asthma. objectives 1.definition of asthma 2.causes of asthma and risk factors 3.diagnosis...

ASTHMAASTHMA

Objectives Objectives

1.1. Definition of asthmaDefinition of asthma

2.2. Causes of asthma and risk factorsCauses of asthma and risk factors

3.3. DiagnosisDiagnosis

4.4. TreatmentTreatment

5.5. Acute exacerbation of asthmaAcute exacerbation of asthma

AsthmaAsthma

Chronic disease of the airways that may Chronic disease of the airways that may causecauseWheezingWheezingBreathlessnessBreathlessnessChest tightnessChest tightnessNighttime or early morning coughingNighttime or early morning coughing

Episodes are usually associated with Episodes are usually associated with widespread, but variable, widespread, but variable, airflow airflow obstruction obstruction within the lung that is often within the lung that is often reversible either spontaneously or with reversible either spontaneously or with treatmenttreatment..

DefinitionDefinition: :

• Chronic lung disease Chronic lung disease characterized by:characterized by:– Airway narrowing that is Airway narrowing that is

reversible (± completely) either reversible (± completely) either spontaneously or with treatmentspontaneously or with treatment

– Airway inflammationAirway inflammation– Airway hyper-responsiveness to a Airway hyper-responsiveness to a

variety of stimuli.variety of stimuli.

The Spirogram

Asthma Mortality Rates by RaceAsthma Mortality Rates by RaceUnited States: 1979-2005United States: 1979-2005

0

10

20

30

40

50

60

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004 Year

Rat

e pe

r m

illi

on

White

Black

Source: Underlying Cause of Death; CDC National Center for Health Statistics *Age-adjusted to 2000 U.S. population

ICD-9 ICD-10

Other

Risk Factors for Developing Asthma: Risk Factors for Developing Asthma: Genetic CharacteristicsGenetic Characteristics

The body’s predisposition to develop The body’s predisposition to develop an antibody called immunoglobulin an antibody called immunoglobulin E (IgE) in response to exposure to E (IgE) in response to exposure to environmental allergensenvironmental allergens

Environmental Facotors:

Viral/Bacterial infections Chemical irritants:

industrial, householdAir pollution: CO, ozone

Tobacco smokeDust mite/cockroach

allergensAnimal dander,

Exercise, cold air, emotion, stress

Genetic Factors:Genetic alterations on chromosomes 5

and 11, and polymorphisms of

IgE

INFLAMMATION

Airway Hyper-responsiveness

Airflow Obstruction

Asthma Symptoms

Environmental Factors:

Biological AgentsBiological Agents•Sufficient evidence of causal Sufficient evidence of causal

relationshiprelationship–House dust miteHouse dust mite

•Sufficient evidence of Sufficient evidence of associationassociation

–None foundNone found

•Limited or suggestive Limited or suggestive evidence of associationevidence of association

–Cockroach (among pre-Cockroach (among pre-school aged children)school aged children)

–Respiratory syncytial virus Respiratory syncytial virus (RSV)(RSV)

Chemical AgentsChemical Agents•Sufficient evidence of Sufficient evidence of

causal relationshipcausal relationship–None foundNone found

•Sufficient evidence of Sufficient evidence of associationassociation

–Environmental Environmental Tobacco SmokeTobacco Smoke (among pre-school (among pre-school aged children)aged children)

•Limited or suggestive Limited or suggestive evidence of associationevidence of association

–None foundNone found

Diagnosing AsthmaDiagnosing Asthma

**Troublesome cough, particularly at Troublesome cough, particularly at nightnight

**Awakened by coughingAwakened by coughing

**Coughing or wheezing after physical Coughing or wheezing after physical activityactivity

**Breathing problems during particular Breathing problems during particular seasonsseasons

**Coughing, wheezing, or chest Coughing, wheezing, or chest tightness after allergen exposuretightness after allergen exposure

**Colds that last more than 10 daysColds that last more than 10 days

**Relief when medication is usedRelief when medication is used

Diagnosis of AsthmaDiagnosis of Asthma

• History of exercise or cold air History of exercise or cold air participating dyspnea.participating dyspnea.

• PFT using spirometry with ≥ 12% PFT using spirometry with ≥ 12% improvement in peak expiratory flow rate improvement in peak expiratory flow rate (PEFR) or peak expiratory volume in one (PEFR) or peak expiratory volume in one second (FEV1) after bronchodilator second (FEV1) after bronchodilator administration helps in diagnosis.administration helps in diagnosis.

• Skin prick tests to identify allergens. Skin prick tests to identify allergens.

Diagnosing Asthma:Diagnosing Asthma:SpirometrySpirometry

TTest lung function when diagnosing est lung function when diagnosing asthmaasthma

The Spirogram

Treatment of AsthmaTreatment of AsthmaGoals f oAsthma Management:Goals f oAsthma Management: Prevent chronic and troublesome symptoms Prevent chronic and troublesome symptoms

(e.g., coughing or breathlessness at night, in (e.g., coughing or breathlessness at night, in the early morning, or after exertion ). the early morning, or after exertion ).

Maintain normal or near normal pulmonary Maintain normal or near normal pulmonary function.function.

Maintain normal activity levels ( including Maintain normal activity levels ( including exercise and other physical activity. exercise and other physical activity.

Prevent recurrent exacerbations of asthma Prevent recurrent exacerbations of asthma and minimize the need for emergency and minimize the need for emergency department visits or hospitalizations.department visits or hospitalizations.

Provide optimal pharmacotherapy with Provide optimal pharmacotherapy with minimal or no adverse effects.minimal or no adverse effects.

Meet patientsMeet patients’’ and families and families’’ expectations of expectations of and satisfaction with asthma care.and satisfaction with asthma care.

Pharmacological Pharmacological treatment of treatment of

asthmaasthma

1-Short-acting Inhaled1-Short-acting Inhaled 22--agonistsagonists

• Short-acting inhaled Short-acting inhaled 22-agonists are the -agonists are the fastest acting and most effective therapies fastest acting and most effective therapies for the relief of acute asthma symptoms, for the relief of acute asthma symptoms, including wheezing, dyspnea, and chest including wheezing, dyspnea, and chest tightness.tightness.

22-selective therapies (e.g., albuterol, -selective therapies (e.g., albuterol, pirbuterol, and terbutaline) pirbuterol, and terbutaline)

• No clinical advantages among agents. No clinical advantages among agents. Product selection decisions should be based Product selection decisions should be based on factors, including patient preference, cost on factors, including patient preference, cost of treatment, and availability of various of treatment, and availability of various choices for delivery of inhalation therapy . choices for delivery of inhalation therapy .

2-Long-acting 2-Long-acting InhaledInhaled 22--agonistsagonists

• Currently, Formoterol and salmeterol are the Currently, Formoterol and salmeterol are the only long-acting inhaled only long-acting inhaled 22-agonists-agonists available available in the United States in the United States

• Causing bronchodilation by relaxing the Causing bronchodilation by relaxing the smooth muscle in the airway smooth muscle in the airway

• Monotherapy of LABA chronic use in the Monotherapy of LABA chronic use in the absence of inhaled corticosteroids is not absence of inhaled corticosteroids is not recommended recommended

• Studies in adults and children with asthma Studies in adults and children with asthma have shown that LABA monotherapy have shown that LABA monotherapy increases in the frequency of asthma increases in the frequency of asthma exacerbationsexacerbations

3-Leukotriene Modifiers3-Leukotriene Modifiers• Montelukast and zafirlukast Montelukast and zafirlukast • Leukotriene modifiers prevent the action of Leukotriene modifiers prevent the action of

leukotrienes in the body. Leukotrienes are leukotrienes in the body. Leukotrienes are released from mast cells, basophils and released from mast cells, basophils and eosinophils. The release of leukotrienes causes eosinophils. The release of leukotrienes causes airway constriction, increased mucus airway constriction, increased mucus production, swelling and inflammation in the production, swelling and inflammation in the lungs. This presents as wheezing, shortness of lungs. This presents as wheezing, shortness of breath in asthmabreath in asthma

• These agents should be considered as These agents should be considered as alternatives to inhaled corticosteroids and alternatives to inhaled corticosteroids and other treatments for patients 12 years old and other treatments for patients 12 years old and older with mild asthmaolder with mild asthma

Leukotriene Modifiers Leukotriene Modifiers contcont

• Zafirlukast 10 mg 2 times/day is now Zafirlukast 10 mg 2 times/day is now approved by the FDA for asthma approved by the FDA for asthma management in children 7-11 years of management in children 7-11 years of age. age.

• Montelukast 10 mg/day is indicated for Montelukast 10 mg/day is indicated for treating asthma in patients 15 years and treating asthma in patients 15 years and older, children ages 6-14 years at 5 older, children ages 6-14 years at 5 mg/day. and 2-5 years at 4mg/day. mg/day. and 2-5 years at 4mg/day.

• Both Zafirlukast and montelukast are Both Zafirlukast and montelukast are effective as monotherapy in asthma.effective as monotherapy in asthma.

• Corticosteroids are the most potent and Corticosteroids are the most potent and effective therapy currently available for effective therapy currently available for treating asthma .treating asthma .

• Topical used reduce the systemic exposure Topical used reduce the systemic exposure to these agents by reducing absorption to these agents by reducing absorption through the gastrointestinal tract.through the gastrointestinal tract.

• Children should use spacer devices when Children should use spacer devices when using inhaled corticosteroid .using inhaled corticosteroid .

• ICSs suppress inflammation in the lungs ICSs suppress inflammation in the lungs and are recommended for prophylactic and are recommended for prophylactic treatment of asthma. treatment of asthma.

4- Inhaled 4- Inhaled Corticosteroids:Corticosteroids:

LOW DOSELOW DOSEMEDIUMMEDIUMHIGHHIGH

Child Child Adult Adult ChilChild d

AdulAdult t

ChilChild d

AdulAdultt

Beclomethasone dipropionate

CFC-MDICFC-MDI

(42& (42& 8484μμg/MD)g/MD)

HFA-MDIHFA-MDI

(40& (40& 8080μμg/MD)g/MD)

Budesonide DPI( 200 μg/MD)NEB( 200 & 500 μg/amp)

84-33684-336

80 -80 -160160

200-200-400400

250 -250 -500500

168 -168 -504504

80 -80 -240240

200 -200 -600600UnknowUnknownn

336-336-672672

160-160-320320

400-400-800800500-500-1.0001.000

504-504-840840

240-240-480480

600-600-1.2001.200

UnknoUnknownwn

>672>672

>320>320

>800>800

>1.0>1.00000

>840>840

>480>480

>1.20>1.2000UnknoUnknownwn

LOW DOSELOW DOSEMEDIUMMEDIUMHIGHHIGH

Child Child Adult Adult ChilChild d

AdulAdult t

ChilChild d

AdulAdultt

Flonisolid

CFC-MDICFC-MDI

(250 (250 μμg/MD)g/MD)

Fluticasone propionateCFC-MDI(44,110,220 μg/MD)

Triamcinolone acetonideCFC-MDI(100 μg/MD)

500 -500 -750750

88 -88 -176176

400 -400 -800800

500-500-1.0001.000

88-26488-264

400-400-1.0001.000

750-750-1.2501.250

176-176-440440

800-800-1.2001.200

1.000-1.000-2.0002.000

264-264-660660

1.000-1.000-2.0002.000

>1.25>1.2500

>440>440

>1.20>1.2000

>2.00>2.0000

>660>660

>2.00>2.0000

CorticosteroidCorticosteroidT T ½½(hrs)(hrs)

InhaleInhaledd

InhaledInhaled

BioavailabilityBioavailability )%()%(

Receptor-Receptor-bindingbinding

AffinityAffinity

FlunisolideFlunisolide

TriamcinoloTriamcinolonene

BeclomethaBeclomethasonesone

BudesonideBudesonide

FluticasoneFluticasone

1.61.6

3.63.6

UKUK

2.02.0

14.414.4

3939

2222

2525

3838

16-3016-30

1.81.8

3.63.6

13.513.5

9.49.4

1818

Nebulizer Nebulizer Budesonide Inhalation Suspension :Budesonide Inhalation Suspension :• First inhaled corticosteroid product available First inhaled corticosteroid product available

for inhalation by nebulizer. Two dosage for inhalation by nebulizer. Two dosage strengths are available in 2 ml single-dose strengths are available in 2 ml single-dose ampules, 0.25 mg and 0.5 mg.ampules, 0.25 mg and 0.5 mg.

• The recommended starting dose depends on The recommended starting dose depends on previous corticosteroids therapy; 0.5 mg/day previous corticosteroids therapy; 0.5 mg/day is suggested for patients on previous inhaled is suggested for patients on previous inhaled asthma therapy, and 1 mg/day is asthma therapy, and 1 mg/day is recommended for patients on oral recommended for patients on oral corticosteroidscorticosteroids . .

New therapiesNew therapies

3- Formoterol:3- Formoterol:

• is a long-acting inhaled is a long-acting inhaled 22-agonist with a -agonist with a duration of effect similar to that of duration of effect similar to that of salmeterol.salmeterol.

The faster onset of effect for The faster onset of effect for formoterol, formoterol, less than 5 minutes, is an advantage that less than 5 minutes, is an advantage that distinguishes it from salmeterol ( the distinguishes it from salmeterol ( the onset of which is about 20 minutes ) .onset of which is about 20 minutes ) .

””

)1( Environmental control and education

)2( Short-acting 2-agonist on demand

Subclinical Intermittent Persistent

Symptom characteristics

Very mild Mild Moderate Moderately severe

severe

Severity of asthma

Inhaled glucocorticosteroid (daily dose )

Additional therapy

+ P

red

nis

on

e

low

mediumHigh

3

DeviceDeviceAdvantagesAdvantagesDisadvantagesDisadvantagesNebulizerNebulizerSimple to use (requires Simple to use (requires

minimal coordination) minimal coordination) can be used in can be used in mechanically ventialated mechanically ventialated patientspatients

Requires water-Requires water-soluble drug .soluble drug .

Significant drug Significant drug wasted (residual wasted (residual volume) volume)

Numerous factors Numerous factors can affect delivery can affect delivery

Device variability Device variability ( brand to brand, lt ( brand to brand, lt to lot ) to lot )

Inconvenient, bulky, Inconvenient, bulky, costly, and time costly, and time consumingconsuming

Requires electrical Requires electrical power sourcepower source

Nebulizer must be Nebulizer must be kept clean ( potential kept clean ( potential for infection) for infection)

costlycostly

DeviceDeviceAdvantagesAdvantagesDisadvantagesDisadvantagesMetered-Metered-dose dose inhalerinhaler

MDI + MDI + spacerspacer

Requires minimal time Requires minimal time for treatmentsfor treatments

Small, portable Small, portable

Can be used in Can be used in mechanically ventilated mechanically ventilated patients.patients.

Reduce coordination Reduce coordination required.required.

Improve pulmonary drug Improve pulmonary drug deposition.deposition.

Reduces risk for adverse Reduces risk for adverse effects.effects.

Requires significant Requires significant coordinationcoordination

DeviceDeviceAdvantagesAdvantagesDusadvantagesDusadvantagesDry Dry powder powder inhaler.inhaler.

Minimal coordination.Minimal coordination.

Improve pulmonary drug Improve pulmonary drug deposition.deposition.

Lactose excipients.Lactose excipients.

Children+obstructed pt Children+obstructed pt may not generate may not generate adequate inspiratory adequate inspiratory flow.flow.

Increase cough. Increase cough.

Cannot be used in Cannot be used in mechanically ventilated mechanically ventilated pt. pt.

Potential of drug Potential of drug aggregation.aggregation.

Increase oropharyngeal Increase oropharyngeal drug deposition and drug deposition and systemic absorption.systemic absorption.

Acute Asthma Acute Asthma ExacerbationExacerbation

Levels of severity ofLevels of severity ofacute asthma exacerbationsacute asthma exacerbations

Near fatal Near fatal asthmaasthma

Raised PaCORaised PaCO22 and/or requiring mechanical ventilation with and/or requiring mechanical ventilation with raised inflation pressuresraised inflation pressures

Although there are no universally agreed diagnostic criteria for NFA, it is typically associated with the presence of hypercapnia, acidemia, altered state of consciousness and the development of cardiorespiratory arrest requiring endotracheal intubation and mechanical ventilation

Levels of severity ofLevels of severity ofacute asthma exacerbationsacute asthma exacerbations

Near fatal Near fatal asthmaasthma

Raised PaCORaised PaCO22 and/or requiring mechanical ventilation with and/or requiring mechanical ventilation with raised inflation pressuresraised inflation pressures

Life Life threatening threatening asthmaasthma

Any one of the following in a patient with severe asthma:Any one of the following in a patient with severe asthma:•PEF <33% best orPEF <33% best or

predictedpredicted•SpOSpO22 <92% <92%•PaOPaO22 <60 mmgh <60 mmgh•normal PaCOnormal PaCO22 (34 – 45 (34 – 45

mmgh)mmgh)

•silent chestsilent chest•cyanosiscyanosis• feeble feeble

respiratory respiratory efforteffort

•bradycardiabradycardia

•dysrhythmidysrhythmiaa

•hypotensiohypotensionn

•exhaustionexhaustion•confusionconfusion•comacoma

Levels of severity ofLevels of severity ofacute asthma exacerbationsacute asthma exacerbations

Near fatal Near fatal asthmaasthma

Raised PaCORaised PaCO22 and/or requiring mechanical ventilation with and/or requiring mechanical ventilation with raised inflation pressuresraised inflation pressures

Life Life threatening threatening asthmaasthma

Any one of the following in a patient with severe asthma:Any one of the following in a patient with severe asthma:•PEF <33% best orPEF <33% best or

predictedpredicted•SpOSpO22 <92% <92%•PaO2 <60 mmghPaO2 <60 mmgh•normal PaCO2 (34 – 45 normal PaCO2 (34 – 45

mmgh)mmgh)

•silent chestsilent chest•cyanosiscyanosis• feeble feeble

respiratory respiratory efforteffort

•bradycardiabradycardia

•dysrhythmidysrhythmiaa

•hypotensiohypotensionn

•exhaustionexhaustion•confusionconfusion•comacoma

Acute severe Acute severe asthmaasthma

Any one of:Any one of:•PEF 33-50% best or PEF 33-50% best or

predictedpredicted•respiratory rate respiratory rate 25/min25/min•heart rate heart rate 110/min110/min

• inability to complete inability to complete sentences in one breathsentences in one breath

Levels of severity ofLevels of severity ofacute asthma exacerbationsacute asthma exacerbations

Near fatal Near fatal asthmaasthma

Raised PaCORaised PaCO22 and/or requiring mechanical ventilation with and/or requiring mechanical ventilation with raised inflation pressuresraised inflation pressures

Life Life threatening threatening asthmaasthma

Any one of the following in a patient with severe asthma:Any one of the following in a patient with severe asthma:•PEF <33% best or PEF <33% best or

predictedpredicted•SpOSpO22 <92% <92%•PaO2 <60 mmghPaO2 <60 mmgh•normal PaCO2 (34 – 45 normal PaCO2 (34 – 45

mmgh)mmgh)

•silent chestsilent chest•cyanosiscyanosis• feeble feeble

respiratory respiratory efforteffort

•bradycardiabradycardia

•dysrhythmidysrhythmiaa

•hypotensiohypotensionn

•exhaustionexhaustion•confusionconfusion•comacoma

Acute severe Acute severe asthmaasthma

Any one of:Any one of:•PEF 33-50% best or PEF 33-50% best or

predictedpredicted•respiratory rate respiratory rate 25/min25/min•heart rate heart rate 110/min110/min

• inability to complete inability to complete sentences in one breathsentences in one breath

Moderate Moderate asthma asthma exacerbationexacerbation

• Increasing symptomsIncreasing symptoms•PEF >50-75% best or PEF >50-75% best or

predictedpredicted

•No features of acute severe No features of acute severe asthmaasthma

Levels of severity ofLevels of severity ofacute asthma exacerbationsacute asthma exacerbations

Near fatal Near fatal asthmaasthma

Raised PaCORaised PaCO22 and/or requiring mechanical ventilation with and/or requiring mechanical ventilation with raised inflation pressuresraised inflation pressures

Life Life threatening threatening asthmaasthma

Any one of the following in a patient with severe asthma:Any one of the following in a patient with severe asthma:•PEF <33% best or PEF <33% best or

predictedpredicted•SpOSpO22 <92% <92%•PaO2 <60 mmghPaO2 <60 mmgh•normal PaCO2 (34 – 45 normal PaCO2 (34 – 45

mmgh)mmgh)

•silent chestsilent chest•cyanosiscyanosis• feeble feeble

respiratory respiratory efforteffort

•bradycardiabradycardia

• dysrhythmiadysrhythmia• hypotensionhypotension• exhaustionexhaustion• confusionconfusion• comacoma

Acute severe Acute severe asthmaasthma

Any one of:Any one of:•PEF 33-50% best or PEF 33-50% best or

predictedpredicted•respiratory rate respiratory rate 25/min25/min•heart rate heart rate 110/min110/min

• inability to complete inability to complete sentences in one breathsentences in one breath

Moderate Moderate asthma asthma exacerbationexacerbation

• Increasing symptomsIncreasing symptoms•PEF >50-75% best or PEF >50-75% best or

predictedpredicted

•No features of acute severe No features of acute severe asthmaasthma

Brittle Brittle asthmaasthma

•Type 1: wide PEF variability (>40% diurnal variation for Type 1: wide PEF variability (>40% diurnal variation for >50% of>50% ofthe time over a period >150 days) despite intense therapythe time over a period >150 days) despite intense therapy

•Type 2: sudden severe attacks on a background of Type 2: sudden severe attacks on a background of apparentlyapparentlywell-controlled asthmawell-controlled asthma

Management of Asthma Exacerbations: Home Treatment

Management of acute severe asthma Management of acute severe asthma PEF >75% predictedPEF >75% predicted

TimeTimeMeasure PEF and arterial Measure PEF and arterial saturationssaturations

PEF >75% best or predicted: mildPEF >75% best or predicted: mild

5 min5 minGive usual bronchodilatorGive usual bronchodilator

15-30 15-30 minminClinically stable AND PEF >75%Clinically stable AND PEF >75%

60 min60 min

120 120 minminPOTENTIAL DISCHARGEPOTENTIAL DISCHARGE