3 Asthma and COPD Management
- 1. Asthma Exacerbations • It is an asthma episode characterized by progressive increase in symptoms and progressive decline in lung functions sufficient to require a change in treatment. • Occasionally occurs as the 1st presentation of asthma. • Usually occurs in response to exposure to an external agent (viral infection, allergen) or poor adherence to controller treatment. • Exacerbations may be poorly perceived by persons in whom respiratory function declines out of proportion to symptoms. • Management may be started by the patient (self management) until hospital care, if needed, is provided.
- 2. Asthma Exacerbation Self Management Inhaled SABA • Repeated dosing with inhaled SABA provides temporarily relief until the cause of worsening symptoms passes or increased controller treatment had time to make effect. ICS • Higher ICS may help prevent worsening asthma progressing to a severe exacerbation. • High dose ICS for 7 – 14 days have an equal effect to a short course of OCS. Combined ICS + Rapid Onset LABA (Formeterol) Inhaler • Used as both controller and reliever. • If used during early stage of worsening asthma, it may prevent exacerbation.
- 3. OCS • For most patients, the written asthma action plan should provide instructions for when and how to start OCS. • Indications: o Failed response to ↑ controller and reliever medications for 2 – 3 days. o Rapid deterioration of symptoms. o FEV1 or PEF < 60% of predicted or personal best. o History of sudden severe exacerbation. o Previous exacerbation requiring OCS. • Dose: Prednisone or equivalent, once daily in the morning o Adults: 40 – 50 mg / day for 5 – 7 days. o Children 1 – 2 mg/kg/day (up to 40 mg) for 3 – 5 days.
- 4. Asthma Exacerbation Hospital Management Oxygen • By nasal cannula or mask to achieve SO2 93 – 95% Inhaled SABA • The most cost effective and efficient delivery system is by pMDI with a spacer. Nebulizer may be used in the critically ill. Adrenaline SC or IM may be used only for treatment of asthma associated with anaphylaxis or angioedema. OCS should be used in all but the mildest exacerbations in adults; should be given within 1 hour of presentation. IV route may be used in case of vomiting or severe dyspnoea eg, Hydrocortisobe 100 – 200 mg / 6 – 8 h Ipratropium inhaled with other bronchodilators (Ventolin + Atrovent + Pulmicort)
- 5. Magnesium Sulphate 2 gm IV infusion over 20 mins. It may be used in patients with persistent hypoxemia who fail to respond to initial treatment. Antibiotics Not recommended unless there is strong evidence of infection. Do NOT Give: Methylxanthines • Poor efficacy, high toxicity. • IV aminophylline is associated with severe and potentially fatal SE, particularly in patients already treated with sustained release theophylline. Sedatives / Narcotics should be strictly avoided as they cause respiratory depression. Patients should not be seadted in order to receive ventilation.
- 6. Management of Aspirin Exacerbated Respiratory Disease In addition to guideline based management of asthma and sinus disease: NSAID Avoidance Alternatives are selected according to their potential to cross react with aspirin (and cause the same problem). This potential is based on the degree of COX1 inhibition. Leukotriene Receptor Antagonists (LTRAs) • Should be part of any treatment course of AERD to deal with the actual dysregulation of leukotriene production and safeguard patients from severe reaction to accidental NSAID exposure. • If patients do not improve after using LTRAs for 4 – 6 days, Zileuton (5 lipoxygenase inhibitor) may be added. This drug was recognized by AERD patients as “very effective” more frequently than LTRAs, but it requires periodic monitoring of liver functions.
- 7. Group Potential of Cross Reaction with Aspirin Examples Non-selective COX1/COX2 Inhibitors At time of 1st administration, with low dose Diclofenac, ketoprofen, indomethacin Poor Inhibitors of COX1, COX2 Occasional, with high dose Paracetamol Relatively COX2 Selective With high dose, mild reaction Meloxicam (Mobic) COX 2 Selective Should not cross react (no controlled trial) Celecoxib (Celebrex), Etoricoxib (Arcoxia) Non-Cox Inhibitors No potential to cross react Tramadol
- 8. Aspirin Desensitization • Almost all AERD patients can be effectively desensitized to aspirin. • Effects on rhinosinusitis are usually more dramatic than on BA. • Indications: o Nasal polyposis that recurs or becomes worse after surgery despite LTMAs and nasal steroids. o Inflammatory disease requiring daily NSAIDs, eg, RA. o Compelling indications for aspirin as CVD, recurrent headache. • Aspirin is given daily for 1 month, eg, 650 mg twice daily, then dose is reduced gradually. • Patient specific optimal doses are not predictable. Biologic Agents Omalizumab 4 – 8 doses given in line with dosing recommendations for BA (according to serum IgE level and body weight) → substantial reduction in total endoscopic nasal polyposis score. Mepolizumab 2 IV doses, 4 weeks apart also significantly ↓ nasal polyposis score.
- 9. Sympathomimetics used as Bronchodilators Catecholamines Non-Catecholamines Adrenaline amp 1 mg Adrenaline (Epinephrine) Isoprenaline amp 0.2 mg Isuprel / Isoprenol Short Acting Salbutamol inhaler, syp, tab, cap Ventolin / Vental i soln Farcolin Terbutaline syp, tab, cap Bricanyl / Aironyl Bambuterol syp, tab Bambec Fenoterol inhaler, syp, tab Berotec Long Acting Salmeterol inhaler Serevent / Metrovent Formeterol inhaler, i cap Foradil / Metrohaler Indacaterol i cap Onbrez
- 10. Muscarinic Antagonists Short Acting (6 h) Long Acting (24 h) Ipratropium inhaler, vial for nebulizer Atrovent Tiotropium i cap Spiriva Methylxanthines Aminophylline amp 500 mg Aminophylline Theophylline cap 100, 200, 300 mg Theo SR tab 300 mg Quibron supp 100, 300 mg Amriphylline syp 100 mg/5mL Amriphylline Inhaled Steroids Budesonide i vial 0.25, 0.5 mg (2) Pulmicort Beclomethasone inhaler Beclosone
- 11. • Inhaled steroids are the most effective anti- inflammatory medications for treatment of asthma. • Most of the clinical benefit from ICS is seen at low doses. • Add on therapy with another controller (eg, LABA) is preferred over increasing the dose of ICS. • However, some patients with severe asthma may benefit from long term treatment with higher doses of ICS.
- 12. Combinations LABA + ICS SABA + SAMA SABA + Expectorant Formeterol + Budesonide Symbicort Turbohaler Salmeterol + Fluticasone Seretide Diskus Salbutamol + Ipratropium Combivent Inhaler Salbutamol + Guaiphenesin Ventolin Expectorant Salbutamol + Ammonium Chloride Farcolin
- 13. Mast Cell Stabilizers Leukotriene Antagonists Moonoclonal Antibodies Ketotifen tab 1mg, syp 1 mg/5mL Zaditen / Prophallerge Montelukast tab 4, 5 mg (Ped), sachet 4 mg, tab 10 mg Singulair Zafirlukast tab 20 mg Ventair Omalizumab vial 150 mg Xolair Mepolizumab
- 14. Leukotriene Modifying Agents (LTMAs) Leukotriene Receptor Antagonists (LTRAs) 5 Lipo-oxygenase Inhibitors (Zileuton) • Cysteinyl leukotrienes (CyLts) are 1000 times more potent than histamine in causing airway obstruction and their effect lasts longer. • LTRAs are particularly useful in o EIB: If given 2 hours before exercise, they ↓ FEV1 decline after exercise. o AERD. o To improve asthma control not completely achieved with steroids and also as steroid sparing drugs. Since LTRAs are given systemically, they suppress the airway inflammation beyond the reach of inhaled steroids. Side effects are not significantly different from placebo. Commonest SE: headache, GIT upset
- 15. Montelukast Zafirlukast Effect of Food on Bioavailability ---------- ↓ Drug Interactions ---------- ↑ Plasma level of warfarin Use in Hepatic Impairment No dose adjustment unless severe Not recommended
- 16. Omalizumab - Indications: • Severe persistent allergic asthma with elevated serum IgE (confirmed IgE dependent allergic asthma). • Chronic idiopathic urticaria which remains symptomaic despite treatment with antihistaminics. - Not Indicated for: • Other forms of urticaria or other allergic conditions. • Acute bronchospasm or status asthmaticus. - Mechanism of Action: • ↓ IgE receptors (Fc receptors) on surface of mast cells, basophis. • ↓ Binding of IgE to its receptors on these cells. • ↓ Serum free IgE.
- 17. - Problems: • Expensive. • Requires regular injection and observation after each injection. • Boxed Warning: Anaphylaxis, presenting as bronchospasm, hypotension, syncope, angioedema of throat or tongue occurred after administration. It has occurred after the 1st dose and also beyond one year after start of treatment. Patient should be closely observed after injection with available facilities to manage anaphylaxis which can be life threatening. - Reconstitution of Lyophilized Vial: • The powder takes 15 – 20 mins to dissolve. • The solution is viscous and slightly opalescent. • It should be used within: o 4 h (room temp). o 8 h (2 - 8 O C). • Administration should be slow and forceful enough.
- 18. - Dose: 75 – 375 mg SC every 2 – 4 weeks. - Dose and dosing frequency are determined according to body weight and serum IgE level measured before start of treatment. - IgE levels remain elevated for up to 1 year after discontinuation of treatment, so, retesting during treatment can not be used as a guide for dose. - Follow Up: • The main outcome measure is frequency and severity of asthma attacks and exacerbations. • If the patient does not respond within 4 months of starting treatment, it is unlikely that further administration will be beneficial.
- 19. - Adverse Reactions: - Anaphylaxis which may be life threatening. - Serum sickness: fever, arthralgia, rash. - Eosinophilc conditions: eosinophilia, vasculitic rash, worsening pulmonary symptoms. - Commonest reactions: arthralgia, pain, fatigue, dizziness, headache. - Injection site reactions: redness, warmth, burning sensation. These generally ↓ at subsequent doses. - Malignancy: was observed in clinical studies.
- 20. Management of COPD 2017 Report
- 21. Diagnosis Spirometry Chest X-ray: Seldom diagnostic but valuable to exclude alternative diagnoses and establish presence of significant comorbidities. Diffusing Capacity: to characterize severity. Arterial Blood Gases: in advanced cases. Alpha-1 Antitrypsin Level: required when: • COPD develops under 45. • COPD develops in non- smoker. • Strong family history of COPD. N: > 150 mg/dL . In disease: < 45 mg/dL
- 23. Risk Reduction Reduction of exposures in the workplace. Reduce indoor air pollution eg, from heating in poorly ventilated home. Smoking cessation has the greatest capacity to improve the natural history of COPD.
- 24. Pharmacologic Treatment of COPD Beta Agonists • Inhaled bronchodilators (mainly long acting, LABDs) should be given on a regular basis to ↓ resting and dynamic hyperinflation and prevent or reduce symptoms. • Use of SABDs on regular basis is not generally recommended, except for patients with only occasional dyspnoea. • LABA use does not preclude additional benefit from as needed SABA. • SE of Beta Agonists (tend to ↓ over time: tachyphylaxis) o Sinus tachycardia → palpitations. o ↑ myocardial oxygen consumption They may precipitate myocardial ischemia and decompensation, particulary in presence of pre-existing coronary heart disease. o Tremors (exaggerating the senile tremor). o Hypokalemia (may be intentionally used to treat hyperkalaemia).
- 25. Muscarinic Antagonists • They have a small advantage over beta agonists (contrary to the situation in BA). (Why? Better response and more favorable adverse effect profile noting the hazards of beta agonists in middle aged and elderly people with pre- existing heart disease). • SAMA are better than SABA for immediate relief. • LAMA are better than LABA for reduction of exacerbation rate. • Side Effects o Dryness of mouth (main SE). o Difficult micturition (particularly in presence of prostatic enlargement). o ↑ Intra-ocular pressure → may precipitate acute angle closure glaucoma if given by face mask due to direct contact with the eye.
- 26. Methylxanthines • Not recommended unless other LABDs are unavailable. • Mechanism of Benefit controversial: o Non- selective inhibition of phosphodiesterase → ↑ cAMP which mediates bronchodilatation. o Improved respiratory muscle function (? 1ry or 2ry to ↓ hyperinflation). o Respiratory stimulant. o Mild diuretic. Adverse Effects: dose related Therapeutic window is narrow. Most of the benefit occurs near the toxic doses. - Tachyarrhythmias: atrial tachycardia or fibrillation, ventricular tachycrdia or fibrillation (last 2 rapidly fatal) - Tremors, convulsions: even grand mal convulsions irrespective of prior epileptic history. - Insomnia, headache. - Nausea, vomiting, heart burn.
- 27. Inhaled Steroids Other Drugs Mucolytics: Only in patients with viscid sputum; overall benefits are very small. Antitussives: Not recommended. Macrolide Antibiotics: Decrease exacerbation rate, possibly due to both antibacterial and immune-modulating action. Combinations of Bronchodilators • Combination of SABA/SAMA is superior to either medication alone. • Combination of LABA/LAMA ↓ exacerbation rate to a greater extent than LABA/ICS. Long term monotherapy with ICS is generally not recommended, but it may be considered in association with LABA for patients with a history of exacerbation despite appropriate treatment with LABA.
- 28. Alpha-1 antitrypsin augmentation (replacement) therapy: • The only specific therapy for 1 antitrypsin deficiency. • Prepared from pooled plasma of healthy donors. • Given as weekly IV infusion (60 mg/Kg). • Not well tolerated (fever, chills, flu like symptoms. • Very expensive.
- 29. Non-Pharmacologic Treatment of COPD Oxygen Therapy Assisted Ventilation Surgery • Intermittent domiciliary oxygen ↑ survival in patients with severe resting hypoxemia. • It aims to keep SaO2 > 90%. • Caution: may ↑ CO2 due to reduction of ventilatory drive caused by hpoxemia. Bullectomy and Lung volume reduction surgery
- 30. COPD Exacerbations • Exacerbations are acute episodes of worsening symptoms and airway obstruction that require additional therapy. • Exacerbation contribute to disease progression, especially if recovery from exacerbation is slow. • Frequent exacerbations: having > 2 exacerbations/year. The best predictor for having frequent exacerbations is the number of previous exacerbations. • Grades: o Mild: treated with SABA, SAMA only (SABDs). o Moderate: Treated with SABDs + antibiotics and/or OCS. o Severe: requires hospital care.
- 31. • DD: comorbid events as acute coronary syndrome, and worsening heart failure. • Management: o ↑ Dose and/or frequency of SABDs. o Combine SABAs and SAMAs. o Consider LABDs when the pt becomes stable. o Use spacers or nebulizers as needed. o OCS (eg, Prednisone 40 mg once daily) may be used for no more than 5 – 7 days. o Antibiotics may be used if signs of bacterial infection are present (sputum ↑ in amount and purulence). Methyxanthines are not recommended due to ↑ risk profile. o O2 Therapy: targeting SaO2 88 – 92%.
- 32. COPD and Comorbidities • Lung Cancer is frequently seen in COPD and is a main cause of death. • Hypertension is the most frequently occurring comorbidity with COPD. There is no evidence that hypertension should be treated differently in presence of COPD, apart from avoidance of non- cardioselective beta blockers. • Obstructive Sleep Apnoea → overlap syndrome → more severe and more prolonged sleep time hypoxia and hypercapnoea → worse prognosis.
- 33. Cardiovascular Disease with COPD COPD Exacerbation Heart Failure Atrial Fibrillation CVD is commonly associated with COPD. Any one of these conditions can be a cause or a consequence of the other. Any can cause worsening dyspnoea.
- 34. • Although all beta agonists and muscarinic antagonists may potentially precipitate AF or make rate control difficult, it seems that the risk is significant only with SABA. • Theophylline should not be used in COPD exacerbations as it may precipitate AF and make control of ventricular rate difficult. • Treatment with beta blockers improves survival in heart failure. However, beta blockers are often not prescribed in COPD patients despite available evidence showing that their use in COPD is safe. • Selective beta 1 (cardioselective) agents should be preferred. Beta Blockers Non-Cardioselective Cardioselective (Beta 1) Propranolol amp 1 mg, tab 10, 40 mg Inderal Atenolol tab 50, 100 mg Tenormin Metoprolol tab 50, 100 mg Blokium Bisoprolol tab 2.5, 5, 10 mg Concor α, β Blocker Carvedilol tab 6.25, 25 mg Dilatrend