
  • 7. Stimuli:  Allergens (mites, fur, feathers,molds etc)  Pharmacological (NSAIDS, B-blockers etc)  Environmental (NO2, sulphur dioxide)  Occupational (wood/vegetable dust,pharmaceuticals etc)  Infections (viruses-RSV, para-influenza)  Exercise  Emotional stress (vagal efferent activity, endorphins)
  • 8.
  • 9. Gross overdistention of lungs, non-collapsible  Gelatinous plugs of exudate in bronchial branches, down to terminal bronchioles  Hypertrophy of bronchial smooth muscle  Hyperplasia of mucosal & submucosal blood vessels  Mucosal oedema  Thickening of basement membrane  Eosinophilic infiltrates in the bronchial walls
  • 10. History and patterns of symptoms  Physical examination  Measurements of lung function  Measurements of allergic status to identify risk factors
  • 11. Recurrent episodes of wheezing  Troublesome cough at night  Cough or wheeze after exercise  Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants  Colds ―go to the chest‖ or take more than 10 days to clear
  • 12. Lung function tests- FEV1/FVC ratio (<70%or normal), PEFR  Bronchodilator test- reversibility (>15% improvement in FEV1)  CXR  Sputum (thick, with eosinophils + Charcots- Leyden crystals), blood (IgE levels, eosinophilia)  Allergy tests- skin, inhalants, catecholamines etc.
  • 13. Asthma COPD cannot be fully prevented can be prevented can be fully controlled cannot be fully reversed does not progress is progressive
  • 14. COPD and Asthma are different diseases! Asthma COPD Allergic Small airway inflammation of COPD narrowing airways & & Asthma Bronchospasm Hyper- (15%) & responsiveness Airway collapse Bronchospasm Maintain Control inflammation bronchodilatation with ICS with regular Minimal bronchodilator bronchodilator
  • 15. History COPD Asthma Smoker or ex- Nearly always Variable smoker Onset Usually > 40 Most < 30 years years Breathlessness Gradual and Paroxysmal progressive Chronic cough Common Infrequent with sputum
  • 16. Investigation COPD Asthma s FEV1 Always reduced Variable Daily variation in Minimal ―Morning dip‖ PEF + day-to-day Reversibility <15% >15%
  • 17.
  • 18. To effectively controll asthma by… A. Suppressing and reversing inflammation B. Treating bronchoconstriction and related symptoms
  • 19. Life-threatening medical emergencies  Treatment is often most safely undertaken in a hospital or hospital-based emergency department
  • 20. Initial Assessment History, Physical Examination, PEF or FEV1 Initial Therapy Bronchodilators; O2 if needed Good Response Incomplete/Poor Response Respiratory Failure Observe for at Add Systemic Glucocorticosteroids least 1 hour Good Response Poor Response If Stable, Discharge to Discharge Admit to Hospital Admit to ICU Home
  • 21. Goals of Long-term Management  Achieve and maintain control of symptoms  Prevent asthma episodes or attacks  Maintain pulmonary function as close to normal levels as possible  Maintain normal activity levels, including exercise  Avoid adverse effects from asthma medications  Prevent development of irreversible airflow limitation  Prevent asthma mortality
  • 22. Uncontrolled Controlled (mild Partly controlled (moderate- Characteristic intermittent) (mild persistent) severe (All of the following) (Any present in any week) persistent) None (2 or less / More than Daytime symptoms week) twice / week Limitations of 3 or more None Any features of activities partly Nocturnal controlled symptoms / None Any asthma awakening present in Need for rescue / None (2 or less / More than any week “reliever” treatment week) twice / week < 80% predicted or Lung function Normal personal best (if (PEF or FEV1) known) on any day Exacerbation None One or more / year 1 in any week
  • 23. Preventers - anti-inflammatory  Relievers - short acting bronchodilators that provide rapid relief of symptoms  Controllers - sustained bronchodilator action with unproven or mild anti-inflammatory action
  • 24. Classification of drugs used in the maintenance treatment of asthma PREVENTERS CONTROLLERS RELIEVERS Anti-inflammatory Sustained broncho- For quick relief of action to prevent dilator action but weak symptoms and use in asthma attacks or unproven anti- acute attacks as p.r.n. inflammatory effect dose only Inhaled Long-acting ß2 Short-acting ß2 corticosteroids agonists agonists Beclomethasone Salmeterol Salbutamol Budesonide Formoterol Fenoterol Fluticasone Methylxanthines Terbutaline Flunisolide Hexoprenaline Triamcinolone Sustained-release Orciprenaline theophyllines Oral Anti-cholinergics corticosteroids Leukotriene Ipratropium Prednisone receptor Short-acting Prednisolone antagonists** theophyllines Methylprednisolone Montelukast Zafirlukast ** Provisional categorisation pending further data
  • 25. MILD Increasing Severity SEVERE INTERMITTENT Inhaled corticosteroids > 1000 µg/day Inhaled (BDP corticosteroids equivalent) 500 - 1000 +/- Inhaled µg/day corticosteroids Oral (BDP corticosteroids 200 - 500 µg/day equivalent) (BDP equivalent) +/- + Long-acting ß2 + Long-acting ß2 Long-acting ß2 agonist agonist (preferred) agonist +/- or SR theophyllines (preferred) SR Inhaled and/or or theophyllines corticosteroids SR Inhaled 200 - 500 µg/day theophyllines corticosteroids 500 (BDP - 1000 µg/day (BDP equivalent) equivalent) Refer pulmonologist ß2 agonists prn ß2 agonists prn ß2 agonists prn ß2 agonists prn ß2 agonists prn may be required 4-6 x/day LTRA? LTRA
  • 26. A convenient and reliable multi-dose device  New propellant is HFA (ozone-friendly)  Rapidly moving, short- duration plume  Impaction of spray in oropharynx likely  Evaporating spray feels cold  70% of dose lodges in pharynx and much may be swallowed, 15 -20% in lung
  • 27. Remove mouthpiece cap  Shake inhaler (suspensions only)  Breathe out  Place actuator mouthpiece between lips  Fire while breathing in slowly and deeply  Continue to inhale  Hold breath (for 10 sec)
  • 28. CRUCIAL ERRORS  Firing device at or after end of inhalation  Stopping inhalation / inhaling through nose (―cold Freon‖ effect)  Bizarre errors (e.g. not removing mouthpiece cap)  NON-CRUCIAL ERRORS  Firing device before start of inhalation  Fast inhalation  No breath-hold / short breath-hold  Failure to shake inhaler (suspensions only)
  • 29. Useful for small children (used with snug-fitting face mask)  Useful in improving inhaled steroid deposition in those with difficulty co- ordinating firing of pMDI during or before inhalation  Shake inhaler (suspensions only)  Insert pMDI into spacer  Breathe out  Fire while (or before) breathing in slowly and deeply  Continue to inhale  Hold breath (for 10 sec)  Repeat with second puff
  • 30.
  • 31. Remove cover (device-specific)  Prepare device / load dose (device-specific)  Pierce capsule (single-dose devices only)  Breathe out gently  Place mouthpiece between lips  Inhale deeply and quickly*  Breath-hold (device-specific)  Replace cover and store in dry cool environment
  • 32. Montelukast - Singulair Zafirlukast - Accolate Advantages: • Unique mode of action • Anti-inflammatory – no bronchodilator effect • Very simple dosing: taken by mouth; single dose strength for children, another for adults • Safe • Use: – Add to inhaled corticosteroids – Monotherapy in mild allergic asthma (children) Disadvantages: • Poor efficacy (not better than theophylline for most endpoints especially in adults ( More useful in children) • Expensive !
  • 33. DISADVANTAGES ADVANTAGES  Bulky, inconvenient  Easy to use correctly once Electricity supply usually needed prepared: relaxed tidal  Preparation and assembly a problem, breathing especially for the elderly?  Convenient way of  Long treatment times delivering high doses  Patients find them  Cleaning / contamination issues reassuring  Expensive  Dose control possible in  Patients rely on them instead of using sophisticated devices controller medications  No propellants needed  Their use can delay patients presenting to emergency departments and lead to asthma deaths (false sense of security)  They are air and not oxygen-driven, so do not correct hypoxia
  • 34. Reasons for poor patient adherence to treatment  Misunderstanding about need for both long-term preventive and quick-relief medications  Difficulty with inhaler devices  Fear of side effects or addiction  Cost of medication  Dislike of medication
  • 35. Follow-up At regular visits (every one to six months):  Monitor asthma control – Review symptoms – Measure lung function – Assess compliance  Modify the treatment plan – Reinforce compliance – Adjust medications
  • 36. Kasper et-al. Harrison’s Principles of Internal Medicine, 16th edition: 2005; McGraw-Hill, New York, USA: pp1508-1516  Zhiwen Zhu. Pulmonary & Critical Care Medicine, 1st Affiliated Hospital of Sun Yat-Sen University, China