7/7/2015. Somboon Chansakulporn, MD. History of variable respiratory symptoms. 1. Documented excessive variability in PFT ( 1 test)

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1 Definition of Asthma GINA 2010: Chronic inflammatory disorder of the airways Airway hyper-responsiveness Recurrent wheezing, breathlessness, chest tightness, coughing Variable, reversible airflow obstruction Somboon Chansakulporn, MD Division of Allergy and Immunology Department of Pediatrics Srinakarinwirot University GINA 2015: (add on definition) Heterogeneous disease Based on typical characteristic symptoms Emphasize of asthma phenotypes Asthma phenotype Phenotype Characteristics 1. Allergic asthma Common in children / associated with atopy in family Eosinophilic airway inflammation 2. Non-allergic asthma Usually in adults / not associated with allergy Neutrophilic, eosinophilic or paucigranulocytic AW inflammation Less well respond to corticosteroids 3. Late-onset asthma Adult onset / women / non-allergic asthma characteristics Refractory to corticosteroids 4. Asthma with fixed airflow limitation Long-standing asthma fixed airflow limitation Airway remodeling 5. Asthma with obesity Obese asthmatic patients / prominent respiratory symptoms Little eosinophilic airway inflammation Making diagnosis of Asthma History of variable respiratory symptoms Typical asthma symptoms > 1 symptoms (wheeze, SOB, cough, chest tightness) Worse at night / in the morning Vary over time and in intensity Several particular triggers: viral infection, exercise, allergens, weather changes, laughing, common irritants (pollutions, smoke, strong smells) May not have asthma Isolated cough Chronic production of sputum SOB associated with dizziness, light-headedness or paresthesia Chest pain Exercise-induced dyspnea with noisy inspiration Making diagnosis of Asthma Confirmed variable expiratory airflow limitation 1. Documented excessive variability in PFT ( 1 test) Positive bronchodilator reversibility test Excessive variability in PEF over 2 weeks Significant increase in PFT after treatment Positive exercise challenge test Positive bronchial challenge test Excessive variation in PFT between visits 2. Documented airflow limitation (at least once) GINA GINA (updated) (Updated) Confirmed variable expiratory airflow limitation (1) Documented airflow limitation (before treatment, at least once) Spirometry (with reversibility test) Low FEV 1 reduced FEV 1 / FVC (children > 0.9, adults > ) 1

2 Confirmed variable expiratory airflow limitation (2) Documented excessive variability in PFT ( 1 test) Positive BD reversibility test (should withheld SABA 4 hr, LABA 15 hr) Children: FEV 1 > 12% predicted Adults: FEV 1 > 12% predicted and 200 ml from baseline Excessive variability in twice-daily PEF over 2 wk Average daily diurnal PEF variability; Children > 10%, Adults > 13% day s highest day s lowest x 100 mean of day s highest and lowest Significant increase PFT after 4 wk of anti-inflammatory treatment Confirmed variable expiratory airflow limitation (3) Other tests to confirm airflow limitation Positive bronchial challenge test FEV 1 20% from baseline (methocholine or histamine test) FEV 1 15% from baseline (hyperventilation, hypertonic saline or mannitol challenge) Positive exercise challenge test Children: FEV 1 > 12% predicted, or PEF > 15% Adults: FEV 1 > 10% predicted and 200 ml from baseline Excessive variation in PFT between visits (without respiratory infection) Other tests in Asthma assessment Sputum eosinophils Assess 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 smoking Not use in diagnosis, may be useful in monitoring asthma control Allergy tests Inexpensive, high sensitivity, not exclude non-allergic asthma Positive skin test / spf IgE does not mean that the allergen is causing symptoms (should correlate with history of symptoms) Diagnosis of Asthma in patients on controllers Need confirming Depends on the patient s symptom and PFT Current status Steps to confirm the diagnosis of asthma Resp. symptoms Airflow limitation Variable Variable Confirmed / Assess asthma control / Review treatment Variable Few Persistent SOB No No Fixed Repeat reversibility test, if normal: FEV 1 > 70% pred bronchial provocation test (Negative step down, reassess in 2-4 wk) FEV 1 < 70% pred step up, reassess in 3 mo Repeat reversibility test, if normal step down Worsen symptoms & PFT confirmed, step up No change of symptoms & PFT off, reassess Step up, reassess symptoms & PFT in 3 mo: No change resume treatment and refer Improvement consider ACOS Step 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. 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 yr 2

3 How to diagnosis of asthma in 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 Asthma symptom control tools for adults and adolescents Simple screening tools: The consensus-based Royal College of Physicians (RCP) Three Questions tool The 30-second Asthma Test 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) Level of Asthma Control (GINA 2010) Level of Asthma Control (GINA 2015) A. Assessment of current clinical control (preferably over 4 weeks) Characteristic Controlled (All of the following) Partly Controlled (1-2 measure present) Daytime symptoms None ( 2 /week) > 2 /week Nocturnal symptoms/awakening None Any Need for reliever/ rescue treatment None ( 2 /week) > 2 /week Limitations of activities None Any Lung functions (PEF or FEV 1 ) Normal < 80% predicted or personal best B. Assess future risks (risk of exacerbation, instability, rapid decline in lung function, side-effects) effects) Uncontrolled 3-4 features of partly controlled asthma GINA 2010 A. Asthma symptom control (in the past 4 weeks) Symptoms questions Well controlled Partly controlled Uncontrolled Daytime asthma symptoms > 2 /week Any night waking due to asthma Need for reliever > 2 /week Limitations of activities due to asthma None of these 1-2 of these 3-4 of these B. Risk factors of poor asthma outcomes Assess at diagnosis & periodically PFT (FEV 1 ) at start of and after treatment 3 6 mo and periodically Assess 3 groups of risk factors potentially independent risk factors for exacerbations risk factors for developing fixed airflow limitation risk factors for medication side effectseffects Independent risk factors for exacerbations 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 FEV 1, esp if <60% predicted Major psychological or socioeconomic problems Exposures (smoking, allergens) Comorbidities (obesity, rhinosinusitis, food allergy) Sputum or blood eosinophilia Pregnancy Major risk factors Ever intubated or in intensive care unit for asthma 1 severe exacerbation in last 12 months Risk factors for developing fixed airflow limitation Lack of ICS treatment Exposures: tobacco smoke, noxious chemicals, occupational exposures Low initial FEV 1, chronic mucus hypersecretion, sputum or blood eosinophilia 3

4 Risk factors for medication side effects effects Systemic Local frequent OCS long-term, high dose and/or potent ICS also taking P450 inhibitors high-dose or potent ICS poor inhaler technique How to assess asthma severity in clinical practice 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 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 Stepwise approach to control symptoms and minimize future risk Recommended initial controller for asthma Presenting symptoms Well controlled + no risk factors + no exacerbation last year Infrequent asthma symptoms + 1 risk factors for exacerbations Partly controlled Partly controlled + risk factors Severely uncontrolled ± acute exacerbation Preferred initial controller No controller Low dose ICS Low dose ICS or alternative Medium/high dose ICS or Low dose ICS/LABA Short course of oral CS AND High-dose ICS, or Moderate-dose ICS/LABA Stepping down treatment (once well 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). Stepping down treatment 4

5 Definition : ACOS Asthma chronic airway inflammation defined by the history of typical respiratory symptoms with variable expiratory airflow limitation COPD persistent airflow limitation, usually progressive associated with enhanced chronic inflammatory responses to noxious particles or gases (smoking) Asthma-COPD overlap syndrome (ACOS) persistent airflow limitation several shared features usually with both asthma and COPD no specific definition now, need more evidences Usual features of asthma, COPD and ACOS Feature Asthma COPD ACOS Age of onset Usually childhood Usually > 40 yr Usually > 40 yr Pattern of respir. symptoms Lung function Lung function between symptoms Vary over time, several triggers variable airflow limitation Chronic usually continuous Persist post-bd FEV1/FVC < 0 7 Persistent exertional dyspnea but variable Not fully reversible airflow limitation limitation FEV1/FVC < 0.7 airflow limitation May be normal Persistent airflow limitation Past history Atopy Smoking exposure both CXR Normal Severe hyperinflation and COPD changes AW inflammation Eo (± Neu) Neu (± Eo in sputum, Lymph in AW) Persistent airflow limitation Severe hyperinflation and COPD changes Eo (± Neu) in sputum Stepwise approach to diagnosis of patients with respiratory symptoms Clinical History Chronic or recurrent cough, sputum production, dyspnea, or wheezing; Previous Dx / Rx with inhaled medications, smoking tobacco / pollutants exposure Physical examination May be normal / hyperinflation / chronic lung disease Abnormal breath sound (wheeze and/or crackles) Radiology May be normal / hyperinflation / bullae / emphysema Other alternative diagnosis (bronchiectasis, TB, interstitial lung diseases or cardiac failure) Step 2: Syndromic diagnosis in adults Step 5: Refer for special investigations (if necessary) 3 features of both asthma or COPD Special investigations Asthma COPD DLCO Normal (or slightly elevated) Often reduced Arterial blood gas Normal Chronic abnormal HR CT Scan Normal or Air trapping & increased bronchial wall thickness Either air trapping or emphysematous change or pulmonary hypertension FENO A high level (>50 ppb) in non-smokers Normal 5

6 Wheezing in preschool children: Variety in medical-term use Asthmatic bronchitis Wheezing associated respiratory infection (WARI) Hyperreactive / Reactive airway disease Viral-induced wheezing All are the same meaning Wheezing 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 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): ) 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. (Bacharier LB, 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 ( 5 Yo): Time trend-based classification 1. Transient early wheezer begin & end before 3 yo associated with prematurity and parental smoking 2. Persistent early wheezer begin before 3 yo continue beyond 6 yo associated with acute viral respiratory infections (esp. Rhinovirus, RSV) no evidence of atopic background 3. Late-onset wheezer (asthma) begin after 3 yo continue to adulthood typically have atopic background. Taussig LM, Martinez FD et al. JACI. 2003;111: Preschool wheezing / phenotypes: Symptom based classification 1. Multiple-trigger trigger 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. Episodic (viral) wheeze Wheezing, mostly triggered by apparent viral respiratory infections Symptom-free between episodes. Brand PLP, et al. ERJ 2008; 32: Garcia-Marcos L and Martinez FD. JACI 2010;126: Asthma Phenotype ( 5 Yo): Trigger-based classification 1. Viral-induced asthma Symptom-free between episode Usually follow cold / viral URI 2. Exercise-induced asthma Symptom occurred only on exercise 3. Allergen-induced d asthma Positive SPT or Spf IgE Clinical relevant with allergen exposure 4. Multitrigger asthma Wheezing associated with multiple triggers 5. Unresolved asthma / wheezing Cannot identify specific triggers Features suggesting "Asthma" in children 5 years old 1. 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 breath Occurring with triggers 4. Reduced activity 5. 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 Papadopoulos NG, et al. Allergy 2012; 67: GINA 2015 (Update) 6

7 Diagnosis of asthma in young children Viral induced wheeze Likely to have asthma 1. Based on symptom patterns 2. Combined with a careful clinical assessment of family history and (May change over time) physical findings. Symptoms < 10 days during URI Symptom pattern Symptoms > 10 days during URI Symptoms > 10 days during URI Positive family history of allergic disorders d Presence of atopy or allergic sensitization 2 3 episodes/yr No symptoms between episodes >3 episodes/yr or Severe episodes and/or night worsening May have symptoms between episodes >3 episodes/yr or Severe episodes and/or night worsening Symptoms between episodes during play / laughing Increases the likelihood that a wheezing child will develop persistent asthma Atopy or FH of asthma Additional tests to diagnose asthma in children years old 1. Therapeutic trial of treatment Low-dose ICS + as needed SABA for 2-3 months then try to stop 2. Test of atopy Skin prick test / specific IgE Absence of atopy does not rule out a diagnosis of asthma!!! 3. 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 Modified Asthma Predictive Index (mapi mapi) > 3 wheeze episodes in past year that last > 24 hours Major ( 1) Minor ( 2) 1. Parental history of asthma 1. Wheezing unrelated to colds 2. Physician-diagnosed AD 2. Blood eosinophils 4% 3. Allergic sensitization to 1 aeroallergen PPV = 77% NPV = 90% 3. Allergic sensitization to milk, egg, or peanuts Guilbert TW et al. JACI 2004;114: Castro-Rodriguez JA et al. AJRCCM 2000;162: Asthma symptom control tools for children 6 11 years Numerical asthma control tools: Childhood Asthma Control Test (c-act) Asthma Control Questionnaire (ACQ) Asthma control scores: 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 Level of Asthma Control (GINA 2015) A. Asthma symptom control (in the past 4 weeks) Symptoms questions Well controlled Partly controlled Uncontrolled Daytime asthma symptoms > 1 /week Any night waking due to asthma Need for reliever > 1 /week Limitations of activities due to asthma None of these 1-2 of these 3-4 of these B. Future risk for poor asthma outcomes (3 groups) risk factors for asthma exacerbations risk factors for developing fixed airflow limitation risk factors for medication side effects effects 7

8 Future risks 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 Poor adherence or incorrect inhaler technique Risk factors for fixed airflow limitation Severe asthma with several hospitalizations History of bronchiolitis Risk factors for medication side-effects Systemic: Frequent courses of OCS; high-dose and/or potent ICS Local: incorrect inhaler technique; unprotect skin or eyes Long term management of asthma in children < 5 years Symptom asthma pattern + not well-controlled Infrequent Asthma + not wellcontrolled on low viral 3 exacerbations / yr wheezing / dose ICS Not symptom asthma pattern but frequent no interval wheezing give diagnostic trial (3 mo) symptoms not wellcontrolled on double ICS Choosing an inhaler device for children < 5 years Age (yr) Preferred device Alternate device pmdi plus spacer with face mask Nebulizer with face mask pmdi plus spacer with mouthpiece pmdi plus spacer with face mask or Nebulizer with mouthpiece or face mask Thank you for your attention 8