Transcript
Adult Asthma for UPCM LU4 Aileen David – Wang MD MSc FPCCP Clinical Associate Professor
Learning Objectives At the end of the session, the student should be able to: • define asthma • describe the local prevalence, epidemiology, an natural history of asthma • recognize the risk factors for asthma development and persistence • recognize its characteristic symptomatology
Learning Objectives t the end of the session, the student should be le to: recognize diseases that may mimic asthma enumerate and interpret laboratory tests that support or confirm the diagnosis of asthma classify asthmatics according to their level of chronic severity and control, and give recommendations on the appropriate drug thera become familiar with asthma pharmacotherapy
Recent Asthma Guidelines
Global Initiative for Asthma (GINA) Update
NAEPP Expert Panel Report Update by US NHLBI
December 2008 www. gin ina asth thm ma .o .org rg
NIH Public lica atio tion n No. 02 02 -50 -507 75; Ju July 2007 www.nhlbi.nih.gov/guidelines/asthma
Philippine Con onsen sensus sus Rep eport ort on the Mx of As Asth thm ma
Dx an and d
2004 Evidenc 2004 vidence e -Based ased Upd pdate ate;; 20 2009 09 Upd pdate ate soon to be released
Definition of Asthma
Definition of Asthma • Asthma, irrespective of the severity, is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. • The chronic inflammation causes an associated increase in airway hyperresponsiveness that leads to airflow limitation and respiratory symptoms Global Initiative for Asthma (GINA 2004)
Mechanisms behind Asthma Symptoms Environmental Risk Factors (Causes)
Bronchial HyperResponsiveness
Airflow Limitation TRIGGERS
Symptoms
Bronchial Hyperresponsiveness (BHR)
or Airway Hyperresponsiveness Hyperresponsiveness (AHR)
Airways narrow too easily and too much in response to exogenous or endogenous stimuli
Allergens Sensitizers Viruses Air pollutants
t c i t w S h n ” “ o
Genetically Predispose d Airway Hyperresponsiveness
Chronic Inflammat ion
Triggers:
Symptoms: cough dyspnea wheezing
Allergens Exercise Cold air SO2 Particulates
Airway Inflammation in Asthma
Normal
Asthmatic P Jeffery, in: Asthma, Academic Press 1998
Normal
Denuded mucosa Thickened basement membrane Inflammatory cells Wall edema Hypertrophied airway sm muscles
Airflow Limitation in Asthma
TRIGGER BHR
1. Acute bronchoc bronchoconstri onstriction/ ction/spasm spasm 2. Swel Swelling ling of of the airway airway wall wall 3. Chron Chronic ic mucus mucus plug formati formation on 4. Airway wall remode remodelling lling
Airflow Limitation in Asthma
TRIGGER BHR
Widespread, variable and often reversible
Asthma
• • • •
Hypoventilation Respiratory acidosis Pneumothorax Hypotension
Severe Asthma Exacerbation
Asthma Inflammation: Cells and Mediators
Inflammatory Mediator Soup in Asthma
Asthma Symptoms
Inflammation Airway Hyperresponsiveness Airway Remodeling
Prevalence and Natural Hx of Asthma
Asthma Epidemiology
Asthma is a very common disease
Found in all countries
Prevalence seems to be increasing
Occurs at all ages but predominantly in early life
About half develop before age 10 and another 1/3 before age 40
Asthma Epidemiology
Can begin in the elderly
In childhood, 2:1 male/female preponderance; difference disappears after age 10
During puberty and thereafter, more females develop asthma than males
Asthma Epidemiology
Disappears in 30 to 50% of children c hildren at puberty, but often reappears in adult life
In a recent survey of Filipinos living in urban communities, about 22% of adults, 33% of adolescents and 27% of children aged 6 to 7 years have asthma and asthma-like symptoms National Asthma Epidemiology Study: Urban Focus 2003
Risk Factors for Asthma
Factors that Influence Asthma Development and Expression Host Factors Genetic - ATOPY - BHR Gender Obesity Race/ Ethnicity
Environmental Factors Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections Diet
Factors
Risk Odds Ratio
95% C.I.
pvalue
Smoker in the household when the child was 1-3 years old
1.81
1.17 - 2.80
0.007
Severe Respiratory Infection
4.92
2.81 - 8.62
<0.001
3.74
2.49 - 5.61
<0.001
Father
4.27
2.33 - 7.82
<0.001
Mother
4.12
2.21 - 7.70
<0.001
Other Relatives
2.07
1.29 – 3.31
0.002
Allergy Family History
Note: Gender and breastfeeding were not
Risk Factors for Persistence of Asthma Symptoms (Triggers)
House Dust Mite (Dermatophagoides pteronyssinus)
Risk Factors for Persistence of Asthma Symptoms (Triggers)
Risk Factors for Persistence of Asthma Symptoms (Triggers)
Indoor Allergens – house dust mite, cockroach, animal allergens (cats, dogs), fungi, molds, yeasts
Outdoor Outdoor Allergens- Pollens
Tobacco Smoke
Air Pollution
Factors that Precipitate Asthma Exacerbations
Respiratory Infections esp. viral- most common Weather changes Indoor and outdoor allergens/ air pollutants Exercise Drugs – aspirin, beta-blockers, coloring agents Food Irritants- household sprays, paints, fumes Extreme emotional expression/ stress- laughter
Diagnosis of Asthma
Who is unlikely to be an asthmatic?
A. 18 y.o./F, on and off dyspnea and chest tightness for the past 10 years
B. 50 y.o y.o./ ./F, F, sol sole e comp complai laint nt of of on and off cough for the past 2 years, treated with various antibiotics C. 15 y.o. y.o. athle athlete te who who deve develo lops ps SOB after running D. 48 y.o. y.o. smoker smoker with progre progress ssive ive SOB x 4 y and recent active hemoptysis E. All can be considered asthmatics
Triad of Asthma
• Dyspnea • Cough • Wheeze
Pulmonary Pearls: Diagnosis of Asthma
Episodic or Intermittent Symptoms Usually triggered by exogenous factors Seasonal variability Typical early morning symptoms Typical atopic history Family history of asthma Positive response to bronchodilators
Is it Asthma?
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
Pulmonary Pearls: Diagnosis of Asthma No
pathognomic manifestation
“Not all that wheezes is asthma, not all asthma wheezes”
Differential Diagnosis of Asthma Foreign body aspiration esp. in children Tracheal, laryngeal and bronchial lesions/ tumors Extrinsic obstruction of the airways Other chronic obstructive airways diseases – COPD, bronchiectasis, diffuse panbronchiolitis, cystic fibrosis Pulmonary embolism “Cardiac asthma” – CHF, mitral stenosis Vocal cord dysfunction
Confirmatory Tests for Asthma Measurements
of airflow limitation, its reversibility and its variability are critical in establishing a clear diagnosis
Bronchoprovocation
Test measures non-specific BHR Methacholine/ Histamine Inhalation Challenge high sensitivity but low specificity t o exclude a diagnosis of persistent a negative test can be useful to asthma Can be positive in recent viral URTI, COPD, bronchiectasis, allergic rhinitis, etc.
Bronchoprovocation Test
0
V E F
ll a F %
1
5
Normal
10 15 20 25
Asthma
30
b
35 0
0.125
0.25
0.5
1
2
4
8
16
32
PC20of Methacholine (mg/ml) Concentration PC20
PC20 FEV1 – concentration of bronchoprovoking agent that causes the FEV1 to fall by 20%
Confirmatory Tests for Asthma
Spirometry FEV1/FVC < 75% Obstructive Airways Disease Acute Bronchodilator Response (Reversibility): > 12 % increase + absolute increase of 200 ml in FEV1 and/or FVC
GINA 2004
Forced
expiratory volume in 1 second (FEV 1)
– 4.0 L Forced vital capacity (FVC) – 5.0 L FEV1 /FVC = 80%
FEV1
FVC
Since asthma is an episodic disease, the spirometr
L i t e r s
F E V 1
Asthma: FEV1 > 12%
COPD: Obstructive pattern FEV1 < 12%
Asthma Normal
COPD
Seconds
Confirmatory Tests for Asthma Bronchodilator
Reversibility
%
= post-BD FEV1 - pre-BD FEV1
x 100
pre-BD FEV1
GINA 2004
Confirmatory Tests for Asthma Peak
Flow Monitoring
Acute BD Response: > 15%
increase in PEF
Diurnal variability > 10% (if no BD) or > 20% (if on BD)
Drop of >15% with 6-minute running/exercise
GINA 2004
Confirmatory Tests for Asthma Peak
Flow Diurnal Variability > 20%
DV = 100
PEFevening
½ (PEFevening
- PEFmorn rnin ing
x
+ PEFmorn ) rnin ing
GINA 2004
Other Laboratory Tests in Asthma Chest
Radiograph
no role in making a diagnosis of asthma
usually normal, but may show hyperinflation
useful in excluding other causes of wheezing and detecting complications of asthma exacerbations (e.g., pneumothorax) and concomitant conditions (e.g., pneumonia)
Sputum/ Allergy
Blood Eosinophilia }
skin tests/ IgE
}
Not specific for asthma
Asthma Pharmacotherapy
Drugs Available for Asthma ASTHMA MEDICATIO IONS
TRIGGER BHR
CONTROLLER (Maintenance)
RELIEVER (As Needed)
Current Asthma Medications Relievers
Controllers
Cromolyn Sodium
Nedocromil Na
Corticosteroids
Long Acting Theophylline
Long Acting Beta agonists
Anti-Leukotrienes
Anti-IgE
Short acting Beta agonist + Anti – cholinergics Systemic Steroids
Short acting Theophyllines
Inhalational is superior to oral therapy.
Relievers • • • •
quick relief bronchodilators “rescue” medicine use as-needed relieve bronchoconstriction and the accompanying symptoms • no effect on airway inflammatio and BHR • frequent need for rescue is a sig of poor asthma control
Short Acting Beta2 Agonists • drug of choice for treatment of acute asthma exa’s and episodes • useful as prophylaxis against EIA • stimulate beta-adrenergic receptors and activate G proteins to produce cAMP • decrease release of mediators • improve mucociliary transport • Salbutamol (Albuterol), Levalbuter Terbutaline, Fenoterol
Anticholinergics • slower in onset and of modest potency compared to SABAs • reliever of choice for betablocker induced asthma • additive effect when combined with SABA • Ipratropium bromide
Controllers • used daily on a long-term basis to achieve and maintain control of persistent asthma • act on airway inflammation and BHR
on ro ers: n a e Steroids • Most potent and most effective anti-inflammatory medications currently available • Budesonide, Fluticasone, Beclomethasone, Flunisolide, Triamcinolone • Preferred Rx for all levels of persistent asthma • Most common side effects: dysphonia, oral thrush gargle after use
Clinical Effects of Inhaled Corticosteroids on Asthma
improved BHR reduced symptoms reduced frequency and severity of exacerbations reduced oral steroid rescues reduced prn SABA use improved lung function decreased ER visits and hospitalization improved quality of life reduced relapse after an acute attack
LEVEL OF EVIDENCE: A
(GINA 2006)
Effects of Corticosteroids on istopathologic istopathologic Characteristics Characteristics in Asthm • Decreased Decrease d cellularity usually resulting from ffrom rom decreases Decreased decreases in in eosinophils, mast cells, and lymphocytes l ymphocytes lymphocyte s • Decreased Decrease d Decreased d numbers numbers of dendritic dendritic cells cells and HLA-DR HLA-DR expression expression • Decreased Decrease d numbers Decreased numbers of of cells expressing mRNA for IL-4 and IL-5 • Increased numbers of cells expressing mRNA for IFNI FN-γ • Increased area of ciliated epithelium • Decreased thickness of basement membrane • Decreased d tenasein Decrease basement membrane membrane Decreased tenasein in basement Fish. J Allergy Clin Immunol 1999; 104: 509-516
Systemic Steroids • Considered as “relievers” for treatment of moderate to severe exacerbations, in short-courses of moderate to high daily dose • Onset of action > 4 -6 h • Also used as “controllers” for chronic severe asthma, in low dose daily or alternate-day therapy • Long term use is limited by systemic side effects including adrenal suppression
Inhaled Long Acting Beta 2 Agonists (LABA)
Same effects as SABAs
May modulate mediator release from mast cells and basophils
Activity persists for > 12 h
Provide long-term protection against bronchobronchoconstrictor stimuli and for EIA
The preferred add-on therapy for asthmatics who remain symptomatic despite the use of inhaled steroid
Should never be used as sole controller in asthma as thma
Inhaled Long Acting Beta 2 Agonists (LABA)
Formoterol – onset of action similar to Salbutamol Salmeterol Fixed dose combination inhaled steroid – LABA are now available Budesonide – Formoterol (Symbicort) Fluticasone – Salmeterol (Seretide)
Theophylline and derivatives As
a bronchodilator: Weak phosphodiesterase phosphodiesterase inhibition, adenosine antagonism Use as add-on therapy in moderate to severe As asthma esp. nocturnal symptoms a controller: Weak Anti - Inflammatory Properties Eosinophil infiltration of airways T - lymphocytes in alveolar epithelium mucociliary clearance Alternative but not preferred controller in mild persistent asthma (Philippine Guidelines) Oral preparation 2002 NHLBI guidelines
Anti-Leukotrienes Arachidonic Acid 5-LO Inhibitor e.g. Zileuton
5-Lipoxygenase
FLAP Cysteinyl-LT Antagonist e.g. Zafirlukast, Montelukast
LTA4
LTB4
Chemotaxis Immunomodulation
LTC4 LTD4 LTE4
Bronchoconstriction Mucus secretion Oedema Hyperresponsiveness Eosinophilia
Anti-Leukotrienes Monotherapy
as alternative first-line controller Second-Line Controller Add-On Steroid Sparing Effect Drug of choice for aspirin induced asthma
Cromones Mast
cell stabilizers: inhibit degranulation Alternative but not preferred controller in mild persistent asthma, esp. in children Also useful for EIA prophylaxis 4 to 6 week therapeutic trial may be required to determine efficacy Oral preparation Cromolyn sodium, Nedocromil sodium
Classification of Asthma
Classification of Asthma • Traditional classification into Endogenous vs Exogenous Asthma: classification clinically not useful • Classification Based on Chronic Severity Assessment vs. Control of asthma • Severity assessed at the initial consult • Control assessed on follow up
lassification of Chronic Asthma Severit Clinical features before treatment Daytime Symptoms STEP 4 Severe persistent STEP 3 Moderate persistent STEP 2 Mild persistent STEP 1 Intermittent
Night-time symptoms
Continuous Limited physical activity, freq exa Daily symptoms and 2-agonist use
Frequent
b >1 X a week
Attacks affect activity > 1 a week but <1 x a day
<60% predicted Variability >30% >60% - <80% predicted Variability >30%
>2 X a month But < 1 x a week
<1 a week Asymptomatic and normal PEF between attacks
PEF or FEV1
<2 X a month
>80% predicted Variability 20-30% >80% predicted Variability <20%
Meds to control Multiple Controllers
> 2 Controllers
One Controller
No Controllers Needed
GINA, 2005
Asthma as an Evolving Concept: Shift in Paradigm of Asthma Treatment from Severity to Control AW Remodelling Airway Inflammation
Bronchospasm 1975
1980
1985
1990
1995
2000
Asthma as an Evolving Concept: Shift in Paradigm of Asthma Treatment from Severity to Control • Asthma severity involves both the severity of the underlying disease AND its responsiveness to treatment • Asthma severity may change over months or years • Thus, for ongoing Mx of asthma, GINA 2007 classification
GINA 2007 Asthma Management and Prevention Program
Assess, Treat and Monitor Asthma
The choice of treatment should be guided by:
Level of asthma control
Current treatment
Pharmacological properties and availability of the various forms of asthma treatment
Economic considerations
Cultural preferences and differing health care systems need to be considered
Characteristi c
ssess ng ev eve o s Control (GINA 2008) Controlled
Partly controlled
(All of the following)
(Any present in any week)
Daytime Sx’s
None (2 or less / week)
More than twice / week
Activity limitation
None
Any
Nocturnal Sx’s / awakening
None
Any
Need for “reliever” Rx
None (2 or less / week)
More than twice / week
Lung function (PEF or FEV1)
Normal
< 80% predicted or personal best (if known) on any day
Exacerbation
None
One or more / year
ma
Uncontrolled
3 or more features of partly controlled asthma present in any week
1 in any week*
LEVEL OF CONTROL
E C U D E R
TREATMENT OF ACTION
controlled
maintain and find lowest controlling step
partly controlled
consider stepping up to gain control
uncontrolled exacerbation
E S A E R C N I
step up until controlled treat as exacerbation
REDUCE
INCREASE
TREATMENT STEPS STEP
STEP
STEP
STEP
STEP
1
2
3
4
5
Treating to Maintain Asthma Control When control has been achieved, ongoing monitoring is essential to: - maintain control - establish lowest step and least l east drug/dose treatment necessary to maintain
control
If control is maintained for at least 3 months, consider step down to the next lower step
Asthma episode versus exacerbation
Exacerbations of asthma (asthma attacks) are episodes of rapidly progressive (in minutes to hours to days) increase in shortness of breath, cough, wheezing, or chest tightness, or some combination of these symptoms. GINA 2004
Asthma Severity and Exacerbations
Severe asthmatics tend to have the most severe and the most frequent exacerbations The more severe the underlying inflammation, the more difficult and dangerous the exacerbation Even mild asthmatics can have severe, life- threatening exacerbations!
Acute Exacerbation of Asthma
= Failure of Chronic Management + Trigger
Acute Exacerbation of Asthma
= Indicator of Poor Asthma Control
Asthma Management and Prevention Program
Component 4: Manage Asthma Exacerbations
Primary therapies for exacerbations:
Repetitive administration of rapid-acting inhaled β 2agonist
Early introduction of systemic glucocorticosteroids
Oxygen supplementation
Closely monitor response to treatment with serial measures of lung function
