Chronic Obstructive Pulmonary Disease - COPD Materials

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

AMANDA MAYER, PharmD

Amanda Mayer is a graduate of the University of Montana, Skaggs School of Pharmacy. She has clinical experience working in inpatient mental health, which is her passion. She has also done fill-in work at retail pharmacies throughout her career. Amanda appreciates the wide variety of professional opportunities available to pharmacists. Amanda loves spending time with her family and spends most of her free time exploring new restaurants, hiking in the summer, and snowboarding and cross-country skiing in the winter.

Topic Overview

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable public health challenge that is now one of the top three causes of death worldwide. COPD is characterized by chronic respiratory symptoms which cause airflow obstruction that is persistent and often progressive. The appropriate and early diagnosis of COPD can help guide treatment and increase the quality of life in those with COPD. Pharmacotherapy reduces symptoms, frequency, and severity of COPD exacerbations. Fortunately, there are several available options for the treatment of COPD, and treatment regimens should be individualized for the specific patient.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-23-165-H01-P

Pharmacy Technician  0669-0000-23-166-H01-T

Credits: 1 hour of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $4.99

Estimated time to complete activity: 1 hour, including Course Test and course evaluation

Release Date: September 28, 2023 Expiration Date: September 28, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From September 28, 2023, through September 28, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

List the diagnostic criteria and common clinical presentation of COPD

Identify risk factors that can increase the risk of developing COPD or increase COPD exacerbations

Discuss pharmacotherapy options for COPD exacerbations

Outline treatment options for the management of stable COPD

Disclosures

The following individuals were involved in developing this activity: Amanda Mayer, PharmD, Jeff Goldberg, PharmD, BCPP, and Pamela Sardo, PharmD, BS. Pamela Sardo was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Introduction

Chronic obstructive pulmonary disease is a chronic respiratory lung condition. It results from a combination of genetic and environmental factors that can lead to lung damage over time. Symptoms include dyspnea, cough, and sputum production, which may be due to abnormalities of the airways or alveoli, leading to progressive airflow obstruction. Pharmacologic therapy and lifestyle changes can help to manage chronic obstructive pulmonary disease. Choosing medications for a patient should be individualized, with the availability, cost, side effects, and clinical response all being considered.

The Prevalence and Burden of COPD

Chronic Obstructive Pulmonary Disease (COPD) is an important public health challenge that remains one of the top three causes of death worldwide despite being preventable and treatable.1 In 2012, more than 3 million people died of COPD, which accounted for 6% of all deaths globally.2 In the United States, almost 15.7 million Americans (6.4%) reported having a COPD diagnosis, with some adults unaware that they have COPD.3 The prevalence of COPD varies across countries; however, it has been found that COPD prevalence is directly related to the prevalence of tobacco smoking.4 Continued exposure to COPD risk factors, and the aging of the world population, are expected to increase the prevalence and burden of COPD over the coming decades.5

The initial goal of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report was to increase awareness of the burden of COPD and improve the prevention and management of COPD.6 The current GOLD Report provides a non-biased review of current evidence regarding the assessment, diagnosis, and treatment of people with COPD.6 Treatment for COPD can be broken into objectives directed toward relieving and reducing the impact of symptoms and objectives that reduce the risk of adverse health events that may affect the patient at some point in the future.6

What is COPD

COPD is a lung condition characterized by chronic respiratory symptoms such as dyspnea, cough, sputum production, and/or exacerbations. COPD may be due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema), which can cause persistent and often progressive airflow obstruction.7 COPD results from gene(G)-environment(E) interactions that occur over the lifetime(T) of an individual (GETomics), which can damage the lungs. These GETomics can damage the lungs and/or alter their normal development and aging processes.8

Tobacco smoking and the inhalation of toxic particles and gasses from household and outdoor air pollution are the main environmental exposures that can lead to COPD.9 Individuals who smoke cigarettes have a higher prevalence of respiratory symptoms and lung function abnormalities. Smokers have a greater annual rate of decline in FEV1 (forced expiratory volume over 1 second) and a greater COPD mortality rate than non-smokers.10 Smoking during pregnancy may increase the risk of altered lung growth in the fetus.11 Tobacco use is the leading risk for COPD in high-income countries; however, in low to middle-income countries, the risk of developing COPD is sometimes attributed more to environmental exposures.9 Examples of outdoor, occupational, and household air pollution include the burning of wood and other biomass fuels.12 Genetic risk factors can also lead to COPD - the most relevant being a mutation in the SERPINA1 gene, which is epidemiologically rare.6

The current GOLD report has proposed taxonomy (etiotypes) for COPD that extend past the traditionally known smoking causation. These proposed etiotypes have little impact on clinical practice but highlight the need to explore current and future therapies based on COPD causes. These include the following:6,13

Genetically determined COPD (COPD-G): Alpha-1 antitrypsin deficiency and other genetic variants with smaller effects acting in combination

COPD due to abnormal lung development (COPD-D): early life events, including premature birth and low birth weight

Cigarette smoking COPD (COPD-C): exposure to tobacco smoke, including in utero or via passive smoking, vaping or e-cigarette use, and cannabis

Biomass and pollution exposure COPD (COPD-P): household pollution, ambient air pollution, wildfire smoke, occupational hazards

COPD due to infections (COPD-I): childhood infections, tuberculosis- associated COPD, HIV-associated COPD

COPD and asthma (COPD-A): particularly childhood asthma

COPD of unknown cause (COPD-U)

Diagnosis and Clinical Presentation

Airflow obstruction can be caused by a mixture of small airway disease and parenchymal destruction.6 Small airway disease increases airway resistance and parenchymal destruction, also known as emphysema, which can reduce the normal elastic recoil of the lung parenchyma.6 The reduction of normal elastic recoil of the lung parenchyma can also be caused by chronic inflammation of the lungs, which may cause structural changes. These changes decrease the ability of the airways to remain open during expiration and can limit the emptying of the lungs during forced expiration, decrease the FEV1 and FEV1/FVC ratio (forced expiratory volume/forced vital capacity), and contribute to gas trapping as well as lung hyperinflation.6 The outcomes of these various airflow obstruction causes may be measured by spirometry, a widely available and reproducible lung function test.6

The presence of non-fully reversible airflow limitation (a post- bronchodilator FEV1/FVC <0.7 spirometry reading) is mandatory to diagnose a patient with COPD.6 Patients with dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors should be considered for testing.6 Some individuals are labeled as ‘Pre-COPD’ which includes the presence of structural lung lesions such as emphysema and/or physiological abnormalities without airflow obstruction. These physiological abnormalities

may include low-normal FEV1, gas trapping, hyperinflation, reduced lung diffusing capacity, and/or rapid FEV1 decline. Individuals with a normal FEV1/FVC ratio but abnormal spirometry may be termed with ‘PRISm,’ meaning Preserved Ratio Impaired Spirometry.6 Individuals with Pre-COPD or PRISm may be at risk of developing airflow obstruction over time; however, not all patients do. Under and misdiagnosis of COPD can cause individuals to receive no treatment or incorrect treatment.6

Once COPD has been diagnosed and confirmed by spirometry, there are four fundamental aspects to help guide therapy: severity of airflow limitation, nature and magnitude of current symptoms, previous history of moderate and severe exacerbations, and the presence and type of other diseases.6 The GOLD grades and severity of airflow obstruction based on post-bronchodilator FEV1 (% reference) in COPD are as follows:6

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

If a patient is suspected to have COPD, a thorough medical history should be collected.6 An important aspect of medical history collection is a patient’s exposure to risk factors, past medical history, and family history. The pattern of development of symptoms can help to differentiate between COPD and other lung issues.6

The impact of disease on a patient’s life should also be evaluated. This assessment should review the economic impact and general well-being of the patient. More specifically, the limitation of activities, missed work, impact on family routines, depression or anxiety, and sexual activity should all be considered. While collecting medical history, inquiring about social and family support available to the patient and possibilities for reducing risk factors may help to guide treatment.6

COPD may have a clinical presentation that includes dyspnea, wheezing, chest tightness, fatigue, activity limitation, and cough (with or without sputum production).6 Some or all of these symptoms may be present, and symptoms may vary on a daily basis. It may be useful to use the Dyspnea questionnaire or other multidimensional questionnaires to help gauge a patient's symptoms. Dyspnea may be progressive over time, worse with exercise, and/or persistent.6 Patients may describe dyspnea as a sense of increased effort to breathe, chest heaviness, air hunger, or gasping.14 Chronic cough can often be an overlooked symptom of COPD as it is an expected consequence of smoking and/or environmental exposure.6 Other causes of chronic cough may include asthma, lung cancer, tuberculosis, bronchiectasis, left heart failure, interstitial lung disease, cystic fibrosis, idiopathic cough, chronic allergic rhinitis, post nasal drip syndrome, upper airway cough syndrome, gastroesophageal reflux, and due to medication. The cough (productive or unproductive) may be intermittent and, over time, more prevalent.6

Individuals with COPD may experience exacerbations, which are acute events characterized by an increase in respiratory symptoms.6 Patients with COPD may have other comorbidities that can mimic or aggravate an acute exacerbation. Individuals with asthma have been found to have an increased risk of developing chronic airflow obstruction and COPD. Differentiating the symptoms of asthma and COPD in adults may be clinically difficult due to similar symptoms.6 When comparing the symptoms of COPD and asthma, the following suggestive features might help. COPD symptoms are slowly progressive, with a history of tobacco smoking or other risk factors.6 Suggestive features of asthma include variable airflow obstruction, symptoms that vary widely from day to day, symptoms that are worse at night/early morning, allergy, rhinitis, and/or eczema are also present, often occurring in children. The patient’s family history of asthma is also reviewed and considered.15

Patients with COPD may also present with chronic bronchitis.6 Chronic bronchitis is defined as the presence of cough with expectorated sputum for at least 3 months per year for two consecutive years. A caveat to the definition

of chronic bronchitis is that those symptoms are present in the absence of other conditions that can explain the symptoms.6

Two commonly used scales to help assess COPD in a patient include the modified Medical Research Council dyspnea scale (mMRC) (Table 1) and the COPD Assessment Test (CATTM) (Table 2).6 The mMRC is a scale that helps to measure breathlessness and grades a patient from 0 to 4. The CATTM is more multidimensional and is an 8-item questionnaire to help assess the health status of a patient with COPD. The CATTM has scores that can range from 0 to 40.6

Table 1: mMRC Dyspnea Scale6,16

Table 2: CATTM Assessment6,17

CATTM Assessment - patients are to rate 0 to 5 on each of the following items. Score of 0 being closer to “I have no limitation” with the examples on the left, and score of 5 being limitations and closer to the statements on the right.

Smoking Cessation and Vaccinations

Despite smoking cessation being a key to decreasing the risks and progression of COPD, approximately 40% of those with COPD are current smokers.18 There are several pharmacotherapies for smoking cessation, including nicotine replacement products (nicotine gum, inhaler, nasal spray, transdermal patch, sublingual tablet, or lozenge), bupropion, varenicline, naltrexone, nortriptyline, and clonidine.6 Patients must be willing to stop smoking, and healthcare providers should recognize that relapse is common and reflects the chronic nature of dependence and addiction to tobacco products.6 The five-step program (also called the 5A’s) for intervention to help the patient willing to quit includes the “ask, advise, assess, assist, and

arrange.”19 All patients should be asked about tobacco use at every visit. Patients who use tobacco, with or without a diagnosis of COPD, should be strongly urged to quit. If the patient uses tobacco, the provider should assess the willingness and rationale of the patient’s desire to make a quit attempt. Providers should assist the patient in quitting and help to come up with a plan, support, and pharmacotherapy. Follow-up contact should be arranged to help the patient succeed.19

The current GOLD guidelines recommend patients with COPD receive the following vaccinations:6

Yearly Influenza vaccine to protect against influenza

SARS-CoV-2 in line with national recommendations to protect against COVID-19

One dose of 20-valent pneumococcal conjugate vaccine (PCV20) or one dose of 15-valent pneumococcal conjugate vaccine (PCV15) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to protect against community-acquired pneumonia and exacerbations in people with COPD

Tdap (dTap/dTPa) to protect against pertussis if not vaccinated in adolescence

Zoster vaccine to protect against shingles for people with COPD over 50 years

Pharmacotherapy

Reduction in symptoms, frequency, and severity of exacerbations, along with improving exercise tolerance and health status, are the goals of pharmacologic therapy for COPD.6 While no trials have been sufficiently conclusive showing that pharmacotherapy can reduce the rate of FEV1 decline, maintenance therapy can help to manage COPD.6 Choosing medications for a patient should be individualized, and the availability, cost, side effects, and clinical response should all be considered. The availability of agents is constantly changing, and consideration of the patient’s ability to use a

metered dose inhaler (MDI), dry powder inhaler (DPI), soft mist inhaler (SMI), and nebulizer should be considered. Combination products are available and should be considered when appropriate. Package insert material should be referenced for all dosing-related questions.6

Delivery of many medications used for COPD is done through inhalation delivery devices such as nebulizers, MDI, DPI, and SMIs.6 The proper education and training on the use of these devices is key to treatment success. Instructions vary for each type of device, and pharmacy staff should familiarize themselves with each device that is carried.6 Errors in device use often lead to problems with inspiratory flow, coordination, inhalation duration, preparation of dose, exhalation maneuver prior to inhalation, and breath- holding following dose inhalation.20 Dry powder inhalers are only appropriate if the patient is able to make forceful and deep inhalations.6 The ‘teach-back’ method can be used to help gauge a patient's understanding of inhaler use. Patients should be prescribed a spacer/valved holding chamber if there is doubt they will be able to use a pressurized metered dose inhaler correctly.6 Spacers help to reduce difficulties that can be caused by poor coordination, increase pulmonary and reduce oropharyngeal deposition, and minimize the risk of oropharyngeal candidiasis with ICS.21

Adherence to medication can be a challenge with COPD, and along with other factors, medication delivery device consideration can be a key part of increasing adherence.6 Non-adherence is associated with poor symptom control, increased risk of exacerbation, increased healthcare costs and utilization, increased mortality risk, and decreased quality of life. Proper inhaler technique and medication adherence should be assessed prior to determining that current therapy is insufficient.6

Bronchodilators

Bronchodilators include beta2-agonists and antimuscarinic agents. Bronchodilators are commonly used as maintenance therapy; however, they

may also be used for some occasional symptoms or immediate symptom relief.6

Beta2-agonists

Beta2-agonists help to relax the airway smooth muscle by stimulating beta2-adrenergic receptors that increase cyclic AMP and produce antagonism to bronchoconstriction to help prevent or reduce symptoms of COPD.6 The improvements in expiratory flow and potential increase in FEV1 reflect a widening of the airways rather than changes in elastic lung recoil.6 Short- acting beta2-agonists (SABA) have an effect that lasts 4 to 6 hours and can be used on a regular or as-needed basis to help improve FEV1 and symptoms.22-24 SABA include fenoterol, levalbuterol, albuterol, and terbutaline.6 Although concerns of loss of lung function or increased mortality have been reported with the use of SABAs in asthma treatment, no association between SABAs and these outcomes has been reported in COPD.6 Long-acting beta2-agonists (LABA) have a duration of action of 12 or more hours. LABA include arformoterol, formoterol, indacaterol, olodaterol, and salmeterol. Resting sinus tachycardia that has the potential to precipitate cardiac rhythm disturbances in susceptible patients is an adverse effect to monitor for with the stimulation of beta2-adrenergic receptors.6

Antimuscarinic Drugs

Antimuscarinic drugs also referred to as anticholinergics work by blocking the bronchoconstriction effects of acetylcholine on M3 muscarinic receptors that are expressed in airway smooth muscle.25 Some antimuscarinic agents also bind to M2 receptors that can potentially cause vagally induced bronchoconstriction. Short-acting antimuscarinics include ipratropium bromide and oxitropium bromide, which have a duration of action lasting 6 to 9 hours.6 SAMAs have been shown to provide small benefits over SABAs for lung function, health status, and requirement for oral steroids.26 Long-acting antimuscarinic (LAMA) agents that can help improve symptoms such as cough, sputum, and health status include aclidinium bromide, glycopyrronium

bromide, tiotropium, umeclidinium, glycopyrrolate, and revefenacin.6 Dosing schedules for LAMAs should be confirmed as there are some that may be administered once a day and others require twice daily dosing. LAMAs can help to reduce exacerbations and related hospitalizations. Systemic adverse effects are limited as inhaled anticholinergic drugs are poorly absorbed. One of the main side effects is mouth dryness, and some patients who have taken ipratropium report a bitter, metallic taste.6 Cardiovascular function should be monitored as there has been a small increase in cardiovascular events in patients regularly treated with ipratropium bromide.27,28

Methylxanthines

Methylxanthines such as aminophylline and theophylline sustained release are systemic oral medications whose exact effects on COPD are unknown. It is thought that they may act as non-selective phosphodiesterase inhibitors. Although the significance has been disputed, methylxanthines have been reported to have a range of non-bronchodilator actions.29,30 Theophylline does exert a small bronchodilator effect in patients with stable COPD.6 Methylxanthines cause more side effects (insomnia, headache, nausea, heartburn) and have significant interactions with commonly used medications (erythromycin, ciprofloxacin, allopurinol, cimetidine, fluvoxamine) than medications previously discussed. Atrial and ventricular arrhythmias and grand mal convulsions are side effects that may steer a provider away from choosing a methylxanthine over other options for COPD. Toxicity is dose- related, and clearance of the drug declines with age.6

Combination Bronchodilator Therapy

Combination products of LABA+LAMA, SABA+SAMA, and LABA+ICS (inhaled corticosteroids), and LABA+LAMA+ICS, exist and may be considered.6 Combining bronchodilators with different mechanisms and durations of action can help to increase the degree of bronchodilation and lower the side effects of having a high dose of a single bronchodilator. The combination of SABA+SAMA has been shown to be superior to either

medication alone.6 Combining LABAs and LAMAs helps to improve lung function significantly, as well as health status. It also improves dyspnea, reduces exacerbations, helps to increase FEV1, and reduces symptoms when compared to monotherapy. Also, in patients with moderate to very severe COPD, LABA+ICS therapy is more effective at improving health status by helping lung function and reducing exacerbations when comparing the results from using either product alone. Combination therapy can be helpful as single inhaler therapy is more convenient than having multiple inhalers.6

Table 3: Current Combinations Available Per GOLD Guidelines6

Anti-inflammatory agents

The main clinically relevant end-point to assess the efficacy of anti- inflammatory drugs is the exacerbation rate. Anti-inflammatory therapy

recommended in stable COPD includes inhaled corticosteroids, PDE4 inhibitors, and antibiotics.6

Inhaled Corticosteroids

Inhaled corticosteroids that can be used for COPD include beclomethasone, budesonide, fluticasone, and mometasone.6 Inhaled respiratory corticosteroids help to reduce bronchial inflammation by binding to glucocorticoid cytoplasmic receptors. This action leads to either the induction of potent anti-inflammatory mediators or the repression of transcription of proinflammatory mediators.31,32 Regular treatment with ICS can be of concern as it may increase the risk of pneumonia, especially in patients with severe disease.6 A higher risk of pneumonia in patients taking ICS is seen in patients who are 55 or older, with a history of prior pneumonia or exacerbations, BMI < 25 kt/m2, a poor dyspnea grade, and/or severe airflow obstruction.6 Evidence has shown that ICS use can modify the airway microbiome and is associated with a higher prevalence of oral candidiasis, hoarse voice, skin bruising, and pneumonia.6 Patients should always rinse their mouth after using an inhaler containing ICS. Most studies have found that treatment with an ICS alone does not modify the long-term decline of FEV1 or mortality in patients with COPD, and long-term monotherapy is not recommended.6

The GOLD Report strongly favors adding ICS to long-acting treatment when there is a history of hospitalization for COPD exacerbation, 2 or more moderate exacerbations of COPD per year, blood eosinophils ≥ 300 cells/µL, and history of or concomitant asthma.6 Use of an add-on ICS is favorable when there is 1 moderate exacerbation of COPD per year and blood eosinophils range from 100 to <300 cells/µL. Use of ICS as an add-on treatment should not be done if a patient has had repeat pneumonia events, blood eosinophils

<100 cells/µL, or a history of mycobacterial infection.6

Phosphodiesterase-4 (PDE4) Inhibitors

Phosphodiesterase-4 inhibitors, such as roflumilast, reduce inflammation by inhibiting the breakdown of intracellular cyclic AMP.33 Roflumilast does not have direct bronchodilator activity and is taken as a once- daily oral medication.6 Roflumilast helps patients with moderate to severe COPD exacerbations with chronic bronchitis treated with systemic corticosteroids, severe to very severe COPD, and patients with a history of exacerbations. Roflumilast is an option for patients who are not controlled on fixed-dose LABA+ICS combinations, and positive effects on lung function can be seen when roflumilast is added to long-acting bronchodilators.6 Side effects commonly seen with PDE4 inhibitors are diarrhea, nausea, reduced appetite, abdominal pain, weight loss, headaches, and sleep disturbances. These side effects seem to occur early in treatment and diminish over time with continued treatment.6

Antibiotics

Controversy over the efficacy in reduced exacerbations with the prophylactic continuous use of antibiotics exists.6 Older studies show no effect, while some later studies show they may help reduce the exacerbation rate. The two antibiotics most frequently used are azithromycin 250 mg per day or 500 mg three times per week or erythromycin 250 mg twice daily for one year. These medications can be used for patients prone to exacerbation; however, the risk of increased bacterial resistance, prolonged QTc interval, and impaired hearing tests limit their use.6

Treatment and Management of Stable COPD

Initial treatment of COPD should be based on the patient’s GOLD group.6 The severity of airflow obstruction, symptoms, history of exacerbations, exposure to risk factors, and comorbidities guide treatment of COPD.6 Treatable traits of COPD include breathlessness and exercise limitation as well as exacerbation frequency while on maintenance therapy, which helps guide

escalation and de-escalation. Although asthma and COPD may coexist in an individual patient, pharmacotherapy should primarily follow asthma guidelines while considering pharmacologic and nonpharmacologic approaches that may also be needed for their COPD. Treatment goals for stable COPD include reducing symptoms (relieving symptoms, improving exercise tolerance, improving health status) and reducing risk (preventing disease progression, preventing and treating exacerbations, and reducing mortality).6

Of the bronchodilators, long-acting agents are preferred over short- acting agents except in patients with only occasional dyspnea.6 Rescue short- acting bronchodilators should be provided for patients who need immediate symptom relief and may also be used in patients who are already on long- acting bronchodilators for maintenance therapy. Initial therapy should include a LAMA+LABA combination. When an ICS is indicated, the combination of LABA+LAMA+ICS has been shown to be superior to LABA+ICS therapy. If a patient has COPD and asthma, treatment should contain an ICS.6

Initial therapy can be broken off based on mMRC and CATTM scores as follows.6

Patients considered Group A have zero to one moderate exacerbations that do not lead to hospital admission.

mMRC score of 0-1 or a CATTM score of less than 10.

Initial treatment with a bronchodilator (long- or short-acting) may be appropriate.

Patients considered Group B with zero to one moderate exacerbations that do not lead to hospital admission.

mMRC score of 2 or more or a CATTM score of more than 10.

LABA+LAMA initial treatment is preferred.

Patients considered Group E with 2 or more moderate exacerbations or one or more exacerbations leading to hospitalization.

Initial treatment should be LABA+LAMA therapy with the consideration of LABA+LAMA+ICS if blood eosinophils are greater than 300.

This therapy may be more convenient and effective if given in a single inhaler instead of using multiple inhalers.

After initial treatment, a review of management includes symptoms such as dyspnea and exacerbations.6 Inhaler technique and adherence should be assessed, as well as non-pharmacological approaches such as pulmonary rehabilitation and self-management education. After review and assessment, the therapy may be adjusted, which may include escalating, switching the inhaler device or medication type, or de-escalating. The cycle of review, assessment, and adjustment should be done frequently to help ensure optimal treatment.6 If the response to initial treatment is appropriate, it is advised to maintain that treatment option. If the response to initial treatment is not as expected, therapy should be evaluated.6

If dyspnea remains uncontrolled

The first step is to introduce a LABA or LAMA.

If there is still no symptom control, the next step is a LABA+LAMA.

If there is still no control, switching inhaler device or molecule, implementing or escalating non-pharmacologic treatments, and investigating and treating other causes of dyspnea should be done.

If exacerbation control is being targeted, there are two routes to take depending on blood eosinophil count. Blood eosinophils play a role in identifying if patients may have a greater likelihood of benefits in response to ICS. Both routes start with LABA or LAMA therapy.

If the blood eosinophils are less than 300, the next step is LABA+LAMA therapy.

If blood eosinophils remain under 100 but a patient is still having exacerbations, roflumilast (if a patient has an FEV1 less than 50% with chronic bronchitis) or azithromycin (if the patient is a former smoker).

If a patient with blood eosinophils less than 300 who is started on LABA+LAMA needs further treatment:

If blood eosinophils are greater than 100, the next step would be LABA+LAMA+ICS

If that is unsuccessful, roflumilast and azithromycin may be an option.

Patients with uncontrolled exacerbations who have started the first step of LABA or LAMA without success will go straight to LABA+LAMA+ICS if their blood eosinophils are greater than 300.

If treatment is unsuccessful, patients can be considered for roflumilast or azithromycin.

ICS can be withdrawn from therapy if pneumonia or other considerable side effects develop.

Smoking cessation and pulmonary rehabilitation are essential parts of nonpharmacologic COPD management.6 Physical activity is also recommended, and depending on local guidelines, vaccinations including influenza, pneumococcal, pertussis, COVID-19, and shingles may be recommended. Education and self-management interventions, including a written action plan, should be ongoing in treatment.6

Management of Exacerbations

COPD exacerbations are events characterized by increased dyspnea and/or cough and sputum that worsens in <14 days.6 These exacerbations may be accompanied by tachypnea and/or tachycardia. Exacerbations are often associated with increased local and systemic inflammation. COPD exacerbations may be triggered by a number of different factors that include respiratory infections (bacterial, viral, or a combination of both), environmental pollutants, or unknown factors. When a patient is experiencing an exacerbation, there is evidence of increased airway and systemic inflammation, increased gas trapping and hyperinflation with reduced expiratory flow, dyspnea, and worsening of ventilation-perfusion distribution abnormalities that can result in arterial hypoxemia.6 A key symptom of exacerbations is dyspnea and other symptoms may include increased sputum, cough, and wheezing.6 Classification of exacerbations is typically retrospective based on the treatment used. Mild exacerbation can be treated with short- acting bronchodilators only, moderate exacerbations are treated with short- acting bronchodilators and oral corticosteroids ± antibiotics, and severe

exacerbations require hospitalization or emergency room visits.6 A differential diagnosis of heart failure, pneumonia, or pulmonary embolism should be ruled out when a patient is being diagnosed with a COPD exacerbation.6

Treatment goals for COPD exacerbations include minimizing the negative impact of the current exacerbation and preventing the development of subsequent events.6 Exacerbations can be managed inpatient or outpatient, depending on the severity of the exacerbation and underlying disease.6 Potential indications for hospitalization may include severe symptoms, acute respiratory failure, cyanosis, peripheral edema, failure of exacerbation to respond to initial treatment, serious comorbidities, or insufficient support at home. Hospital management of exacerbations consists of respiratory support, which may include oxygen therapy or ventilation.6 In severe but not life- threatening exacerbation, the severity of symptoms, blood gasses, and a chest radiograph should be assessed. Supplemental oxygen therapy, bronchodilators, oral corticosteroids, oral antibiotics (when signs of bacterial infection are present), and noninvasive mechanical ventilation are treatments that may be considered.6

The initial medication regimen recommended to treat an acute exacerbation is SABA±ICS.6 These medications may be used as MDI or nebulizers, with nebulizers potentially being an easier delivery method for sicker patients. The GOLD report recommends continuing long-acting bronchodilators during an exacerbation or restarting as soon as possible. Systemic corticosteroids may help improve FEV1 and oxygenation and shorten recovery time and hospitalization.6 Prednisone-equivalent 40 mg per day for 5 days is the current recommendation.6,34 Some patients may respond well to nebulized budesonide.6 Oral glucocorticoids play a role in managing acute exacerbations and should not be used in the daily maintenance of COPD due to the high rate of systemic complications.6 If indicated, antibiotics can help shorten the recovery time, reduce the risk of early relapse or treatment failure, and reduce hospitalization duration. Increased sputum purulence may indicate a bacterial infection, which would warrant antibiotic treatment. Duration of antibiotics is typically 5 to 7 days, with 5 or less days being

preferred. The choice of antibiotics should be based on local resistance patterns with initial empirical treatments often including amoxicillin with clavulanic acid, macrolide, tetracycline, or quinolone.6 If a patient does require ventilation, non-invasive mechanical ventilation should be the first mode used in patients with acute respiratory failure.6

Summary

COPD is a lung condition characterized by chronic respiratory symptoms such as dyspnea, cough, sputum production, and/or exacerbations. COPD may be due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema), which can cause persistent and often progressive airflow obstruction. Airflow obstruction can be caused by a mixture of small airway disease and parenchymal destruction. The presence of non-fully reversible airflow limitation (a post-bronchodilator FEV1/FVC <0.7 spirometry reading) is mandatory to diagnose a patient with COPD.

Smoking cessation helps to decrease the severity and progression of COPD. Reduction in symptoms, frequency, and severity of exacerbations, along with improving exercise tolerance and health status, are the goals of pharmacologic therapy for COPD. Choosing medications for a patient should be individualized, with the availability, cost, side effects, and clinical response all being considered.

Course Test

Which of the following is not true regarding COPD?

COPD is a lung condition characterized by chronic respiratory symptoms

COPD may be due to abnormalities of the airways and/or alveoli that can cause persistent and progressive airflow obstruction.

Smoking status does not affect COPD

COPD results from gene-environment interactions over the lifetime of an individual

Which of the following GOLD report proposed etiotypes is matched correctly?

COPD-G: COPD due to abnormal lung development

COPD-C: COPD due to infections

COPD–A: COPD and Asthma

COPD-P: Genetically determined COPD

What post-bronchodilator FEV1/FVC spirometry reading is mandatory to diagnose a patient with COPD?

FEV1/FVC <0.9

FEV1/FVC <0.8

FEV1/FVC <0.7

FEV1/FVC <0.5

Patients who may be labeled as pre-COPD include

the presence of structural lung lesions such as emphysema and/or physiological abnormalities without airflow obstruction.

individuals who have a normal FEV1/FVC ratio but abnormal spirometry.

all individuals who smoke tobacco products.

patients with a diagnosis of asthma.

Which of the following is untrue of COPD symptoms?

Includes dyspnea, wheezing, chest tightness, fatigue

Can limit normal activity or exercise

Cough may or may not contain sputum production

All COPD symptoms must be present daily

Which of the following is true about inhalation devices?

Dry powder inhalers are the best option for patients unable to make forceful and deep inhalations.

The ‘teach-back’ method can help gauge a patient’s understanding of inhaler use.

Spacers/valved holding chambers are only used for inhaled corticosteroids.

The most important aspect of inhaler use is the availability to the patient, proper use does not play a role in effectiveness.

Which of the following is not considered a bronchodilator?

Beta2-agonists

Antimuscarinic agents

Methylxanthines

Phosphodiesterase-4 inhibitors

Initial therapy for patients with COPD should include which of the following?

LAMA+LABA

LABA+LAMA+ICS

SABA alone

ICS alone

How can blood eosinophils help to guide treatment?

Help to identify patients who may have a greater likelihood of benefits in response to SAMA.

Help to identify patients who may have a greater likelihood of benefits in response to LAMA.

Help to identify patients who may have a greater likelihood of benefits in response to ICS.

Help to identify patients who may have a greater likelihood of benefits in response to LABA.

Which of the following is true regarding a COPD exacerbation?

COPD exacerbations are characterized by increased dyspnea and/or cough and sputum that worsens in <14 days.

Local and systemic inflammation is typically not seen with a COPD exacerbation.

Viral and bacterial respiratory infections never cause COPD exacerbations.

Exacerbations must be managed in an inpatient hospital setting

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