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: Stepped therapy: start high, back down 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 Methylxanthines 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: Mild persistent: symptoms < 2X/wk nights<2/month Mild persistent: > 2X/wk but < 1/day Nights > 2/month

(cont.) Moderate: SEVERE: Daily symptoms Nights > 1/week Continual symptoms Frequent nighttime symptoms

Rules of 2 Sx > 2/week PM sx > 2 nights/month > 2 rescue MDIs/year

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 vs. COPD Sensitizing agent ↓ Inflammation CD4 T-lymphocytes Eosinophils Completely reversible airflow limitation 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 >70% > 80% + Symptoms I >70% > 80% + Symptoms I < 70% ≥ 80% ± Symptoms II ≥ 50% but < 80% ± Sx III ≥ 30% but < 50% ± Sx IV < 30% or < 50% + chronic respiratory failure

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 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 Lung volume reduction surgery 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/