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Management of Asthma and COPD W.S. Krell M.D. Wayne State University NIH Statement (1992, ‘97) Chronic inflammatory disorder multiple cellular components, mediators recurrent wheeze, shortness of breath, chest tightness, cough (pm & early am) reversible airflow obstruction secondary: hyperresponsiveness Sub-basement membrane fibrosis Treating Asthma Medications: – long term or controller medications – quick relief medications Stepped therapy: start high, back down Asthma monitoring and action plans Environmental controls Overview of Medications Controller medications – control inflammation – long duration bronchodilation – multiple medications Quick relief medications – for intermittent or breakthrough symptoms Controller Agents Inhaled corticosteroids Systemic corticosteroids Long acting 2 agonists Cromolyn and derivatives Methylxanthines Leukotriene Modifiers Inhaled Corticosteroids Control airway inflammation locally Ideal: control asthma (high local potency); no side effects (low systemic effects) fluticasone, budesonide **** beclomethasone * (triamcinolone, flunisolide) Systemic Corticosteroids May be needed initially Side effect profile well known Step down therapy Alternatives: high dose inhaled corticosteroids; methotrexate; other immunosuppressive drugs; Omalizumab Omalizumab (Xolair) Recomb. DNA derived IgG - selectively binds human IgE Indication: mod. to severe persistent asthma not controlled w/inhaled CS IgE > 30, RAST A or skin tests + Given SQ/ mo. or biweekly Dose based on wt. and IgE level Long acting ß2 Agonists Salmeterol Formoterol Prolonged duration Potentiate steroid effects? Should we be using them???????? Leukotriene Modifiers Anti-inflammatory Precursor step affected Compliance may be better than MDIs Few side effects Other Controllers Cromolyn derivatives – Safe, effective – Less predictable, frequent dosing Methylxanthines – Mechanism not fully understood – Therapeutic/Toxic ratio high – Multiple drug interactions Quick Relief Medications ß2 Agonists Systemic corticosteroids Exacerbation of Asthma History: Sudden (exposure) vs gradual worsening vs viral infection vs non-compliance Tachypnea, tachycardia Accessory muscles Wheezing, prolonged expiration, silent Speaking ability compromised ABGs - Asthma Respiratory alkalosis Normal PCO2 is worrisome Rising PCO2 is near respiratory failure Note: O2 doesn’t fall until late so pulse oximetry is not very sensitive Emergency Management Nebulized albuterol x 3 Monitor exam, peak flows, ABGs If no improvement, start IV corticosteroids and admit DOSE?? (30 to 180 mg/day) Asthma: CXR not likely helpful Further Mgt of Asthma Continue bronchodilators Q 6 hour steroids Hydration Mucomyst may exacerbate If failing: consider anticholinergics, theophylline, single isomer β2, Mg2+ Impending Respiratory Failure Respiratory acidosis Decreasing mental status Asthma: PCO2 above 40 or rising despite therapy Outpatient Asthma Management Classify by severity Step up and down number of medications based on symptoms and peak flows Severity of Asthma Mild Intermittant: – symptoms < 2X/wk – nights<2/month Mild persistent: – > 2X/wk but < 1/day – Nights > 2/month (cont.) Moderate: – Daily symptoms – Nights > 1/week SEVERE: – Continual symptoms – Frequent nighttime symptoms Rules of 2 2/week PM sx > 2 nights/month > 2 rescue MDIs/year Sx > Stepped Therapy Inhaled beta agonist Inhaled corticosteroid Long acting beta agonist Leukotriene modifiers (Cromolyn derivatives) (Theophyllines) Systemic corticosteroids Patient Education Avoid triggers Home monitoring Proper inhaler techniques Spacers “Asthma Action Plan” Compliance? Few patients continue to document Always give them Action Plans Simple in office questionnaire – validated in testing – Snap shot of asthma control Asthma Sensitizing agent ↓ Inflammation CD4 T-lymphocytes Eosinophils ↓ Completely reversible airflow limitation vs. COPD Noxious agent ↓ Inflammation CD8 T-lymphocytes Macrophages, PMNs ↓ Irreversible airflow limitation Treating COPD Step up Long acting Anticholinergics Long acting beta agonists Short acting bronchodilators (steroids: inhaled and oral) Soon: Cilomalist? Exacerbation of COPD Viral or secondary bacterial infection Non-compliance Cor pulmonale Tachypnea, tachycardia Rhonchi, wheezes, prolonged expiration Signs of right heart failure, pulmonary hypertension Causes Infections (bacterial) Environmental (↑ pollution) Unknown in 1/3 Management Increase bronchodilators Systemic steroids (PO if possible) (A) – Shortens recovery time – Quicker return to baseline function – ↓ risk of early exacerbation – 10 day to 2 week course Antibiotics (B) Additional Management: COPD Nebulized anticholinergics, β agonists Antibiotics Steroids Manage other complications: pneumonia, pneumothorax, right heart failure Oxygen to keep saturation near 90% ABGs - COPD Pay more attention to pH, bicarb PCO2 elevations more significant when acute Expect increased (A-a)DO2 Hypoxia must be treated, despite fears of hypercarbia Impending Respiratory Failure Non Invasive Ventilation – Bi-level Positive Pressure – Increase inspiratory P to ↓ pCO2 – Start expiratory P at 5-6 cm H2O and ↑ if needed for oxygenation – Evidence A for success Management of COPD Smoking cessation Spirometry Yearly influenza vaccine Pneumovax Antibiotics for exacerbations Monitor rest and exercise oxygenation Spirometry is KEY FEV1 FEV1/FVC Ratio Screen based on exposure and symptoms Follow at least yearly Patients should KNOW THEIR NUMBERS Spirograms Classification STAGE FEV1/FVC FEV1 0 >70% > 80% + Symptoms I < 70% ≥ 80% ± Symptoms II < 70% ≥ 50% but < 80% ± Sx III < 70% ≥ 30% but < 50% ± Sx < 70% < 30% or < 50% + chronic respiratory failure IV Management: All Stages Avoidance of noxious exposures – SMOKING CESSATION (Evidence: A) – Avoid occupational/environmental exposures (Evidence: B) Vaccination – Influenza – Pneumovax Smoking Cessation Strategies Repeated counseling Nicotine replacement agents Buproprion, anxiolytics This is the ONLY measure available proven to halt the decline in lung function Evidence: A COPD Outpatient SHORT ACTING BETA AGONISTS ANTICHOLINERGICS **** – Ipatropium – Tiotropium LONG ACTING BETA AGONISTS Theophyllines Inhaled corticosteroids Management: Stage I Short acting bronchodilator used PRN Albuterol: beta 2 agonist Ipatropium: M3 anticholinergic blocker Both are effective Albuterol has faster onset of action Combination is additive for bronchodilation Evidence: A Management: Stage II Long acting bronchodilators – Long acting beta agonists – Long acting anticholinergic Short acting bronchodilators PRN Education Inhaled corticosteroids if frequent exacerbations Evidence: A Long Acting Beta Agonists Formoterol – Onset comparable to short acting agents – Duration: 12 hours Salmeterol – Slower onset – Duration: 12 hours – Cautions re: use without inhaled steroids applies to asthmatics not COPD patients Tiotropium Duration: 24 hours Blocks M1 and M3 receptors Stop ipatropium (M3 only) Few side effects (some caution with BPH) Sustained improvement in FEV1 What about Theophylline? Old drug, proven useful If chosen, careful monitoring required – High toxic to therapeutic ratio – Multiple drug and food interactions Aim for levels 8 – 12 mcg/mL Cilomalist Orally active PDE4 inhibitor cAMP (inflam, bronchial reactivity) Positives – Improved FEV1, reduced sx (SGRQ) Negatives – Significant GI toxicity – Study done prior to release of tiotropium Rennard, CHEST 2006 Inhaled Corticosteroids If indicated, choose long acting agents Fluticasone – Combination drug with salmeterol Budesonide – Also available for use in nebulizer More is better??? Combinations can produce benefits Long acting agents are ALL expensive Optimal combinations not known Management: Stage III One or More Long acting Bronchodilators Short acting bronchodilators PRN Inhaled corticosteroids if frequent exacerbations Pulmonary Rehabilitation Evidence: A Management: Stage IV Long acting bronchodilators Short acting bronchodilators PRN Inhaled corticosteroids Education Evaluate need for oxygen therapy Nighttime non-invasive ventilation? Consider surgical options Surgical Options Lung transplantation – Upper age limit: 60 years – Consider for younger patients without serious co-morbidities – Few last long enough to get transplanted Lung volume reduction surgery – Consider if no serious co-morbidities – Improves diaphragmatic function Resources NIH Asthma Guidelines: www.nhlbi.gov/guidelines/asthma/ Global Initiative for chronic obstructive lung disease: www.goldcopd.com Resource for asthma action plans, info: www.cine-med.com/asthma/