Asthma

Pio T. Esguerra II, MD, FPCP, FPCCP

Pulmonary & Critical Care
FEU-NRMF Medical Center
1
 Definition
• Chronic, inflammatory disorder of the airways
• Mast cells, eosinophils, T lymphocytes,
macrophages, neutrophils and epithelial cells play a
role
• In susceptible individuals, the chronic inflammation
causes recurrent epiosodes of wheezing,
breathlessness, chest tightness and cough especially
at night or early morning

2
 Definition
• Associated with widespread but variable
airflow obstruction
• reversible with treatment or spontaneously
• Inflammation-causes hyperresponsiveness to
variable stimuli

3
 Definition
• Consistent feature found in bronchial
biopsies: thickening of the lamina reticularis

No feature is unique to asthma

4
Epidemiology and risk factors

5
 Risk factors
• Strongest risk factor: family history of atopic disease
( 3x-4x)
• Serum IgE
• Low or high birth weight, high intake of salt
• Prematurity
• Maternal smoking during pregnancy
• Parental smoking
• obesity

6
 Risk factors
• Fish oil: protective
• Breast feeding: increase risk of allergies and
asthma
• Outdoor air pollution : not a major risk factor
• Indoor house allergen: dust mite
cat dander
cockroach

7
 Risk factors
Viral respiratory infection
“Hygiene hypothesis” : exposure to infections
early in life influences the development of a
child’s immune system leading to a reduced
risk of asthma and other allergic diseases.

8
 Risk factors
Viral respiratory infections
• Viral infections might be protective against
the later development of allergies or asthma
• Rhinovirus- most frequent cause

9
 Risk factors
Genetic
• Strong genetic component
• Increase prevalence among first degree
relatives ( 20-25% versus a general population
prevalence of 4% )

10
 Risk Factors for Death from
Bronchial Asthma

 Past history of sudden severe exacerbation

 Prior intubation for asthma
 Prior admission for asthma to an ICU
 Two or more hospitalizations for asthma in the past year
 Three or more ER visits for asthma in the past year
 Hospitalization or ER visit for asthma within the past month
 Use of > 2 canisters per month of inhaled short-acting
2-agonist

Phil Consensus Report on Asthma

Diagnosis and Management, 1996
GINA
11 2002
• Asthma deaths are often preventable.
• Patients at high-risk for asthma-related death
require special attention—particularly intensive
education, monitoring and care.
• These are the risk factors for asthma –related
death…
• Note that the list has been expanded from the
one contained in our Phil. Consensus.
Pathology

13
 Pathology
Chronic stable asthma characteristics:
inflammation of the airway wall
abnormal accumulation of eosinophils, lymphocytes, mast
cells, macrophages, dendritic cells, myofibroblast
structural changes found in the epithelium and the submucosa
( hyperplasia and hypertrophy of goblet cells, submucosal
gland cells, smooth muscle cells and blood vessel cells )

14
 Pathology
Epithelial changes
• Epithelial desquamation or denudation
• Squamous metaplasia in intact epithelium
• Goblet cell hyperplasia/hypertrophy
consistent feature

15
 Pathology
Eosinophilic inflammation
• Increase in the number of activated
eosinophils in airway epithelium: pathologic
hallmark
• Eosinophils increased in peripheral blood
• Sputum eosinophilia more sensitive

16
 Pathology
Subepithelial changes
• Increase amounts of type III and V collagen
• Number and size of bronchial blood vessels
increased

17
 Pathology
Changes in airway mucus
• Mucin concentrations are higher than normal
( MUC5AC and MUC5B )
• Abnormal mucus in airways  airflow
obstruction  cough and sputum production

18
 Pathology
Large airway versus small airway pathology
• Changes similar in large and small airway

19
Pathophysiology

20
 Pathophysiology
Complex disease:
a) variable airflow obstruction
b) Pathologically, abnormalities in airway
epithelium, lamina propria and submucosa

21
 Disease risk Disease induction Disease consolidation

Disease progresssion
Acute inflammation mediators

Allergens
Viruses symptoms
Pollutants
Susceptibility genes cytokines
diet
Growth factors
Th2 Chronic
Immune inflammation Tissue remodelling
deviation
cytokines cytokines
Early life environment
Maternal programing
Allergen (+)
22
Infection (-)
Pollutants
 Cellular and mediator basis
• Airway immune response responsible for
the clinical manifestation
• Dendritic cells:
a.) most important antigen presenting cell
b.) most potent at initiating and sustaining
airway inflammation
c.) langerhans cells, found below the
epithelium

23
 Cellular and mediator basis
• CD4 cells- principal recipients of antigen
presented by dendritic cells
• Important interleukins in asthma:
IL 4- growth and differentiation factor for TH2
and promote IgE secretion by B cell
IL 13- elicit allergic lung disease
IL 10- negatively regulates TH1 and TH2
IL 12- maximal production of IFN

24
 B cells, Mast cells, basophils and IgE
• Type 1 hypersensitivity reactions- important
cause of acute asthma exacerbation
• Reaction cross links IgE to mast cells or
basophils  histamine, tryptase, chymase,
leukotrienes airway hyperesponsiveness,
mucus overproduction, neuropeptide
degradation

25
 Eosinophils
Most important effector in asthma:
1. Numbers increase dramatically in airways of
asthmatic subjects 4-24hours– coincides
with devt of late phase asthmatic response
2. Numbers increase in airway secretion during
asthma exacerbations induced by
corticosteroid withdrawal

26
3.) there is a relationship between airway
eosinophilia and asthma severity
4.) beneficial effects of corticosteroids are due
to the eosinophilic effects of these drugs

27
 Neutrophils
• Increase in biopsies and secretions
• Potentiate asthma, particularly acute
exacerbation, inducing mucin hypersecretion
and possible increasing bronchovascular
permeability

28
 Macrophages
• Involve in both induction and effector phase
of immune response

29
Mechanism of mucus hypersecretion
1. Hypersecretion of mucin glycoproteins from
airway goblet cells and submucosal gland
cells
2. Excessive leakage of plasma proteins from
the bronchial vasculature
3. Accumulation of products of cell lysis
4. Abnormal mucociliary clearance

30
 Physiology
• Physiologic disturbances

31
• Disturbances clearly seen during attacks
• Narrrowing of the airways: maximal in small bronchi
2-5 mm in diameter
• Test of airway function is abnormal:
airway resistance is increased
maximal expiratory flow is reduced
maximal inspiratory flow is also reduced
Increase in residual volume

32
• Narrowing of peripheral airways  premature
closure at high volumes
Due to:
inability to empty during expiratory phase
sustained increase in the activity of the inspiratory
muscles even during expiration
Advantages: increase in the circumferential traction
on intrapulmonary airways
increase in elastic recoil of the lungs

33
• Consequences: increase work of breathing
• Perceived : dyspnea

34
 Pathophysiology

Normal airway

Airway during Post-mortem airways

acute attack 35
• Progressive airway narrowing due to airway inflammation
and/or increased bronchiolar smooth muscle tone is the
hallmark of an asthma attack.
• The figures on your left show contrasting features of normal
airway vs that during an acute asthma attack.
• The bronchoconstriction leads to increased flow resistance,
pulmonary hyperinflation, and ventilation/perfusion (V /Q )
mismatching.
• Without correction of the airway obstruction, respiratory
failure is a consequence of increased work of breathing, gas
exchange inefficiency, and respiratory muscle exhaustion.
• In severe exacerbations, as shown in this histopathologic
cross-sectional view ( R ) of the lung of a patient who died
from status asthmaticus, the process is severely
exaggerated and the lumen of the airways are often
occluded by mucus plugs.
• Clinically, this leads to progressive hypoxemia and CO2
retention, and eventually, acute respiratory failure.
• Airway narrowing affects gas exchange
• Severity of obstruction not uniform  uneven
blood flow  v/q mismatch
• Arterial oxygen tension in acute severe
asthma: 60 and 69 mm Hg

37
 Pulmonary function testing
• FEV1- most widely used and best standardized
test for airflow obstruction
• Hallmark of asthma: 12% improvement
or >200 ml improvement of FEV1 after
bronchodilator
• FEF 25-75 – selective of obstruction of small
airways, a normal value makes asthma
unlikely

38
 History

• Cardinal symptoms: wheezing

chest tightness
shortness of breath
• Precipitants: exercise
exposure to allergens
viral respiratory infections
• Day to day variability of symptoms

39
• Cough: nonproductive,
nocturnal, chronic, sometimes
persisting for years
• Worsened: exercise, inhalation of
cold air, allergen exposure, upper
respiratory infections

40
• Sputum production: dominant symptom
• Frequently misdiagnosed “ recurrent acute
bronchitis”, clue: youth, family hx of atopy,
symptoms of breathlessness and wheezing
• Marked predominance of eosinophilia in
sputum

41
 Physical examination
• Polyphonic expiratory wheezing (absence
does not indicate airflow obstruction )
• Overinflation of thoracic cage

42
 Laboratory studies
• Peak flow and FEV1
• Asthma recommended spirometry:
at the time diagnosis is made
change in the severity of symptoms
within 2 years in all cases

43
 Laboratory studies
• Measurement of bronchial responsiveness
highly sensitive
non specific
• Elevated IgE levels
positive skin prick
Supportive evidence of asthma
blood eosinophilia

44
category example

Disease causing recurrent Chronic obstructive pulmonary disease,

coronary artery disease, congestive heart
Episodic dyspnea failure, pulmonary emboli, recurrent
anaphylaxis, carcinoid syndrome

Common disease causing Rhinitis, sinusitis, otitis, bronchitis,

bornchiectasis, pneumonia, diffuse pulmonary
cough fibrosis

Common diseases Chronic obstructive bronchitis and

emphysema, bronchiolitis obliterans, cystic
causing airflow fibrosis, organic or functional laryngeal

obstruction narrowing , extrinsic or intrinsic narrowing of

trachea

46
 Special consideration
• Often overlooked in the elderly
• Morbidity and mortality greater in older
patients
• Poor perceivers (blunted ability to detect
airflow obstruction) - increase risk of fatal or
near fatal asthma

47
48
 Subcategories
• Steroid dependent asthma:
 include patients who require continuous or
frequent treatment with an oral glucocorticoid
 does not include pt who require daily inhalation of
inhaled corticosteroid
 partially a function of the quality of care

49
 Subcategories
• Steroid resistant asthma:
 patients who do poorly despite treatment,
defined as failure of 2 weeks of tx with 40mg
methylprednisolone to cause 15%
improvement in FEV 1

50
 Subcategories
• Severe asthma:
 asthma prone to recurrent sudden attacks

51
 Subcategories
• Brittle asthma:
 asthma that rarely causes severe
exacerbation but that regularly interferes with
sleep , exercise tolerance, or the ability to
work , study or play

52
 Subcategories
• Seasonal asthma:
 patients who develop symptoms only during
seasons of high levels of a particular allergen,
such as grass or bird pollen

53
 Subcategories
• Exercise induced asthma/ exercise induce
bronchoconstriction:
 exercise provokes airway narrowing
 due to evaporative loss of water and
possibly also heat from the bronchial mucosa
 increase osmolality
 mast cell activation release of mediators

54
 Subcategories
• Nocturnal asthma:
 asthma causing awakening from sleep
circadian increase in eosinophils and
neutrophils  inflammation

55
 Subcategories
• Drug induced asthma:
aspirin, NSAIDS, beta blockers, ACE inhibitors

56
 Subcategories
• Asthmatic bronchitis:
coincidence of asthma and chronic obstructive
bronchitis in a cigarette smoker
no formal criteria
recurrent dyspnea and wheezing, chronic productive
cough, airflow obstruction that is partially but not
completely reversible

57
 Subcategories
• Asthmatic bronchitis:
“ Dutch hypothesis” mechanism responsible for
asthma predispose to to the development of
COPD and the rate of decline in FEV1 is
indeed faster in smoking asthmatics than in
non smoking asthmatics or in healthy persons

58
 Subcategories
• Asthmatic bronchitis:
 episodes of prolonged production of cough
and sputum purulence that often follows viral
respiratory infections in asthmatic patients

59
 General principles
1. Use of objective measures of lung function
to assess the severity and to monitor
efficacy of therapy
2. Identification and elimination of factors that
worsen symptoms, precipitate
exacerbations, or promote ongoing airway
inflammation

60
 General principles
3. Comprehensive pharmacologic therapy to
reverse bronchoconstriction and to reverse
and prevent airway inflammation
4. Creation of a therapeutic partnership
between patient and the provider of care

61
Major components of asthma management
Periodic asssessment and monitoring
Monitor signs and symptoms of asthma
Monitor pulmonary function
Monitor quality of life and functional status
Monitor history of asthma exacerbation
Monitor pharmacotherapy
Monitor patient provider communications and patient satisfaction

Avoidance of contibuting factors

Skin testing to identify allergens
Control of household and workplace allergens and irritants
Prevention and treatment of viral infections
Prevention and treatment of gastroesophageal relux

Pharmacotherapy
Explain and reinforce role of medications ( quick relief, long terms agents )
Stepwise therapy recommended with provision for step up and step down therapy

Patient education
Provide basic asthma education
Teach and reinforce inhaler and peak flow technique
Develop action plans
Encourage self management
62
 Short term relievers
• Reverse bronchoconstriction
• Beta adrenergic agonist ( albuterol,
metaproterenol, pirbuterol),ipratropium
bromide, methylxanthine
• Relaxes airway smooth muscle
• Best delivered by inhalation

63
 Short term relievers
• Salmeterol and formoterol- long acting ( >12
hours )
onset of action is slow
best use in combination w/ inhaled
corticosteroid

64
 Short term relievers
Anticholinergic agent:
Tiotropium- a.)24 hour duration of action
b.) does not inhibit M-2 receptor
mediated inhibition of acetylcholine
release from parasympathetic nerve
endings

65
 Long term controllers
• Improve overall asthma control
• Inhaled corticosteroids, leukotriene receptor
antagonist, putative inhibitors of mast cell
degranulation
• Do not relax airway smooth muscle but
reduce bronchial reactivity

66
 Long term controllers
• Inhaled corticosteroids are recommended for all
asthmatics
• Oral and parenteral corticosteroids are reserve for pt
who require urgent treatment or who experience
recurrent symptoms
• Inhaled steroids minimize systemic adverse effects
1000ucg of budesonide = 35-50 mg of pred

67
 Long term controllers
Leukotriene receptor antagonist
• Zafirlukast and montelukast
• Orally
• Effective in aspirin induce asthma

68
 Long term controllers
Theophylline
 Inexpensive
 Anti inflammatory effect
 Induces histone deacetylase activity
 Down regulating expression of inflammatory
genes

69
 Long term controllers
New approach:
• Omalizumab : humanized anti IgE antibody
• Intravenous or subcutaneous

70
71
Acute exacerbation of asthma

72
 Assessment of Severity of
Asthma Exacerbations
MILD MODERATE SEVERE RESP. ARREST
IMMINENT
Breathless when Walking Talking At rest May be cyanotic,
Can lie down Prefers sitting Hunched forward exhausted

Talks in Sentences Phrases Words

Alertness May be agitated Usually agitated Usually agitated Drowsy/ confused or

comatose

Resp. rate Increased Increased Often > 30/min

Use of accessory muscles Usually not Usually Usually Paradoxical breathing
of resp

Wheeze Mod. often end- Loud Usually loud Absent

expiratory

Pulse rate / min < 100/min 100-200 /min > 120/min Bradycardia
Pulsus paradoxus Absent May be present Often present Absence suggests resp
< 10 mmHg 10-25 mmHg > 25 mmHg muscle fatigue

PEF after initial > 80% 60 - 80 % < 60 %

73
bronchodilator PCRADM 1996
GINA 2002
• The severity of asthma exacerbations determines the treatment.
• GINA and our Phil asthma consensus both emphasize the importance of assessing the
severity of the acute asthma exacerbation, just as we grade the chronic severity when the
asthmatic is not having an attack.
• Asthma exacerbations are graded as mild, moderate, severe, or respiratory arrest imminent.
• The ER physician can hone his clinical acumen by remembering only 9 parameters as
guidelines for assessing severity of asthma attack and these are the :
• level of breathlessness
• manner of speech
• alertness
• respiratory rate
• use of accessory muscles
• presence or absence of wheezing
• pulse rate
• pulsus paradoxus
• peak expiratory flow after initial bronchodilator therapy
• The presence of several parameters, but not necessarily all, indicates the severity
classification of that exacerbation.
• However, a more severe grading should be given if :
• the patient has a lack of response to the initial treatment
• if the exacerbation has progressed quickly
• if the patient is a high-risk asthmatic : (+) risk factors for asthma-related death
 Acute severe asthma
• Most common precipitant: respiratory viral pathogen
• FEV 1 and peak expiratory flow measured
• Clues to life threatening attack: altered sensorium
upright posture
diaphoresis
telegraphic speech
cyanosis
fatigue
pulsus paradoxus
intercostal retractions
PF < 25% of predicted
<1.0 L

75
 What is the ideal first-line therapy for
asthma exacerbations ?

• Inhaled B2-agonists, due to their rapid

onset of action, are recommended as
first-line therapy in the management of
acute asthma.
Grade A
• They are effective bronchodilators and
have the fewest side effects.
Level 1
PCRADM 2004

76
Salbutamol in Acute Exacerbations

 Salbutamol alone still has a major

role in the management of acute
asthma.
 Must be given at the right dose and
frequency :
 2.5 - 5 mg/dose in adults
 0.15 mg/kg/dose in children
 Given every 20 minutes for the firstGINA
hour2002

77
 Treatment
• Inhaled beta 2 agonist or MDI every 20 to 30
minutes for 1 hour
• For severe exacerbation: continuous
administration of a nebulized beta agonist
addt’l anitcholinergic
• Supplemental oxygen- maintain oxygen sat
>90%

78
• For moderate to severe exacerbations:
steroids started and continued for 7-10 days
• Methylxanthines not recommended for acute
asthma
• Antibiotics not routinely recommended
except for those having co-morbid conditions
( macrolide )

79
What is the role of Corticosteroids in
Asthma Exacerbations ?

 Systemic glucocorticosteroids :
 speed up resolution of exacerbations
 should be considered integral to the
management of all but the mildest
exacerbations

 Inhaled glucocorticosteroids :
 effective as part of combination therapy
for
asthma exacerbations that have already
developed
GINA 80
2002
• Although onset of action of systemic
corticosteroids is 4 to 6 hours, they are important
in the treatment of acute exacerbations because :
• they prevent progression of the exacerbation and
speed up resolution
• decrease the need for ER visits or hospitalizations
• prevent early relapse after ER treatment
• reduce morbidity of the illness
• should be considered integral to the
management of all but the mildest of
exacerbations.
 Hospital-Based Management of
Asthma Exacerbations

Criteria for hospital admission :

 Inadequate response to therapy within 1 – 2
hours
 Persistent PEF < 50 % after 1 hour of treatment
 Presence of risk factors
 Prolonged symptoms prior to ER consult
 Inadequate access to medical care and
medications
 Difficult home conditions
 Difficulty in obtaining transport to hospital in
event of further deterioration
PCRADM 1996

82
 Hospital-Based Management of
Asthma Exacerbations
Incomplete Response

Admit to Hospital:
 Inh. SABA + Inh. anti-cholinergic
 Continue systemic steroids
 Continue oxygen
 Consider IV aminophylline

Improved Not Improved

 PEF > 70 % within 6 – 12 h
 Sustained on meds

Discharge Home Admit to ICU

83

PCRADM 1996
• Those patients with incomplete response are best admitted to the
hospital with the ff. treatment :
• Inhaled SABA with or without inhaled anticholinergic, systemic
steroids, and oxygen.
• IV aminophylline may be considered although its role in
exacerbations is still controversial.
• They provide no additive bronchodilator effect over adequate doses
of SAB but may benefit respiratory drive or respiratory muscle
function and prolong or sustain response to SABA between doses.
• It may have a role in hospitalized patients with severe attack
requiring ICU monitoring.
• Symptoms should be controlled in 6 to 12 hours,
• If the patient improves clinically, PEF > 70 % pred/best and this is
sustained on medications, the patient may subsequently be
discharged to home.
• If no improvement is seen within 6-12 hours, ICU admission should
be done.
 Hospital-Based Management of
Asthma Exacerbations
Moderate Exacerbation Severe Exacerbation

Good Response Incomplete Poor Response w/in

No risk factors: Response 1 hr and/or
w/in 1 hour and/or (+) risk factors:
 Response sustained (+) risk factors :
for 1 hr after last tx  S/SX: severe,
 S/SX: no distress, drowsiness, confusion
 S/SX: mild to mod
normal PE  PEF: <30%
 PEF: >50% - < 70 %
 PEF > 70 %  ABG:
 SaO2 not improving
 SaO2 > 90% PaCO2 > 45 mmHg
PaO2 < 60 mmHg

85

PCRADM 1996
•Response is poor if within one hour after the
last treatment,signs and symptoms remain
severe or there is drowsiness or confusion.
•Also, if the PEF remains lower than 30 %
pred/best and ABG indicates hypercapnea or
persistent hypoxemia despite oxygen
supplementation, these would indicate a poor
response to initial treatment.
Hospital-Based Management of
Asthma Exacerbations

Poor Response

Admit to ICU

87

PCRADM 1996
 Hospital-Based Management of
Asthma Exacerbations

Criteria for ICU admission:

 Lack of response to initial therapy in ED
 Presence of confusion, drowsiness, other signs
of impending respiratory arrest or loss of
consciousness
 Impending respiratory arrest:
 PaO2 <60 mm Hg on supplemental oxygen
 PaCO2 > 45 mm Hg
PCRADM 1996

88
 Hospital-Based Management of
Asthma Exacerbations

Poor Response

Admit to ICU:
 Continue inh SABA + inh. anti-cholinergic
 Consider SQ,IV, or IM 2- agonist
 IV steroids
 IV aminophylline
 Continue oxygen
 Possible intubation/ mechanical ventilation

89

PCRADM 1996
•In the ICU, inhaled bronchodilators and
systemic steroids should be continued.
•The use of parenteral B-2 agonists may be
considered.
•If no improvement is noted, consider IV
aminophylline and possible intubation and
mechanical ventilatory support.
 Goals of asthma management

Prevent chronic and troublesome symptoms

Maintain “normal” pulmonary function
Maintain normal activity levels
Prevent recurrent exacerbations of asthma
Provide optimal pharmacotherapy with minimal
or no adverse effects
Meet patients and families expectations
91
 Levels of asthma control
Characteristics Controlled Partly uncontrolled
controlled
Daytime
symptoms
None > 2x/week Three or more

Limitations of
activities
None Any features of

Nocturnal
symptoms
None Any Partly
controlled
Need for reliever
None > 2x/week Asthma
present in any
Lung function
(PEF of FEV1)
Normal < 80% pred or week
personal best
Exacerbations None One or more/yr One in any
week 92
 What comes next ?

Strategies to Prevent
Future Exacerbations
93
 Rationale for Preventive Strategies
in the ER

 A patient who has been through an asthma exacerbation requiring

ER care is more likely :
 to be receptive to disease education
 to comply better with preventive therapy

 Repeated ER visits and hospitalizations for asthma are markers for

increased risk of dying.

GINA 2002

94
• The ER is the best venue for instituting strategies to prevent
future relapses, further ER visits and hospitalizations
• This should be an integral and essential component of ER
management.
• The rationale involves the fact that this is probably the best
time to introduce asthma education and action plans since
the patient, just recovering from a potentially life-
threatening attack and experiencing the high cost that
comes with every exacerbation, will likely be more
receptive to suggestions on how to avoid future episodes
• They will also more likely comply better with recommended
preventive therapy.
• The patient needs to know from the ER physician that many
studies indicate that asthmatics with previous ER visits and
hospitalizations are at much higher risk of dying from
asthma than stable asthmatics.
 ER Discharge Instructions

 Send home on short course oral steroid

 Continue bronchodilator therapy; dose can be
gradually reduced.
 Start/ Increase/ Add controller medication.
 Provide an Asthma Action Plan.
 Ensure an OPD follow-up schedule.
 Address trigger control, if possible.
 Refer for Patient Education.

GINA 2002

96
• Therefore after treating the acute asthma exacerbation,
ER discharge instructions should include the following…
• A short course of oral steroids to prevent relapses
• Instructions to continue bronchodilator therapy with doses
that could be reduced once recovery is experienced
• Starting or increasing or adding a controller medication as
part of the management of chronic asthma
• Provision of an initial asthma action plan
• Ensuring follow-up
• Addressing trigger control
• Referring further for patient education.
• It is important that the asthmatic contact his/her physician
within 24 hours from ER discharge.
 Summary
• Is an important cause of disability
• It is a disease of misdirected immunity
( direction of immune function being influence by many genes
and probably by airway infections: orchestrated by dendritic
cells and CD4 Th2 lymphocyte)
 Structural changes are now recognized as
potentially irreversible

98
 Summary
• Anti inflammatory and bronchodilator therapy
+ measures to reduce environmental
exposures: reduce cost of asthma

99