Chronic Obstructive Pulmonary Disease (COPD)

Define COPD and common causes

• Respiratory condition that causes obstructed airflow from the lungs

• Most comonly caused by tobacco smoke

Chronic inflammation in lungs can result in emphysema and/or bronchitis

• Emphysema - destruction of small passages in the lungs, called alveoli

• Bronchitis - inflammation and narrowing of the bronchial tubes and results in mucus production

Individuals with what deficiency have a higher risk of developing COPD?

• Alpha-1 antitrypsin (AAT) deficiency (genetic)

• AAT protects lungs from damage caused by inflammation

What are the key differences between COPD and asthma?

What test is used to assess lung function and diagnosis of COPD? What measurement confirms diagnosis?

• Spirometry - measures the total amount of air a person can breathe out (forced vital capacity, or FVC)

• Post-bronchodilator FEV₁ / FVC < 0.70 confirms diagnosis of COPD

Define COPD exacerbation. Why are we trying to decrease hospitalization for an exacerbation?

• Increase in respiratory symptoms that worsen over < 14 days

• Risk of exacerbations increases as airflow limitation worsens

• Hospitalization for an exacerbation is associated with an increased risk of death

Describe the assessment factors that drive treatment for COPD.

1) Degree of airflow limitation

2) Symptom assessment

3) Risk of exacerbations

4) Comorbidities

What are the first line treatment for all COPD patients?

Bronchodilators

• SABA or SAMA - prn for intermittent symptoms

• LABA or LAMA

When is using an ICS indicated for COPD patients?

When is it not recommended and why?

• Recommended in select patients with a hx of exacerbation and an eosinophil count (a marker of inflammation) ≥ 300 cells/uL

• Not recommended if eosinophil count < 100 cells/uL - no demonstrated benefit

• Dupilumab - SC monoclonal antibody that can be used in patients with eosinophilic COPD not well controlled on triple therapy (LABA + LAMA + ICS)

MOA of muscarinic antagonist (anticholinergics)

• Cause bronchodilation by blocking the constricting action of acetylcholine at M3 muscarinic receptors in bronchial smooth muscle

MOA of beta-2 agonists

• Bind to beta 2 receptors in the lung, causing relaxation of bronchial smooth and bronchodilation

Why can’t LABAs be used monotherapy for asthma?

• Increase risk of death in asthma patients

  • Should only use if currently receiving but are not adequately controlled on an inhaled corticosteroid

• Can be used monotherapy ONLY for COPD

How does roflumilast work and when is it indicated?

• Roflumilast - PDE-4 inhibitor that ↑ cAMP levels, leading to reduction in lung inflammation

• Should use for very severe COPD - use in combo with at least one long-acting bronchodilator

Roflumilast DDIs

• Substrate of CYP450 3A4 and 1A2

• Inducers (carbamazepine, phenobarbital, phenytoin, rifampin)

• Inhibitors (erythromycin, ketoconazole, fluvoxamine, cimetidine)