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BACKGROUND

Chronic obstructive pulmonary disease (COPD) is defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a “common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.”¹ The prevalence of COPD is significant: in 2014, approximately 15.7 million (6.4%) Americans reported a diagnosis of COPD.² The mortality impact is also substantial: chronic lower lung disease, predominantly COPD, is the third leading cause of death in the United States (U.S.).^3,4 Comorbidities, including cardiovascular disease, hypertension, and diabetes, also play an important role in the morbidity of patients with COPD.^4,5 The direct and indirect costs of COPD in the U.S. are estimated to be $32 billion and $20.4 billion, respectively.¹ COPD exacerbations are responsible for most of the economic burden; therefore, prevention of COPD exacerbations is an integral part of COPD management.¹

COPD is a complex disease with multiple systemic effects and comorbidities, and it requires an integrated approach for optimal management. As members of the health care team, pharmacists provide care for patients with COPD in a variety of practice settings. Knowledge of evidence-based recommendations for COPD management, the proper use of inhaled delivery devices, and the chronic care model for preventing COPD exacerbations will help pharmacists positively impact the care of these patients.

COPD RISK FACTORS AND PATHOLOGY

Cigarette smoking is a leading factor for COPD development and COPD exacerbations, and it accounts for 80% of COPD-related deaths.⁶ Despite this fact, as many as 25% of people with COPD never smoked.⁷ Other factors that impact disease development and progression include age, gender, affected lung growth during development and childhood, occupational and environmental exposures, low socioeconomic status, asthma, bronchitis, and respiratory infections.¹ Genetics may also play a role in the development of COPD: specifically, alpha-1 antitrypsin (AAT) deficiency is believed to be a factor for COPD development in non-smokers. AAT is a protein produced by the liver that protects the lungs from inflammation, and deficiency of AAT can lead to lung destruction. AAT deficiency is a genetic condition that affects an estimated 1% to 5% of patients diagnosed with COPD.^8,9

The pathophysiology of COPD development is complex. In general, the inhalation of cigarette smoke, harmful occupational exposures, or toxic environmental exposures results in lung inflammation. Chronic inflammation causes damage to lung tissue and airflow narrowing. Inflammation is often described as neutrophilic in nature; however, other inflammatory cells are also involved. Additional causative factors include oxidative stress and an imbalance between harmful and protective mechanisms in the lungs. Overall, the large and small airways, lung tissue, and vasculature are affected, which makes breathing difficult.¹⁰

EVIDENCE-BASED CARE FOR COPD

GOLD is an international collaboration between the U.S. National Heart, Lung, and Blood Institute and the World Health Organization. Initially released in 2001, the GOLD Consensus Report, Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, is an important guide for health care professionals to use in providing evidence-based and effective care for patients with COPD. Recommendations from the 2017 GOLD Report are described throughout this activity. “Level A” evidence from the Report is based on randomized controlled trials and a rich body of high-quality evidence without any significant limitation or bias. “Level B” evidence is based on randomized controlled trials with important limitations and a limited body of evidence.¹

Symptoms, assessment, and diagnosis

The characteristic symptoms of COPD include dyspnea or difficulty breathing, chronic cough, sputum production, wheezing, and chest tightness. A clinical diagnosis of COPD should be considered in any patient over the age of 40 years with chronic and progressive dyspnea, cough, and sputum production, as well as a history of exposure to COPD risk factors. Dyspnea is progressive and typically worsens with exercise. Cough is often the first symptom to develop and may or may not be productive.¹

Airflow limitation is objectively assessed using post-bronchodilator spirometry measurements. The ratio of 2 pulmonary function tests, forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC), is calculated. FVC is defined as the volume of air a person can exhale during a forced breath, and FEV₁ is the volume of air exhaled during the first second. A post-bronchodilator FEV₁/FVC ratio of less than 0.70 indicates airflow limitation and a diagnosis of COPD. FEV₁ values can be predicted by a person’s age, height, gender, and race and compared with spirometry findings to stage the severity of airflow limitation in COPD from mild (FEV₁ ≥ 80% predicted) to very severe (FEV₁ ≤ 30% predicted), as shown in Table 1.¹

Table 1. 2017 GOLD Report Severity of Airflow Limitation in COPD1
GOLD classification	Severity of airflow limitation	Post-bronchodilator FEV1 findings
GOLD 1	Mild	FEV1 80% predicted
GOLD 2	Moderate	50% ≤ FEV1 < 80% predicted
GOLD 3	Severe	30% ≤ FEV1 < 50% predicted
GOLD 4	Very severe	FEV1 ≤ 30% predicted
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease. Reprinted with permission from: Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org.

In 2011, the GOLD Report created an “ABCD” tool to assess the severity of COPD and recommend therapeutic options. Since then, the tool has been refined, and the 2017 GOLD “ABCD” tool, summarized in Table 2, takes into account an assessment of the patient’s symptoms and risk of exacerbations.¹ Recommendations for chronic care, including pharmacologic treatments, are based solely on the patient’s symptoms and exacerbation history, unlike previous versions of the “ABCD” tool, which also incorporated an assessment of airflow limitation (i.e., patient’s FEV₁ as a percentage of predicted value).^1,11

Table 2. 2017 GOLD Report "ABCD" Categories1
GOLD grade	Risk	Symptoms	Exacerbations	CAT score	mMRC grade
Group A	Low	Less	0-1 exacerbations/year and no prior hospitalization for exacerbation	<10	0-1
Group B	Low	More	0-1 exacerbations/year and no prior hospitalization for exacerbation	≥10	≥2
Group C	High	Less	≥2 exacerbations/year or ≥1 hospitalization for exacerbation	<10	0-1
Group D	High	More	≥2 exacerbations/year or ≥1 hospitalization for exacerbation	≥10	≥2
Abbreviations: CAT, COPD Assessment Test; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, Modified British Medical Research Council Questionnaire. Reprinted with permission from: Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org.

Symptom assessment tests are used to evaluate symptoms and the impact of COPD on a patient’s health. The Modified British Medical Research Council (mMRC) Questionnaire, which evaluates breathlessness on a scale of 0 to 4, and the COPD Assessment Test (CAT), which measures impairment of health status using 8 questions scaled from 0 to 5, are 2 examples of symptom assessment tests. A score of 2 or higher on the mMRC and a score of 10 or higher on the CAT indicate more severe symptoms.^1,12,13

An exacerbation is defined as an acute worsening of COPD symptoms, typically triggered by respiratory tract infections or environmental factors, that warrants additional therapy. Patients with a history of COPD exacerbations are more likely to experience frequent exacerbations (defined as 2 or more exacerbations per year).¹

Pharmacotherapy for stable COPD

Overall goals for the management of stable COPD are to reduce and relieve symptoms, improve exercise tolerance, improve health status, prevent disease progression, prevent and treat exacerbations, and reduce mortality.¹ Preventing exacerbations is especially important since they are associated with quicker decline in lung function, reduced quality of life, hospitalization, increased mortality, and costs to the health care system.¹⁴ To date, pharmacologic therapies for the chronic management of COPD have only been shown to reduce symptoms, reduce the risk and severity of exacerbations, improve health status, and improve exercise tolerance.¹ The classes of medications used for the management of stable COPD are bronchodilators, inhaled corticosteroids (ICS), phosphodiesterase-4 (PDE-4) inhibitors, and methylxanthines.

Bronchodilators

Inhaled bronchodilators, which include beta2-agonists and antimuscarinics, exert their effects by relaxing smooth muscle: they are the cornerstone of COPD management.¹ Both can be classified as short-acting or long-acting based on their duration of action. In general, short-acting bronchodilators are useful for patients with occasional dyspnea, and long-acting bronchodilators are convenient and preferred for those with frequent and persistent symptoms due to their longer duration of action.^1,10

The short-acting beta2-agonists (SABAs) are levalbuterol and albuterol. They have durations of action of 4 to 6 hours and are dosed accordingly.¹ The long-acting beta2-agonists (LABAs) are arformoterol, formoterol, indacaterol, olodaterol, salmeterol, and vilanterol (combination product only). They have durations of action of 12 or more hours and are dosed either once or twice daily.¹ Ipratropium is a short-acting muscarinic antagonist (SAMA). Compared to beta2-agonists, ipratropium has a slower onset of action and a longer bronchodilator effect.¹⁰ Aclidinium, glycopyrrolate, tiotropium, and umeclidinium are the long-acting muscarinic antagonists (LAMAs), which are dosed either once or twice daily.¹ The dosing frequencies of these products and other inhaled therapies are provided in Table 3.^15-32

Table 3. Dosing Frequencies of Long-acting Bronchodilators and Combination Products15-32
Drug (generic name)	Brand name	Once-daily dosing frequency	Twice-daily dosing frequency
LABAs
Arformoterol	Brovana		✓
Formoterol	Perforomist		✓
Indacaterol	Arcapta Neohaler	✓
Olodaterol	Striverdi Respimat	✓*
Salmeterol	Serevent Diskus		✓
LAMAs
Aclidinium bromide	Tudorza Pressair		✓
Glycopyrrolate	Seebri Neohaler		✓
Tiotropium	Spiriva HandiHaler; Spiriva Respimat	✓†‡
Umeclidinium	Incruse Ellipta	✓
Combination LABA + LAMA
Formoterol/glycopyrrolate	Bevespi Aerosphere		✓‡
Indacaterol/glycopyrrolate	Utibron Neohaler		✓
Vilanterol/umeclidinium	Anoro Ellipta	✓
Olodaterol/tiotropium	Stiolto Respimat	✓*
Combination LABA + ICS
Formoterol/budesonide	Symbicort		✓*
Formoterol/mometasone	Dulera		✓§
Salmeterol/fluticasone	Advair Diskus		✓
Vilanterol/fluticasone	Breo Ellipta	✓
Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist. *Dose requires 2 inhalations. †Respimat product: dose requires 2 inhalations. ‡Handihaler product: contents of 1 capsule should be inhaled twice. §Off-label indication for chronic obstructive pulmonary disease.

Inhaled bronchodilators are generally well tolerated and side effects are dose dependent. Patients taking inhaled beta2-agonists may experience tachycardia, anxiety, headache, insomnia, nervousness, tremors, and restlessness.¹ The most common side effect of inhaled anticholinergics is dry mouth¹; other anticholinergic effects include constipation, urinary retention, tachycardia, blurred vision, and precipitation of narrow angle glaucoma.¹⁰ Combining beta2-agonists with antimuscarinics can enhance the degree of bronchodilation while lowering the risk of side effects from escalation of monotherapy. Several inhaler devices containing both classes of bronchodilators in a single inhaler are now available: formoterol/glycopyrrolate, indacaterol/glycopyrrolate, vilanterol/umeclidinium, and olodaterol/tiotropium.¹

Evidence for use of bronchodilators according to GOLD 2017 Report¹:

• Regular and as-needed use of short-acting bronchodilators improves FEV₁ and symptoms (Evidence level A)
• Combinations of SABAs and SAMAs are superior to either medication alone in improving FEV₁ and symptoms (Evidence level A)
• LABAs and LAMAs significantly improve lung function, dyspnea, and health status and reduce exacerbation rates (Evidence level A)
• LAMAs have a greater effect on exacerbation reduction than LABAs (Evidence level A) and decrease hospitalizations (Evidence level B)
• Combination treatment with a LABA and a LAMA increases FEV₁ and reduces symptoms compared to monotherapy (Evidence level A)
• Combination treatment with a LABA and a LAMA reduces exacerbations compared to monotherapy (Evidence level B) or combination treatment with an ICS and a LABA (Evidence level B)

Inhaled corticosteroids

ICS exert anti-inflammatory effects and are recommended for use in combination with a long- acting bronchodilator, but not as monotherapy, for the management of stable COPD. Several combination products containing a LABA plus an ICS in a single inhaler device are available: formoterol/beclomethasone, formoterol/budesonide, formoterol/mometasone, salmeterol/fluticasone, and vilanterol/fluticasone furoate. Vilanterol/fluticasone is the only combination LABA/ICS that is dosed once daily; the other combination products have a twice-daily dosing frequency.¹

Side effects of ICS use include oral candidiasis, hoarse voice, skin bruising, and pneumonia. To reduce the risk of oral candidiasis, patients should be instructed to rinse their mouths with water after each use and spit the water out. Oral corticosteroids are not recommended for the chronic management of COPD, but they do play a role in the management of COPD exacerbations.¹

Evidence for use of ICS according to GOLD 2017 Report¹:

• Long-term treatment with ICS may be considered in association with LABAs for patients with a history of exacerbations despite appropriate treatment with long-acting bronchodilators (Evidence level A)
• Combination treatment with ICS and a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD (Evidence level A)
• Triple inhaled therapy with ICS, a LABA, and a LAMA improves lung function, symptoms, and health status (Evidence level A) and reduces exacerbations (Evidence level B) compared to ICS plus a LABA or LAMA monotherapy

PDE-4 inhibitors

Roflumilast (Daliresp), a PDE-4 inhibitor, reduces inflammation by inhibiting the breakdown of cyclic adenosine monophosphate within lung cells. It is indicated to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The GOLD 2017 Report recommends use of this medication for patients in Group D with FEV₁ lower than 50% predicted and chronic bronchitis who experience exacerbations despite being on combination therapy with a LAMA, a LABA, and ICS.¹ The dose of roflumilast is 500 μg (1 tablet) by mouth daily, with or without food.³³

Roflumilast is contraindicated in patients with severe hepatic impairment, defined as a Child-Pugh score of B or C. Use with strong cytochrome P450 (CYP) inducers, such as rifampicin, phenobarbital, carbamazepine, and phenytoin, is not recommended due to the decreased serum concentration of roflumilast. In contrast, use with CYP3A4 inhibitors or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, cimetidine) will increase exposure to roflumilast; therefore, risk versus benefit must be evaluated.³¹ Common (≥ 2%) adverse reactions to this product are diarrhea, weight decrease (2 kg average),¹ nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite. In addition, the medication should be used cautiously in patients with a history of depression, and psychiatric events, including suicidality, have occurred in patients using roflumilast.³³

Evidence for use of PDE-4 inhibitors according to GOLD 2017 Report¹:

• In patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations, a PDE-4 inhibitor improves lung function and reduces moderate and severe exacerbations (Evidence level A) and improves lung function and decreases exacerbations in patients who are on fixed-dose LABA and ICS combinations (Evidence level A)

Methylxanthines

The methylxanthines, theophylline and aminophylline, are orally administered bronchodilators that have fallen out of favor due to the availability of inhaled therapies. According to the 2017 GOLD Report, theophylline should not be used for the chronic management of COPD unless the inhaled bronchodilators are unavailable or unaffordable (Evidence level B).¹

Theophylline is available as an oral solution and as an oral extended-release formulation, which is preferred for maintenance therapy. The initial dose is 300 mg daily administered in divided doses every 6 to 8 hours for the oral solution; 300 mg daily divided every 12 hours for the oral extended-release 12-hour formulation; and 300 to 400 mg once daily for the oral extended-release 24-hour formulation. Maintenance doses are typically between 400 and 600 mg daily. Doses need to be individualized on the basis of patient-specific factors and steady-state serum concentrations.³⁴

Theophylline serum levels should be checked after 3 days of oral dosing and monitoring of peak drug levels is recommended. Traditionally, the therapeutic range for theophylline has been defined as 10 to 20 μg/mL; however, adequate bronchodilation is often achieved at concentrations of 8 to 12 μg/mL.³⁵ Once an appropriate dose and drug level has been achieved, monitoring should be completed at 6- to 12- month intervals or if the patient’s clinical status changes, concomitant interacting medications such as CYP3A4 inhibitors (e.g., cimetidine, erythromycin) or inducers (e.g., carbamazepine, rifampin) are added or discontinued, or if toxicity is suspected.³⁴ Side effects of theophylline include dyspepsia, nausea, vomiting, diarrhea, headache, dizziness, and tachycardia.¹⁰

GUIDELINE-DIRECTED TREATMENT ALGORITHMS

The 2017 GOLD Report recommends a treatment algorithm for therapy initiation, escalation, and de-escalation based on the patient’s GOLD grade and emphasizes an individualized approach to management.¹¹ This update is helpful for health care professionals, since previous algorithms were solely limited to recommendations for initial therapy.¹ Recommendations for each group are summarized below:

Group A: Initially, either a short-acting or long-acting bronchodilator is preferred. The effect should be evaluated and the bronchodilator should be continued, changed, or discontinued depending on the patient’s symptoms.¹

Group B: Initial therapy should consist of either a LABA or a LAMA; evidence is not available to suggest one bronchodilator class over another. If symptoms remain persistent, escalation to combination bronchodilation (LAMA + LABA) is recommended (Evidence level A). If combination bronchodilation does not improve the patient’s symptoms, de-escalation to a single bronchodilator is suggested.¹

Group C: Initially, therapy with a LAMA is recommended, since head-to-head trials have shown that a LAMA is superior to a LABA for prevention of exacerbations.¹ The Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) study showed that once-daily tiotropium was more effective than twice-daily salmeterol at reducing the risk of exacerbations in patients with moderate to very severe COPD and a history of exacerbations in the previous year (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.77-0.90; P < 0.001).³⁶ If the patient continues to experience exacerbations while on LAMA monotherapy, therapy should be escalated to combination therapy with a LAMA and a LABA (preferred pathway) or a LABA and ICS.¹

Group D: Initially, combination therapy with a LABA and a LAMA is recommended with either escalation to triple combination therapy with a LAMA, a LABA, and ICS (preferred pathway) or a switch to a LABA plus ICS if the patient experiences further exacerbations.¹ The Effect of Indacaterol- Glycopyrronium Versus Fluticasone-Salmeterol on COPD Exacerbations (FLAME) trial showed that the combination of a LABA and a LAMA was noninferior and superior to combination LABA plus ICS therapy in reducing the annual rate of all COPD exacerbations (rate ratio, 0.89; 95% CI, 0.83-0.96; P = 0.003).¹⁴ Other treatment pathways are also provided for Group D. For example, if monotherapy is initially selected, LAMA is preferred over LABA. Combination therapy with a LABA and ICS may be preferred for initial therapy in patients with asthma-COPD overlap. Adding roflumilast, adding a macrolide, or stopping the ICS can be considered if the patient continues to have exacerbations while on triple therapy with a LABA, a LAMA, and ICS.¹

Macrolides

The 2017 GOLD Report states that the addition of a macrolide, specifically azithromycin, can be considered in Group D patients who are former smokers and still have exacerbations while on triple combination therapy with a LABA, a LAMA, and ICS (Evidence level B).¹ A study by Albert and colleagues³⁷ showed that azithromycin 250 mg by mouth daily for 1 year in addition to standard care decreased the risk for having an acute exacerbation of COPD per patient-year compared to placebo (HR, 0.73; 95% CI, 0.63-0.84; P < 0.001). Uzun and colleagues³⁸ showed that azithromycin 500 mg by mouth 3 times a week for 1 year significantly reduced the COPD exacerbation rate compared to placebo (0.58, 95% CI 0.42-0.79; p = 0.001). Prior to initiating macrolide therapy, consideration must be given to the increased risk for bacterial resistance, medication side effects (including hearing loss), and drug-drug interactions.¹

INHALED DELIVERY DEVICES IN COPD

Inhaled delivery devices are the cornerstone of COPD management, since they deliver medication directly to the lungs and minimize the risks of side effects.³⁹ In addition to selecting the proper medication on the basis of the patient’s symptoms and risks for exacerbations, an appropriate inhaler device must also be chosen.⁴⁰ Several types of inhalation devices are available, each with its own directions for use, advantages, and disadvantages.¹³ Most importantly, the inhaled delivery device needs to be tailored to the patient. The patient’s cognitive function, comorbidities, dexterity, and strength, as well as the medication’s availability, cost, and reimbursement should be considered.¹

In general, inhalation devices can be classified as pressurized metered-dose inhalers (pMDIs), soft-mist inhalers (SMIs), and dry powder inhalers (DPIs). Studies have not shown superiority of one inhaled delivery device over another; however, findings may not be generalizable, since patients in trials typically have adequate inhaler technique and receive thorough education and follow-up.⁴¹ Several bronchodilators are also available as solutions for nebulization.¹ Product availability as of August 2017 is summarized in Table 4.^15-32,42-45

Table 4. Product Availability of Inhaled Delivery Devices Used in the Management of COPD15-32,42-45
Drug (generic name)	Brand name	pMDI	SMI	DPI	Nebulizer Solution
SABAs
Levalbuterol	Xopenex	✓			✓
Albuterol	ProAir HFA; ProAir RespiClick; Proventil HFA; Ventolin HFA	✓		✓	✓
LABAs
Arformoterol	Brovana				✓
Formoterol	Perforomist				✓
Indacaterol	Arcapta Neohaler			✓*
Olodaterol	Striverdi Respimat		✓
Salmeterol	Serevent Diskus			✓
SAMA
Ipratropium	Atrovent HFA	✓
LAMAs
Aclidinium bromide	Tudorza Pressair			✓
Glycopyrrolate	Seebri Neohaler			✓*
Tiotropium	Spiriva HandiHaler; Spiriva Respimat		✓	✓*
Umeclidinium	Incruse Ellipta			✓
Combination SABA + SAMA
Albuterol/ipratropium	Combivent Respimat		✓		✓
Combination LABA + LAMA
Formoterol/glycopyrrolate	Bevespi Aerosphere	✓
Indacaterol/glycopyrrolate	Utibron Neohaler			✓*
Vilanterol/umeclidinium	Anoro Ellipta			✓
Olodaterol/tiotropium	Stiolto Respimat		✓
Combination LABA + ICS
Formoterol/budesonide	Symbicort	✓
Formoterol/mometasone	Dulera	✓
Salmeterol/fluticasone	Advair Diskus	✓†		✓
Vilanterol/fluticasone	Breo Ellipta			✓
Abbreviations: COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; ICS, inhaled corticosteroids; LABA, long-acting beta2-agonist; LAMA, long-acting muscarinic antagonist; pMDI, pressurized metered-dose inhaler; SABA, short-acting beta2-agonist; SAMA, short-acting muscarinic antagonist; SMI, soft-mist inhaler. *Capsule must be loaded and pierced for oral inhalation. †Off-label indication for COPD.

Pressurized metered-dose inhalers

The oldest type of inhaled delivery device,⁴⁶ pMDIs, consist of a canister containing a pressurized suspension of medication and propellant, a metering chamber, and a mouthpiece actuator.¹⁰ Medication is released when the patient pushes the top of the canister down into the actuator. Coordination of inhaler activation with a slow, deep inhalation (“hand-breath coordination”) is required.⁴⁸ Spacers, which are classified as tube extensions to the inhaler mouthpiece and valved holding chambers, can be used with a pMDI to make hand-breath coordination easier and lessen oropharyngeal drug deposition.⁴⁷ pMDIs are portable and compact, provide consistent dosing and rapid delivery, are relatively inexpensive, are available for most inhaled medications, and may have a dose-counter.⁴⁶

Soft-mist inhalers

SMIs, the newest inhaled delivery device, offer a convenient dosing option. In contrast to the mist from a pMDI, an SMI delivers a propellant-free, slow-moving, very fine liquid mist that aids in hand-breath coordination and drug deposition.⁴⁸ SMIs are portable, compact, and contain a dose counter, but they do require the patient to have manual dexterity and strength to load the drug-containing canister prior to first use.⁴⁶

Dry powder inhalers

DPIs deliver a dry powder formulation of drug to the lungs upon breath actuation, thereby eliminating the need for hand-breath coordination. Like pMDIs, they are portable and compact. In addition, DPIs may have feedbacks (e.g., audible clicking sound) that indicate correct drug administration, and they may contain a dose counter. Several different types of DPIs exist, each with multiple different steps for use, which may require manual dexterity. For example, some DPIs require the patient to load and pierce a capsule (single-dose devices), while others come with multiple doses that are loaded when the patient performs a function (e.g., opening a cap, sliding a lever, or pressing a button). Since the devices are breath actuated, consideration must also be given to the patient’s ability to generate sufficient inspiratory flow.⁴⁹

Nebulizers

Nebulizers are another widespread method for aerosol medication delivery, especially in the institutional setting. Various types of nebulizers are available, but all work by aerosolizing a liquid to a mist. Nebulizers allow the patient to breathe calmly, deeply, and evenly through a mouthpiece or facemask and require less coordination than inhaled delivery devices. Some patients and care providers consider nebulizers to be the easiest device to use, but assembly, disassembly, cleaning, and maintenance may be complex. Additionally, nebulizers are bulky, require approximately 10 to 15 minutes for medication delivery, and can be costly.⁴⁷

Inhaler counseling

Proper use of inhaled delivery devices is essential to achieve the desired effect. Studies have shown that only 6% of patients have optimal skill and adherence with inhaled delivery devices.¹¹ Reduced dosing frequency and simplicity of a medication regimen may improve adherence.⁵⁰ Additionally, it has been reported that 76% of patients using an MDI make at least 1 error when using an inhaler device, and between 4% and 94% of patients using a DPI do not use it correctly. The most commonly reported errors are related to dose preparation, exhaling prior to dose, inspiratory flow, inhalation duration, and hand- breath coordination.⁴¹ Literature also suggests that prescribing multiple types of inhaled delivery devices could reduce the effectiveness of a regimen due to incorrect inhaler technique from “device dementia.”^51,52 This emphasizes the need for education on proper inhaler technique and represents an excellent opportunity for pharmacists to provide COPD education.

Product-specific prescribing information should always be consulted in preparation for patient counseling; however, the following general counseling points can be used as a guide when educating patients about proper inhaler technique.

For proper pMDI use⁵³:

1. Take off mouthpiece cap and shake inhaler well before each spray
2. Prime pMDI before first use and per manufacturer’s instructions
3. Breathe out through mouth completely to empty lungs
4. Put mouthpiece between lips and close lips tightly around mouthpiece
5. Push top of canister down while breathing in deeply and slowly through mouth (3 to 5 seconds)
6. Hold breath as long as possible, up to 10 seconds
7. Take inhaler out of mouth and breathe out slowly
8. If needed, wait 1 minute between sprays then repeat steps above from “step 4”
9. Replace cap on mouthpiece
10. Store and maintain pMDI per device-specific instructions

For proper SMI use^18,23,28:

1. Prepare device for use per manufacturer-specific instructions
2. Prime SMI before first use and per device-specific instructions
3. Hold inhaler upright with cap closed and turn base half of a turn until it clicks
4. Flip cap open
5. Breath out slowly and fully, then close lips around end of mouthpiece
6. Point SMI toward back of throat
7. Take slow, deep breath through mouth while pressing dose-release button
8. Hold breath for 10 seconds or for as long as possible
9. Store and maintain per device-specific instructions

For proper DPI use⁵³:

1. Remove cover and/or open per manufacturer-specific instructions
2. Hold device upright and do not shake
3. Load dose according to manufacturer-specific instructions (if necessary)
4. Breathe out completely to empty lungs, but do not exhale into device
5. Place mouthpiece between lips and close lips tightly around it
6. Take fast, deep, forceful breathin through mouth; may need to repeat if not empty
7. Hold breath as long as possible, at least 10 seconds
8. Take inhaler out of mouth and breathe out slowly, away from inhaler
9. If needed, wait 1 minute between inhalations, then repeat steps above from “step 2”
10. Close device, and store and maintain per device-specific instructions

For proper use of nebulizer solution⁵³:

1. Assemble nebulizer machine, tubing, medicine cup, and mouthpiece or mask according to manufacturer’s instructions
2. Pour prescribed amount of medicine into medicine cup
3. Place mouthpiece in mouth and seal lips tightly around it or place face mask over nose and mouth
4. Turn on nebulizer machine
5. Breathe normally through mouth until all medication is gone (approximately 10 minutes)
6. Take mouthpiece out of mouth or remove mask and turn off nebulizer machine

Pharmacists and other health care professionals should remember to provide clear, verbal instructions at the appropriate level of patient understanding. Pharmacists can demonstrate proper inhaler technique and then allow the patient to repeat the demonstration while providing feedback and correcting improper technique, if necessary. Ideally, patients should receive inhaler technique education at initial prescribing and upon each medication refill to ensure adequate technique and adherence to therapy.

NONPHARMACOLOGIC THERAPY FOR COPD

Despite the availability of pharmacologic therapies available for COPD management, nonpharmacologic approaches and lifestyle changes are vital to improving outcomes.

Smoking cessation

Smoking cessation is fundamental to the management of COPD. Smoking cessation is associated with a decrease in symptoms, improvement in health status, and improvements in the rates of lung loss and survival among patients with mild to moderate COPD.⁵⁴ Patients with COPD who continue to smoke should receive education about smoking cessation and be encouraged to quit. A 5-step strategy for smoking cessation, known as the “5 A’s” is recommended for successful intervention.

First, tobacco use should be identified by asking the patient about use at each contact and documenting findings. Patients identified as tobacco users should be advised to quit in a personalized and motivational manner. The next step is to assess the patient’s readiness to quit. If the patient is ready to quit, assistance, consisting of counseling with or without medication therapy, should be provided.⁵⁵ First-line pharmacologic agents for smoking cessation are varenicline and bupropion extended release. Prescription and over-the-counter nicotine replacement products (i.e., patches, lozenges, gums, nasal sprays, oral inhalers) are also available.¹ Finally, follow-up care should be arranged. Expert counselors trained to help smokers quit and provide a variety of smoking cessation resources can be reached at 1- 800-QUIT-NOW (1-800-784-8669).

Vaccinations

The Centers for Disease Control and Prevention recommend that people with COPD receive proper vaccinations. Specifically, those with COPD are at higher risk for complications from influenza, such as pneumonia; therefore, a yearly influenza vaccine should be administered. Influenza vaccination reduces serious illness and death in COPD patients (Evidence level B).¹ In addition, the pneumococcal vaccines are recommended for people with COPD.¹ According to the 2017 Immunization Schedule for Adults, patients 19 through 64 years of age with COPD should receive the pneumococcal polysaccharide vaccine (PPSV23).⁵⁶ It has been shown to reduce the incidence of community-acquired pneumonia in COPD patients younger than 65 years with an FEV₁ lower than 40% predicted and in those with comorbidities (Evidence level B).¹ After age 65 years, they should receive the pneumococcal conjugate vaccine (PCV13) and 1 more dose of PPSV23 at least 1 year after PCV13 and at least 5 years after the most recent dose of PPSV23.⁵⁶

Pulmonary rehabilitation

Pulmonary rehabilitation is another nonpharmacologic component of COPD care. It is defined by the American Thoracic Society and the European Respiratory Society as “a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.”⁵⁷ Pulmonary rehabilitation should be a part of COPD management for patients categorized as having B, C, or D severity disease. Pulmonary rehabilitation improves dyspnea, health status, and exercise tolerance in stable patients (Evidence level A) and reduces hospitalizations among patients who have had a recent exacerbation (Evidence level B).¹

CHRONIC CARE MODEL FOR COPD

The Chronic Care Model (CCM) is an approach to caring for people with chronic disease in the primary care setting that incorporates 6 components of patient-centered and evidence-based care: the community; the health system; self-management support; delivery system design; decision support; and clinical information systems.⁵⁸ This model is helpful to shift the focus of COPD management from acute exacerbation treatment to proactive diagnosis and chronic care.

Patient and caregiver education for self-management is fundamental to the CCM. Education topics to actively engage patients in COPD management can include basic disease state education; approaches to therapy; inhalation devices and instructions for use, including differentiation between long- term control and quick-relief medications; desired therapeutic outcomes; smoking cessation and avoidance of harmful exposures; methods to lessen dyspnea; and end-of-life care. Instructions on when to seek help and decision-making during exacerbations can be outlined through COPD action plans.¹ An example of a COPD action plan that is intended to be developed by the patient with his/her physician or health care provider is available from the American Lung Association.⁵⁹ Comprehensive approaches that not only address COPD knowledge and education but also health literacy, motivation, beliefs, experiences, and behavioral changes are effective. Addressing comorbid disease states is also important.^60,61

Addressing comorbidities

COPD is associated with many systemic manifestations and comorbid conditions that impact health outcomes, risk for hospital admission, and mortality.⁶² Optimal care for a patient with COPD also involves proper care of coexisting conditions according to the disease state’s guideline recommendations. Pharmacologic considerations mentioned in the 2017 GOLD Report for the management of specific comorbidities include using β1-selective beta-blockers for patients with COPD and heart failure; using caution with SABAs and theophylline in patients with atrial fibrillation; and avoiding repeated courses of systemic corticosteroids for the management of COPD exacerbations due to the risk for osteoporosis. Management of comorbid anxiety and depression is also helpful for overcoming therapy nonadherence.⁶⁰ Overall, treatment regimens should be simplified as much as possible to avoid polypharmacy in patients with COPD and 1 or more chronic conditions.¹

SUMMARY

COPD is the third leading cause of death in the U.S. It is a common, preventable, and treatable chronic respiratory disease. The 2017 GOLD Consensus Report is a helpful guide for health care professionals to use in providing evidence-based and effective care for patients with COPD and focuses on the prevention of exacerbations. Since inhaled therapies are central to the chronic management of COPD, patient education on proper inhaler technique is essential to achieve the desired therapeutic effect. Additionally, pharmacists can ensure that appropriate nonpharmacologic management, including smoking cessation and vaccinations, as well as the management of comorbidities, is provided as part of a comprehensive management plan.

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