Pharmacologic Treatment

Inhaled medications such as bronchodilators and corticosteroids are the primary treatment modality in COPD (Table 3).13 Long-acting bronchodilators include long-acting beta2-adrenergic agonists (LABAs) and long-acting antimuscarinic (ie, anticholinergic) agents (LAMAs). Beta2-adrenergic agonists stimulate the sympathetic nervous system action of bronchodilation, whereas antimuscarinic agents counteract bronchoconstriction of the airways. Long-acting bronchodilators are used as daily maintenance therapy; short-acting beta2-adrenergic agonists (SABAs) and short-acting antimuscarinic agents (SAMAs) are bronchodilators used for rapid control of intermittent episodes of bronchospasm. Inhaled corticosteroids (ICS) are also used for maintenance therapy daily,27 and a combination of long-acting bronchodilators and corticosteroids dispensed from one inhaler is commonly used.

Table 3. Common Inhaled Medications for COPD27,37

Type of Inhaler ActionUseExamples
Short-acting beta2-adrenergic agonist   Rapid stimulation of sympathetic
nervous system bronchodilation  
Rescue medication for acute attacks of bronchospasm• Albuterol
• Levalbuterol
Short-acting antimuscarinic agent Rapid anticholinergic
action that opposes bronchoconstriction  
Rescue medication for acute attacks of bronchospasm • Ipratropium
Long-acting beta2-adrenergic agonist Long-acting stimulation
of sympathetic
nervous system bronchodilation
Maintenance medication used once or twice daily • Salmeterol
• Formoterol
• Arformoterol
• Indacaterol
• Olodaterol
• Vilanterol
Long-acting antimuscarinic agent Long-acting
anticholinergic action that opposes bronchoconstriction
Maintenance medication used once or twice daily • Ipratropium
• Tiotropium
• Aclidinium
• Umeclidinium
• Glycopyrrolate    
Inhaled corticosteroids Long-acting
anti-inflammatory
action
Maintenance medication used once or twice daily • Fluticasone
• Budesonide
• Mometasone    
Combination inhalers Bronchodilator plus corticosteroid Maintenance medication used once daily • Albuterol/ ipratropium
• Salmeterol/ fluticasone
• Formoterol/ budesonide
• Formoterol/ mometasone
• Vilanterol/ fluticasone
• Ipratropium/ albuterol
• Umeclidinium/ vilanterol

Inhaled medications are usually delivered using pressurized metered-dose inhalers (MDIs) and dry powder inhalers (DPIs).28 Due to the chronic nature of COPD, long-term self-administration of medications is paramount for preventing disease progression.

Patients should be taught which inhaler is used for rapid-action, rescue treatment and which is used daily for maintenance treatment. If a bronchodilator and an inhaled corticosteroid are used separately, the bronchodilator should be used first to open the airways. Most medications are easy to use because they consist of a combination of bronchodilator and corticosteroid.

Adherence to medication is essential for optimal disease management. MDIs and DPIs require specific inhalation techniques to obtain the full effect of the medication. However, correct inhaler technique can  be difficult for many patients to achieve, particularly older adults with comorbidities as they often cannot mount the inspiratory force needed to inhale the medication sufficiently.29 MDIs are the most commonly prescribed inhalation device, but these can be difficult to use due to the high level of coordination required to activate the device while taking a slow and deep inhalation. Studies show that up to 94% of patients demonstrate incorrect inhaler technique with either conventional pressurized MDIs or DPIs.28 Primary care clinicians should demonstrate proper inhaler use, ask patients for a return demonstration, and distribute a handout depicting the correct technique. Patients can also be referred to online resources for learning the appropriate use of inhalers.

Using a spacer with an MDI may be helpful for patients who have difficulty with this type of device; it is the preferred method of delivery. When using an MDI with a spacer, the medication is delivered by pushing down on the canister to produce a measured “puff” of medication into the holding container. The medication is then inhaled through a mouthpiece, which allows for a higher and more accurate dose to be delivered into the lungs.30

Nebulizers

If patients are unable to use MDIs or DPIs properly, they may not receive accurate treatment and should be evaluated for nebulized therapy instead. Both rescue and maintenance therapies can be delivered with a nebulizer, which is a motorized apparatus that converts medications from a liquid form to a mist.

Nebulizers are handheld devices that do not require a specific breathing technique for effective drug delivery and offer a convenient way of delivering a higher dose of medication to the airways. Nebulizers are also effective for maintenance dosing in populations who are unable to use other devices, particularly patients with cognitive, neuromuscular, or ventilatory impairments.31

Acute Exacerbations of COPD

Acute exacerbations of COPD (AECOPD) are defined as an acute worsening of respiratory symptoms that require additional therapy and usually last 7 to 10 days. Bacterial infection is the most common cause, contributing to approximately 70% of AECOPD cases, with viral causes responsible for approximately 30%.32  A change in color of the sputum and increase in purulence is a good marker for a bacterial cause of exacerbation. Common bacteria responsible for AECOPD include Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Patients with the most impaired lung function (lowest FEV1) may have other bacterial infectious causes, such as Pseudomonas aeruginosa or Gram-negative bacteria. Upper respiratory infections caused by viruses, usually rhinovirus, can also trigger AECOPD. It is important to recognize that a viral infection can subject the patient with COPD to a bacterial infection.32

Major findings associated with an exacerbation include increased dyspnea, sputum volume, and/or sputum purulence. Patients may also have increased cough, fever, myalgia, and pharyngitis.33 Diagnosing exacerbations relies on patients reporting their symptoms; as they often do not report these to their clinician, AECOPD can go untreated. The COPD Assessment test (CAT) is an 8-item questionnaire that can be completed by the patient to evaluate their current state of symptoms of COPD. Serum biomarkers, C-reactive protein, and procalcitonin are commonly elevated in patients with positive bacterial sputum cultures.34

Exacerbations can have a negative effect on a patient’s health status, increase the risk for hospitalization, decrease quality of life, and reduce exercise capacity and lung function. Recovery can take several weeks, and significant mortality is associated with AECOPD. Exacerbations most commonly occur in patients with moderate or severe COPD, GOLD grade 3 or 4.35 AECOPD is classified as mild, moderate, or severe, and each classification is associated with different treatment recommendations (Table 4).33,36

Table 4. Classification of AECOPD Severity36,37

Classification Symptoms Treatment Recommendations
Mild One of the following:
• Increased dyspnea
• Increased sputum volume               
• Increased sputum purulence
Short-acting bronchodilators
ModerateTwo of the following:
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
Short-acting bronchodilators plus oral corticosteroids and antibiotics
Severe Acute respiratory failure and at least 2 of the following:
• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence
Emergency department/ hospitalization