The. Treating patients with COPD with medications

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1 Treating patients with COPD with medications Gilbert E. D Alonzo Jr, MS, DO, FACOI; Fredric Jaffe, DO, FCCP; Samuel L. Krachman, DO SHUTTERSTOCK.COM The management treatment of chronic obstructive pulmonary disease (COPD) involve both medications nonpharmacological interventions. There are a variety of national international management treatment guidelines available. They include avoiding risk facts, such as cigarette smoking, the appropriate use of medications supplemental oxygen, pulmonary rehabilitation, surgery. Additionally, these guidelines address the treatment of COPD in exacerbation. 1-3 April 2015 COPD: Practical approaches to diagnosis management AOA Health Watch 7

2 Goals of therapy The goals of COPD management include improving lung function, preventing disease progression, the relief of symptoms, improvement in exercise tolerance, prevention of exacerbations, reduction of complications, minimizing adverse effects from treatment, reducing mtality. Preferred pharmacological management of chronic COPD has been advocated by evidence-based guidelines. 1-4 Treatment recommendations are based on a determination of a specific patient s disease severity. Therefe, spirometry becomes an essential tool in this process. But other facts, such as disease symptoms, frequency of exacerbations, certain patient preferences abilities, must be considered. Spirometry is needed in patients with symptoms of cough, dyspnea on exertion, fatigue, reduced functionality. 3 Many of these patients are at risk f COPD already have combidities associated with COPD. COPD treatment goals include improving lung function symptoms; preventing disease progression, exacerbations, complications; improving exercise tolerance;, ultimately, reducing mtality. These airflow measurements are helpful in determining treatment steps. F example, a fced expiraty volume in 1 second (FEV 1 ) less than 60% of predicted generally indicates the need Table 1. Classification of severity of airflow limitation in COPD (based on post-bronchodilat FEV 1 ) In patients with FEV 1 /FVC < 0.70 GOLD 1 Mild FEV 1 80% predicted GOLD 2 Moderate 50% FEV 1 < 80% predicted GOLD 3 Severe 30% FEV 1 < 50% predicted GOLD 4 Very Severe FEV 1 < 30% predicted From the Global Strategy f Diagnosis, Management Prevention of COPD 2015, Global Initiative f Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from f regular maintenance therapy, values below 30% of predicted signal the need to create a treatment plan f me severe disease. Spirometry generally should not be used to romly screen f airflow obstruction in individuals without respiraty symptoms. 3 Pharmacology accding to treatment guidelines Previously, COPD treatment hinged on spirometry results only (Figure 1). The current approach to COPD care is based on disease severity, taking into account airflow measurement, symptoms, exacerbation histy (Figure 2). Valid questionnaires such as the COPD Assessment Test the modified Medical Research Council scale are used f symptom assessment; spirometry helps determine the severity of airflow limitation (Table 1), exacerbations during the last year are recded counted. By considering these components together, a patient can often be placed into a certain categy, A through D. Using this process, the clinician can decide on which treatment strategy to use, both nonpharmacological (Table 2) pharmacological (Table 3). This approach hopefully improves the efficacy of interventions, reduces health care costs by avoiding unnecessary interventions, minimizes complications. Initial drug therapy f patients with mild COPD who have preserved lung function few symptoms is a shtacting inhaled bronchodilat, either albuterol ipratropium. If the patient Table 2. Non-pharmacologic management of COPD PATIENT GROUP ESSENTIAL RECOMMENDED DEPENDING ON LOCAL GUIDELINES A B, C, D Smoking cessation (can include pharmacologic treatment) Smoking cessation (can include pharmacologic treatment) Pulmonary rehabilitation Physical activity Physical activity Flu vaccination Pneumococcal vaccination Flu vaccination Pneumococcal vaccination From the Global Strategy f Diagnosis, Management Prevention of COPD 2015, Global Initiative f Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from 8 AOA Health Watch COPD: Practical approaches to diagnosis management April 2015

3 is me symptomatic has not had an exacerbation, then either a longacting anticholinergic a long-acting beta 2 should be tried. There is convincing evidence that the once-daily anticholinergic, tiotropium, is me effective than twice-daily salmeterol in preventing COPD exacerbations. 5 F patients with me severe disease, a long-acting beta 2 with an inhaled cticosteroid a long-acting anticholinergic should be considered. 6 It may be necessary to use all 3 agents in patients with even me severe COPD. 7 Certainly, patients with frequent exacerbations tend to have me severe airflow obstruction they require an inhaled cticosteroid therapy. The combination of a long-acting beta 2 an inhaled cticosteroid is me effective than its individual components in reducing exacerbations in improving lung function exercise capacity. 8 Roflumilast, a phosphodiesterase type 4 inhibit, has been shown to prevent cticosteroid-treated exacerbations in patients who have chronic bronchitis a low FEV 1. 9 therapy has been used to treat COPD f many years. At higher doses, numerous adverse effects have hampered its use, but at lower doses theophylline may have anti-inflammaty effects likely have value in preventing exacerbations. 10 Even when used at lower dosages, theophylline has been associated with gastrointestinal side effects. All treatments have the potential f side effects. Beta 2 s are associated with palpitations, trem, electrolyte imbalances. Patients with existing cardiac disease often have COPD are at risk f many of the adverse effects associated with these medications. Long-acting anticholinergic medications have been associated with urinary retention, dry mouth,, rarely, glaucoma. Concerns about cardiac death with long-acting anticholinergic therapy have not been substantiated. Common adverse effects of roflumilast include gastrointestinal upset, weight loss, depression. A variety of new medications belonging to the long-acting beta 2, long-acting anticholinergic, inhaled cticosteroid classes are currently available f once-daily use. Patients with moderate-tosevere COPD, who have a histy of COPD exacerbations despite optimal maintenance therapy, often benefit from the long-term use of an al macrolide in preventing exacerbations. 11 When using macrolide therapies, individual patients should be assessed f prolonged QT interval, hearing loss, bacterial resistance consequences. To date, there is no consensus on the dose duration of macrolide therapy. Macrolide antibiotics have been used f years in the management of chronic airway diseases f their antimicrobial, anti-inflammaty, immune-modulating effects. Systemic al cticosteroids f the long-term treatment of COPD should generally not be used beyond the 30 days after an acute exacerbation, 12 unlike their use during an acute attack, f which they can be used routinely. Figure 1. Therapy at each stage of COPD.* From the Global Strategy f Diagnosis, Management Prevention of COPD 2006, Global Initiative f Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from April 2015 COPD: Practical approaches to diagnosis management AOA Health Watch 9

4 Treatment of acute exacerbation Acute exacerbations of COPD substantially influence patient mtality often drive the clinical course of the disease to a higher level of severity. 13 Shtness of breath, the dominant symptom during an exacerbation, is related not only to severe airflow obstruction, but also to both static dynamic hyperinflation that severely restricts the tidal volume of each breath. 14 In addition to deteriation in respiraty mechanics, pulmonary gas exchange wsens, leading to hypoxemia with without hypercapnia. Often, the need f supplemental oxygen is imperative, in the most severe COPD patients, oxygen-induced hypercapnia can develop. 15 An inhaled Current COPD care is driven by disease severity through consideration of airflow, symptoms, exacerbations. bronchodilat is the initial medication used because of the speed of onset of action the minimal risk f severe adverse effects, compared with parenteral bronchodilat therapy. A variety of both inhaled beta 2 s an anticholinergic therapy is used. There are no good data to indicate just how these inhaled bronchodilats should be used. The dose the frequency of administration of these medications are empiric selected by the attending physician. Many physicians use albuterol at doses of 2.5 to 5.0 mg by nebulization 2 to 3 puffs me by inhaler. The inhaler can be used every 3 to 4 hours the nebulizer every 4 to 6 hours, but often even me frequent therapy is necessary. Ipratropium bromide 0.5 mg by nebulizer inhaler is used in combination with albuterol. Continuous inhaled albuterol therapy is also used in many institutions. Frequency of use of these bronchodilats should decrease over 48 to 72 hours as the exacerbation SPL / SCIENCE SOURCE Bronchodilat inhaler with a spacer device is used at home by an elderly male patient with COPD. The inhaler provides a drug which opens the airways assists breathing. slowly resolves. When using continuous bronchodilat therapy, it is imptant to monit the patient f systemic toxicity, including severe tachycardia other arrhythmias. Hypokalemia is not a particular problem in clinical practice, but induced glaucoma by anticholinergic therapy can occur if the mist of the nebulizer treatment the spray from the inhaler enters the eyes of a susceptible patient. F years, intravenous aminophylline was used as a principal treatment f acute COPD exacerbation, but with the institution of safer inhaled bronchodilats, this medication is reserved f the most severe patients who are not responding to nebulized bronchodilat therapy. Aminophylline is a weak bronchodilat has significant potential toxicity. Therefe, it is not commonly used. Parenteral cticosteroids are used in the acute management of COPD. Again, data on how to use these medications are scarce. It does appear that the use of 10 AOA Health Watch COPD: Practical approaches to diagnosis management April 2015

5 cticosteroid therapy reduces relapse, treatment failures, accelerates the rate at which lung function improves seems to reduce hospital length of stay when hospitalization is necessary. 16,17 Cticosteroid dose, frequency of administration, duration of treatment remain empiric selected by the attending physician, similar to that of bronchodilat therapies. Inpatient cticosteroid therapy is generally hled differently than outpatient therapy. Cticosteroids are initially administered parenterally in Table 3. Pharmacologic therapy f stable COPD* the inpatient setting ally in the outpatient setting. Methylprednisolone 30 to 40 mg every 6 to 8 hours intravenously is a common practice used in hospitalized patients, whereas a tapering daily dose of prednisone therapy 40 to 60 mg a day is used in the outpatient setting. After 1 2 days, the parenteral therapy f the inpatient is often switched to al therapy using prednisone. In both groups, the duration of therapy is generally 7 to 14 days. The way in which daily dose tapering occurs is very physician-specific generally PATIENT RECOMMENDED ALTERNATIVE OTHER POSSIBLE GROUP FIRST CHOICE CHOICE TREATMENTS** A B C prn prn ICS + PDE-4 inhibit PDE-4 inhibit / / D ICS + / ICS + ICS + PDE-4 inhibit PDE-4 inhibit Carbocysteine / *Medications in each box are mentioned in alphabetical der therefe not necessarily in der of preference. ** Medications in this column can be used alone in combination with other options in the First Alternative Choice columns Glossary: SA: sht-acting; LA: long-acting; ICS: inhaled cticosteroid; PDE-4: phosphodiesterase-4; prn: when necessary. From the Global Strategy f Diagnosis, Management Prevention of COPD 2015, Global Initiative f Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from based on no objective data published in the literature. Hyperglycemia is common in patients treated with cticosteroid therapy. F individuals treated f a prolonged period of time with cticosteroid therapy, one must be aware of the development of muscle weakness, especially if the patient is immobile. 18 Antibiotic therapy is often used in patients with COPD exacerbation, especially if fever, chills, purulent sputum are present also if the patient has severe COPD with little physical reserve. 19 The choice of treatment often focuses on local antibiotic sensitivities to the 2 predominant causes of bacterial bronchitis during a COPD exacerbation, namely, Haemophilus influenzae Streptococcus pneumoniae. 20 When employed, antibiotics are generally used f 5-7 days. It is imptant to remember that many individuals with COPD exacerbation do not have bacterial bronchitis may derive no benefit from using antibiotic therapy. There is some evidence, however, that critically ill patients with COPD exacerbation who receive antibiotics have better outcomes. 21 Viral infections likely play a significant role in COPD infections, not only as a primary infection, but also by altering the respiraty microbiome allowing bacterial proliferation. Recently, the American College of Chest Physicians the Canadian Thacic Society developed a joint evidence-based guideline to describe the current state of knowledge regarding the prevention of acute COPD exacerbations. 22 This guideline covers both pharmacological nonpharmacological therapies that can be employed to both prevent decrease these exacerbations. New therapies Many therapies exist f COPD (Table 4). Several new therapies are now available under development f use alone in combination with other agents in the management of COPD. These new medications include once-daily long-acting beta 2 - agonists indacaterol, vilanterol, olodaterol as well as long-acting April 2015 COPD: Practical approaches to diagnosis management AOA Health Watch 11

6 muscarinic antagonists umeclidinium, aclidinium, glycopyrronium. These agents are delivered through novel delivery systems are dosed once daily. Combinations of once-daily, long-acting beta 2 s longacting muscarinic antagonists include vilanterol umeclidinium, tiotropium olodaterol, glycopyrronium indacaterol, glycopyrronium fmoterol, aclidinium fmoterol; the combinations of vilanterol umeclidinium of tiotropium olodaterol are currently available to physicians in the United States. Also available is a once-daily, long-acting beta 2 an inhaled cticosteroid, fluticasone furoate vilanterol. At this time, no triple oncedaily fmulation exists f use. Other novel agents are also being investigated, agents that target airway inflammation in COPD by inhibiting proinflammaty pathways activating certain Figure 2. Combined assessment of COPD When assessing risk, choose the highest risk accding to GOLD grade exacerbation histy. (One me hospitalizations f COPD exacerbations should be considered high risk.) From the Global Strategy f Diagnosis, Management Prevention of COPD 2015, Global Initiative f Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from Table 4. COPD medications Sht-acting Fenoterol Levalbuterol Albuterol Terbutaline Sht-acting Ipratropium bromide Oxitropium bromide BETA 2 -AGONISTS ANTICHOLINERGICS Long-acting Fmoterol Arfmoterol Indacaterol Salmeterol Tulobuterol Olodaterol Long-acting Aclidinium bromide Glycopyrronium bromide Tiotropium Umeclidinium COMBINATION Sht-acting beta 2 plus anticholinergic in one inhaler Fenoterol/Ipratropium Salbutamol/Ipratropium COMBINATION Long-acting beta 2 plus anticholinergic in one inhaler Indacaterol/Glycopyrronium Vilanterol/Umeclidinium METHYLXANTHINES Aminophylline (SR) INHALED CORTICOSTEROIDS Beclomethasone Budesonide Fluticasone COMBINATION Long-acting beta 2 plus cticosteroid in one inhaler Fmoterol/Budesonide Fmoterol/Mometasone Salmeterol/Fluticasone Vilanterol/Fluticasone furoate SYSTEMIC CORTICOSTEROIDS Prednisone Methylprednisolone PHOSPHODIESTERASE-4 INHIBITORS Roflumilast 12 AOA Health Watch COPD: Practical approaches to diagnosis management April 2015

7 Patients with COPD can benefit from certain vaccinations during the course of their illness. It is recommended that the influenza vaccine should be given to all patients with COPD on a yearly basis. intrinsic anti-inflammaty pathways, even some that focus on lung regeneration mucociliary actions. Immunizations Patients with COPD can benefit from certain vaccinations during the course of their illness. It is recommended that the influenza vaccine should be given to all patients with COPD on a yearly basis. Influenza vaccination is associated with a substantial reduction in the risk f hospitalization f pneumonia influenza as well as f a reduction in the risk f death. 23 On the other h, there is less evidence f the role of the pneumococcal vaccine in preventing exacerbations. However, vaccination of all COPD patients with 23-valent pneumococcal polysaccharide vaccine is recommended by the Advisy Committee on Immunization Practices. References 1. 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N Engl J Med. 2007;356(8): Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; Ms-124 M2-125 study. Roflumilast in symptomatic chronic obstructive pulmonary disease: two romised clinical trials. Lancet. 2009;374(9691): Zhou Y, Wang X, Zeng X, et al. Positive benefits of theophylline in a romized, double-blind, parallel-group, placebocontrolled study of low-dose, slow-release theophylline in the treatment of COPD f 1 year. Respirology. 2006;11(5): Albert RK, Connett J, Bailey WC, et al; COPD Clinical Research Netwk. Azithromycin f prevention of exacerbations of COPD. N Engl J Med. 2011;365(8): Rice KL, Rubins JB, Lebahn F, et al. Withdrawal of chronic systemic cticosteroids in patients with COPD: a romized trial. Am J Respir Crit Care Med. 2000;162(1): Suissa S, Dell Aniello S, Ernst P. Longterm natural histy of chronic obstructive pulmonary disease: severe exacerbations mtality. Thax. 2012;67(11): Stevenson NJ, Walker PP, Costello RW, Calverley PM. Lung mechanics dyspnea during exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172(12): Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mtality in chronic obstructive pulmonary disease patients in the prehospital setting: romised controlled trial. BMJ. 2010;341:c Niewoehner DE, Erbl ML, Deupree RH, et al. Effect of systemic glucocticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340(25): Aaron SD, Vemheen KL, Hebert P, et al. Outpatient al prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003;348(26): Decramer M, de Bock V, Dom R. Functional histologic picture of steroidinduced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;153(6 pt 1): Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic cticosteroids f acute exacerbations of chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 2010;181(2): Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause prevention. Lancet. 2007;370(9589): Rothberg MD, Pekow PS, Lahti M, Brody O, Skiest DJ, Lindenauer PK. Antibiotic therapy treatment failure in patients hospitalized f acute xacerbations of chronic obstructive pulmonary disease. JAMA. 2010;303(20): Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians Canadian Thacic Society Guideline. Chest. 2015;147(4): Nichol KL, Ndin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med. 2007;357(14): Gilbert E. D Alonzo Jr, MS, DO, FACOI, is profess of medicine at Temple University School of Medicine (TUSM). He also is the deputy direct at the Temple Lung Center (TLC), edit emeritus at the American Osteopathic Association. Dr D Alonzo can be reached at Gilbert.D [email protected]. Fredric Jaffe, DO, is associate profess of medicine at the Temple University School of Medicine. He specializes in COPD smoking cessation. Dr Jaffe can be reached at fjaffe@ temple.edu. Samuel L. Krachman, DO, is profess of medicine at the Temple University School of Medicine. He specializes in COPD sleep disders. Dr Krachman can be reached at [email protected]. April 2015 COPD: Practical approaches to diagnosis management AOA Health Watch 13