Recent Advances in the Management of COPD

Joelle Ayoub, PharmDAssistant Professor of Pharmacy Practice and AdministrationWestern University of Health Sciences College of Pharmacy

Objectives

• Classify, assess, control, select, and monitor appropriate treatment in adult patients with chronic obstructive pulmonary disease (COPD)• Educate patients about their therapy for COPD, including the proper

use of inhalers, holding chambers, and medications• Differentiate between classes of medications used in the treatment of

COPD and recognize commonly used medications• Delineate GOLD guidelines and recent evidence• Apply GOLD treatment algorithm to a patient case to determine the

best possible therapy for the patient

BackgroundPathophysiologyPrevalence

DiagnosisRisk factorsSpirometry Assessment

ManagementPharmacologic therapyEmerging evidencePatient educationMonitoring

ExacerbationPatient Case

Agenda

Signs and Symptoms

Chronic coughMucus

production

Chest tightnessWheezing

https://emedprimarycare.com/2018/02/26/copd-can-treated-risks/

DyspneaFatigueWeight

loss

Patho-physiology

© 2019 Global Initiative for Chronic Obstructive Lung Disease

Prevalence • In the US, COPD ranks third in causes of mortality with 100,000 deaths annually• An estimated 15 million people had diagnosed COPD in 2010, and an estimated 12

million potential cases remain undiagnosed (in the US)• The estimated total annual cost of COPD for 2010 was $49.9 billion

• Approximately 25% of adults with COPD have never smoked, and workplace exposures likely contribute to much of their disease• During 2013–2017, an estimated 2.4 million (2.2%) U.S. working adults aged ≥18 years who

never smoked had COPD

• The number of women dying of COPD in the United States now surpasses men• Women may be at a greater risk of smoking-induced lung function impairment for the same

level of tobacco exposure as men

• African-Americans have a lower prevalence of COPD in the United States, but may develop COPD with less cumulative smoking and at younger ages

Weekly / April 5, 2019 / 68(13);303–307J Occup Environ Med. 2014 Oct; 56(10): 1088–1093.

Diagnosis

© 2019 Global Initiative for Chronic Obstructive Lung Disease

Diagnosis: Key IndicatorsKey indicators for considering a diagnosis of COPD

Consider COPD and perform spirometry if any of the following are present in ages >40

Dyspnea Progressive over timeCharacteristically worse with exercise

Chronic cough May be intermittent and may be unproductive Recurrent wheeze

Chronic sputum production Any pattern of chronic sputum production may indicate COPD

Recurrent lower respiratory tract infections

History of risk factors Host factors (genetic, congenital/developmental abnormalities)Tobacco smoke (popular local preparations included)Smoke from home cooking and heating fuelsOccupational dusts, vapors, fumes, gases and other chemicals

Family history of COPD or childhood factors Low birthweight, childhood respiratory infections

Spirometric Values

• FVC: Forced vital capacity; the total volume of air that can be exhaled during a maximal forced expiration effort (exhaling everything in the lungs for as long as possible)• FEV1 = forced expiratory volume in 1 second (the amount of air that

you breathe out in the first second)

AAFP VOLUME 69, NUMBER 5 / MARCH 1, 2004

-Diagnosis: FEV1/FVC <0.7(post bronchodilation)

Spirometry Interpretation

AAFP VOLUME 69, NUMBER 5 / MARCH 1, 2004

COPDFVC

FEV1

Peak expiratory flow

Inhalation

Exhalation

FEV1

Spirometry Example

Measured Measured Predicted % Predicted PostbronchodilatorMeasured

Postbronchodilator% Predicted

% Change

FVC (L) 1.78 3.28 54 2.3 70 29

FEV1 (L) 0.92 2.53 36 1.55 L 67 37

FEV1/FVC (%) 52 81 64 55 68 6

Post BD increase in FEV1 >12% and 200ml from baseline (reversible airflow limitation), usually when FEV1 is low

ABCD Assessment Tool

•FEV1, FVC•Symptoms (CAT, mMRC)•Exacerbation history

COPD Symptom Assessments

mMRC. educatehealth.caCAT. catestonline.org

COPD Assessment Test (CAT)

Modified Medical Research Council Dyspnea Scale (mMRC)

GOLD Guidelines Initial TreatmentGroup C

LAMA

Group D

LAMA or LAMA+LABA* or ICS+LABA**

*Consider is CAT>20**Consider if Eos >300

Group A

Bronchodilator

Group B

LABA or LAMA

Adapted from: Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 Report. Available at www.goldcopd.org/.

mMRC 0-1CAT <10

mMRC ≥2CAT ≥10

Exacerbations:0 or 1 (not requiring

hospitalization)

Exacerbations:≥2 or ≥1 requiring

hospitalization

Terminology• Inhaler classes:

• Short-acting Beta2 agonists (SABA)• Short-acting Anticholinergics (SAMA)• Long-acting Beta2 agonists (LABA)• Long-acting Anticholinergics (LAMA)• Inhaled corticosteroids (ICS)• Combos (SABA/SAMA)• Combos (LABA/LAMA)• Combos (LABA/ICS)• Triple therapy (LABA/LAMA/ICS)

Oral Medications:• Methylxanthines

• Aminophylline• Theophylline

• Phosphidesterase -4 inhibitors (Roflumilast)

IV alpha anti-trypsin augmentation therapy

1981

• Proventil• Ventolin

1986

• Atrovent

1996

• Combivent

2004

• Spiriva

2006

• Advair• Symbicort

2007

• Dulera

Key:LABALAMALABA/LAMALABA/ICS

ICS Black-SABASABA/SAMASAMALAMA/LABA/ICS

https://www.accessdata.fda.gov/scripts/cder/daf/

Inhaler Progression Timeline

2011

• Arcapta

2012

• TudorzaPressair

2013

• Breo Ellipta• Anoro Ellipta

2014

• IncruseEllipta

• Striverdi Respimat

• ArnuityEllipta

• Spiriva Respimat

2015

• StioltoRespimat

• SeebriNeohaler

• UtibronNeohaler

2016

• BevespiAerosphere

2017

• AirDuo

2018

• Trelegy

InhalersShort-Acting Beta2-Agonist Bronchodilators (SABA):• -ProAir HFA (Albuterol)• -ProAir RespiClick (Albuterol)• -Proventil HFA (Albuterol)• -Ventolin HFA (Albuterol)• -Xopenex HFA (Albuterol)• (SABA/SAMA): Combivent (Albuterol and Ipratropium)

Long-Acting Beta2-Agonist Bronchodilators (LABA):• -Servent Diskus (salmeterol)• -Striverdi Respimat (olodaterol)

Long-Acting Muscarinic Antagonist (LAMA):• -Atrovent HFA (Ipratropium)• -Incruse Ellipta (umeclidinium)• -Spiriva HandiHaler (tiotropium)• -Spiriva Respimat (tiotropium)

Inhaled Corticosteroids (ICS):• Arnuity Ellipta (fluticasone furoate)• Asmanex HFA (mometasone)• Asmanex Twisthaler• Flovent Diskus (fluticasone propionate)• Flovent HFA (fluticasone propionate)• Pulmicort Flexhaler (budesonide)• QVar Redihaler (beclamethosone)

Combination Medications:LABA/ICS• Advair Diskus (fluticasone/salmeterol)• Advair HFA (fluticasone/salmeterol)• AirDuo RespiClick (fluticasone/salmeterol)• Breo Ellipta (fluticasone/vilanterol)• Dulera (mometasone/formoterol)• Symbicort HFA (budesonide/formoterol)LABA/LAMA• Anoro Ellipta (umeclidinium/vilanterol)• Stiolto Respimat (glycopyriolate/formoterol)LABA/LAMA/ICS (Triple Therapy)• Trelegy Ellipta (fluticasone/umeclidinium/vilanterol)

• Nebulizer solutions:• Albuterol• Levalbuterol• Ipratropium• Ipratropium/albuterol

Green = DPIPurple = SMIBlue = MDI

Suffixes:OL = Beta Agonist =SABA/LABAIUM =Anti-muscarinic= LAMA/SAMA SONE/NIDE=Steroid Inhaler = ICS

Metered dose Inhaler (MDI)• Contains propellant “HFA”

• Common problems:• Holding inhaler in wrong position• Not breathing at the same time as pressing the

canister• Not breathing deeply enough or holding breath

long enough

• Spacers improve amount of drug reaching the lungs

• All MDIs must be primed before first use• Priming: Number of sprays before first use

varies; range two to four times. • Must be re-primed after dropping inhaler or if

not used for a certain number of days (range 3–28 days).

• Propellant may build up (clean case)

• Hold your breath for 10 seconds (if possible)

Types of DPIs• Powders contain lactose: caution in patients

with lactose allergies• Different feel; no “spray” or “puff” • Do not shake• Inhale (quick, deep, forceful inhalation)

• Multi-dose and pre-loaded• Multi-dose: reservoir, multi-unit, blister pack• Devices: Diskus, Flexhaler, Twisthaler, Pressair,

Ellipta

• Single dose gelatin capsule• Devices: HandiHaler, Neohaler

• Breath-actuated• Device: RespiClik

Soft Mist Inhaler (SMI)

• Respimat = soft mist inhalers

• Propellant-free soft mist inhaler; slower velocity • Drug in solution

• Improved lung deposition

• Needs assembly• Priming:4 sprays initially and each month (every 21 days)

• 1 spray every 3 days (if not used)

Aerosol Generation

Energy from device Energy from patient

Metered Dose Inhalers Nebulizers Dry Powder Inhalers Soft Mist Inhalers

Coiled spring

Inhale forcefullyInhale slowly

https://www.nationalasthma.org.au/living-with-asthma/how-to-videos

https://www.nationaljewish.org/treatment-programs/medications/inhaled-medication-asthma-inhaler-copd-inhaler/instructional-videos

Inhaler Type Considerations DPI (Ellipta) MDI (Proair) SMI: (Respimat)

Less coordination, Breathe activated

Requires dexterity Less medication in the throat with more reaching the lungs in comparison to MDI

Cannot be used with spacers

Delivery enhanced with spacer

Mist comes out slowly, no coordination or dexterity needed

Irritant, causes patients to cough

Irritant, chemical propellant

Difficult to load the dose into the device

Fast deep full inhalation

Breathe in slowly and deeply for 10 seconds

GOLD Guidelines Initial TreatmentGroup C

LAMA

Group D

LAMA or LAMA+LABA* or ICS+LABA**

*Consider is CAT>20**Consider if Eos >300

Group A

Bronchodilator

Group B

LABA or LAMA

Adapted from: Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 Report. Available at www.goldcopd.org/.

mMRC 0-1CAT <10

mMRC ≥2CAT ≥10

Exacerbations:0 or 1 (not requiring

hospitalization)

Exacerbations:≥2 or ≥1 requiring

hospitalization

Eosinophils and COPD

• Elevated eosinophil counts are associated with reduced lung function and increased risk of exacerbations • High blood eosinophil are considered a

parameter to support use of ICS• A reduction in eosinophilic inflammation is

associated with reduced exacerbation frequency

Int J Chron Obstruct PulmonDis. 2018;13:335-349The Lancet. 2017;5(9):747-759

COPD and Pneumonia

• Pneumonia is a common complication of COPD• TORCH, INSPIRE and other studies showed pneumonia

was more common with ICS therapy• Dose related association between ICS and pneumonia • PATHOS: Fluticasone/salmeterol group more likely to

experience pneumonia than patients treated with budesonide/formoterol • Recent study showed ICS prevented severe

exacerbations at the onset of URTI symptoms

Am J Respir Crit Care Med 2007;176:162-6.European Respiratory Journal 2004 24: 206-210Nat Commun. 2018;9(1):2229

BMJ 2013;346:f3306.Am J Respir Crit Care Med. 2018;197(9):1136-1146.Am J Respir Crit Care Med. 2008;177(1);19-26.

Bronchodilators

• Bronchodilators improve FEV1 (but do not prevent rate of decline), symptoms, and exercise capacity• Combination bronchodilators may be superior to either component alone

β2-Agonists• LABAs have been shown to also improve health status exacerbation rates• Indacaterol is a LABA with a significantly greater bronchodilator effect than

formoterol and salmeterol• Indacaterol significantly improves breathlessness, health status, and exacerbation rate

• Adverse effects: Sinus tachycardia, somatic tremor (higher doses), hypokalemia (especially with thiazide diuretic), cough (indacterol)

Antimuscarinic

• Antimuscarinic• LAMA versus SAMA: LAMA showed improved lung function, health status and

oral steroid need compared to SAMA• Tiotropium improved effectiveness of pulmonary rehabilitation, reduced

exacerbations and hospitalizations.

• Conflicting differences found between tiotropium respimat SMI and the tiotropium DPI on mortality rates• Most recent study shows no difference

• Adverse effects: Dry mouth, bitter metallic taste (ipratropium), small increase in cardiovascular events (ipratropium)

(TIOSPIR; N Engl J Med 2013;369:1491-501).

LAMA vs LABA• LAMAs have a greater effect on exacerbation rates compared to LABAs and

decrease hospitalizations • POET-COPD study (Tiotropium versus salmeterol for COPD)

• 736 patients with moderate to severe COPD and 1+exacerbation in the past year• Results: Tiotropium (vs. salmeterol) significantly: Increased time to first exacerbation (187

days vs. 145 days [42-day difference]) (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.77–0.9; p<0.001) was significant for both moderate and severe exacerbations

• Conclusion: Tiotropium is more effective than a LABA as initial long-acting bronchodilator therapy in moderate to very severe COPD with respect to time to first exacerbation and annual number of exacerbations

• Cochrane review concluded: Tiotropium is more effective than LABAs in preventing COPD exacerbations and COPD-related hospitalization but not in overall hospitalization or mortality

(N Engl J Med 2011;364:1093- 103)Cochrane Database Syst Rev 2012;9:CD009157).

ICS

• Combined with a LABA, is more effective for lung function, health status and reducing exacerbations (in patients with exacerbations in moderate to very severe COPD) than alone• Monotherapy with ICS is not recommended; in combination, may not provide

much benefit in patients with frequent exacerbations in severe COPD• The dose response with ICS in COPD is unknown (in contrast to asthma

treatment)• Moderate to high doses have been used in COPD clinical trials

• Regular treatment increases the incidence of pneumonia• Blood eosinophil counts may be a predictor for likelihood of efficacy in using ICS

for preventing exacerbation• Adverse effects: Oral candidiasis, hoarse voice, skin bruising, pneumonia (risk

factors)

TORCH study: N Engl J Med 2007;356:775-89WISDOM trial: Magnussen 2014

Follow-Up Treatment

Triple TherapyFL

AME

(201

6) LABA/LAMA>LABA /ICS in preventing exacerbations in patients with Group D COPD

TRIN

ITY

(201

7) Fixed triple therapy superior to tiotropium, and non-inferior to open triple therapy

FULF

IL (2

017)

Triple therapy > ICS/LABA for lung function, health status and exacerbation rate at 24 weeks

IMPA

CT (2

018) Compared to dual

therapy, once-daily combination of vilanterol/umeclidinium/ fluticasone resulted in:• A lower rate of moderate or

severe COPD exacerbations• Better lung function• Better health-related quality

of life

N Engl J Med (2016); 374: 2222-2234Lancet 2017; 389(10082):1919–29Am J Respir Crit Care Med. 2017;196(4):438-446

N Engl J Med (2018); 378:(18)1671-1680

CareOregon COPD Treatment Pathway

Roflumilast (Daliresp)• Phosphodiesterase-4 (PDE4) Inhibitor

• Use in severe to very severe COPD (FEV <50% pred), history of exacerbations, and chronic bronchitis

• Mechanism: Reduces inflammation through inhibition of the breakdown of intracellular cyclic adenosine monophosphate; no direct bronchodilator activity

• Benefits: Improve lung function and reduce moderate to severe exacerbations• Improve lung function and decrease

exacerbation for patients with fixed dose ICS/LABA combination

• Also shown when roflumilast added to long-acting bronchodilators

Roflumilast contd

• Dose: 500 mcg orally once daily • Contraindications: Do not use in moderate to severe liver impairment; Do not use in

nursing mothers • Precautions: Weight loss (monitor), psychiatric events including suicidality (monitor;

weigh risks vs. benefits in patients with preexisting psychiatric illness); average weight loss is 2 kg. • Adverse effects: Diarrhea, weight loss/decreased appetite, nausea, headache, back

pain, influenza, insomnia, and dizziness • Drug interactions:• Use with strong cytochrome P450 enzyme inducers is not recommended (e.g.,

rifampin, phenobarbital, carbamazepine, phenytoin)• Use with CYP3A4 inhibitors or dual inhibitors of CYP 3A4 and 1A2 (e.g.,

erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) increases roflumilast exposure and adverse effects (risk-benefit must be weighed)

Chronic Antibiotics• In former smokers with exacerbations despite appropriate therapy, macrolides (specifically

azithromycin) can be considered• Chronic azithromycin for prevention of COPD exacerbations (azithromycin vs placebo x 1 year)

• 1577 subjects at increased risk of exacerbations (moderate or worse COPD receiving either continuous O2 or systemic corticosteroids in the past year) and history of a COPD exacerbation (ED visit or hospitalization)

• Results: Median time to exacerbation: 266 days (azithromycin group) versus 174 days (placebo) (p<0.001) • Rate of acute exacerbation: 1.48 versus 1.83 for azithromycin versus placebo (p=0.01) (NNT =3)• Quality of life improved more with azithromycin than with placebo; p=0.03)

• Adverse effects: Bacterial resistance and hearing impairment• Hearing decrements (by audiometry) were more common with azithromycin than with placebo (25% vs. 20%,

p=0.04) (NNH= 20)• Increased incidence of colonization with macrolide-resistant organisms (81% vs. 41%, p<0.001)

• Conclusion: Daily azithromycin lengthens time to first exacerbation, decreases rate of exacerbations, and improves quality of life in patients with COPD at increased risk of exacerbations• However, the GOLD guidelines still do not recommend general treatment with macrolide antibiotics, especially

greater than one year, except when indicated during acute exacerbations or those on triple therapy with continued exacerbations

Albert RK, Connett J, Bailey WC, et al.N Engl J Med 2011;365:689-98.

Non-Pharmacologic Treatment

• Home oxygen therapy • Pulmonary rehabilitation and exercise training• Vaccinations PCV13 and PPSV 23, Influenza

• Tobacco cessation

Summary

• Smoking cessation• Pharmacologic therapy (individualized)• Inhaler technique assessed regularly• Vaccinations (pneumonia and flu)• Eosinophil count• Pulmonary rehabilitation• Exacerbations

Managing Exacerbations

• Short-acting albuterol is preferred 2.5 mg via nebulizer every 1-4 hours or 4-8 puffs via MDI/holding chamber every 1-4 hr• Generally, short acting ipratropium is also given

• Systemic corticosteroids are effective and shorten recovery time, improve FEV1, and improve hypoxemia. They also lower the risk of treatment failure and early relapse, and reduce the length of a hospital stay.

• Prednisone 40 mg once daily for 5 days

• Consider oral antibiotics Dose 5-7 days

JAMA 2013;309:2223-31

Antibiotics

• Empiric antibiotics are used to cover the most common pathogens: Streptococcus pneumonia, Hemophilus influenzaeand Moraxella catarrhalis. In Gold 3 and 4 patients, Pseudomonas aeruginosa is more prevalent

•Recommended antibiotic duration is 5 –7 days

• Three cardinal signs: increase in dyspnea, increase in sputum volume, and sputum purulence

Antibiotics should be given if:• COPD exacerbation with all THREE cardinal symptoms• COPD exacerbation with TWO cardinal symptoms, if one is increased sputum

purulence• Severe COPD exacerbation requiring mechanical ventilation

Recommended Antibiotics• If recent (less than 3 months) use of antibiotics, use alternative class• If exacerbation does not respond to initial antibiotic, sputum culture and

sensitivity should be performed. COPD severity Recommended Antibiotic Risk Factors

Uncomplicated Azithromycin, clarithromycin, doxycycline, trimethoprim/sulfamethoxazole, or amoxicillin, with or without clavulanate

N/A

Complicated with risk factors

Amoxicillin/clavulanate, levofloxacin, moxifloxacin

Comorbid diseases, severe COPD (FEV1 less than 50% of predicted), more than 3 exacerbations/year, antibiotic use in past 3 months.

Risk of pseudomonas infection

High dose levofloxacin (750 mg) or ciprofloxacin; obtain sputum culture

Four or more courses of antibiotics in past year, recent hospitalization (past 90 days), isolation of Pseudomonas during past hospitalization, severe COPD (FEV1 less than 50% of predicted).

Home oxygen therapy

• Long-term (more than 15 hours a day) use in patients with chronic respiratory failure improves survival• Long-term use does not

lengthen lifespan or time to first hospitalization

Pulmonary rehabilitation

Includes exercise training, nutrition counseling, and education• Improves dyspnea, health status, exercise tolerance• Reduces hospitalization among patients with a recent exacerbation

with 4 weeks from a prior hospitalization • GOLD recommends for patient groups B-D

Asthma-COPD Overlap Syndrome (ACOS)

• At least three characteristics of asthma and three of COPD should be fulfilled in the same patient• Initial treatment: LABA/ICS

ACOS GOLD and GINA Guideline 2015

Feature ACOS

Age of Onset Usually age >40, but may have had symptoms in early childhood

Pattern of respiratory symptoms Exertional dyspnea is persistent but variability prominent

Lung function between symptoms Persistent airflow limitation

Past history or family history Frequently a history of doctor diagnosed asthma, allergies and a family history of asthma, and/or a history of noxious exposures

Time course Symptoms are partly but significantly reduced with treatment

Chest X-Ray Similar to COPD (severe hyperinflation)

Key Management Strategies• Smoking cessation is a critical component of COPD management• Pharmacologic therapy should be individualized and can reduce symptoms, reduce

frequency and severity of exacerbations, and improve health and exercise tolerance• Follow-up Management:

• Review – symptoms and risk• Assess – inhaler technique, adherence, and non-pharmacological approaches• Adjust – treatment (escalation and de-escalation)• Inhaler technique should be assessed regularly

• Influenza and pneumococcal vaccination decreases lower respiratory tract infections• Patients 19–64 years should receive PPSV23.• Patients 65 years and older should receive both PCV13 and PPSV23

Key Management Strategies contd

• Blood eosinophil count – COPD associated inflammation has limited responsiveness to corticosteroids. Blood eosinophil counts can predict the magnitude of the ICS effect in preventing further exacerbations (on top of a bronchodilator).• Fewer than 100 cells/mm3 = ICS have little to no effect• More than 300 cells/mm3 = ICS have greatest likelihood of effect

• Pulmonary rehabilitation improves symptoms, quality of life, and participation in everyday activities.• Rescue short-acting bronchodilators should be prescribed for immediate

symptom relief• Exacerbation management requires steroid therapy and antibiotics if

appropriate based on cardinal symptoms

Patient Case #1

• A 62-year-old man was recently given a diagnosis of COPD. Spirometry shows he has an FEV1/FVC 60%; pre- bronchodilator FEV1 70% of predicted; and post-bronchodilator FEV1 72% of predicted. His symptoms are very bothersome, and he is walking slower than others because of shortness of breath and is having to stop to catch his breath every so often when walking on level ground (mMRC = 2). He had one exacerbation in the past year without hospitalization. • Which is the most appropriate grade and patient group classification for

him, according to the GOLD guidelines? • A. GOLD grade 2 group A • B. GOLD grade 2 group B • C. GOLD grade 3 group C • D. GOLD grade 3 group D

Patient Case #1 Cntd.

• In addition to albuterol HFA two puffs every 4–6 hours as needed, which pharmacotherapy option is most appropriate to initiate? • A. No additional therapy needed

B. Formoterol: Inhale contents of one capsule twice daily.C. Salmeterol-fluticasone 50/500 one puff twice dailyD. Salmeterol-fluticasone 50/500 one puff twice daily plus roflumilast 500 mcg orally once daily

Patient Case #2

• A 52-year-old woman with COPD has experienced a gradual worsening in shortness of breath during the past few years. Spirometry shows FEV1/FVC 55% and FEV1 63% of predicted. Her CAT score is 10. She has not had a COPD exacerbation or received systemic corticosteroids in the past 2 years. Her current COPD medications are tiotropium inhaler once daily and albuterol HFA as needed. According to the GOLD guidelines, which is the most appropriate course of action? • A. Add salmeterol 50 mcg one inhalation twice daily.

B. Add long-term azithromycin 250 mg once daily.C. Add fluticasone 110 mcg two puffs twice daily.D. Discontinue tiotropium, and start salmeterol-fluticasone 250/50 one puff twice daily.

Patient Case #3

• A 64-year-old woman with COPD in GOLD grade 3 group C presents for a clinic visit. In the past few days, she has had a worsening in shortness of breath and a productive cough with more “cloudy” and more copious sputum than usual. Pulse oximetry is 95% on room air. She is currently taking tiotropium and salmeterol daily. She has a nebulizer at home. In addition to regular use of albuterol plus ipratropium by nebulizer every 1–4 hours, which is the best course of action? • A. No additional therapy is necessary.

B. Add oral prednisone 40 mg once daily for 5 days.C. Add trimethoprim/sulfamethoxazole double strength one tablet twice daily for 7 days.D. Add oral prednisone 40 mg once daily for 5 days and trimethoprim/sulfamethoxazole double strength one tablet twice daily for 7 days.