Therapies for Acute Asthma Dr K Sathiamoorthy Consultant Paediatrician Shree Sakthi Hospital

Asthma is More Prevalent n Asthma is the most common disease of childhood n Affects 9% of kids (groups 15-20%) n 10 million missed days of school n 570,000 ED visits (1995, < 15 year olds)

Is Asthma More Severe? n Hospitalization rates  till mid 90’s n Death- rates for all ages –2.1/1,000,000 kids < 5 years –3.7/1,000,000 kids 5-14 years n Intubation rates –  in mid 80’s - 90’s ( of hospital admits for children with asthma

Asthma Death n Half at home n Some unpredictable n Risk factors –poor compliance, hx severe disease, poverty –Late presentation

Established Therapies for Asthma Exacerbation n Oxygen n Steroids n Beta agonists n Anticholinergics

Steroids for an “Inflammatory” Disease n Systemic steroids for all hospitalized pts n Equally effective IV vs PO n Some effect in several hrs, peak 9-12 hrs n Recommended dose is 1 mg/kg per dose q 4-6 hours of prednisone or IV Hydrocortisone

Mechanism of Action n Multiple effects: Am J Resp Crit Care 1996; 154: S21-27, Barnes n  production of: interleukins, TNF alpha, GMCSF n  breakdown of IL-2 n  iNO synthase, cyclo-oxygenase, phospholipase A 2 n  protease inhibitors, β -2 receptors n  cellular immune function & mucus formation

Steroid Therapy n t 1/2 of prednisone 2-4 hours n Regimens 3- 5 days - stop w/o taper n Inhaled budesonide (1600 μgm/day) for 21 days after admit  relapse (JAMA 1999; 281: , by Rowe et al)

Beta agonists n Most used and effective bronchodilators n actives adenyl cyclase  cAMP n cAMP activates protein kinase leading to smooth muscle relaxation n Available PO, inhaled, SC and IV

Inhaled β agonists n Greater bronchial dilatation  systemic effects n All dosed to effect n When to give continuous not crystal clear n Continuous cheaper, associated with faster improvement &  LOS

Delivery of Inhaled Medication n Affected by particle size & shape, pt breathing factors and airway caliber n particle size (1-5 μm ideal) n Jet nebulizers - (average particle μm) (1-5% inhaled) n MDI’s - powder and a liquid propellant (15 m/sec) (7-14 % inhaled)

MDI vs Nebs n ED & hospital asthma- MDI’s-  cost and same to slightly  LOS (Arch Dis Child 1999; 80: , Dewar et al) n MDI’s hard to give continuously n If intubated MDI’s have better drug delivery (3-4% with 6.5 ETT vs < 1% neb)

Continuous Salbutamol n Recommended doses 1-5 mg/kg/hr n Toxicity- hypokalemia, agitation, tremulousness, tachycardia, ventricular dysrhythmias, hypoxia n dosed to effect n IV Terbutaline alternative

Anticholinergics n Ipatropium- quarternary amino acid blocks cholinergic bronchoconstriction n About 10% improvement in PEF over B2 agonist alone n Three repeat doses in ED-  admission and  PEF. Schuh et al (250 μgm/dose, J Pediatr 1995; 126: ) n dosed q 6 hours after admission

Other Therapies n Theophylline n Magnesium sulfate n Heliox

Theophylline n Still recommended as a second line agent for asthma n Mechanism of action: nonselective III and IV PDE inhibitor-  cAMP & cGMP n immunomodulatory, anti-inflammatory and bronchoprotective effects n toxicity can be unpredictable

Theophylline for Status Asthmaticus n Yung and South (Arch Dis Child 1998; 79: ) studies 163 kids n 0/81 Aminophylline patients intubated compared to 5/82 n 2/3’s had nausea and vomiting

Magnesium Sulfate n Decreases free Ca ++ - smooth muscle relaxation, may stabilize Mast cells and  histamine release n No definitive studies n Bloch et al (Chest 1995; 107: ) –67 adults 2 gm MgSO 4 –subset of severe  FEV 1 (< 25%) had  admission rates

Magnesium Sulfate n Paediatric dose mg/kg over 20 minutes n Target serum level mg/dL n ?dose response relationship is present n May or may not work- but nontoxic

Heliox n ?Established therapies n Post extubation stridor RCT Kemper et al (Crit Care Med 1991; 19: 356-9) n Heliox improves delivery of nebulized meds. Anderson et al (Am Rev Respir Dis 1993; 147: )

Mechanical Ventilation n Indications - profound hypoxemia, life- threatening respiratory muscle fatigue or altered mental status

Mechanical Ventilation n Historically associated with increased risk of death. n Problematic- patients have severe airway obstruction and develop air trapping, pneumothorax & bronchopleural fistula. n Limits delivery of inhaled meds.

Severity of Asthma Exacerbation

Management Mild-Moderate Asthma Exacerbation n PEF > 50% Oxygen sats > 90%, repeated inhaled  -2 agonist, systemic steroids n Reassess PEF 50-80%, treat 1-3 hrs n If PEF > 70% 1 hr after tx- Discharge –with written plan –course of steroids –close medical follow –education

Management Moderate Asthma Exacerbation n PEF < 50% n Oxygen sats > 90%, repeated inhaled β - 2 agonist & anti-cholinergics, systemic steroids n Reassess PEF 50-70%, Admit ward n Oxygen sats > 90%, repeated inhaled β - 2 agonist q 1-3 hours & inhaled anti-cholinergics, systemic steroids

Management of Severe Asthma Exacerbation n PEF < 50% Oxygen sats > 90%, repeated inhaled  ß-2 agonist & anti-cholinergics, systemic steroids n Reassess PEF < 50% admit PICU Oxygen sats > 90%, continuous inhaled  ß-2 agonist & inhaled anti- cholinergics, systemic steroids

Near or Impending Respiratory Failure n Oxygen > 90% (goal) n IV steroids n Continuous ß-2 agonist inhaled n Repeated anti-cholinergics inhaled n Move to ICU for intubation

My Treatment for Severe Asthma n IV Hydrocortisone(4mg/kg/dose q6) n Salbutamol (5-10mg) X three + ipatroprium 500mcg n Move to PICU if life threatening n Continuous salbutamol nebs. n If not improving, consider IV salbutamol/Aminiphyline

My Treatment for Severe Asthma n If still clinically in marked distress n Blood gases worsening n Try MgSO 4 n If intubating expect problems

My Treatment for Severe Asthma n Intubate with Sedation +paralysis n Sedative infusion n Handbag pt to determine initial rate and pressure limits n Allow spontaneous ventilation n Volume support or pressure support mode

Thank you

2008 Guidelines 2.4 DIAGNOSIS IN ADULTS (1) - based on the recognition of a characteristic pattern of symptoms and signs and the absence of an alternative explanation for them - the key is to take a careful clinical history - if asthma is a likely diagnosis, the history should explore possible causes, particularly occupational - even in relatively clear-cut cases, to try to obtain objective support for the diagnosis

2008 Guidelines 2.4 DIAGNOSIS IN ADULTS (2) - whether or not this should happen before starting treatment depends on the certainty of the initial diagnosis and the severity of presenting symptoms - repeated assessment and measurement may be necessary before confirmatory evidence is acquired.

2008 Guidelines 2.4 DIAGNOSIS IN ADULTS (3) n Confirmation hinges on demonstration of airflow obstruction varying over short periods of time n Spirometry is preferable to measurement of peak expiratory flow because it allows clearer identification of airflow obstruction, and the results are less dependent on effort

2008 Guidelines 2.4 DIAGNOSIS IN ADULTS (4) n Spirometry should be the preferred test where available (training is required to obtain reliable recordings and to interpret the results) n A normal spirogram (or PEF) obtained when the patient is not symptomatic does not exclude the diagnosis of asthma.

2008 Guidelines With airflow obstruction n COPD n Bronchiectasis* n Inhaled foreign body* n Obliterative bronchiolitis n Large airway stenosis n Lung cancer* n Sarcoidosis* n *may also be associated with non-obstructive spirometry Differential diagnosis of asthma in adults, according to the presence or absence of airflow obstruction (FEV1/FVC <0.7) Without airflow obstruction Chronic cough syndromes Hyperventilation syndrome Vocal cord dysfunction Rhinitis Gastro-oesophageal reflux Cardiac failure Pulmonary fibrosis

39 ADULT with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Low Probability Intermediate Probability Yes No Obstructive FEV/FVC <70% Manage according to alternative diagnosis Response? Investigate and treat alternative diagnosis Yes Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx No Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Normal FEV/FVC >70% Reconsider probable diagnosis Further investigation

40 High Probability Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) 1)Symptoms (cough, wheeze, SOB or chest tightness): worse at night and in the morning in response to exercise, allergen exposure and cold air after taking aspirin or beta blockers 2) History of atopic disease 3) Family history of asthma or atopic disease 4) Widespread wheeze 5) Evidence of airway narrowing (NB Normal spirometry when free of symptoms does not exclude asthma)

41 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx Yes

42 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx Yes No Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral

43 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Low probability equals: 1)Cough in the absence of wheeze or breathlessness 2)Prominent dizziness, light headedness, peripheral tingling 3)Repeatedly normal clinical examination even when symptomatic 4)No evidence of airway narrowing when symptomatic 5)Voice disturbance 6)Symptoms with colds only 7)Chronic productive cough 8)Significant smoking history (>20 pack years) 9)Cardiac disease Low Probability

44 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Low Probability Manage according to alternative diagnosis Investigate and treat alternative diagnosis Response? Yes

45 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Low Probability Manage according to alternative diagnosis Response? Investigate and treat alternative diagnosis Yes Reconsider probable diagnosis Further investigation No

46 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Low Probability Manage according to alternative diagnosis Response? Investigate and treat alternative diagnosis Yes Reconsider probable diagnosis Further investigation No Intermediate Probability Obstructive FEV/FVC <70% Normal FEV/FVC >70%

47 Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Low Probability Manage according to alternative diagnosis Response? Investigate and treat alternative diagnosis Yes Reconsider probable diagnosis Further investigation No Intermediate Probability Obstructive FEV/FVC <70% Normal FEV/FVC >70% Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral

48 Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx YesNo Assess compliance and inhaler technique. Reconsider the diagnosis Consider further tests or referral Patient with symptoms that may be due to asthma Clinical History and examination Spirometry (or PEF if spirometry not available) High Probability Low Probability Manage according to alternative diagnosis Response? Investigate and treat alternative diagnosis YesNo Intermediate Probability Obstructive FEV/FVC <70% Normal FEV/FVC >70% Reconsider probable diagnosis Further investigation

© Imperial College LondonPage 49 Assessment: Royal College of Physicians of London three questions Outcomes and audit. Thorax 2003; 58 (Suppl I): i1-i92 Applies to all patients with asthma aged 16 and over. Only use after diagnosis has been established. IN THE LAST WEEK / MONTH YES NO “Have you had difficulty sleeping because of your asthma symptoms (including cough)?” “Have you had your usual asthma symptoms during the day (cough, wheeze, chest tightness or breathlessness)?” “Has your asthma interfered with your usual activities (e.g. housework, work, school, etc)?” Date / / /

1.In the past 4 weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home? 2.During the past 4 weeks, how often have you had shortness of breath? 3.During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night, or earlier than usual in the morning? 4.During the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as salbutamol)? 5.How would you rate your asthma control during the past 4 weeks? Score Patient Total Score Copyright 2002, QualityMetric Incorporated. Asthma Control Test Is a Trademark of QualityMetric Incorporated. Asthma Control Test™ (ACT)

Adults

2008 Guidelines 2.1 DIAGNOSIS IN CHILDREN (1) Asthma in children causes recurrent respiratory symptoms of: n wheezing n cough n difficulty breathing n chest tightness

2008 Guidelines 2.1 DIAGNOSIS IN CHILDREN (2) Clinical features that increase the probability of asthma n More than one of the following symptoms: wheeze, cough, difficulty breathing, chest tightness, particularly if these symptoms: –are frequent and recurrent –are worse at night and in the early morning –occur in response to, or are worse after, exercise or other triggers, such as exposure to pets, cold or damp air, or with emotions or laughter –occur apart from colds n Personal history of atopic disorder n Family history of atopic disorder and/or asthma n Widespread wheeze heard on auscultation n History of improvement in symptoms or lung function in response to adequate therapy

2008 Guidelines 2.4 DIAGNOSIS IN CHILDREN (3) Clinical features that lower the probability of asthma n Symptoms with colds only, with no interval symptoms n Isolated cough in the absence of wheeze or difficulty breathing n History of moist cough n Prominent dizziness, light-headedness, peripheral tingling n Repeatedly normal physical examination of chest when symptomatic n Normal PEF or spirometry when symptomatic n No response to a trial of asthma therapy n Clinical features pointing to alternative diagnosis

61 CHILD with symptoms that may be due to asthma Clinical assessment High Probability Low Probability Intermediate Probability Yes No Continue Rx Response? Consider referral Yes Trial of Treatment Response? Asthma diagnosis confirmed Continue Rx and find minimum effective dose No Assess compliance and inhaler technique. Consider further investigation and/or referral Consider tests of lung function and atopy Investigate/treat other condition Further investigation Consider referral

Children age 5-12 yrs

Children Less than 5 yrs