Definition of AsthmaDefinition of Asthma
1950s, 1950s, ClinicalClinical - Widespread airway - Widespread airway narrowing which changes in severity narrowing which changes in severity over short periods of time, either over short periods of time, either spontaneously or in response to spontaneously or in response to treatmenttreatment
1960s, 1960s, PhysiologicalPhysiological - Bronchial - Bronchial HyperresponsivenessHyperresponsiveness
1990s, 1990s, PathologicalPathological - Airway - Airway inflammationinflammation
Definition of AsthmaDefinition of Asthma
A chronic inflammatory disorder of the airways
Many cells and cellular elements play a role
Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing
Widespread, variable, and often reversible airflow limitation
A chronic inflammatory disorder of the airways
Many cells and cellular elements play a role
Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing
Widespread, variable, and often reversible airflow limitation
Classification of SeverityClassification of Severity
CLASSIFY SEVERITYClinical Features Before Treatment
SymptomsSymptoms NocturnalNocturnalSymptomsSymptoms
FEVFEV1 1 or PEFor PEF
STEP 4STEP 4
Severe Severe PersistentPersistent
STEP 3STEP 3
Moderate Moderate PersistentPersistent
STEP 2STEP 2
Mild Mild PersistentPersistent
STEP 1STEP 1
IntermittentIntermittent
ContinuousContinuous
Limited physical Limited physical activityactivity
DailyDailyAttacks affect activityAttacks affect activity
> 1 time a week > 1 time a week but < 1 time a day but < 1 time a day
< 1 time a week< 1 time a week
Asymptomatic Asymptomatic and normal PEF and normal PEF between attacksbetween attacks
FrequentFrequent
> 1 time week> 1 time week
> 2 times a month> 2 times a month
2 times a 2 times a monthmonth2 times a 2 times a monthmonth
60% predicted60% predicted
Variability > 30%Variability > 30%
60 - 80% predicted 60 - 80% predicted
Variability > 30%Variability > 30%
80% predicted80% predicted
Variability 20 - 30%Variability 20 - 30%
80% predicted80% predicted
Variability < 20%Variability < 20%
The presence of one feature of severity is sufficient to place patient in that category.The presence of one feature of severity is sufficient to place patient in that category.
Levels of Asthma Control
CharacteristicCharacteristicControlledControlled
((All of the All of the followingfollowing))
Partly controlledPartly controlled(Any present in any (Any present in any
week)week)
UncontrollUncontrolleded
Daytime Daytime symptomssymptoms
None (2 or None (2 or less / week)less / week)
More than More than twice / weektwice / week
33 or more or more features of features of
partly partly controlled controlled
asthma asthma present in present in any weekany week
Limitations of Limitations of activitiesactivitiesNoneNoneAnyAny
Nocturnal Nocturnal symptoms / symptoms / awakeningawakening
NoneNoneAnyAny
Need for rescue / Need for rescue / ““relieverreliever”” treatmenttreatment
None (2 or None (2 or less / week)less / week)
More than More than twice / weektwice / week
Lung function Lung function (PEF or FEV(PEF or FEV11))
NormalNormal
< <80%80% predicted or predicted or personal best (if personal best (if known) on any known) on any
dayday
ExacerbationExacerbationNoneNone One or more / year 1 in any One or more / year 1 in any weekweek
controlled
partly controlled
uncontrolled
exacerbation
LEVEL OF CONTROLLEVEL OF CONTROL
maintain and find lowest controlling step
consider stepping up to gain control
step up until controlled
treat as exacerbation
TREATMENT OF ACTIONTREATMENT OF ACTION
TREATMENT STEPSREDUCE INCREASE
STEP
1STEP
2STEP
3STEP
4STEP
5
RE
DU
CE
INC
RE
AS
E
Step 1 – As-needed reliever medication
Patients with occasional daytime symptoms of short duration
A rapid-acting inhaled β2-agonist is the recommended reliever treatment (Evidence A)
When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment (step 2 or higher)
Treating to Achieve Asthma Control
Step 2 – Reliever medication plus a single controller
A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A)
Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids
Treating to Achieve Asthma Control
Treating to Maintain Asthma Control
Stepping down treatment when asthma is controlled
When controlled on medium- to high-dose inhaled glucocorticosteroids: 50% dose reduction at 3 month intervals (Evidence B)
When controlled on low-dose inhaled glucocorticosteroids: switch to once-daily dosing (Evidence A)
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Childhood and adult asthma share the same underlying mechanisms. However, because of processes of growth and development, effects of asthma treatments in children differ from those in adults.
Childhood and adult asthma share the same underlying mechanisms. However, because of processes of growth and development, effects of asthma treatments in children differ from those in adults.
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Many asthma medications (e.g. glucocorticosteroids, β2- agonists, theophylline) are metabolized faster in children than in adults, and younger children tend to metabolize medications faster than older children
Many asthma medications (e.g. glucocorticosteroids, β2- agonists, theophylline) are metabolized faster in children than in adults, and younger children tend to metabolize medications faster than older children
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Long-term treatment with inhaled glucocorticosteroids has not been shown to be associated with any increase in osteoporosis or bone fracture
Studies including a total of over 3,500 children treated for periods of 1 – 13 years have found no sustained adverse effect of inhaled glucocorticosteroids on growth
Long-term treatment with inhaled glucocorticosteroids has not been shown to be associated with any increase in osteoporosis or bone fracture
Studies including a total of over 3,500 children treated for periods of 1 – 13 years have found no sustained adverse effect of inhaled glucocorticosteroids on growth
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Asthma Management and Prevention Program
Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger
Rapid-acting inhaled β2-agonists are the most effective reliever therapy for children
These medications are the most effective bronchodilators available and are the treatment of choice for acute asthma symptoms
Rapid-acting inhaled β2-agonists are the most effective reliever therapy for children
These medications are the most effective bronchodilators available and are the treatment of choice for acute asthma symptoms
Drugs are delivered to a pediatric asthmatic patient through four routes
Orally Rectally By Injections By Inhalations
Inhalation therapy has revolutionized asthma management
Rapid onset of action Less Side Effects In Egypt misbelieves from parents
and doctors as well, make inhalations therapy less popular than it should be
Inhalation therapy is delivered by Pressurized metered dose
inhaler (pMDI) Pressurized metered dose
inhaler (pMDI) with spacer Nebulizer Dry powder inhalers
For an aerosol device to deliver medications efficiently to lower respiratory tract
Aerosol particle should be in the respirable range
Patient should inhale the aerosol with slow deep inspiration followed by a breath hold to allow sedimentation of medication particles
An aerosol is a group of particles that remain suspended in air for a relatively long time because of low terminal settling velocity (the velocity at which particle will fall in air because of gravity(
This terminal settling velocity is related to the size and density of the particle which is expressed as the mass median aerodynamic diameter MMAD
Respirable fraction between 0.5-5 um
Larger particles tend to deposit in the device or upper airway
Very small particles do not settle in the airway and can be exhaled
Mechanisms of aerosol deposition in lower airways (Inertial Impaction, Gravitational Sedimentation & Diffusion
Inertial Impaction For particles > 3 um
#smaller diameter of upper airway in infants and children, preferential nose breathing
#Inertial impaction is highly flow dependant
Gravitational Sedimentation for particles smaller than 2 um and larger particles under low-flow conditions
#The longer particles remain in the lungs,
the greater is their rate of deposition
# Breath holding for 5-10 sec is recommended after inhalation of an aerosol
# Low tidal volume and small vital capacity of infants decrease gravitational sedimentation
Diffusion affect particles so small that Brownian motion has greater influence on particle movement than gravity
Random Brownian movement result in coalescence of particles with airway structures and with other particles
The earliest aerosol device used abulb atomizer similar to those used for some perfume spray which is quite inefficient
In 1945, the daughter of an executive of the Ricker company complained to her father that her asthma atomizer kept breaking
Pressurized metered dose inhaler pMDI Advantages : small size , portable inexpensive,
deliver medication in the respirable range , most asthma medications are available as pMDI
Disadvantages : # Need co-ordinations between actuation and
inhalations # Use of too rapid inspiratory flow # Damaging effect of CFC propellants on ozone # Alternative propellants hydrofluoroalkans (HFA)
may have impact on global warming. With HFA beclomethazone lung deposition increase by 3 to 4 folds while with fluticasone & budesonide remain the same
# Cold freon effect # Patient does not know exactly when canister is
empty
pMDI disadvantages (Continued)#Paradoxical Broncho-constriction even when the
drug is bronchodilator#It is difficult to asses how much drug remain in
the pMDI#Delivered dose may vary, particularly if pMDI is
not properly shaken# Pressurized MDI have a high initial velocity and
the droplets have high initial MMAD (30 um)
Pressurized metered-dose inhalers with spacer Disadvantages: # Large size and lack of portability # Much of the first 10-20 doses of
aerosol fired into a new plastic spacer is deposited on its wall because of its electrostatic charges. Frequent washing may restore the charges.
# Multiple actuations into a spacer before inhalation may reduce delivered dose to the patient because of expansion of CFC within the spacer
pMDI with spacer (Continued)
Advantages : # Overcome the problem of co-ordination
between actuation and inhalations # Overcome the problem of high initial
velocity & high initial MMAD of pMDI (30um) The velocity of the aerosol decreases
within the spacer, the large particles either deposit within the spacer or reduced in size by evaporation to MMAD < 5 um
Nebulizers
Two main types : jet & ultrasonic nebulizer
Jet nebulizer effective for all types of medications including particulate suspension such as inhaled steroids
Ultrasonic Nebulizers
Use high frequency sound waves produced from piezoelectric crystal, which bounce on the surface of the liquid to generate aerosol
Less efficient than jet nebulizer, can not nebulize particulate suspension
The heat of crystal can denature some medications (particularly proteins)
Crystal can develop coating or cracking that can be difficult to detect
Have medication volumes of up to 1.2 ml remaining in the reservoir after nebulization
Jet nebulizer therapy for hospitalized patients
Administered using compressed air or O2 at 50 pound/square inch to generate a flow of 6-8L/minute. This produce acceptable particle size and acceptable nebulization time of 5-10 minute for a 4 ml
fill volume The greater the pressure of O2, the
smaller the particle size
Factors affecting nebulizer performance Type of nebulizer Residual volume remaining in
nebulizer cup (0.5-2ml) is unavailable to the patient
Increasing the fill volume by adding saline allow nebulization of greater proportion of medication at the coast of increased time
The longer the nebulization time, the less likely the patient will consistently take deep breath allowing maximal drug delivery to lower airways
Factors affecting nebulizer performance ( Continued)
Infant crying markedly decrease medication delivery to lower airways since crying is a very long expiration followed by a rapid & brief inspiration. During rapid inspiration the nebulized particles will be deposited in the upper airway by inertial impaction
Patient agitation makes achieving a good seal on either face mask or mouth piece almost impossible
Face mask should be of appropriate size comfortable and fit tightly on the face
Advantages & Disadvantages of Nebulizers
#Advantages The ability to deliver high dose of drugs
particularly bronchodilator Allow patient to receive treatment who are
otherwise unable to inhale drugs (infants) #Disadvantages Complex, time consuming less portable and less
convenient to the patient More coasty than dry powder inhaler or pMDI If they are not perfectly cleaned, nebulizer can become
colonized by microorganisms Even with good care nebulizer performance can decline
overtime
Dry powder inhalers (DPIs)
Dry powder inhalers use the patient inspiratory force to generate drug aerosol from dry powder
Because significant surface force can cause small particles to clump together, medications are hold medications in humidity-protected blisters or mixed with a carrier agent such as lactose to aid dispersion
Two main types of DPIs are available for pediatric use in Egypt ; Turbhaler (Astra-Zenica) & Diskus (GSK)
A moderate to high resistance inhaler device (60-90 L/M) , suitable for children >5 y
Affected by humidity especially if the child exhales into the device
However, when used appropriately it deliver aerosol more effectively than nebulizrsas & as effective as pMDI with spacer
Diskus is a lower resistance multi-dose DPI (30 ml/m)
Medication is contained in individual blister packs better protected from humidity, but still exhalation into the devise will aggregate the preloaded dose
Drug Delivery to the lung from different inhalers
Can be assessed in vitro using scintigraphy, where the aerosol is prelabelled with particle containing a radio-isotope
Systemic availability of inhaled drugs
The relationship between clinical efficacy, local side effects & systemic side effects is more complex with inhaled steroids
Beclomethasone have lower first pass metabolism than fluticasone and budesonide