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Somboon Chansakulporn, MDDivision of Allergy and Immunology

Department of PediatricsSrinakarinwirot University

Definition of AsthmaDefinition of Asthma

GINA GINA 20102010: : Chronic inflammatory disorder of the airways Airway hyper-responsivenessRecurrent wheezing, breathlessness, chest tightness, coughingVariable reversible airflow obstructionVariable, reversible airflow obstruction

GINA GINA 20152015: (add on definition): (add on definition)Heterogeneous diseaseHeterogeneous diseaseBased on typical characteristic symptomsBased on typical characteristic symptomsEmphasize of asthma phenotypesEmphasize of asthma phenotypes

Asthma phenotypeAsthma phenotype

Phenotype Characteristics1. Allergic asthma Common in children / associated with atopy in family

Eosinophilic airway inflammation

2. Non-allergic asthma Usually in adults / not associated with allergyNeutrophilic, eosinophilic or paucigranulocytic AW inflammationLess well respond to corticosteroids

3. Late-onset asthma Adult onset / women / non-allergic asthma characteristicsRefractory to corticosteroids

4. Asthma with fixed airflow limitation

Long-standing asthma → fixed airflow limitationAirway remodeling

5. Asthma with obesity Obese asthmatic patients / prominent respiratory symptomsLittle eosinophilic airway inflammation

GINA 2015 (update)

Making diagnosis of AsthmaMaking diagnosis of Asthma

Typical asthma symptoms> 1 symptoms (wheeze, SOB,

h h t ti ht )

May not have asthmaIsolated cough

History of variable respiratory symptoms

cough, chest tightness)Worse at night / in the morningVary over time and in intensitySeveral particular triggers: viral infection, exercise, allergens, weather changes, laughing, common irritants (pollutions, smoke, strong smells)

Chronic production of sputumSOB associated with dizziness, light-headedness or paresthesiaChest painExercise-induced dyspnea with noisy inspiration

GINA 2015 (update)

Making diagnosis of AsthmaMaking diagnosis of Asthma

Confirmed variable expiratory airflow Confirmed variable expiratory airflow limitationlimitation1. Documented excessive variability in PFT (≥ 1 test)

Positive bronchodilator reversibility testPositive bronchodilator reversibility testExcessive Excessive variability in PEF over variability in PEF over 2 2 weeksweeksExcessive Excessive variability in PEF over variability in PEF over 2 2 weeksweeksSignificant increase in Significant increase in PFT after treatmentPFT after treatmentPositive exercise challenge Positive exercise challenge testtestPositive bronchial challenge Positive bronchial challenge testtestExcessive variation Excessive variation in PFT between visitsin PFT between visits

2. Documented airflow limitation (at least once)

GINA 2015 (Updated)GINA 2015 (updated)

Confirmed variable expiratory airflow Confirmed variable expiratory airflow limitation (limitation (11))

Documented airflow limitation Documented airflow limitation (before treatment, at (before treatment, at least least once)once)

SpirometrySpirometry

GINA 2015 (update)

SpirometrySpirometry(with reversibility test)(with reversibility test)

• Low FEV1

• reduced FEV1 / FVC (children > 0.9, adults >0.75-0.8)

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Confirmed variable expiratory airflow Confirmed variable expiratory airflow limitation limitation ((22))Documented excessive variability in PFT (≥ 1 test)

•• Positive BD reversibility test (should withheld SABA ≥ Positive BD reversibility test (should withheld SABA ≥ 4 4 hr, LABA ≥ hr, LABA ≥ 15 15 hr)hr)•• Children: Children: ↑↑ FEVFEV1 1 > > 1212% predicted% predicted

↑↑•• Adults: Adults: ↑↑ FEVFEV1 1 > > 1212% predicted and % predicted and 200 200 mLmL from baselinefrom baseline

•• Excessive variability in twiceExcessive variability in twice--daily PEF over daily PEF over 2 2 wkwk•• Average daily diurnal PEF variability; Children > Average daily diurnal PEF variability; Children > 1010%, Adults > %, Adults > 1313%%•• day’s highest day’s highest –– day’s lowest x day’s lowest x 100100

mean of day’s highest and lowestmean of day’s highest and lowest

• Significant increase PFT after 4 wk of anti-inflammatory treatment

GINA 2015 (update)

Confirmed variable expiratory airflow Confirmed variable expiratory airflow limitation limitation ((33))Other tests to confirm airflow limitation• Positive bronchial challenge test

• ↓ FEV1 ≥ 20% from baseline (methocholine or histamine test)• ↓ FEV1 ≥ 15% from baseline (hyperventilation, hypertonic saline or mannitol

challenge)challenge)

• Positive exercise challenge test• Children: ↓ FEV1 > 12% predicted, or PEF > 15%• Adults: ↓ FEV1 > 10% predicted and 200 mL from baseline

• Excessive variation in PFT between visits (without respiratory infection)

GINA 2015 (update)

Other testsOther tests in Asthma assessmentin Asthma assessment

Sputum eosinophilsAssess airway inflammation (normal < 4%)Difficult to perform in practice

Fractional concentration of exhaled nitric oxide (FENO)Increased in eosinophilic asthma, non-asthma conditions (eosinophilic bronchitis, atopy, AR)Decreased in smokingNot use in diagnosis, may be useful in monitoring asthma control

Allergy testsInexpensive, high sensitivity, not exclude non-allergic asthmaPositive skin test / spf IgE does not mean that the allergen is causing symptoms (should correlate with history of symptoms)

GINA 2015 (update) GINA 2015 (update)

Diagnosis of Asthma in patients on controllersDiagnosis of Asthma in patients on controllers

Need confirmingDepends on the patient’s symptom and PFT

Current statusSteps to confirm the diagnosis of asthma

Resp. symptoms Airflow limitation

Variable Variable Confirmed / Assess asthma control / Review treatment

Variable No

Repeat reversibility test, if normal:• FEV1 > 70% pred → bronchial provocation test

(Negative → step down, reassess in 2-4 wk)• FEV1 < 70% pred → step up, reassess in 3 mo

Few NoRepeat reversibility test, if normal → step down• Worsen symptoms & PFT → confirmed, step up• No change of symptoms & PFT → off, reassess

Persistent SOB FixedStep up, reassess symptoms & PFT in 3 mo:• No change → resume treatment and refer• Improvement → consider ACOS

Step down strategy to diagnosis of  AsthmaStep down strategy to diagnosis of  Asthma

1. Assess• Current asthma control & PFT• Appropriate status to step down: no future risks, suitable time

(no infection, not travel, not pregnant)

2 Adjust2. Adjust• Reduce ICS 25-50% or stop extra controllers

3. Review response• Reassess asthma control & PFT in 2-4 wk• Worsen symptoms & PFT → confirmed asthma, step up• No change of symptoms &PFT → stop controllers, reassess in

2-3 wk, F/U for 1 yrGINA 2015 (update)

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How to diagnosis of asthma How to diagnosis of asthma in low resource settingsin low resource settings

Use symptom-based of syndromic approached instead.

Variable airflow limitation → use PEF meter

Therapeutic trials

As-needed SABA + regular ICS

1 week course of oral corticosteroids

GINA 2015 (update)

Asthma symptom control tools Asthma symptom control tools for for adults and adolescentsadults and adolescents

Simple screening tools:The consensus-based ‘Royal College of Physicians (RCP) Three Questions’ toolThe 30-second Asthma Test

Categorical symptom control tools:Categorical symptom control tools:The consensus-based GINA symptom control tool

Numerical ‘asthma control’ tools:Asthma Control Questionnaire (ACQ) (0-6)Asthma Control Test (ACT) (5-25)

GINA 2015 (update)

Level of Asthma Control (GINA Level of Asthma Control (GINA 20102010))

A. Assessment of current clinical control (preferably over 4 weeks)

CharacteristicControlled

(All of the following)Partly Controlled

(1-2 measure present) Uncontrolled

Daytime symptoms None (≤ 2 /week) > 2 /weekNocturnal symptoms/awakening None Any

3-4 features of partly controlled

asthma

y p g

Need for reliever/rescue treatment None (≤ 2 /week) > 2 /week

Limitations of activities None Any

Lung functions (PEF or FEV1)

Normal < 80% predicted or personal best

B. AssessB. Assess future risksfuture risks(risk of exacerbation, instability, rapid decline in lung function, side(risk of exacerbation, instability, rapid decline in lung function, side--effects)effects)

GINA 2010

Level of Asthma Control (GINA Level of Asthma Control (GINA 20152015))

A. Asthma symptom control (in the past 4 weeks)

Symptoms’ questions Well controlled Partly controlled UncontrolledDaytime asthma symptoms > 2 /week

None of these 1-2 of these 3-4 of theseAny night waking due to asthmaNeed for reliever > 2 /weekNeed for reliever > 2 /weekLimitations of activities due to asthma

B. RiskB. Risk factors of poor asthma outcomesfactors of poor asthma outcomes•• Assess at diagnosis & periodicallyAssess at diagnosis & periodically•• PFT (FEVPFT (FEV11) at start of and after treatment 3) at start of and after treatment 3‐‐6 6 momo and periodicallyand periodically•• Assess 3 groups of risk factorsAssess 3 groups of risk factors

•• potentially independent risk factors for exacerbationspotentially independent risk factors for exacerbations•• risk factors for developing fixed airflow limitationrisk factors for developing fixed airflow limitation•• risk factors for medication siderisk factors for medication side‐‐effectseffects

GINA 2015 (update)

Independent Independent risk factors for risk factors for exacerbationsexacerbations

Modifiable risk factors (≥ 1, even well controlled)• Uncontrolled asthma symptoms• High SABA use (esp if >1 canister/ month)• Inadequate ICS; poor adherence; incorrect inhaler technique• Low FEV1, esp if <60% predicted• Major psychological or socioeconomic problems• Exposures (smoking, allergens)• Comorbidities (obesity, rhinosinusitis, food allergy)• Sputum or blood eosinophilia• PregnancyMajor risk factors• Ever intubated or in intensive care unit for asthma• ≥ 1 severe exacerbation in last 12 months

GINA 2015 (update)

Risk factors for developing fixed airflow Risk factors for developing fixed airflow limitationlimitation

Lack of ICS treatment

Exposures: tobacco smoke, noxious chemicals, occupational

exposures

Low initial FEV chronic mucus hypersecretion sputum or blood Low initial FEV1, chronic mucus hypersecretion, sputum or blood

eosinophilia

GINA 2015 (update)

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Risk factors for medication sideRisk factors for medication side‐‐effectseffects

Systemic

frequent OCS

long-term, high dose and/or potent ICS

also taking P450 inhibitors

Local

high-dose or potent ICS

poor inhaler technique

GINA 2015 (update)

How to assess asthma severity How to assess asthma severity in in clinical clinical practicepractice

Asthma severity - not static / may change over time

Retrospectively assess when patients has been on controllers for several months

Assess form the level of treatment Assess form the level of treatment 1. Mild asthma = well controlled with Step 1 or Step 2 treatment 2. Moderate asthma = well controlled with Step 3 treatment 3. Severe asthma = requires Step 4 or 5 treatment to prevent it from

becoming ‘uncontrolled’

GINA 2015 (update)

Stepwise approach to control symptoms Stepwise approach to control symptoms and and minimize future riskminimize future risk

GINA 2015 (update)

Recommended Recommended initial controller for asthmainitial controller for asthma

Presenting symptoms Preferred initial controller

Well controlled + no risk factors + no exacerbation last year

No controller

Infrequent asthma symptoms + ≥ 1 risk factors for exacerbations

Low dose ICSrisk factors for exacerbationsPartly controlled Low dose ICS or alternative Partly controlled + risk factors Medium/high dose ICS or

Low dose ICS/LABASeverely uncontrolled ±acute exacerbation

Short course of oral CS AND• High-dose ICS , or• Moderate-dose ICS/LABA

GINA 2015 (update)

Stepping Stepping down treatment down treatment (once well(once well‐‐controlled asthma)controlled asthma)General principle in stepping down

Consider stepping down when well controlled + stable and normal PFT for ≥ 3 months (D). Well controlled + risk factors for exacerbations or fixed airflow limitation, may step down with close supervision.Choose an appropriate time (no respiratory infection, patient not travelling, not pregnant).Ensure patient has sufficient medication to resume previous treatment. Stepping down ICS doses by 25–50% at 3-month interval (B).

GINA 2015 (update)

Stepping Stepping down treatmentdown treatment

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Definition : ACOSDefinition : ACOS

AsthmaAsthmachronic chronic airway airway inflammationinflammationdefined by the history of typical respiratory defined by the history of typical respiratory symptoms symptoms with with variable expiratory airflow variable expiratory airflow limitationlimitation

COPD COPD persistent persistent airflow airflow limitation, usually progressive limitation, usually progressive associated associated with enhanced chronic inflammatory responses with enhanced chronic inflammatory responses to to noxious particles or gases (smoking)noxious particles or gases (smoking)

AsthmaAsthma--COPD overlap syndrome (ACOS) COPD overlap syndrome (ACOS) persistent persistent airflow limitation airflow limitation several shared features usually with both asthma and COPDseveral shared features usually with both asthma and COPDnno specific definition now, need more evidenceso specific definition now, need more evidences

Usual features of asthma, COPD and ACOSUsual features of asthma, COPD and ACOS

FeatureFeature AsthmaAsthma COPDCOPD ACOSACOSAge of onset Usually childhood Usually > 40 yr Usually > 40 yrPattern of respir.symptoms

Vary over time, several triggers

Chronic usually continuous

Persistent exertionaldyspnea but variable

Lung function variable airflow limitation

Persist post-BDFEV1/FVC < 0 7

Not fully reversible airflow limitationlimitation FEV1/FVC < 0.7 airflow limitation

Lung functionbetween symptoms

May be normal Persistent airflow limitation

Persistent airflow limitation

Past history Atopy Smoking exposure bothCXR Normal Severe

hyperinflation and COPD changes

Severe hyperinflation and COPD changes

AW inflammation Eo (± Neu) Neu (± Eo in sputum,Lymph in AW)

Eo (± Neu) in sputum

Stepwise approach to diagnosis  of Stepwise approach to diagnosis  of patients with respiratory  symptomspatients with respiratory  symptoms

Clinical HistoryClinical History•• Chronic Chronic or recurrent cough, sputum production, dyspnea, or wheezing; or recurrent cough, sputum production, dyspnea, or wheezing; •• Previous Previous DxDx / Rx / Rx with inhaled with inhaled medications, smoking tobacco / pollutants exposuremedications, smoking tobacco / pollutants exposurePhysical Physical examinationexamination•• May May be be normal / hyperinflation / chronic normal / hyperinflation / chronic lung disease lung disease •• Abnormal breath sound Abnormal breath sound (wheeze and/or crackles(wheeze and/or crackles))RadiologyRadiology•• May May be be normal / hyperinflation / bullae / emphysemanormal / hyperinflation / bullae / emphysema•• Other alternative diagnosis (bronchiectasisOther alternative diagnosis (bronchiectasis, , TB, interstitial TB, interstitial lung diseases or cardiac lung diseases or cardiac

failure)failure)

Step Step 22: : SyndromicSyndromicdiagnosis in adultsdiagnosis in adults

≥ ≥ 3 3 features features features features of both of both asthma asthma

or or COPDCOPD

Step Step 55: : Refer for special investigations Refer for special investigations ((if necessary)if necessary)

Special investigations Asthma COPD

DLCO Normal (or slightly elevated) Often reduced

Arterial blood gas Normal Chronic abnormal

HR CT Scan Normal orAir trapping & increased bronchial wall thickness

Either air trapping or emphysematous change or pulmonary hypertension

FENO A high level (>50 ppb) in non-smokers Normal

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Wheezing in preschool children: Wheezing in preschool children: Variety inVariety in medicalmedical--term useterm use

• Asthmatic bronchitis

• Wheezing associated respiratory infection (WARI)

• Hyperreactive / Reactive airway diseaseHyperreactive / Reactive airway disease

• Viral-induced wheezing

“ All are the same meaning”“ All are the same meaning”

Wheezing phenotypesWheezing phenotypes

1. Time trend-based classification• Data from the Tuscon’s birth cohort study

• Asthma and wheezing in the first six years of life. The Group Health Medical Associates. (Martinez FD, et al. N Engl J Med. 1995 Jan 19;332(3):133-8.)

2. Symptom-based classification• Based on frequency of wheezing

• Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. (Brand PL, et al. Eur Respir J. 2008;32(4):1096-110.)

3. Trigger-based classification• Based on the significant trigger which is associated with wheezing

• Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. (BacharierLB, et al. Allergy 2008;63:5–34)

• International consensus on (ICON) pediatric asthma. Papadopoulos NG, et al. Allergy 2012;67:976-97)

GINA 2015 (Updated)

Wheezing phenotypes (Wheezing phenotypes (≤≤5 5 YoYo): ): Time trendTime trend--based classification based classification

1.1. Transient early Transient early wheezerwheezerbegin & end before 3 yoassociated with prematurity and parental smoking

2.2. Persistent early Persistent early wheezerwheezerbegin before 3 yo → continue beyond 6 yo

i t d ith t i l i t i f tiassociated with acute viral respiratory infections(esp. Rhinovirus, RSV)no evidence of atopic background

3.3. LateLate--onset onset wheezerwheezer (asthma)(asthma)begin after 3 yo → continue to adulthoodtypically have atopic background

GINA 2015 (update).Taussig LM, Martinez FD et al. JACI. 2003;111:661-75.

Preschool wheezing / phenotypes:Preschool wheezing / phenotypes:SymptomSymptom‐‐based classificationbased classification

1.1. MultipleMultiple--trigger wheezetrigger wheeze• Wheezing, triggered by viral infections and other triggers

(allergens, exercise, or cigarette smoke)• show symptoms between episodes (during sleep or with

triggers; activity, laughing, crying)• Persistent wheezing

2.2. Episodic (viral) wheezeEpisodic (viral) wheeze• Wheezing, mostly triggered by apparent viral respiratory

infections• Symptom-free between episodes

GINA 2015 (update).Brand PLP, et al. ERJ 2008; 32: 1096–1110.

Garcia-Marcos L and Martinez FD. JACI 2010;126:489-90.

Asthma Phenotype (≤ Asthma Phenotype (≤ 5 5 YoYo):): TriggerTrigger--based classificationbased classification1. Viral-induced asthma

• Symptom-free between episode• Usually follow cold / viral URI

2. Exercise-induced asthma• Symptom occurred only on exercise

3 All i d d th3. Allergen-induced asthma• Positive SPT or Spf IgE• Clinical relevant with allergen exposure

Papadopoulos NG, et al. Allergy 2012; 67: 976–97.

4. Multitrigger asthma• Wheezing associated with multiple triggers

5. Unresolved asthma / wheezing• Cannot identify specific triggers

Features suggesting "Asthma"Features suggesting "Asthma" in children in children ≤≤ 5 5 years oldyears old1. Cough

• Recurrent / persistent non-productive, worse at night, ± wheeze / dyspnea• Occurring with triggers (exercise, laughing, crying, smoking) without URI

2. Wheezing• Recurrent, with or without triggers

3. Shortness of breath3. Shortness of breath• Occurring with triggers

4. Reduced activity5. Past / family history

• Other allergic diseases (AD, AR, Asthma in first degree)6. Response of therapeutic trial (low dose ICS + SABA)

• Clinical improvement during 2-3 months• Worsening when treatment is stopped

GINA 2015 (Update)

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(May change over time)

Viral –induced wheeze

Likely to have 

asthma

Symptoms < 10 days during URI

2‐3 episodes/yr

No symptoms between episodes

Symptoms > 10 days during URI

>3 episodes/yr orSevere episodes and/or night worsening

May have symptomsbetween episodes

Symptoms > 10 days during URI

>3 episodes/yr orSevere episodes and/or night worsening

Symptomsbetween episodes during play / laughing

Atopy or FH of asthma

Symptom pattern

Diagnosis Diagnosis of asthma in young children of asthma in young children 

1. Based on symptom patterns

2. Combined with a careful clinical assessment of family history and

physical findings.

P iti f il hi t f ll i di d • Positive family history of allergic disorders

• Presence of atopy or allergic sensitization

• Increases the likelihood that a wheezing child will develop persistent asthma

GINA 2015 (update)

Additional tests to diagnoseAdditional tests to diagnose asthma asthma in children in children ≤≤ years oldyears old1. Therapeutic trial of treatment

• Low-dose ICS + as needed SABA for 2-3 months then try to stop2. Test of atopy

• Skin prick test / specific IgE• Absence of atopy does not rule out a diagnosis of asthma !!!

3 Ch t X3. Chest X-ray• Only to exclude structural abnormalities, chronic infections, foreign body

aspiration• Just only in doubtful cases

4. Exhaled nitric oxide (FENO)• Elevated FENO > 4 weeks from any URI may predict asthma

5. Risk profiles tools• Positive API → have 4-10 times of developing asthma

GINA 2015 (update)

Modified Asthma Predictive Modified Asthma Predictive IIndex (ndex (mAPImAPI))

Major (≥ 1) Minor (≥ 2)1. Parental history of asthma 1. Wheezing unrelated to colds

> 3 wheeze episodes in past year that last > 24 hours

2. Physician-diagnosed AD 2. Blood eosinophils ≥ 4%

3. Allergic sensitization to ≥ 1 aeroallergen

3. Allergic sensitization to milk, egg, or peanuts

Guilbert TW et al. JACI 2004;114:1282-7.Castro-Rodriguez JA et al. AJRCCM 2000;162:1403-6.

PPV = 77%NPV = 90%

Asthma symptom control tools Asthma symptom control tools for children for children 66‐‐11 11 yearsyears

Numerical ‘asthma control’ tools:Childhood Asthma Control Test (c-ACT)Asthma Control Questionnaire (ACQ)

Asthma control scores:T f R i d A h C l i Kid (TRACK)Test for Respiratory and Asthma Control in Kids (TRACK)Composite Asthma Severity Index (CASI)

Categorical symptom control tools:The consensus-based GINA symptom control tool

GINA 2015 (update)

Level of Asthma Control (GINA Level of Asthma Control (GINA 20152015))

A. Asthma symptom control (in the past 4 weeks)

Symptoms’ questions Well controlled Partly controlled UncontrolledDaytime asthma symptoms > 1 /week

None of these 1-2 of these 3-4 of theseAny night waking due to asthmaNeed for reliever > 1 /weekNeed for reliever > 1 /weekLimitations of activities due to asthma

B. Future riskB. Future risk for poor asthma outcomes (3 groups)for poor asthma outcomes (3 groups)•• risk factors for asthma exacerbationsrisk factors for asthma exacerbations•• risk factors for developing fixed airflow limitationrisk factors for developing fixed airflow limitation•• risk factors for medication siderisk factors for medication side‐‐effectseffects

GINA 2015 (update)

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Future Future risks risks for poor asthma outcomes for poor asthma outcomes 

Risk factors for asthma exacerbations• Uncontrolled asthma symptoms• ≥ 1 severe exacerbation in previous year• The beginning of usual ‘flare-up’ season• Exposures to smoking / pollution / allergens ± viral infection• Major psychological or socio-economic problems• Major psychological or socio-economic problems• Poor adherence or incorrect inhaler techniqueRisk factors for fixed airflow limitation• Severe asthma with several hospitalizations• History of bronchiolitisRisk factors for medication side-effects• Systemic: Frequent courses of OCS; high-dose and/or potent ICS• Local: incorrect inhaler technique; unprotect skin or eyes

GINA 2015 (update)

LongLong‐‐term term management of asthma management of asthma in in children children < < 5 5 yearsyears

Infrequent viral

wheezing / no interval symptoms

Symptom asthma pattern + not well-controlled

≥ 3 exacerbations / yr

Not symptom asthma pattern but frequent wheezing → give diagnostic trial (3 mo)

Asthma + not well-controlled on low dose ICS

not well-controlled on double

ICS

GINA 2015 (update)

Choosing an inhaler device Choosing an inhaler device for for children children < < 5 5 years years 

Age (yr) Preferred device Alternate device

0-3

pMDI plus spacer with face mask Nebulizer with face mask

4-5

pMDI plus spacer with mouthpiece pMDI plus spacer with face mask orNebulizer with mouthpiece or face mask

GINA 2015 (update)

Thank you for your attention