Pharmacist CE LESSON. Breathe easy: with asthma/copd 1 MAY 2016

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1 to this lesson. By Clark Kebodeaux, Pharm.D., BCACP, assistant professor pharmacy practice and science, University of Kentucky College of Pharmacy Author Disclosures: Clark Kebodeaux and the DSN editorial and continuing education staff do not have any actual or potential conflicts of interest in relation Universal program number: H01-P Activity type: Knowledge-based Initial release date: May 13, 2016 Planned expiration date: May 13, 2019 This program is worth 2 contact hours (0.2 CEUs). Target Audience Pharmacists in community-based practice. Program Goal To provide pharmacists the foundational knowledge to impact care for patients with asthma and COPD. Learning Objectives Upon completion of this program, the pharmacist should be able to: 1. Recognize the pathophysiologic differences of asthma and COPD. 2. Describe classification criteria to help guide therapeutic choices in asthma and COPD. 3. Define emerging pharmacotherapy treatments for asthma and COPD. 4. Apply treatment recommendations and best practices in making therapy decisions for patients with asthma and COPD. 5. Identify educational opportunities to support patient adherence and clinical outcomes in asthma and COPD. To obtain credit: Complete the learning assessment and evaluation questions online at DrugStoreNewsCE.com. A minimum test score of 70% is needed to obtain a statement of credit. Your statement of credit will be available at CPE Monitor (NABP.net). Your correct e-pid number must be included in your DSN CE profile to ensure transmission of credit to CPE Monitor. Questions: Contact the DSN customer service team at (800) Drug Store News is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Breathe easy: Pharmacologic considerations in patients with asthma/copd INTRODUCTION Diseases of the lung, including asthma and chronic obstructive pulmonary disease, or COPD, remain a large public health burden in the United States, with direct and indirect medical costs in the billions. Recent prevalence data indicates that asthma affects more than 7% of the total population, and 8% of children, as of While this data shows a plateau from a peak of childhood prevalence in 2009, asthma remains the most common chronic disease among children. 1,2 COPD, as part of a larger group known as chronic lower respiratory diseases, is the third-leading cause of death in the United States. 3 These diseases primarily include emphysema and chronic bronchitis driven most often by a patient history of smoking. Mortality remains high in the United States even as age-adjusted mortality decreased over the past two decades in the European community. 4 Clearly, interventions with patients affected by diseases of the lung are needed to impact national statistics and individual patient quality of life. Community pharmacists are well positioned to impact patient care for those living with asthma and COPD. Both diseases require heightened awareness of appropriate management of acute episodes and effective long-term chronic management to improve and maintain lung function. By proactively evaluating patients and making appropriate medication and educational interventions, pharmacists can have an impact. BACKGROUND Asthma and COPD share some pathophysiologic characteristics of chronic inflammation, such as airway inflammation, airway obstruction and airway hyperreponsiveness. 5 One pathologic distinction of asthma and COPD is based in the immune system, where eosinophils and CD4 cells contribute to worsening asthma. Conversely, neutrophils and CD8 cells contribute to COPD. 6,7 The main pathophysiologic distinction is the level of airway obstruction. Asthma is typically reversible without progressive deterioration, and COPD is not reversible with progressive deterioration caused by the disease. Overlap syndrome is less commonly defined but has features of both diseases. This syndrome is the functional and pathologic overlap of asthma and COPD, and is more prevalent in the elderly. 5,8 Factors for diagnosis Smoking is the main risk factor for COPD worldwide. 9 Other risk factors for COPD include both indoor and outdoor pollution, occupational hazards and infection control methods. 6,9 Smoking cessation continues to be a mainstay of therapy for patients with COPD and patients with asthma. Hallmark symptoms of COPD include the presence of dyspnea, chronic cough and chronic sputum production. 7 If a patient experiences any hallmark symptom combined with a history of risk factors, spirometry should be performed to confirm a clinical diagnosis of COPD. If the patient has a forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) ratio less than 0.7 in the presence of a bronchodilator, this value confirms nonreversible airflow limitation. Asthma is diagnosed primarily by clinical history and symptomology. Patients should be assessed for signs and symptoms, such as wheezing, coughing and chest tightness, along with fre- 1 MAY

2 quency and time of occurrence. 6 All patients 5 years and older with signs and symptoms should undergo spirometry to determine if the airway obstruction is reversible. 6 In asthma, smoking is categorized with environmental risk factors including allergens, secondhand smoke and patient environment. 7,10 CLASSIFICATION In order for the pharmacist to assess patients and make appropriate therapy recommendations, it is important to be familiar with accepted classification criteria from the most recent clinical guidelines. 6,7 A careful analysis of symptoms reported by the patient can provide critical data even if routine access to spirometry results are not available in the community pharmacy. A thorough assessment can help the pharmacist to collaborate with the patients primary care provider and other members of the healthcare team to make interventions to ensure that patients are on optimal therapy. Clinical guideline-based classification criteria for COPD are included in Table 1. Current clinical standards recommend the use of the Global Initiative for Chronic Obstructive Lung Disease, or GOLD, classification method. The GOLD system is the result of collaborative efforts of the National Institutes of Health and the World Health Organization. Using this well-studied method, patients are placed into assessment groups based on increasing severity of symptoms. In GOLD, the A designation is linked to the lowest risk with minimal symptoms, while the D designation indicates the highest risk with most severe symptoms. There are four components necessary to determine the classification according to the GOLD classification. The components are airflow limitation, presence and severity of symptoms, episodes of breathlessness and exacerbation history. While pharmacists may not be able to determine the grade based on airflow limitations without spirometry data, exacerbations can be determined by a patient-reported history of hospitalization and/or a review of the patients profile for antibiotic use. Breathlessness is measured by the Modified Medical Research Council, or mmrc, Dyspnea Scale, 11 which is described in Table 2. Dyspnea is measured from no breathlessness outside of intense exercise to an inability to leave the house. Symptoms are measured by the COPD Assessment Test, or CAT, score on a symptom assessment. 12 The CAT system is a proprietary tool but consists of eight questions in which patients answer each statement on a scale from zero to five to help determine the impact of COPD. While there is some variability in applying either the mmrc or the CAT for classification, 13,14 using the exacerbation history and mmrc Table 1 GOLD classification guidelines (updated 2016) 7 Risk 4 2 (or 1 with 3 C D hospital admission) 2 1 A B 1 0 GOLD classification of airflow limitation mmrc 0-1 can allow the community pharmacist to help assess the patient for appropriate medication therapy for COPD. The classification criteria for asthma are more complex but can allow the pharmacist opportunities to assess impairment in multiple ways in the community pharmacy setting. According to guidelines published by the NIH and National Heart, Lung and Blood Institute, or NHLBI, the severity of asthma is divided into four components. Those are intermittent, mild-persistent, moderate-persistent and severe-persistent. 6 Control is classified in three ways once the patient has started therapy. The classification of control includes well-controlled, not well-controlled and very poorly controlled. Both severity and control are further broken down based on the patients age. Five measures of impairment are used to help classify and determine control of asthma: 1. Patients lung function; 2. Frequency of symptoms; 3. Amount of nighttime awakenings per week or month; 4. Frequency of short-action beta agonist (SABA) therapy per week; and 5. Interference with normal activity. mmrc 2 CAT < 10 CAT 10 Symptoms (mmrc or CAT score) Table 2 Modified medical research council (mmrc) dyspnea score 11 GRADE LEVEL OF DYSPNEA SYMPTOMS Grade 0 No dyspnea Not troubled by breathlessness except with strenuous exercise Grade 1 Slight dyspnea Troubled by shortness of breath when hurrying on a level surface or walking up a slight hill Grade 2 Moderate dyspnea Walks slower than normal based on age on a level surface due to breathlessness or has to stop for breath when walking on level surface at own pace Grade 3 Severe dyspnea Stops for breath after walking 100 yards or after a few minutes on a level surface Grade 4 Very severe dyspnea Too breathless to leave the house or becomes breathless while dressing or undressing Four of the five previous measures could be assessed during a pharmacist-patient encounter independent of lung function measurement. There is ample opportunity for this assessment given the frequency of interaction that patients with asthma have with the pharmacist when picking up medication. Taking a few minutes to communicate with the patient, assess overall control and therapy adherence and sharing the results and medication adjustment recommendations with other members of the healthcare team can improve outcomes for patients with asthma. THERAPEUTIC CONSIDERATIONS IN ASTHMA/COPD There are a variety of agents used to treat asthma, COPD or both. This activity will focus on the utility of each class in treatment while providing a summary of available agents in the United States. Table 3 reviews dosing and recommended maximum frequency of use. Short-acting beta agonists Short-acting beta agonist, or SABA, medications remain a consistent choice of therapy for patients with asthma. SABAs MAY Risk Exacerbation history

3 Table 3 Commonly used inhalers for asthma and COPD GENERIC NAME BRAND NAME AVAILABLE DOSES MAXIMUM FREQUENCY CORTICOSTEROIDS Beclomethasone QVAR 40 or 80 mcg/puff Two puffs twice daily Budesonide Pulmicort Flexhaler 90 or 180 mcg/puff Two puffs twice daily Ciclesonide Alvesco 80 or 160 mcg/puff Two puffs twice daily Fluticasone propionate Flovent HFA 44, 110 or 220 mcg/puff Two puffs twice daily Flovent Diskus 50, 100 or 250 mcg/inhalation Two inhalations twice daily Fluticasone furoate Arnuity Ellipta 100 or 200 mcg/inhalation One inhalation once daily Mometasone Asmanex HFA 100 or 200 mcg/puff Two puffs twice daily Asmanex Twisthaler 110 or 220 mcg/inhalation Two inhalations twice daily COMBINATION LABA AND CORTICOSTEROID Formoterol/Budesonide Symbicort 80/4.5 or 160/4.5 mcg/puff Two puffs twice daily Formoterol/Mometasone Dulera 100/5 or 200/5 mcg/puff Two puffs twice daily Salmeterol/Fluticasone Advair Diskus 100/50, 230/50, 500/50 mcg/inhalation One inhalation twice daily Advair HFA 45/21, 115/21, 230/21 mcg/puff Two puffs twice daily Vilanterol/Fluticasone Breo Ellipta 100/25, 200/25 mcg/inhalation One inhalation once daily LONG-ACTING BETA AGONISTS (LABA) Formoterol Foradil Aerolizer 12 mcg/inhalation One inhalation twice daily Indacaterol Arcapta Neohaler 75 mcg/inhalation One inhalation once daily Olodaterol Striverdi Respimat 2.5 mcg/two inhalations One inhalations once daily Salmeterol Serevent Diskus 50 mcg/inhalation One inhalation twice daily LONG-ACTING ANTICHOLINERGICS (LAAC) Aclidinium Tudorza Pressair 400 mcg/inhalation One inhalation twice daily Glycopyrrolate Seebri Neohaler 15.6 mcg/inhalation One inhalation twice daily Tiotropium Spiriva Handihaler 18 mcg/capsule (two inhalations) Two inhalations once daily Spiriva Respimat 1.25, 2.5 mcg/inhalation Two inhalations (2.5 mcg) once daily (Asthma) Two inhalations (5 mcg) once daily (COPD) Umeclidinium Incruse Ellipta 62.5 mcg/inhalation One inhalation once daily COMBINATION LABA AND LAAC Indacaterol/Glycopyrrolate Utibron Neohaler 27.5/15.6 mcg/inhalation One inhalation twice daily Olodaterol/Tiotropium Stiolto Respimat 2.5/2.5 mcg/inhalation Two inhalations once daily Vilanterol/Umeclidinium Anoro Ellipta 25/62.5 mcg/inhalation One inhalation once daily SHORT ACTING BETA AGONISTS (SABA) Albuterol ProAir HFA 90 mcg/puff Two puffs every four to six hours ProAir Respiclick 90 mcg/inhalation Two inhalations every four to six hours Proventil HFA 90 mcg/puff Two puffs every four to six hours Ventolin HFA 90 mcg/puff Two puffs every four to six hours Levalbuterol Xopenex HFA 45 mcg/puff Two puffs every four to six hours SHORT ACTING ANTICHOLINERGICS (SAAC) Ipratropium Atrovent HFA 17 mcg/puff Two puffs every six hours COMBINATION SABA AND SAAC Albuterol/Ipratropium Combivent Respimat 100/20 mcg/inhalation One inhalation every four hours continue to be the initial treatment for patients diagnosed with intermittent asthma and the drug of choice for patients with acute bronchospasm. 6 While not effective for long-term control, SABAs should be prescribed as rescue therapy concurrent with chronic therapy for treatment in cases of acute episodes. The frequency of SABA treatment can help the pharmacist determine the patient s level of asthma control. While patients experience immediate relief with these agents, it is important to counsel patients not to rely on these agents exclusively. Routine use can result in the loss of bronchoprotective effects over time. By assessing the refill history alone, a pharmacist can determine the number of canisters used per month. If the refill frequency is high, the pharmacist should have a discussion with the patient about the actual use, gathering details about times of day and severity of the acute events. The pharmacist can use this time to verify the link between fills of the product and actual use as patients 3 MAY

4 may be increasing fills to have access to treatment in multiple locations. If it is verified that the patient his using a SABA at a high frequency, it is an indication that the patient s asthma is not well-controlled, and he or she may be at an increased risk for a potentially fatal asthma attack. As counseling occurs when patients pick up refills, community pharmacists can play a significant role in overall education of appropriate inhaler technique and medication use. It is crucial to remind patients to always have a SABA inhaler with them to use as a rescue inhaler for acute attacks. Education also should stress the importance of appropriate storage, hygiene and mouthpiece cleaning requirements, as well as the correct positioning of the inhaler during use to achieve therapeutic doses. This education should be initially provided and assessed frequently during therapy to be sure that acute attacks can be quickly and effectively managed. While SABA therapy could help COPD patients experiencing an acute bronchospasm, inhaled short-acting therapy is typically administered in combination with an anticholinergic medication, such as ipratropium. The original HFA version of ipratropium/albuterol has been replaced with a new delivery device under the brand name Combivent Respimat. The Respimat delivery device is available with other inhalers and may be an appropriate recommendation for patients who already are familiar with the device. While both shortacting anticholinergic, or SAAC, therapy and SABA therapy are effective, the use of Combivent may provide additive bronchodilation in the treatment of COPD compared to SABA therapy alone. Inhaled corticosteroids Inhaled corticosteroid, or ICS, medications are effective treatments of asthma due to the high potency anti-inflammatory effect and specific exposure directly to the lungs, limiting potential systemic side effects. 6 These agents provide long-term prevention of symptoms and are the treatment of choice for patients with persistent asthma. ICS use in COPD is limited due to less effective response. Moreover, the GOLD guidelines do not recommend the use of ICS medications as monotherapy. The addition of ICS medications in COPD is limited to severe disease classifications (stages C and D), but are recommended with longacting beta-agonists at any stage. 7 Pharmacists can monitor patients for the presence of larger systemic adverse events typically seen with systemic corticosteroid exposure, such as osteoporosis, adrenal insufficiency and glucose abnormalities The risk of uncontrolled asthma usually outweighs the risk of using ICSs because these agents are so effective. However, titrating to high dose monotherapy of ICS is not as effective due to the marginal benefit gained from the increased dose increase compared with the potential of increased risk of adverse events. Once the patient has reached the medium dose of an ICS, the addition of a second or combination agent will typically be more effective. Pharmacists can ensure the appropriate use of these agents by monitoring the patient s inhaler technique and adherence to therapy. While the total amount of absorption varies by agent, the effectiveness of all ICS therapy can be affected by poor delivery. A common side effect seen with ICS is oral candidiasis, also known as oral thrush. To reduce the risk of oral thrush, patients should be instructed to rinse the mouth with water after each use to avoid prolonged contact of the drug with the oral cavity. If a patient is having particular difficulty with oral thrush, the pharmacist could recommend an agent with less frequent administration requirements, such as fluticasone furoate (Arnuity Ellipta ). 20 For patients who are highly affected by oral thrush or for pediatric patients, the recommendation of a spacer or holding chamber may decrease local side effects. ICSs do not provide immediate relief for asthma symptoms. Because of this, the patient may not appreciate the impact of therapy and the importance of adherence to the ICS as compared with the SABA due to the delayed onset of action. Taking time to educate patients on the basic differences in medication action can add to adherence, especially when the benefits are not immediately evident. Providing patients with important information on the expected time to effect could improve adherence to these medications. Long-acting beta agonists Long-acting beta agonist, or LABA, medications are effective treatments for COPD and asthma when used in combination with an ICS. Similar to the premise that ICSs should not be used as monotherapy for COPD, LABAs should not be used alone to treat asthma. In February 2010, the FDA issued a black box warning for LABA medications that the product s use in treating asthma as monotherapy is associated with increased asthma related death ,47 It was found that this warning did reduce the prescribing of LABAs, but was associated with an increase in LABA prescriptions for those patients with previous controller medications. 48 LABAs may provide more effective symptom control when added to a standard dose ICS than increasing the ICS dose alone. LABA typically are dosed once daily at night and are not used to treat acute symptoms or exacerbations. All four LABA medications prescribed as noncombination products are administered differently This is an important counseling point for the pharmacist as this is most likely the second or third inhaler that the patient needs to learn. Recommending LABAs in combination products can be an effective way to increase patient adherence, decrease cost and assure that a patient with asthma is not using LABA therapy without an ICS. Similar to previously described medications, initiating specific counseling sessions, addressing and managing patient expectations and ensuring appropriate inhaler technique are crucial to patient adherence. Anticholinergics Anticholinergic medications as a class target muscarinic receptors, sometimes referred to as anti-muscarinics, by blocking the effect of acetylcholine to reduce bronchoconstriction. The long-action version of these agents is the treatment of choice as monotherapy for all stages of COPD except as initial therapy in low severity (GOLD classification as group A). Long-acting anticholinergic, or LAAC, medications are effective as long-term treatment of COPD in two ways as monotherapy and as combination therapy. These medications have been shown to improve lung function, dyspnea and exacerbation frequency. 7 Side effects of anticholinergic medications are consistent with typical anticholinergic adverse events such as dry mouth, blurred vision, constipation, urinary retention and tachycardia However, they are effective daily treatments for COPD and the efficacy does not wane over time as is seen in beta agonist therapy. In 2015, the first LAAC, tiotropium (Spiriva Respimat ) was approved for the treatment of asthma. 35 Tiotropium, when added to a medium-dose ICS, improved lung function similar to therapy that included the addition of a LABA. 49 There are no other current LAACs approved for this indication. It is important for the pharmacist to know the appropriate dose by indication when dispensing the product. In asthma, the appropriate dose is 2.5 mcg compared with 5 mcg in the treatment of COPD. However, both products required two inhalations to achieve the appropriate dose, reinforcing the importance of assisting patients in understanding both the correct dose and the appropriate indication based upon their diagnosis. 35 The Respimat inhaler provides an alternative to the technique used by the tiotropium (Spiriva ) Handihaler, which required placing a capsule into the device before inhalation. The physical manipulation requirements of the Handihaler pre- MAY

5 sented problems for patients with arthritis or other dexterity issues. In addition, the product also presented a potential issue in patients who believed the capsule should be taken orally. The newest LAAC, glycopyrrolate (Seebri Neohaler ), was approved in 2016 and also is available in combination with a LABA. The combination product is indacaterol (Indacaterol/Glycopyrrolate, Utibron Neohaler ). 33,37 Glycopyrrolate is similar to other available LAACs on the market for COPD but must be dosed twice daily, in contrast with tiotropium and umeclidinium (Incruse Ellipta ), which are dosed once daily Other therapies Roflumilast (Daliresp ), a phosphodiesterase 4 (PDE-4) inhibitor, helps to decrease the inflammatory cells in airway smooth muscle to reduce the risk of exacerbations in patients with severe COPD. In recent trials, the use of roflumilast demonstrated a decrease COPD exacerbations of 25%. 50 Due to such side effects as nausea, diarrhea and increased risk for drug interactions, these medications typically are reserved for patients with GOLD classifications of three and four with a history of exacerbations despite appropriate inhaler therapy. 7,51 Leukotriene receptor antagonist, or LTRA, medications are used in asthma and have mild efficacy in allergic rhinitis. The three medications in this class improve lung function while decreasing SABA use. While not as effective as ICSs, they can be taken orally and once or twice a day, and are an alternative treatment in combination with an ICS for moderate persistent asthma. 6 In general, the medications are well-tolerated, but the pharmacist should help to monitor for efficacy and symptom relief due to lower efficacy than ICSs. An important counseling point for patients is that LTRAs are not useful for treatment of acute episodes. Methylxanthines, such as theophylline, and mast cell stabilizers, such as cromolyn sodium, are not discussed in detail due to decreased efficacy and increased unwanted requirements and effects as compared to previously discussed agents. Theophylline in particular has increased toxicities and complicated dosing requirements. Theophylline also has significant drug interactions including multiple CYP450 enzymes and smoking. As such, it remains an inappropriate option in patients older than 65 years of age. 52 New therapies A dry powder version of albuterol (Pro- Air Respiclick) was released in This is unique from previous versions of HFA inhalers in that it does not require the PATIENT SCENARIO 1 SS is a 62-year-old male who presents to the pharmacy to pick up a new medication for breathing problems. The medical conditions found in the patient s profile include a history of heart failure, hypertension, diabetes and COPD. Additionally, the patient has smoked one PPD for the past 32 years. His current profile medications include: metoprolol tartrate 50 mg BID lisinopril 20 mg QD glipizide ER 5 mg QD sitagliptin 100 mg QD tiotroprim 18 mg handihaler one inhalation QD During the counseling session, SS states that he has tried to quit smoking several times without luck. His decision to visit the doctor today was driven by his current inability to walk up a flight of stairs without stopping at least once. Additionally, he has been hospitalized three times in the past year for breathingrelated issues. He also handed the technician a copy of his recent lab results that indicated: FEV1 of 41% (after using a SABA) and a CAT score of 14. How can the pharmacist use the data provided, along with the history the patient shared, to assess the appropriateness of the current therapy? Discussion The first step in assessing this patient s therapy is to properly classify the patient s condition. Given the initial information shared, the patient would be classified as B or D based upon: The patients current assessment of symptoms (CAT > 10) The mmrc of four due to the difficulty moving up the stairs When adding the patient s exacerbation history and spirometry results (GOLD 3: Severe) the patient can be classified as a high-risk patient in Group D. First-line therapy for patients in Group D is a long-acting anti-cholinergic, or LAAC, or an inhaled corticosterois, or ICS, plus a long-acting beta-agonist, or LABA. The patient is already on a LAAC, which is appropriate, but the pharmacist should assess the patient for issues with adherence, administration technique and adverse events. While tiotrprium is a once-daily medication, the handihaler can be difficult to use, and patients should be instructed that it might take more than one inhalation to ensure that the patient receives the full dose. The respimat tiotropium inhaler is an acceptable alternative if the patient is not administering it appropriately, but it must be dosed twice daily compared with once daily. Possible adverse events could include anticholinergic side effects, which can be more pronounced because of the patient s age. If SS is adherent to the current LAAC therapy, it is possible to add an LABA, ICS or a combination of both. A PDE-4 inhibitor could be added, but it would be reserved for continued exacerbations despite multiple therapies to treat the condition. The patient should be prescribed short-term relief if needed, and the most appropriate therapy would be an albuterol plus ipratropium combination that also could be delivered via resmipat if the patient prefers. patient to coordinate the administration of the inhaler with appropriate inhalation. Patients should be counseled to inhale deeply to ensure the entire dose of drug powder is delivered. The dry-powder inhaler could be an option for patients who are unable to use a conventional metered dose inhaler, or MDI. This delivery method is approved only in patients older than 12 years of age. 41 Omalizumab (Xolair ) is a recombinant anti-ige antibody approved for the treatment of allergic asthma not well controlled by corticosteroids or ICS treatment. The medication is not dispensed in the pharmacy and must be injected in the providers office due to the risk of anaphylaxis. The subcutaneous injection is based on the patient s serum IgE level and body weight to determine the correct dose. 53 Mepolizumab (Nucala ) is an interleukin-5 antagonist monoclonal antibody indicated for additional treatment for patients with severe asthma specifically targeting eosinophils. Like omalizumab, it is injected subcutaneously in the provider s office to reduce the risk of an anaphylactic reaction. The main difference in this therapy compared with omalizumab is that mepolizumab is dosed at a fixed injection and not based on weight or eosinophil counts. 54 TREATMENT APPROACHES Asthma and COPD each have unique treatment approaches. The approach for asthma is based on an initial staging with subsequent treatment based upon severity. The provider must work with the patient to continue to titrate therapy until optimal control and overall treatment is established. Clinical management of the patient is defined by the level of the patient s asthma control. If a patient is not controlled, the patient steps up and requires a dosage increase the or addition of a new therapy. If the selected therapy adjustment is able help the patient with symptom control, the patient can be stepped down every three months until the treatment reaches the lowest level that provides adequate control. If a patient is stepping down, the most recent drug that 5 MAY

6 was added is typically the first medication to be discontinued. Specific agents associated with each step are presented in Table 4. If a patient in the pharmacy complains of exercise-induced bronchospasm, or EIB, the pharmacist can recommend the use of a SABA to be administered two hours prior to exercise, or the use of a LABA 10 hours prior to the anticipated event. If a patient presents with seasonal asthma, recommend the use of an ICS prior to the anticipated start of symptoms to help increase control. 6 COPD treatment does not have defined step therapy. Therapy is guided by systematic treatment based on classification criteria. Recommendations are based on severity determined by using the GOLD classification and patient characteristics. For example, LAACs are preferred as monotherapy in groups B, C and D as first-line therapy. Depending on the level of control and risk of exacerbation, pharmacists can recommend more intense therapy including combinations and the addition of multiple agents. A summary of appropriate therapies is provided in Table 5. EDUCATIONAL OPPORTUNITIES Pharmacists have ample opportunities to impact the care of patients who suffer from lung disease. While pharmacists are not classified as providers for Medicare under the current social security act, billing mechanisms do exist for asthma education. For future opportunities for pharmacists in community and ambulatory settings, CPT code is Demonstration and/or evaluation of patient utilization of an aerosol generator, nebulizer, metered dose inhaler or IPPB device. 55 Vaccination of patients with asthma and COPD is a cornerstone of therapy in the prevention of morbidity and mortality. Patients with chronic lung disease are disproportionally affected by influenza and pneumococcal disease, and vaccination remains the most effective method to prevent death of influenza and pneumococcal disease. 57 Pharmacists in all patient care settings can advocate, recommend or administer vaccinations to their patients. Pharmacists in community settings should routinely recommend vaccination with the provision of inhalers and conducting immunization assessments as a part of routine counseling. This intervention can PATIENT SCENARIO 2 positively impact patient outcomes and serve as an additional revenue source for the pharmacy. While the provision of immunizations has become commonplace in community pharmacies, vaccination rates remain low overall (25% to 37% by state) 58. Specific, targeted interventions from pharmacists who have existing relationships with patients can impact vaccination rates locally, regionally and nationally. TS, a 32-year-old female, presents to the pharmacy for a refill of her albuterol inhaler. The patient has no known drug allergies, and the only notable medical history in the computer is a routine refill for ethinyl estradiol/norgestimate one tablet by mouth daily. The pharmacist notices that the last refill for albuterol was 20 days ago and asks the patient about her symptoms and if she has had any difficulty breathing. She states she has needed to use the inhaler for shortness of breath, or SOB, two to three times per day and has not been exercising regularly because the SOB makes her nervous. She wakes up at least once a night, but feels that the albuterol is the only thing that helps. What is the appropriate assessment of control for this patient? What should the pharmacist recommend? Discussion TS is an adult who has very poorly controlled asthma. Using the guidelines to assess and adjust therapy, the frequency of her short-acting beta agonist inhaler use and frequent nighttime awakenings would suggest that the patient needs additional therapy to achieve better control. The patient should consider seeking urgent care treatment or an emergency room if she is having severe shortness of breath. A course of corticosteroids may be recommended. Her current therapy indicates she may not have seen a provider recently and is considered step one, and an increase of two steps may be warranted. An ICS plus LABA, in addition to the SABA treatment, is warranted and the patient may require follow-up in two weeks. Table 5 Recommendations for treatment of COPD 7 PATIENT GROUP FIRST CHOICE ALTERNATIVE CHOICE OTHER TREATMENTS A SABA PRN and/or SAAC LAAC or LABA or SABA and Theophylline PRN SAAC B LAAC or LABA LAAC AND LABA SABA and/or SAAC or Theophylline C ICS + LABA or LAAC (LAAC and LABA) or (LAAC and PDE-4) or (LABA and PDE-4) SABA and/or SAAC or Theophylline D ICS + LABA and/or LAAC (ICS + LABA and LAAC) or (ICS + LABA and PDE-4) or (LAAC and LABA) or (LAAC and PDE-4) Carbocysteine or N-acetylcysteine or SABA and/or SAAC or theophylline Table 4 Step therapy in asthma for adults (>12 years of age) 6 STEP THERAPY SUMMARY Intermittent asthma Persistent asthma Mild Moderate Severe Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Preferred SABA PRN Low dose ICS Low dose ICS + LABA or medium dose ICS Alternative N/A Cormolyn LTRA or theophylline Quick relief SABA PRN for symptoms Low dose ICS + LTRA, tehophylline or Zileuton Medium dose ICS + LABA Medium dose ICS + LTRA, theophylline, or zileuton High dose ICS + LABA and consider omalizumab High dose ICS + LABA + oral corticosteroid and consider omalizumab MAY

7 Table 6 Healthy habits and hygiene practices 9,12-14 RESOURCE National Asthma Control Initiative (NACI) Asthma and Allergy Foundation of America Asthma Clinical Research Network (ACRN) Fairview Pharmacy Inhaler Techniques COPD Foundation American Lung Association National Jewish Health: COPD imedicalapps PRACTICE POINTS Smoking cessation also is a cornerstone of therapy for patients with asthma and COPD. The link between smoking and COPD has been previously described in this activity, but smoking also increases the risk for acute respiratory illnesses, which can have a greater impact on patients who suffer from lung disease. While this activity does not focus on specific smoking cessation techniques, studies show that reminders from providers can increase a patient s likelihood to quit 59. It is imperative that pharmacists remain vigilant and continually focus on the smoking status with their patients, employing effective assessments of readiness to change and proven behavior change techniques. 60 A community pharmacy is a very busy environment with multiple demands of the pharmacist s time and energy. Pharmacists who employ synergies combining smoking cessation questionnaires/recommendations with immunization recommendations can increase their impact while not significantly increasing their workload. Engaging and training technicians to facilitate needed interventions also can increase efficiency. Asking technicians to flag prescription receipts to indicate the need for pharmacist recommendations and interventions is critical. Empowering technicians to advocate for patients needing assessments, interventions and education by alerting the pharmacist will help to drive patient adherence. In addition to the routine counseling on new prescriptions, pharmacists increasingly are taking on responsibilities to ensure medication adherence to prescribed therapies. In a 2015 analysis published in the Journal of Clinical Pharmacy Therapeutics, researchers found that nonadherence can be as prevalent as 85% in a chain community pharmacy setting. 61 This finding presents a particular opportunity for pharmacists to improve patient care. Patients often confuse the role of a controller medication versus quick-relief medication and the rationale behind prescribed therapy. The importance, rationale and instructions are crucial to helping patients adhere to inhaler therapy, especially upon a new diagnosis. As quality measures and rates of adherence become a standard part of prescription drug plans, pharmacists play a role in not simply dispensing the prescription but ensuring its proper use. For example, a current Medicare quality measure is the percentage of COPD exacerbations in adults older than 40 years of age who were dispensed a bronchodilator within 30 days of a recent hospitalization. 62 Pharmacists can easily impact this measure of quality by counseling all patients on adherence and appropriate therapy. The pharmacist-patient relationship is crucial to patient education efforts to ensure patients understand the role of their inhalers in therapy. Studies also show that the majority of patients fail to demonstrate appropriate device technique with the prescribed inhalers. 63 Various factors contribute to inappropriate device technique, including complicated device instructions, lack of demonstration opportunities, low health literacy and overburdened providers. The pharmacist-patient relationship in a community pharmacy setting is ongoing. While pharmacists have multiple demands on their time, they can help discuss and demonstrate technique at multiple intervention points before and after primary care visits. This frequency of availability is crucial because even if a patient is able to demonstrate appropriate technique at one visit, it is not guaranteed that the behavior will be WEBSITE naci/index.htm Healthresources/Inhalers/demos/index.htm copd/ When working with patients living with asthma and COPD, implement these five actions: 1. Ask patient to demonstrate inhaler technique when counseling; 2. Assess chronic inhaler therapy for adherence at each refill; 3. Assess smoking status of patients filling a prescription for inhalers, and advise patients with quitting strategies; 4. Evaluate patients immunization status based upon prescription and medical history, and take action if needed; and 5. Build patient trust and relationships to make needed chronic interventions. consistently applied. 64 RESOURCES FOR THE PHARMACIST Many educational resources for asthma and COPD are available for the both the pharmacist and the patient. Table 6 summarizes multiple resources for educational material, health promotion and interventions to be used in the community pharmacy, including online- and app-based resources for patients and providers. CONCLUSION Considering the large burden of lung disease on morbidity, mortality and quality of life in the United States, it is imperative that community pharmacists play a role in helping to improve outcomes in asthma and COPD. Considering the successes of community pharmacists in impacting chronic disease management in other areas, pharmacists are critical members of the healthcare team to provide education, appropriate inhaler technique demonstrations and overall medication therapy management for patients with lung diseases in the community setting. 7 MAY

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