Current Strategies for Asthma and COPD Talmadge E. King, Jr., M.D. Krevins Distinguished Professor of Medicine Chair, Department of Medicine University of California San Francisco (UCSF) San Francisco, CA ASTHMA Asthma 3 A chronic inflammatory disease of the airways; Chronic inflammation leads to hyperresponsiveness to stimuli; Variable and reversible airflow obstruction. 1
Asthma A common chronic diseases worldwide ~ 300 million persons are affected worldwide. ~14.9 million persons in the US Dramatic increases in the prevalence of atopy and asthma in Westernized countries and more recently in less developed nations. Responsible for about 500,000 hospitalizations, 5,000 deaths, and 134 million days of restricted activity a year Asthma Optimal management of asthma (we are better!) improves quality of life decreases the pool of those at risk for death saves healthcare costs in emergency care Diagnosis of Asthma: 3 Steps 1. Obtain a history of episodic symptoms of airflow obstruction 2. Demonstrate that airflow obstruction is at least partially reversible 3. Exclude alternative diagnoses = particularly COPD and vocal cord obstruction in adults, and aspiration and cystic fibrosis in children. Alternative Diagnoses COPD Vocal cord dysfunction CHF Pulmonary embolism Drug induced cough Pulmonary infiltration with eosinophilia Obstructive sleep apnea Mechanical obstruction e.g. benign or malignant tumor 2
Clues to Diagnosis Recurrent episodes of wheezing Troublesome cough at night Cough or wheeze after exercise Cough, wheeze or chest tightness after exposure to airborne dust, allergens Colds that go to the chest or take more than 10 days to clear Spirometry Establishes the Diagnosis By demonstrating obstruction: FEV 1 < 80% predicted FEV 1 /FVC < 65% predicted or below the lower limit of normal By demonstrating reversibility: FEV 1 increases >12% and at least 200 ml Measurement of Peak Flow When spirometry is normal but patients still have symptoms, follow up with peak flow monitoring for 1 2 weeks upon arising and in the afternoon before and after inhaled bronchodilator. Difference of 20% between high and low readings on same day suggests asthma. Asthma Guidelines 4 Essential Components 1. Assessment & monitoring 2. Patient education 3. Control of factors contributing to asthma severity 4. Pharmacologic treatment National Asthma Education and Prevention Program: Expert panel Report 3 3
Asthma Guidelines Stepwise approach to managing Rx expanded to 6 steps with repositioned medications Emphasis on patient education/partnership education at all points of care More attention to control of environmental factors or comorbid conditions multifaceted approaches consideration of SQ immunotherapy in persistent asthma benefit from treating comorbid conditions Asthma Care: 4 Essential Components 1 Assessment & Monitoring Assessment & Monitoring Assess asthma severity to initiate Rx (based on current impairment) Assess asthma control to monitor and adjust Rx (based on the risk of future negative events) Stepwise approach Schedule follow up care assess control medication technique written action plan adherence at each visit Severity vs. Control SEVERITY = intrinsic intensity of the disease process Emphasized for initiating therapy CONTROL = degree of success of Rx Emphasized for monitoring and adjusting therapy Eur Respir J. 2008 Sep;32:545-54 4
Assessment of Impairment Key elements of impairment: Patient s recall of symptoms Nighttime awakenings Physical activity (esp. interference with normal activity) Need for rescue medications in the preceding 2 to 4 weeks (Short acting beta 2 agonist use) Frequency and severity of exacerbations Quality of life Current pulmonary function Assessment of Impairment Patient centric, validated tools to evaluate the current asthma control include: Asthma Therapy Assessment Questionnaire (ATAQ) Asthma Control Questionnaire (ACQ) Asthma Control Test (ACT) Aidan A. Long, MD: www.peerviewpress.com/d/p131 Components of Severity Determine Severity When Initiating Therapy INTERMITTENT PERSISTENT Mild Moderate Severe Symptoms <2 days/week >2 days/week Daily All day Nighttime awakenings Short acting beta 2 agonist use Interference with normal activity <2 days/month 3 4 x/month >1/week <2 Up to 7x/ week Several times a <2 days/week >2 days/week Daily day None Minor Some Extreme Determine Severity When Initiating Therapy Components of Severity INTERMITTENT PERSISTENT Mild Moderate Severe Symptoms <2 days/week >2 days/week Daily All day Nighttime awakenings Short acting beta 2 agonist use Interference with normal activity <2 days/month 3 4 x/month >1/week Up to 7x/ week <2 days/week >2 days/week Daily Several times a day None Minor Some Extreme Lung Function FEV 1 normal FEV 1 > 80% FEV 1 60 80% FEV 1 <60% Lung Function FEV 1 normal FEV 1 > 80% FEV 1 60 80% FEV 1 <60% 5
Assessment of Risk Classification of Asthma Severity: Based on Risk Exacerbations requiring use of oral steroids Intermittent 0 1/yr Persistent Mild Moderate Severe >2/yr Less severe, Longer interval >2/yr >2/yr More severe, shorter interval Aidan A. Long, MD: www.peerviewpress.com/d/p131 6 Steps of Asthma Management Initial Treatment: Based on Classification of Severity Step 1 6
6 Steps of Asthma Management Persistent Asthma Step 2 6 Steps of Asthma Management Persistent Asthma Step 3 Aidan A. Long, MD: www.peerviewpress.com/d/p131 Aidan A. Long, MD: www.peerviewpress.com/d/p131 6 Steps of Asthma Management Persistent Asthma Step 4 6 Steps of Asthma Management Persistent Asthma Step 5 Aidan A. Long, MD: www.peerviewpress.com/d/p131 Aidan A. Long, MD: www.peerviewpress.com/d/p131 7
6 Steps of Asthma Management 6 Steps of Asthma Management Persistent Asthma Step 6 Steps in ICS Dosages Low Medium High Vanceril 84 mcg/puff 2 6 puffs 6 10 puffs > 10 puffs Pulmicort DPI 1 2 inhalations 2 3 >3 200 mcg/ inhalation Flovent 110 mcg/puff 2 puffs 2 6 puffs > 6 puffs Aerobid 250 mcg/puff 2 4 puffs 4 8 puffs > 8 puffs Mometasone DPI 1 inhalation 2 3 200 mcg/inhalation Once treatment is established, the emphasis is on assessing asthma control to determine if the goals for therapy have been met and if adjustments in therapy (step up or step down) would be appropriate. 8
After Initial Classification of Severity, Determine Level of Control Well Controlled Control Not well controlled Very Poorly controlled Symptoms <2 days/wk >2 days/wk All day The Asthma Control Test Interference with daily activities SOB Worse Better 5 5 Nighttime Awakenings Interference with normal activity <2/mo 1 3x/wk >4/wk None Some Extreme SABA use <2 days/wk >2 days/wk Several/day FEV 1 or peak flow >80% best 60 80% best <60% best ACT questionnaire >20 16 19 <15 Nighttime awakening SABA inhaler use Overall rating 5 5 5 25 Adjust Treatment based on Control Step Oral steroids? Follow up Well Controlled Control Not well controlled Maintain, Consider step Step up by 1 step down if well for at least 3 months No Regular, Q 1 6 mos No Reevaluate In 2 6 wks Very Poorly controlled Step up by 1 2 steps Consider short course Reevaluate In 2 weeks Before Step up of Therapy Review adherence Inhaler technique Environmental control Co morbid conditions 9
Asthma Care: 4 Essential Components 2 Patient Education Patient Education/Partnership Self management education Teach and reinforce self monitoring signs of worsening (symptoms or peak flow) difference between long term control and quick relief medications correct inhaler technique avoiding environmental triggers A written asthma action plan Peak Flow Meters Establish patient s personal best value and evaluate the response to changes in therapy. Patients with moderate persistent and severe persistent asthma may benefit from having a peak flow meter at home and measuring their level upon arising each morning. Controller and quick-relief medicine plan PEF values (personal best, 80%, 50%) 10
Normal Peak Flow Varies by Gender, Age, Ethnicity Peak Flow Meters: Caveats Extremely wide variability even in the published predicted peak expiratory flow reference values Effort dependent Poor at detecting mild obstruction Reference values differ for each brand of meter normative brand specific values currently are not available for most brands Helps in monitoring but not diagnosis Particularly useful for patients without good ability to sense symptoms Inhaler Technique Inhaler Technique 43 44 11
Asthma Care: 4 Essential Components 3 Environmental Factors & Comorbid Conditions Environmental factors and comorbid conditions Review exposures advise on ways to reduce exposure In patients with persistent asthma, consider skin allergy testing and immunotherapy Comorbid conditions ABPA, GE reflux, obesity, OSA, rhinitis & sinusitis, stress, depression, tobacco Asthma Care: 4 Essential Components 4 Medications Medications Long term control medications Inhaled Corticosteroids (ICS) Long acting beta agonists (LABA) salmeterol/formoterol last > 12 h NOT for monotherapy / to be used with ICS (Step 3 4) Cromolyn sodium/nedocromil Step 2 (Mild persistent) Preventive Rx before exercise or exposure to allergens Immunomodulators omalizumab (anti IgE) Adjunctive Rx if allergies and Step 5 6 care (Severe persistent) Administered where equipped to treat anaphylaxis 12
Steroid Treatment Tips Inhaled corticosteroids should be used for all persistent asthma ICS must be used with LABA (salmeterol) due to higher than expected death rates with LABA alone Five day course of oral corticosteroids does not require taper Smokers may require higher ICS doses Summary Stepwise assessment used for initial therapy and adjustment of therapy LABA has no role alone only if used together with ICS ICS with all persistent asthma Patients to be partners in care asthma control test for monitoring written asthma action plan for assessment/rx Smokers are Different Up to 1/3 of asthmatics smoke 44 non smokers and 39 light smokers with mild asthma assigned to ICS 2x day or LTA 1x day Even with similar FEV1, smokers had worse quality of life, more symptoms ICS reduced sputum eosinophils in both ICS improved FEV1 only in non smokers LTA improved AM peak flow only in smokers Lazarus et al. Am J Respir Crit Care Med. 2007;175:783-90 13
COPD 53 COPD A preventable and treatable disease state characterized by airflow limitation that is not fully reversible. Airflow limitation usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Celli B. R. Chest 2008;133:1451-1462 COPD COPD Cough or wheeze Sputum production Dyspnea Chest tightness Worsening quality of life (often without clear recognition) Celli B. R. Chest 2008;133:1451-1462 Highly prevalent (7 to 19%; M>W; white > blacks; increases with age) Underdiagnosed (~12M), Undertreated, Underperceived, and Very costly care (~$49.9B in 2010) 14
An Accelerated Decline In Lung Function Is The Single Most Important Feature Of COPD COPD: Cigarette smoking 3rd-ranked cause of death in the US (~100,000 each year). Most important risk factor. Smoking leads to an inflammatory response, oxidative stress, lung destruction, and interference with lung repair Smokers Leukocyte Infiltration in COPD Smoker, Mild COPD Smoker, Severe COPD COPD: Smoking cessation Slows the accelerated decline in COPD related FEV1 Reduces all cause mortality rates by 27% (by reduction in CV mortality) Immunostaining with monoclonal antibody anti-cd45 15
COPD COPD: A persistent Systemic Inflammatory state The mortality rate from COPD for women has doubled over the past 20 yrs. Some studies suggest that women are more susceptible to the effects of tobacco smoke than men Consultant360 12/2011 COPD: A persistent Systemic Inflammatory state Associated with important systemic manifestations, especially in patients with more advanced disease. Imbalanced oxidative stress or abnormal immunologic response decreased fat free mass impaired systemic muscle function anemia osteoporosis depression pulmonary hypertension, and cor pulmonale Celli B. R. Chest 2008;133:1451-1462 all ofwhich are important determinants ofoutcome Spirometry = COPD Essential for diagnosis Significantly underutilized Change in management occurs in >50% of patients with COPD when diagnosed in primary care practice 16
Who Should Get Spirometry? Smoker/ex smoker >40 yrs old who says yes to: Do you cough regularly? Do you cough up phlegm regularly? Do even simple chores make you short of breath? Do you wheeze when you exert yourself, or at night? Do you get frequent colds that persist longer than those of other people you know? Approach to Patients with COPD Celli B. R. Chest 2008;133:1451-1462 BODE Index: Classification of Severity Classification of Severity 17
GOLD Guidelines: COPD Management Assess and monitor the disease Reduce risk factors Manage stable COPD Manage exacerbations COPD: a Treatable Disease Overall goals of treatment to prevent further deterioration in lung function, improve symptoms and quality of life, treat complications, and prolong a meaningful life Celli B. R. Chest 2008;133:1451-1462 COPD: a Treatable Disease Therapeutic Options for Patients at Risk for COPD and Those With Established Disease Improved survival found with: Smoking cessation Long term oxygen therapy in hypoxemic patients Noninvasive mechanical ventilation in some patients with acute on chronic respiratory failure LVRS for patients with upper lobe emphysema and poor exercise capacity The TORCH (Towards a Revolution in COPD Health > 6,000 patients) Combination of salmeterol and fluticasone improved lung function and health status, AND Relative risk of dying decreased by 17.5% (over the 3 years of the study). Pulmonary rehabilitation and lung transplantation improve symptoms and the quality of life Celli B. R. Chest 2008;133:1451-1462 LAMA =LA muscarinic agent LVR = lung volume reduction MV = mechanical ventilation. Celli B. R. Chest 2008;133:1451-1462 18
COPD: Importance of Hyperinflation Dyspnea perceived during exercise, including walking, more closely relates to the development of dynamic hyperinflation than to changes in FEV1. Improvement in exercise brought about by several therapies (bronchodilators, oxygen, lung volume reduction surgery, and even rehabilitation) is more closely related to delaying dynamic hyperinflations than by improving the degree of airflow obstruction. Celli B. R. Chest 2008;133:1451-1462 Approach To Patients With COPD With Exacerbations (Increased SOB, Cough, or Change in Color or Volume of Sputum. Celli B. R. Chest 2008;133:1451-1462 COPD: Corticosteroids In outpatients, exacerbations necessitate a course of systemic corticosteroids (important to wean patients quickly) Standard doses of inhaled corticosteroid (ICS) aerosols, show minimal if any benefits in the rate of decline of lung function. TORCH trial = combination of ICS and LABAs was superior to ICS alone (outcomes evaluated, including survival) Pneumonia (described as an adverse event but not precisely diagnosed) was more frequent in the patients receiving ICS ICS should not be prescribed alone but rather in bi ti ith LABA 19