RES/006/APR16/AR. Speaker : Dr. Pither Sandy Tulak SpP

RES/006/APR16/AR Speaker : Dr. Pither Sandy Tulak SpP

Definition of Asthma (GINA 2015) Asthma is a common and potentially serious chronic disease that imposes a substantial burden on patients, their families and the community. It causes respiratory symptoms, limitation of activity, and flare-ups (attacks) that sometimes require urgent health care and may be fatal Asthma causes symptoms such as wheezing, shortness of breath, chest tightness, and cough that vary over time in their occurrence, frequency and intensity Definition of COPD (GOLD 2015) COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases Exacerbations and comorbidities contribute to the overall severity in individual patients

ACOS? Asthma-COPD overlap syndrome (ACOS) [a description] Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACOS is therefore identified by the features that it shares with both asthma and COPD. GINA Updated 2014; GOLD Updated 2014

Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK

Differential Diagnosis ASTHMA Onset early in life (often childhood) Symptoms vary from day to day Symptoms worse at night/early morning COPD Onset in mid-life Symptoms slowly progressive Long smoking history Allergy, rhinitis, and/or eczema also present Family history of asthma Adaptation from GOLD 2015

Spirometry Spirometric variable Asthma COPD ACOS Normal FEV 1 /FVC pre - or post - BD Compatible with asthma Not compatible with diagnosis (GOLD) Not compatible unless other evidence of chronic airflow limitation Post - BD FEV 1 /FVC <0.7 Indicates airflow limitation; may improve Required for diagnosis by GOLD criteria Usual in ACOS FEV 1 =80% predicted Compatible with asthma (good control, or interval between symptoms) C ompatible with GOLD category A or B if post - BD FEV 1 /FVC <0.7 Compatible with mild ACOS FEV 1 <80% predicted Compatible with asthma. A risk factor for exacerbations Indicates severity of airflow limitation and risk of exacerbations and mortality Indicates severity of airflow limitation and risk of exacerbations and mortality Post - BD increase in FEV 1 >12% and 200mL from baseline (reversible airflow limitation) Usual at some time in course of asthma; not always present Common in COPD and more likely when FEV 1 is low, but consider ACOS Common in ACOS, and more likely when FEV 1 is low Post - BD increase in FEV 1 >12% and 400mL from baseline High probability of asthma Unusual in COPD. Consider ACOS Compatible with diagnosis of ACOS GINA Updated 2015; GOLD Updated 2015 GINA Updated 2014

Acute Exacerbation Flare Up Asthma 2015 COPD 2015 A flare-up or exacerbation is an acute or subacute worsening of symptoms and lung function compared with the patient s usual status Terminology - Flare-up is the preferred term for discussion with patients - Exacerbation is a difficult term for patients - Attack has highly variable meanings for patients and clinicians - Episode does not convey clinical urgency Consider management of worsening asthma as a continuum - Self-management with a written asthma action plan - Management in primary care - Management in the emergency department and hospital - Follow-up after any exacerbation An exacerbation of COPD is: an acute event characterized by a worsening of the patient s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication. GINA Updated 2015; GOLD Updated 2015

ASTHMA

Managing Exacerbations in Acute Care Settings GINA Updated 2015 GINA Updated 2014 Global Initiative for Asthma

GINA Updated 2015 Managing Exacerbations in Acute Care Settings

Managing Exacerbations in Acute Care Settings GINA Updated 2015 GINA Updated 2014

Meta-analysis of the Effects of Ipratropium Bromide in Adults with Acute Asthma Effect sizes and 95% confidence intervals (CI) for 10 studies that compared inhaled Ipratropium Br added to SABA vs. SABA alone. N= number of subjects. Pooled effect size = 0.14 (95%, CI: 0.04 to 0.24, p= 0.008) Rodrigo G, et al. Meta-analysis of the Effects of Ipratropium Bromide in Adults with Acute Asthma. Am J Med. 1999;107:363 370. Global Initiative for Asthma

Efficacy of β 2 -adrenergic Agonists is Comparable 63,0 Fenoterol Salbutamol Salmeterol 61,0 59,0 57,0 55,0 53,0 51,0 49,0 47,0 45,0 1 2 3 4 5 6 7 8 9 Vollmer M, et al. Duration and Intensity of Bronchodilator Action of Salmeterol, Fenoterol, and Salbutamol in Severe Airways Obstruction. Penumologie. 1995;49:528 534. Global Initiative for Asthma

The Effect of Fenoterol, Ipratropium Br and Compound Drug Berodual on Clinical Symptoms and Functional Lung Parameters in Asthmatic Patients After 2 weeks therapy, all this drugs (Berodual, Berotec, Atrovent) statistically significantly reduce : - Dyspnoe - Cough - Sputum The best bronchodilating and protective effect were observed after Berodual compare with Berotec or Atrovent Rutkowski R, et al. The effect of fenoterol, Ipratropium bromide and compound drug Berodual on clinical symptoms and functional lung parameters in asthmatic patients,pneumonologia. 1994; 62(7-8): 358-364 Global Initiative for Asthma

A Single Dose of Nebulized Combivent Confers Additional Bronchodilatation Over Salbutamol Alone in Adults with Acute Asthma Garrett JE, Town GI, Rodwell P, Kelly AM. Nebulized Salbutamol with and without ipratropium bromide in the treatment of acute asthma, J Allergy Clin Immunol. 1997; 100(2): 165-170 Global Initiative for Asthma

Therapy Supplemental oxygen Inhaled SABA Systemic corticosteroids Initial Management of Asthma Exacerbations in Children 5 years Dose and administration 24% delivered by face mask (usually 1L/min) to maintain oxygen saturation 94-98% 2 6 puffs of salbutamol by spacer, or 2.5mg by nebulizer, every 20 min for first hour, then reassess severity. If symptoms persist or recur, give an additional 2-3 puffs per hour. Admit to hospital if >10 puffs required in 3-4 hours. Give initial dose of oral prednisolone (1-2mg/kg up to maximum of 20mg for children <2 years; 30 mg for 2-5 years) Additional options in the first hour of treatment Ipratropium bromide Magnesium sulfate For moderate/severe exacerbations, give 2 puffs of ipratropium bromide 80mcg (or 250mcg by nebulizer) every 20 minutes for one hour only Consider nebulized isotonic MgSO 4 (150mg) 3 doses in first hour for children 2 years with severe exacerbation GINA Updated 2015 GINA Updated 2014 Global Initiative for Asthma

Addition of Frequent Nebulized Ipratropium Br to Frequent High-Dose Albuterol in Severe Childhood Asthma is Safe and More Effective Very Severe Group Schuh S, et al. Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.the Journal of Pediatrics.1995;639-645. Global Initiative for Asthma

COPD

Consequences Of COPD Exacerbations Negative impact on quality of life Impact on symptoms and lung function Accelerated lung function decline EXACERBATIONS Increased economic costs Increased Mortality GOLD Updated 2015

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Assessments Arterial blood gas measurements (in hospital) : PaO 2 < 8.0 kpa with or without PaCO 2 > 6.7 kpa when breathing room air indicates respiratory failure. Chest radiographs: useful to exclude alternative diagnoses. ECG: may aid in the diagnosis of coexisting cardiac problems. Whole blood count: identify polycythemia, anemia or bleeding. Purulent sputum during an exacerbation: indication to begin empirical antibiotic treatment. Ambroxol Biochemical tests: detect electrolyte disturbances, diabetes, and poor nutrition. Spirometric tests: not recommended during an exacerbation. GINA Updated 2015 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Treatment Options Oxygen: titrate to improve the patient s hypoxemia with a target saturation of 88-92% Bronchodilators: Short-acting inhaled beta 2 -agonists with or without shortacting anticholinergics are preferred Atrovent Combivent UDV Berotec Systemic Corticosteroids: Shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay. A dose of 40 mg prednisone per day for 5 days is recommended GOLD Updated 2015

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Treatment Options Antibiotics should be given to patients with: Three cardinal symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence. Who require mechanical ventilation. GINA Updated 2015 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Treatment Options Noninvasive ventilation (NIV) for patients hospitalized for acute exacerbations of COPD: Improves respiratory acidosis, decreases respiratory rate, severity of dyspnea, complications and length of hospital stay. Decreases mortality and needs for intubation. GOLD Updated 2015 2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Exacerbations: Indications for Hospital Admission Marked increase in intensity of symptoms Severe underlying COPD Onset of new physical signs Failure of an exacerbation to respond to initial medical management Presence of serious comorbidities Frequent exacerbations Older age Insufficient home support GOLD Updated 2015 2014 Global Initiative for Chronic Obstructive Lung Disease

ASTHMA

Adaptation from GINA 2015 Stepwise Approach to Control Asthma Symptoms and Reduce Risk STEP 4 STEP 5 PREFERRED CONTROLLER CHOICE STEP 1 STEP 2 Low dose ICS STEP 3 Low dose ICS/LABA* Med/high ICS/LABA Refer for add-on treatment e.g. anti-ige Other controller options Consider low dose ICS Leukotriene receptor antagonists (LTRA) Low dose theophylline* Med/high dose ICS Low dose ICS+LTRA (or + theoph*) Add tiotropium# High dose ICS + LTRA (or + theoph*) Add tiotropium# Add low dose OCS RELIEVER As-needed short-acting beta 2 -agonist (SABA, misal Berotec) As-needed SABA or low dose ICS/formoterol** REMEMBER TO...

COPD

Risk (GOLD Classification of Airflow Limitation)) Risk (Exacerbation history) Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD 4 3 (C) (D) 2 or > 1 leading to hospital admission 2 (A) (B) 1 (not leading to hospital admission) 1 GOLD Updated 2015 CAT < 10 Symptoms CAT > 10 mmrc 0 1 mmrc > 2 Breathlessness 0

Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy (Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference.) Patient A B C RecommendedFir st choice SAMA prn or SABA prn LAMA or LABA ICS + LABA or LAMA Alternative choice Ipratropium (Atrovent) LAMA or LABA Fenoterol or (Berotec) SABA and SAMA LAMA and LABA Tiotropium (Spiriva) LAMA and LABA or LAMA and PDE4-inh. or LABA and PDE4-inh. Other Possible Treatments Theophylline SABA and/or SAMA Theophylline SABA and/or SAMA Theophylline D ICS + LABA and/or LAMA ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and LABA or LAMA and PDE4-inh. Carbocysteine SABA and/or SAMA Theophylline GOLD Updated 2015

Page 14 Fenoterol (Berotec) Ipratropium (Atrovent) Tiotropium (Spiriva) Berodual GOLD Updated 2015

Tiotropium exacerbation trials Tiotropium exacerbation trials Veterans Affairs 1 Tiotropium HandiHaler 18 µg N=1829, 6 months On standard therapy UPLIFT 2 Tiotropium HandiHaler 18 µg N=5993, 4 years On standard therapy POET-COPD 3 Tiotropium HandiHaler 18 µg Head-to-head versus salmeterol 50 µg N=7376, 1 year 205.372 4 Tiotropium Respimat 5 µg N=3991, 1 year Tiotropium is the only long-acting bronchodilator monotherapy to have a COPD exacerbation indication in its label 5-10 COPD, chronic obstructive pulmonary disease; POET-COPD : Prevention Of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease; UPLIFT, Understanding Potential Long-term Impacts on Function with Tiotropium. 1 Niewoehner DE, et al. Ann intern Med. 2005,143;317-326; 2 Tashkin DP, et al. N Engl J Med. 2008;359:1543-1554; 3 Vogelmeier C, et al. N Engl J Med. 2011;364:1093-1103; 4 Bateman ED, et al. Respir Med. 2010;104:1460-1472; 5 SPIRIVA Handihaler Local Product Information 2012, 6 SPIRIVA Respimat Local Product Information 2011, 7 Seebri Product Information, 8 Symbicort Product Information, 9 Onbrez Product Information, 10 Seretide Product Information 11

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