Inhalers in Pediatric Asthma

Inhalers in Pediatric AsthmaInhalers in Pediatric Asthma

Dr. KISHORE Dr. KISHORE CHANDKICHANDKI

Kids’ Care Clinic,Kids’ Care Clinic,

Indore (M.P.) INDIAIndore (M.P.) INDIA

Asthma in ChildrenAsthma in Children

With 30 million asthmatics in the country, India With 30 million asthmatics in the country, India constitutes constitutes 10% of the world10% of the world asthmatics asthmatics

Most Most common chronic diseasecommon chronic disease of childhood of childhood

Up to 20%Up to 20% of children affected in various geographical of children affected in various geographical areasareas

Up to Up to one-fourth one-fourth of the children in the pre-school age in of the children in the pre-school age in Delhi are Delhi are recurrent wheezersrecurrent wheezers. . [Times of India, Dec 18, 2004][Times of India, Dec 18, 2004]

No age is exemptNo age is exempt from asthma & it can even start early from asthma & it can even start early in infancy.in infancy.

In most children, asthma develops In most children, asthma develops before age 5 yearsbefore age 5 years, , and, in more than half, asthma develops before age 3 and, in more than half, asthma develops before age 3 yearsyears

Asthma in ChildrenAsthma in Children

Unfortunately, Unfortunately, prevalence is increasingprevalence is increasing in India in India

Fortunately, asthma Fortunately, asthma can be effectively treatedcan be effectively treated & most & most patients can achieve good control of their diseasepatients can achieve good control of their disease

Most in India are either Most in India are either unaware, undiagnosed or are unaware, undiagnosed or are sub-optimally treatedsub-optimally treated for asthma. This is despite India for asthma. This is despite India having the latest, most effective and extremely affordable having the latest, most effective and extremely affordable inhaled medicines to control asthmainhaled medicines to control asthma

The The most effectivemost effective asthma treatment – Inhalation asthma treatment – Inhalation Therapy is available in India at a Therapy is available in India at a price as low asprice as low as Rs. 4 to Rs. 4 to Rs. 6 per day which means that a year’s supply of Rs. 6 per day which means that a year’s supply of medicine is less than the cost of 1 night’s stay at the medicine is less than the cost of 1 night’s stay at the hospital!hospital!

What is Asthma?What is Asthma?Asthma is a Asthma is a chronic inchronic inflammatory disorderflammatory disorder of the of the airways. Chronically inflamed airways are airways. Chronically inflamed airways are hyperresponsivehyperresponsive; they become obstructed & airflow is ; they become obstructed & airflow is limited (by bronchoconstriction, mucus plugs, & limited (by bronchoconstriction, mucus plugs, & increased inflammation) when airways are exposed to increased inflammation) when airways are exposed to various risk factorsvarious risk factorsAsthma attacks (or exacerbations) are episodic, but Asthma attacks (or exacerbations) are episodic, but airway airway inflammation is chronicallyinflammation is chronically present presentA A stepwise approachstepwise approach to pharmacologic treatment to to pharmacologic treatment to achieve & maintain control of asthma should take into achieve & maintain control of asthma should take into account the safety of treatment, potential for adverse account the safety of treatment, potential for adverse effects, & the cost of treatment required to achieve controleffects, & the cost of treatment required to achieve controlAsthma is Asthma is not a cause for shamenot a cause for shame. Olympic athletes, . Olympic athletes, famous leaders, other celebrities, & ordinary people live famous leaders, other celebrities, & ordinary people live successful livessuccessful lives with asthma with asthma

Components of AsthmaComponents of AsthmaAsthma Triggers

Smooth Muscle Dysfunction

Allergens Exercise Irritants Viruses Weather

Inflammation

Bronchial Constriction

Hypertrophy Hyperplasia

Inflammatory Mediator Release

Bronchial Hyperreactivity

Symptoms

Exacerbations

Inflammatory Cell Infiltration

Architectural Changes

Mucus Secretion

Epithelial Damage

Edema

Impaired Ciliary

Function

Adapted from Creticos. Adv Stud Med. 2002;2(14):499-503

Consequences of Inflammation in Consequences of Inflammation in AsthmaAsthma

StimulusStimulus(Antigen, virus, pollutant, occupational agent)(Antigen, virus, pollutant, occupational agent)

AcuteAcuteInflammationInflammation

ResolutionResolution

Chronic InflammationChronic Inflammation

RemodelingRemodeling(fixed changes in the (fixed changes in the structure of airway)structure of airway)

Injury RepairInjury Repair

Airway dysfunctionAirway dysfunction

““Permanently” alteredPermanently” alteredlung functionlung function

Altered airway physiologyAltered airway physiology Airflow obstruction Airflow obstruction

Triggers for acute exacerbationTriggers for acute exacerbation Bhave et Bhave et

alal

37%

9%

8%

8%

7%

11%

14%

5% 1%Viral infection

Colddrinks/icecreams

Food item

Dust exposure

Change of season

Picnics/camps

Physical stress

Emotional stressN = 1050

Outcome of WheezersOutcome of Wheezers

Among infants, 20% have wheezing with only URIs, & Among infants, 20% have wheezing with only URIs, & 60% 60% no longerno longer have wheezing have wheezing by age 6by age 6 years years

Children who have asthma (recurrent symptoms Children who have asthma (recurrent symptoms continuing at age 6 y) have airway reactivity later in continuing at age 6 y) have airway reactivity later in childhoodchildhood

Children with mild asthma who are Children with mild asthma who are asymptomatic asymptomatic between attacksbetween attacks are likely to are likely to improveimprove and be symptom- and be symptom-free later in lifefree later in life

Children with asthma appear to have less severe Children with asthma appear to have less severe symptoms as they enter adolescence, but symptoms as they enter adolescence, but half of these half of these children continue to havechildren continue to have asthma. Asthma has a asthma. Asthma has a tendency to remit during puberty, with a somewhat tendency to remit during puberty, with a somewhat earlier remission in girls. However, compared with men, earlier remission in girls. However, compared with men, women have more AHRwomen have more AHR

Inhalational Therapy in Pediatric Inhalational Therapy in Pediatric AsthmaAsthma

Inhalation: Inhalation: cornerstonecornerstone of asthma treatment of asthma treatment

Not very popularNot very popular among lay man because of some among lay man because of some misconceptionsmisconceptions

Although asthma can be well controlled by highly Although asthma can be well controlled by highly effective anti-inflammatory therapy (mainly ICS) in effective anti-inflammatory therapy (mainly ICS) in majority, majority, optimal control is not achieved in 50%optimal control is not achieved in 50% of of patients in daily practicepatients in daily practice

There is a confusing There is a confusing array of inhaler devicesarray of inhaler devices & & drug/device combinations available and it can be difficult drug/device combinations available and it can be difficult for a clinician to make informed prescribing decisions for a clinician to make informed prescribing decisions about all the possible permutationsabout all the possible permutations

Inhalational Therapy: AdvantagesInhalational Therapy: Advantages

Aerosol Aerosol doses are generally smallerdoses are generally smaller than systemic than systemic doses; e.g., oral Salbutamol is 2 to 4 mg; inhaled 0.2 mg doses; e.g., oral Salbutamol is 2 to 4 mg; inhaled 0.2 mg (MDI) to 2.5 mg (Nebulized)(MDI) to 2.5 mg (Nebulized)

Onset of effectOnset of effect with inhaled drugs is faster than with with inhaled drugs is faster than with oral dosing; e.g., oral albuterol is ≤ 30 min; inhaled oral dosing; e.g., oral albuterol is ≤ 30 min; inhaled albuterol is ~ 5 minalbuterol is ~ 5 min

Drug is delivered Drug is delivered directlydirectly to the target organ (lung), with to the target organ (lung), with minimal systemic exposureminimal systemic exposure

Systemic side effectsSystemic side effects are less frequent and severe with are less frequent and severe with inhalation compared to systemic delivery (injection, inhalation compared to systemic delivery (injection, oral); e.g., less muscle tremor, tachycardia with ß2-oral); e.g., less muscle tremor, tachycardia with ß2-agonists; lower HPA suppression with corticosteroidsagonists; lower HPA suppression with corticosteroids

Inhaled drug therapy is less painful and relatively Inhaled drug therapy is less painful and relatively comfortablecomfortable

Inhalational Therapy: Inhalational Therapy: DisadvantagesDisadvantages

Lung Lung deposition is a relatively lowdeposition is a relatively low fraction of the total fraction of the total aerosol doseaerosol dose

A number of A number of variablesvariables (correct breathing pattern, use of (correct breathing pattern, use of device) can affect lung deposition and dose device) can affect lung deposition and dose reproducibilityreproducibility

Difficulty coordinatingDifficulty coordinating hand action and inhalation with hand action and inhalation with MDIsMDIs

Lack of knowledgeLack of knowledge of correct or optimal use of aerosol of correct or optimal use of aerosol devices by patients and cliniciansdevices by patients and clinicians

The number and variability of device types confuses The number and variability of device types confuses patients and clinicianspatients and clinicians

Lack of standardizedLack of standardized technical information on inhalers technical information on inhalers for cliniciansfor clinicians

Inhalant Drugs: ListInhalant Drugs: ListBronchodilatorsBronchodilators

ArformoterolArformoterol

BitolterolBitolterol

EpinephrineEpinephrine

FormoterolFormoterol

IpratropiumIpratropium

IsoetharineIsoetharine

IsoproterenolIsoproterenol

LevalbuterolLevalbuterol

MetaproterenolMetaproterenol

PirbuterolPirbuterol

ProcaterolProcaterol

Racepinephrine (racemic Racepinephrine (racemic epinephrine)epinephrine)

SalbutamolSalbutamol

SalmeterolSalmeterol

TerbutalineTerbutaline

TiotropiumTiotropium

Anti-inflammatoryAnti-inflammatory

BeclomethasoneBeclomethasone

BudesonideBudesonide

CiclesonideCiclesonide

CromolynCromolyn

FlunisolideFlunisolide

FluticasoneFluticasone

DexamethasoneDexamethasone

FluticasoneFluticasone

MometasoneMometasone

NedocromilNedocromil

TriamcinoloneTriamcinolone

AntimicrobialsAntimicrobials

PentamidinePentamidine

RibavirinRibavirin

TobramycinTobramycin

ZanamivirZanamivir

MiscellaneousMiscellaneous

Aromatic ammoniaAromatic ammonia

Dornase alfaDornase alfa

GlutathioneGlutathione

InsulinInsulin

MethacholineMethacholine

NicotineNicotine

Sodium chlorideSodium chloride

MucolyticsMucolytics

AmbroxolAmbroxol

N-acetyl cysteineN-acetyl cysteine

Inhalant Drugs: EffectsInhalant Drugs: Effects

Asthma Treatment: EvolutionAsthma Treatment: Evolution

Evolution of Asthma ParadigmsEvolution of Asthma Paradigms

1970s–1980sBronchoconstriction

(Spirometry)

1980s–1990s

Inflammation

(PC20, Inflam cells, FeNO)

1990s–2000s

Remodeling

Relieve SymptomsPrevent Symptoms

Prevent AttacksPrevent Remodeling

Prevent SymptomsPrevent Attacks

Bronchial Hyperreactivity

Fixed ObstructionSymptoms

Therapy for Chronic Asthma in Therapy for Chronic Asthma in ChildrenChildren

Acute relief from symptoms Anti-inflammatory

Sustained bronchodilatorUnproven anti-inflammatory

Oral short acting ß2 agonists & xanthines: not for maintenance TxOral short acting ß2 agonists & xanthines: not for maintenance TxOther drugs: oral steroids, H1 antihistaminesOther drugs: oral steroids, H1 antihistamines

SABA

AnticholinergicIpratropium

Xanthine:Short Acting

ICS

ChromonesNa Cromoglycate

Nedocromil Na

SRTheophyllines

Leukotrieneantagonists

LABA

Slow release xanthines

Leukotrieneantagonists

PRN basis

Adjuncts

Aminophylline

Immunomodulators:Omalizumab (anti-IgE)

Adrenaline/Epi

Relievers Preventers

Controllers

Asthma Classification & Asthma Classification & ManagementManagement

Levels of Asthma Control > 5 yrs Levels of Asthma Control > 5 yrs GINA GINA

20112011

*Any exacerbation should prompt review of maintenance treatment to ensure that is adequate*Any exacerbation should prompt review of maintenance treatment to ensure that is adequateҰҰ By definition, an exacerbation in any week makes that an uncontrolled asthma week By definition, an exacerbation in any week makes that an uncontrolled asthma week¥ Without administration of bronchodilator, lung function is not a reliable test for children 5 years & ¥ Without administration of bronchodilator, lung function is not a reliable test for children 5 years & youngeryounger

Characteristic Controlled(All of the following)

Partly Controlled(Any measure present in any week)

Uncontrolled (3 or more of features of partly controlled asthma in any week)

Daytime symptoms: wheezing, cough, difficult breathing

None(less than twice/week, typically for short periods on the order of minutes and rapidly relieved by use of a rapid acting bronchodilator)

More than twice/week(typically for short periods on the order of minutes and rapidly relieved by use of a rapid-acting bronchodilator)

More than twice a week (typically last minutes or hours or recur, but partially or fully relieved with rapid-acting bronchodilator)

Limitations of activities

None(child is fully active, plays and runs without limitations or symptoms)

Any (may cough, wheeze, or have difficulty breathing during exercise, vigorous play, or laughing)

Any

Nocturnal symptoms/awakening

None(including no nocturnal coughing during sleep)

Any (typically coughs during sleep or wakes with cough, wheezing, and/or difficult breathing)

Any

Need for reliever/rescue Tx

≤2 days/week >2 days/week >2 days/week

Levels of Asthma Control ≤ 5 yrs Levels of Asthma Control ≤ 5 yrs GINA GINA

20092009

Management approach: Children > 5 years Management approach: Children > 5 years & Adults& Adults

Management approach: Children ≤ 5 yearsManagement approach: Children ≤ 5 years

GINA 2009GINA 2009

Controller:None

Controller:Low dose

ICS*

LT modifier

Controller:Double low-Dose ICS*

Low doseICS + LTModifier

Education, Environmental Control, As needed rapid-acting β2 agonist

ControlledPartly

Controlled

Uncontrolled orPartly Controlledon low dose ICS

When asthmaIs controlled:

Reduce therapyMonitor

*Preferred

Reliever: Rapid acting β2 agonist prn

Stepping Up: Inhalation Stepping Up: Inhalation therapytherapy

When asthma is When asthma is NOT controlledNOT controlled with: with:Rapid onset, short acting or LABA bronchodilatorsRapid onset, short acting or LABA bronchodilatorsRepeated dosing with bronchodilators in this class Repeated dosing with bronchodilators in this class provides temporary relief until the cause of the days provides temporary relief until the cause of the days signals the need for review and possible increase of signals the need for review and possible increase of controller therapycontroller therapyInhaled corticosteroidsInhaled corticosteroidsTemporarily doubling the dose of IGCS has not been Temporarily doubling the dose of IGCS has not been demonstrated to effective and is no longer recommended. demonstrated to effective and is no longer recommended. A fourfold or greater increase has been demonstrated to A fourfold or greater increase has been demonstrated to be equivalent to a short course of Oral GCSbe equivalent to a short course of Oral GCSCombination of ICS & LABACombination of ICS & LABAIn a single inhaler both as a controller and a reliever is In a single inhaler both as a controller and a reliever is effective in maintaining a high level of asthma control and effective in maintaining a high level of asthma control and reduces exacerbation requiring systemic GCS and reduces exacerbation requiring systemic GCS and hospitalizationhospitalization

Stopping Inhalation therapyStopping Inhalation therapy

When control is achieved with…When control is achieved with…

Low dose ICS Low dose ICS switch to switch to once dailyonce daily dosing dosing

Mod to high dose ICS Mod to high dose ICS reduce by reduce by 50% after 3 mo50% after 3 mo

ICS + LABA ICS + LABA Reduce ICS by 50% Reduce ICS by 50%

Bring ICS to lowest doseBring ICS to lowest dose

Omit LABAOmit LABA

ICS + Other ICS + Other Same as above Same as above

Stop when no symptoms for Stop when no symptoms for one yearone year

Equipotent Daily Doses of ICS: Age > 5 Equipotent Daily Doses of ICS: Age > 5 years/Adultsyears/Adults

Equipotent Daily Doses of ICSEquipotent Daily Doses of ICS

Beclomethasone 200-500 100-200 >500-1000 >200-400 >1000 >400

Budesonide 200-600 100-200 600-1000 >200-400 >1000 >400

Budesonide-Neb Inhalation Suspension

250-500 >500-1000 >1000

Ciclesonide 80 – 160 80-160 >160-320 >160-320 >320-1280 >320

Flunisolide 500-1000 500-750 >1000-2000 >750-1250 >2000 >1250

Fluticasone 100-250 100-200 >250-500 >200-500 >500 >500

Mometasone furoate

200-400 ?100-200 > 400-800 >200-400 >800-1200 >400

Triamcinolone acetonide

400-1000 ? 400-800 >1000-2000 >800-1200 >2000 >1200

Drug (µg) Low Daily Dose>5 y ≤ 5 y

Medium Daily Dose>5 y ≤ 5 y

High Daily Dose> 5 y ≤ 5 y

Combination InhalersCombination Inhalers

Steroid/LABASteroid/LABA Can improve complianceCan improve compliance Useful when asthma stableUseful when asthma stable Lack of flexibility to Lack of flexibility to or or dose dose

MultidosingMultidosing

Multiple puffsMultiple puffs (up to 10) of a short-acting (up to 10) of a short-acting ßß2 agonist via 2 agonist via a spacer device is a spacer device is as effectiveas effective as nebulised as nebulised

Children (& adults) with mild & moderate exacerbation Children (& adults) with mild & moderate exacerbation of asthma should be treated by bronchodilator given of asthma should be treated by bronchodilator given from a MDI + spacer with doses titrated according to from a MDI + spacer with doses titrated according to clinical responseclinical response

Inhalational Therapy: DevicesInhalational Therapy: Devices

Aerosol Aerosol devices includedevices include::

Metered-dose inhaler (MDI)Metered-dose inhaler (MDI)

Pressurized Metered Dose Inhaler (pMDI)Pressurized Metered Dose Inhaler (pMDI)

Breath-activated metered-dose inhalerBreath-activated metered-dose inhaler

Metered-dose inhaler with spacerMetered-dose inhaler with spacer

Dry powder inhaler (DPI) e.g. RotacapsDry powder inhaler (DPI) e.g. Rotacaps

NebulizerNebulizer

Metered Dose Inhalers Metered Dose Inhalers (MDI)(MDI)

Uses chemical propellants (hydro-fuoroalkane Uses chemical propellants (hydro-fuoroalkane instead of CFC) to deliver medication dose to instead of CFC) to deliver medication dose to lungslungs

Salbutamol (Asthalin, Ventorlin)Salbutamol (Asthalin, Ventorlin) Levosalbutamol (Levolin)Levosalbutamol (Levolin) Salmeterol (Serobid)Salmeterol (Serobid) Terbutaline (Bricanyl)Terbutaline (Bricanyl) Ipratropium (Ipravent)Ipratropium (Ipravent) Triotropium (Tiova)Triotropium (Tiova) Combinations (Duolin, Aerocort, Seroflo)Combinations (Duolin, Aerocort, Seroflo)

Metered Dose Inhalers Metered Dose Inhalers (MDI)(MDI)Reliever bronchodilatorsReliever bronchodilators

(usually blue)(usually blue)

Inhaled steroidsInhaled steroids(usually brown/orange)(usually brown/orange)

Long acting beta 2 Long acting beta 2 agonists (Always green)agonists (Always green)

MDI InhalersMDI Inhalers

Portable, compactPortable, compact

Short treatment timeShort treatment time

Reproducible dose Reproducible dose emitted per actuationemitted per actuation

Most medications are Most medications are available in this formavailable in this form

Hand-breathing Hand-breathing coordination & technique coordination & technique importantimportant

High oropharyngeal High oropharyngeal impaction without spacerimpaction without spacer

Failure to shake can alter Failure to shake can alter drug dosedrug dose

Foreign body aspiration Foreign body aspiration from debris-filled from debris-filled mouthpiecemouthpiece

No dose counterNo dose counter

AdvantagesAdvantages DisadvantagesDisadvantages

Dry Powder Inhalers Dry Powder Inhalers (DPIs)(DPIs)

RotahalerRotahaler DiskhalerDiskhaler DiskusDiskus

DPI: RotahalerDPI: Rotahaler

Small and portableSmall and portable

Built-in dose counterBuilt-in dose counter

Propellant-freePropellant-free

Breath-actuated (drug Breath-actuated (drug comes when patient comes when patient breaths in)breaths in)

Short preparation and Short preparation and administration timeadministration time

Dependence on patient’s Dependence on patient’s inspiratory flowinspiratory flow

Patients less aware of Patients less aware of delivered dosedelivered dose

Relatively high Relatively high oropharyngeal impaction oropharyngeal impaction can occurcan occur

Moisture sensitiveMoisture sensitive

Limited range of drugsLimited range of drugs

More expensive than MDIMore expensive than MDI


Now Now recommended for administration recommended for administration of allof all MDI medications MDI medications

Spacers or holding Spacers or holding chamberschambers

SpacersSpacers

Less/No coordination Less/No coordination required required

Improved delivery of Improved delivery of drug to lower airwaysdrug to lower airways

May breathe in & out May breathe in & out several times to receive several times to receive complete dose complete dose

Faster delivery than Faster delivery than nebulizer & less nebulizer & less expensive expensive

Reduced Reduced oropharyngeal drug oropharyngeal drug impaction & lossimpaction & loss

Large, cumbersome than Large, cumbersome than MDI aloneMDI alone

Expensive wrt MDI aloneExpensive wrt MDI alone

Cleaning requiredCleaning required

Some assembly may be Some assembly may be neededneeded

Patient errors include Patient errors include firing multiple puffs into firing multiple puffs into chamber prior to chamber prior to inhaling, or delay inhaling, or delay between actuation and between actuation and inhalationinhalation


SteroidsSteroids from a MDI from a MDI must always be prescribedmust always be prescribed with a spacer to with a spacer to improve drug delivery and diminish side-effectsimprove drug delivery and diminish side-effectsSmaller volume (250-300 ml) are suitable for children < 5 years and Smaller volume (250-300 ml) are suitable for children < 5 years and larger volume > 500 ml) for older childrenlarger volume > 500 ml) for older childrenShould be Should be washed weeklywashed weekly. To reduce the static electricity in plastic . To reduce the static electricity in plastic spacers the spacer should be washed with a liquid detergent, not spacers the spacer should be washed with a liquid detergent, not rinsed in water, and left to drip-dry overnightrinsed in water, and left to drip-dry overnightIf commercially available spacers are not available a If commercially available spacers are not available a 500 ml plastic500 ml plastic bottlebottle can be used as a spacer. A hole to fit the MDI is cut or melted can be used as a spacer. A hole to fit the MDI is cut or melted into the bottom of the bottle using the hot wire technique. into the bottom of the bottle using the hot wire technique. Polystyrene cups are not efficient spacersPolystyrene cups are not efficient spacersOne puff at a time should be actuated into the spacer and the child One puff at a time should be actuated into the spacer and the child should breathe 4-5 times before the next actuation. After inhalation should breathe 4-5 times before the next actuation. After inhalation of ICS, the of ICS, the mouth should be rinsedmouth should be rinsed..If a spacer with a facemask is used it should be applied tightly to If a spacer with a facemask is used it should be applied tightly to the face. The face should be washed after corticosteroid inhalation the face. The face should be washed after corticosteroid inhalation to prevent skin changes (spider nevi, atrophy)to prevent skin changes (spider nevi, atrophy)

SpacersSpacers

Nebulizers are principally used for Nebulizers are principally used for Children (<5 years) and adults (<55 years) who have Children (<5 years) and adults (<55 years) who have difficulty coordinating the use of MDIs and DPIsdifficulty coordinating the use of MDIs and DPIs

By patients with severe asthma or chronic obstructive By patients with severe asthma or chronic obstructive pulmonary disease (COPD)pulmonary disease (COPD)

In the emergency room for acute episodes of In the emergency room for acute episodes of bronchospasmbronchospasm

NebulizersNebulizers

NebulizersNebulizers

Use of passive Use of passive breathing: Any age breathing: Any age

Easy to teach & useEasy to teach & use

Patient coordination Patient coordination not requirednot required

High drug doses High drug doses possible, Many drugs possible, Many drugs

Can be used with Can be used with supplemental Osupplemental O2

Mixtures (>1 drug), if Mixtures (>1 drug), if drugs are compatibledrugs are compatible

Time intensiveTime intensive

Inefficient & Inefficient & cumbersomecumbersome

Equipment and power Equipment and power source requiredsource required

Cleaning requiredCleaning required

Variability in Variability in performanceperformance

Potential for drug Potential for drug delivery into eyes with delivery into eyes with maskmask


How to choose delivery devices for How to choose delivery devices for asthmaasthma

Arch Dis Child 2000;82:185-187

NebulizerNebulizer Infants & toddlersInfants & toddlers EmergencyEmergency Poor coordination Poor coordination

Inhalational Drugs: Inhalational Drugs: MetabolismMetabolism

The fate of an inhaled drug. The total amount of drug in the The fate of an inhaled drug. The total amount of drug in the systemic circulation is the sum of the systemic absorption systemic circulation is the sum of the systemic absorption via the lungs and via the GI tractvia the lungs and via the GI tract

Inhaler Devices & Drug DeliveryInhaler Devices & Drug Delivery

NebulizerNebulizer 1 – 5% 1 – 5%

DPIDPI 5 – 10% 5 – 10%

MDIMDI 5 – 10%5 – 10%

MDI with Spacer (esp. Steroids)MDI with Spacer (esp. Steroids) 10 – 15% 10 – 15%

Disc DPIDisc DPI ~15%~15%

TurbuhalerTurbuhaler >30%>30%

Asthma By Consensus, IAP

Inhaler Devices & Drug DeliveryInhaler Devices & Drug Delivery

Device & Technique: Device & Technique: ConcernsConcerns

Up to 50%Up to 50% of patients are unable to use of patients are unable to use inhaler correctlyinhaler correctly

Most patients, nurse and doctors are Most patients, nurse and doctors are unable to use unable to use pMDIspMDIs correctly correctly

Patients forget instructions and Patients forget instructions and skills skills deteriorate over timedeteriorate over time – reassessment – reassessment and re-educationand re-education

Need forNeed for clear specific training for clear specific training for patients of correct inhaler techniquepatients of correct inhaler technique

Barriers to Inhalational Barriers to Inhalational TherapyTherapy

Fear about steroids Fear about steroids

Do not like public labeling as asthmaticDo not like public labeling as asthmatic

Fear of addiction Fear of addiction

Feel pumps reserved for serious or severe Feel pumps reserved for serious or severe attacks or will fail to act attacks or will fail to act

Misconception that costly Misconception that costly

Prefer oral medications Prefer oral medications

Physicians lack of knowledge and time Physicians lack of knowledge and time

1 2 4 5 6 7 8 930 10 11 12

Age of Children (Years)

13 14 15 16+

Fluticasone MDI (HFA)

FDA = Food and Drug Administration; DPI = dry-powder inhaler; MDI = metered-dose inhaler; HFA = hydrofluoroalkane

Beclomethasone MDI

Budesonide DPI

Flunisolide MDI

Triamcinolone MDI

Beclomethasone MDI (HFA)

Budesonide Nebulization

Fluticasone DPI

Inhaled Corticosteroids: FDA-Inhaled Corticosteroids: FDA-ApprovalsApprovals

Mometasone DPI

Fluticasone/Salmeterol DPI

Inhaled CorticosteroidsInhaled Corticosteroids

Minimal effective doseMinimal effective dose to control asthma in the patient is to control asthma in the patient is always a goal of ICS therapyalways a goal of ICS therapy

In the past, patients were started on medium to high In the past, patients were started on medium to high doses of ICS until control is achieved & then step down to doses of ICS until control is achieved & then step down to the lowest dose that maintains control. The current the lowest dose that maintains control. The current guidelines recommend starting patients on guidelines recommend starting patients on dosages dosages based upon level of severitybased upon level of severity and then to titrate up or down and then to titrate up or down based upon responsiveness to therapybased upon responsiveness to therapy

Most patients' Most patients' symptoms will improve in 1–2 weekssymptoms will improve in 1–2 weeks of of therapy & will reach maximum improvement in 4–8 weeks. therapy & will reach maximum improvement in 4–8 weeks. Lung function improvement begins in 1–2 weeks and Lung function improvement begins in 1–2 weeks and usually plateaus at 4 weeks but may increase slightly usually plateaus at 4 weeks but may increase slightly thereafter for 6–8 weeks. Improvement in bronchial thereafter for 6–8 weeks. Improvement in bronchial hyperresponsiveness requires 2–3 weeks and approaches hyperresponsiveness requires 2–3 weeks and approaches maximum in 1–3 months but may continue to improve maximum in 1–3 months but may continue to improve over 1 yearover 1 year

Inhaled CorticosteroidsInhaled Corticosteroids

Many patients with mild persistent asthma can be Many patients with mild persistent asthma can be effectively treated with effectively treated with once-daily ICS therapyonce-daily ICS therapy, usually , usually more effective given in the evening.more effective given in the evening.

Currently, mometasone is the only ICS with approved Currently, mometasone is the only ICS with approved US-FDA labeling to begin therapy once daily & US-FDA labeling to begin therapy once daily & BudesonideBudesonide has once-daily approved labeling once has once-daily approved labeling once control is established on twice-daily dosing. All other control is established on twice-daily dosing. All other ICSs are labeled for twice-daily dosing.ICSs are labeled for twice-daily dosing.

The newest ICS, ciclesonide (CIC), is used in Europe on The newest ICS, ciclesonide (CIC), is used in Europe on a once-daily basis in adults and children, but only has a a once-daily basis in adults and children, but only has a twice-daily approved indication in adults in the United twice-daily approved indication in adults in the United States. The US pivotal trials for CIC in children 4–11 States. The US pivotal trials for CIC in children 4–11 years old with moderate-to-severe asthma gave once-years old with moderate-to-severe asthma gave once-daily dosing of 40, 80, & 160 μg.daily dosing of 40, 80, & 160 μg.

Current Opinion in Allergy & Clinical Immunology 2011;11(4):337-344

Common MDI PreparationsCommon MDI Preparations

Drug: Drug: NebulizedNebulized

AvailabilityAvailability DoseDose

SalbutamolSalbutamol Asthalin solAsthalin soln n 5 mg/mL, 5 mg/mL, respule 2.5 mg/2.5 mLrespule 2.5 mg/2.5 mL

0.15 mg/kg (Min 2.5 mg) as often as 20 0.15 mg/kg (Min 2.5 mg) as often as 20 min min × 3, then 0.15-0.3 mg/kg up to 10 mg × 3, then 0.15-0.3 mg/kg up to 10 mg q1-4h PRN, or up to 0.5 mg/kg/hr by q1-4h PRN, or up to 0.5 mg/kg/hr by continuous nebulizationcontinuous nebulization

LevosalbutaLevosalbutamolmol

0.31 mg, 0.63 mg, 1.25 0.31 mg, 0.63 mg, 1.25 mg/2.5 mL Respules mg/2.5 mL Respules Levolin / AerozestLevolin / Aerozest

0.075 mg/kg (Min 1.25 mg) q20 min 0.075 mg/kg (Min 1.25 mg) q20 min × 3, × 3, then 0.075 – 0.15 mg/kg up to 5 mg q1-4 h then 0.075 – 0.15 mg/kg up to 5 mg q1-4 h PRN, or 0.25 mg/kg/hr continuous PRN, or 0.25 mg/kg/hr continuous nebulization. 0.63 mg = 1.25 mg nebulization. 0.63 mg = 1.25 mg salbutamol for both efficacy & SEsalbutamol for both efficacy & SE

BudesonideBudesonide Respule 0.5 mg/2 mL, Respule 0.5 mg/2 mL, 1 mg/2 mL1 mg/2 mLMDI Bunase 100/200MDI Bunase 100/200

Initiating dose 0.5-1 mg BD, Maintenance Initiating dose 0.5-1 mg BD, Maintenance 0.25-0.5 mg BD0.25-0.5 mg BD

FluticasoneFluticasone 0.5 mg/2 mL, 2 mg/2 0.5 mg/2 mL, 2 mg/2 mLmL

1 mg BD1 mg BD

IpratropiumIpratropium Neb respirator Neb respirator solutionsolution0.25 mg/ml, Respule0.25 mg/ml, Respule0.5 mg/2 mL0.5 mg/2 mL

0.5 ml < 1 year, 1 ml >1 year every 20 mins 0.5 ml < 1 year, 1 ml >1 year every 20 mins for 3 doses, then every 6-8 hours solutionfor 3 doses, then every 6-8 hours solution


DrugDrug AvailabilityAvailability DoseDose

SalbutamolSalbutamol Asthalin /Ventorlin Asthalin /Ventorlin MDI 100 MDI 100 µg/dose µg/dose (DPI 200 µg/dose)(DPI 200 µg/dose)

4-8 puff every 20 min 4-8 puff every 20 min × 3, then q1-4h. × 3, then q1-4h. Maintenance 1-2 puff q4-6hMaintenance 1-2 puff q4-6hAdults: 4-8 puffs every 20 min fo up to 4 Adults: 4-8 puffs every 20 min fo up to 4 hrs, then same.hrs, then same.Before exercise 1-2 puff 5 min before.Before exercise 1-2 puff 5 min before.

LevosalbutaLevosalbutamolmol

Levolin/ Aerozest 50 Levolin/ Aerozest 50 µg (DPI 100 µg)µg (DPI 100 µg)

Same puffs as above.Same puffs as above.

BudesonideBudesonide Budecort/Pulmicort Budecort/Pulmicort MDI 100/200 MDI 100/200 µg/dose µg/dose (DPI 100/200/400)(DPI 100/200/400)

FluticasoneFluticasone Flohale MDI Flohale MDI 25/50/125 25/50/125 µg/dose µg/dose (DPI 50/100/250 )(DPI 50/100/250 )

IpratropiumIpratropium Ipravent MDI 20 Ipravent MDI 20 µg/dose (DPI 40)µg/dose (DPI 40)

TiotropiumTiotropium MDI Aerotrop MDI Aerotrop µg µg (DPI 18µg )(DPI 18µg )


DrugDrug AvailabilityAvailability DoseDose

Salmeterol + Salmeterol + FluticasoneFluticasoneS 25S 25µg + F 50/125/250µg + F 50/125/250

Seroflo & Flutrol Seroflo & Flutrol 50/125/250 50/125/250 (Macleods)(Macleods)

Seretide Evohaler Seretide Evohaler 50/125/250 (gsk)50/125/250 (gsk)

>4 yrs: 2 puffs of 50 >4 yrs: 2 puffs of 50 µg BD (up to µg BD (up to 100 BD)100 BD)

Formoterol + Formoterol + BudesonideBudesonideF 6F 6µg + B 100/200/400µg + B 100/200/400

Foracort 100/200/400Foracort 100/200/400

Budetrol 100/200/ 400 Budetrol 100/200/ 400 (Macloeds)(Macloeds)

Vent-FBVent-FB

For For maintenance & reliefmaintenance & relief!!

Formoterol + Formoterol + FluticasoneFluticasone

Flucort-F 125/250Flucort-F 125/250

Tiotropium + Tiotropium + FormoterolFormoterol

MDI Aerotrop-F (9 + 6 MDI Aerotrop-F (9 + 6 µg respectivelyµg respectively) DPI) DPI

Indications for ReferralIndications for ReferralThe The majoritymajority of asthmatics can be managed optimally in of asthmatics can be managed optimally in a a primary health care facilityprimary health care facility, provided the elements of , provided the elements of the asthma guidelines are followed.the asthma guidelines are followed.

ReferralReferral to a specialist is to a specialist is recommended ifrecommended if the goals of the goals of management are not achieved, or for following reasons:management are not achieved, or for following reasons:diagnosis in doubtdiagnosis in doubtunstable asthmaunstable asthmaparents or general practitioners need further supportparents or general practitioners need further supportchild on high dose ICS (>400 µg beclomethasone child on high dose ICS (>400 µg beclomethasone equivalent per day)equivalent per day)oral steroids are required regularlyoral steroids are required regularlyafter a life-threatening episodeafter a life-threatening episodefrequent hospitalizations or visits to an emergency frequent hospitalizations or visits to an emergency roomroom

http://www.pulmonology.co.za/guidelines/asthma%20paed.htm

Inhalational therapy remains the mainstay of Inhalational therapy remains the mainstay of treatment for asthma in children treatment for asthma in children (Preventers)(Preventers)

Medications can be safely and effectively Medications can be safely and effectively delivered to children at any age via MDI + delivered to children at any age via MDI + spacerspacer

Patient instruction is a key component in Patient instruction is a key component in determining the device; that a patient can determining the device; that a patient can use correctly & in teaching the patient how use correctly & in teaching the patient how to properly use the deviceto properly use the device

Take Home PointsTake Home Points

Thank you for your time & Thank you for your time & attention!attention!

Inhalers in Pediatric Asthma

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