The GOLDen Rule: An Update on Chronic Obstructive

Pulmonary Disease (COPD) Guidelines

Rory Johnson, Pharm.D., AE-C

University of Montana

rory.johnson@mso.umt.edu

Disclosures

• Nothing to disclose

Objectives

• At the conclusion of this presentation, participants should be able to:

• Recommend appropriate pharmacologic treatment for COPD patients based on the refined ABCD assessment tool.

• Utilize tools that can improve inhaled medication administration and delivery for patients with COPD.

Definition & Overview

• Common & preventable disease of persistent airflow limitation caused by:

• Mixture of small airways disease (obstructive bronchiolitis)

• Parenchynmal destruction (emphysema)

• Symptoms include dyspnea, cough and/or sputum production

• Main risk factor is smoking

• Other factors: environmental exposures, host factors (genetics, age, asthma, etc.)

Pathophysiology

• Inflammation in respiratory tract to chronic irritants

• Airway edema

• Excess mucus production

• Impaired ciliary motility

• Thickening of smooth muscle and connective tissue in the airways

• Chronic inflammation results in repeated injury and repair process that lead to scarring and fibrosis

COPD Burden

• Leading cause of morbidity & mortality worldwide

• US: projected to be 3rd leading cause of death by 2020

• Significant economic burden

• US: >$50 billion annually in direct & indirect costs

• Social Impact

• US: second leading cause of reduced DALYs (Disability-Adjusted Life Year)

Diagnosis

• Diagnosis may be considered if patient exhibits the following:

• Symptoms: progressive dyspnea, chronic cough, sputum production

• History of exposure to risk factors including intensity and duration

• Family history of COPD

• **SPIROMETRY IS REQUIRED FOR DIAGNOSIS**

• FEV1/FVC of < 0.70 (postbronchodilator) indicates persistent & irreversible airflow limitation

Spirometry

FEV1 – forced

expiratory volume

in 1 second

FVC – Functional

Vital Capacity

(lung volume)

“Normal”spirometry values

predicted by age

and height.

Initial Assessment

• To determine the degree & severity of COPD, the following aspects should be assessed separately:

• Spirometric abnormality

• Nature of patient’s symptoms

• Exacerbation history & future risk

• Comorbidities

Symptoms

• Validated tools to measure symptoms

• Modified British Medical Research Council Questionnaire (mMRC)

• COPD Assessment Test (CAT™) - preferred

• COPD impacts patients beyond dyspnea, so best to use a comprehensive assessment of symptoms including:

• Cough, phlegm, sleep, energy, activities, etc.

Exacerbation History & Risk

• Exacerbation – acute worsening of symptoms resulting in additional therapy

• Mild – treated w/ short acting bronchodilator (SABDs) only

• Moderate – SABDs + antibiotic &/or oral corticosteroid

• Severe – hospitalization or ED visit (possible respiratory failure)

• Best predictor – history of earlier treated event

• Other predictors – deteriorating airflow & blood eosinophil count

Comorbidities

• Common comorbid conditions may affect mortality & hospitalization risk:

• Cardiovascular disease

• Osteoporosis

• Depression/anxiety

• Skeletal muscle dysfunction

• Lung cancer

Practice Case #1

• Use the revised combined COPD assessment tool to classify a 56 year old female’s COPD based on the following information: FEV1 = 55% w/ CAT score <10 and 1 hospitalization 3 months ago for COPD exacerbation.

• GOLD grade 2, group A

• GOLD grade 3, group A

• GOLD grade 2, group C

• GOLD grade 3, group C

Prevention & Maintenance Therapy

• SMOKING CESSATION: most effective intervention to reduce the risk of developing COPD and slow its progression

• Smoking cessation counseling should be done at every visit

• Pharmacotherapy & NRT are effective at increasing abstinence rates

• Five A’s to help patient quit smoking

• Ask, Advise, Assess, Assist, Arrange

Adapted from Fletcher CM, Peto R (1977). The natural history of chronic airflow obstruction. BMJ, 1(6077): 1645–1648.

Artist: Bryan Matthew Boutwell http://www.livefiction.net/content/intervention_inhaler

The Intervention of an Inhaler

Pharmacologic Therapy

• Treatment goals:

• Control & prevent symptoms – can’t modify progression or prolong survival

• Prevent & treat exacerbations – reduce frequency & severity

• Enhance patient quality of life – improve health status & exercise tolerance

Pharmacotherapy Options

Beta2-agonists

Short-acting beta2-agonists (SABA)

Long-acting beta2-agonists (LABA)

Anticholinergics

Short-acting anticholinergics (SAMA)

Long-acting anticholinergics (LAMA)

Combination short-acting beta2-agonists + anticholinergic

Methylxanthines

Inhaled corticosteroids

Combination long-acting beta2-agonists + corticosteroid

Systemic corticosteroids

Phosphodiesterase-4 inhibitors

Short Acting Bronchodilators

• Short-acting B2 agonist (SABA)

• Albuterol 2 puffs q 4 hours

• Short acting anticholinergics

• Ipratropium 2 puffs q 4 hours

• Combination SABA/short-acting anticholinergic

• Albuterol/ipratropium (Combivent®)

• Different mechanisms: improves efficacy

• Reduce potential adverse effects from increasing dose of individual agents

Long Acting Bronchodilators

• Long-acting B2-agonists (LABA)

• Salmeterol DPI: 1 inhalation BID

• Formoterol DPI: 1 inhalation BID

• Arformoterol 15-30 mcg nebulized BID

• Indacterol

• Long-acting anticholinergics (LAMA)

• Tiotropium DPI (Spiriva): 1 inhalation once daily

• Aclidinium (Tudorza): 1 inhalation BID

Methylxanthines

• Theophylline & aminophylline

• Generally not recommended unless other options are not available or not affordable for long-term treatment

• Lower efficacy, increased side effects with theophylline

• Narrow therapeutic index, drug-drug interactions

• Typically reserved as add-on therapy in patients with more severe COPD

Inhaled Corticosteroids

• Unlike ICS use in asthma, regular use does not modify the disease progression or improve FEV1; no decrease in overall mortality

• May increase likelihood of pneumonia

• Combination therapy with LABA is more effective than individual components in decreasing exacerbations; long-term monotherapy is not recommended

• Long-term treatment with ICS is recommended in addition to long-acting bronchodilators for patients with severe to very severe (GOLD 3-4) airflow limitation and frequent exacerbations not controlled by bronchodilators alone

Combination ICS/LABA

• Advair (fluticasone/salmeterol)

• Diskus DPI & HFA

• Symbicort HFA(budesonide/formoterol)

• Dulera HFA (mometasone/formoterol)

• Breo Ellipta DPI (fluticasone/vilanterol)

PDE-4 Inhibitor - Roflumilast

• Selectively inhibits phosphodiesterase-4, increasing accumulation of intracellular cAMP, which is thought to decrease inflammatory activity

• NOT a bronchodilator

• May be added to reduce exacerbations for patients with FEV1 < 50% of predicted, chronic bronchitis, and frequent exacerbations

• Statistically significant reduction in exacerbations in patients with severe COPD associated with chronic bronchitis, with ≥1 exacerbation in the previous year and ≥20 pack-year smoking history

Expectorants & Mucolytics

• No proven benefit in literature

• Guidelines do not suggest that any of the expectorants are more effective than proper hydration

• Still a place in therapy?

Managing Exacerbations

• Most commonly caused by viral URTI

• Diagnosis relies on clinical presentation of patient w/ acute decline that is outside day-to-day variation

• Symptoms of exacerbation:

• Increased wheezing, chest tightness, cough, and sputum production, change in sputum tenaciousness, fever

• Goals:

• Prevention of hospitalization or reduction in hospital stay

• Prevention of acute respiratory failure and death

• Resolution of exacerbation symptoms and a return to clinical status and quality of life

• Prevent development of subsequent exacerbations

Exacerbations: Treatment Options

• Oxygen

• Titrate to target saturation of 88-92%

• Bronchodilators

• SABA ± SAMA usually preferred for treatment of exacerbation

• SABA: Increase dose and/or frequency

• Consider adding ipratropium until symptoms improve

• Systemic Corticosteroids

• Can improve FEV1, oxygenation and shorten recovery time and hospital duration

• Duration of therapy should be 5-7 days

Antibiotics

• Antibiotics should be initiated when 2 of the 3 symptoms are present

• Increased dyspnea, increased sputum volume, increased sputum purulence

• Empirical therapy should be based on most likely organism thought to be responsible for infection

• H. influenzae: 2nd or 3rd generation cephalsporin

• M. catarrhalis: Doxycycline

• S. pneumoniae: Macrolide

• Therapy should be continued for 5-7 days

Azithromycin to Prevent COPD Exacerbations

• 1577 subjects given azithromycin 250mg once daily or placebo, followed for 1 year

• Reduced median time to exacerbation (266 days in azithromycin treatment vs. 174 in placebo group, p<0.001)

• Macrolides may:

• Play anti-inflammatory role in addition to antibacterial effects

• Decrease sputum/mucus production & modify neutrophil response

• Problems with resistance?

http://www.nejm.org/doi/full/10.1056/NEJMoa1104623#t=abstract

Patient Case #2

• Use the revised combined COPD assessment tool to classify a 67 year old male’s COPD based on the following information: FEV1 = 45% w/ CAT score of 9 and 2 hospitalizations for COPD exacerbations in the previous year.

• His last pneumococcal vaccination was when he was 58. He currently uses Combivent Respimat twice daily and doesn’t think it works very well. He also uses Spiriva 3-4 times per week. What action steps would you consider?

Optimum Inspiratory Flow

• Delivery to lungs is dependent on inspiratory airflow and medication

device resistance

• Inspiratory flow requirements may vary between devices

Vaccinations

• Influenza vaccine decreases serious illness and death by 50%

• Pneumococcal polysaccharide (PPSV23) vaccine is recommended for all COPD patients

• Recently the Advisory Committee on Immunization Practices(ACIP) updated recommendations on Pneumococcal Polysaccharide Vaccine (PPSV23) to include a single vaccination for patients <65 with asthma and smokers ages 19-64

References

• Global Initiative for Chronic Obstructive Lung Disease (GOLD). GOLD 2017 global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, 2017 report. November 17, 2016. http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-preve.... Accessed November 28, 2017.