Pharmacotherapy - COPD

Risk factors for COPD

How does smoking lead to COPD?

Staging of airflow obstruction (GOLD)

GOLD 1 (Mild) - FEV1 is less than 80% of the expected value

GOLD 2 (Moderate) - FEV1 is between 50 and 80% of the expected value

GOLD 3 (Severe) - FEV1 is between 30 and 50% of the expected value

GOLD 4 (Very Severe) - FEV1 is less than 30% of the expected value

mMRC Dyspnea Scale

* Grade 0 - Only breathless during periods of strenuous exercise
* Grade 1 - Becomes short of breath when hurrying on a level, or when walking up a slight hill
* Grade 2 - Walks slower than others of the same age due to breathlessness, or has to stop for breath when walking at own pace

Grade 3 - Has to stop for breath when walking for \~100 meters, or after a few minutes

Grade 4 - Too breathless to leave the house, or becomes breathless while dressing/undressing

GOLD Category A

GOLD Category B

GOLD Category E

FVC

Forced vital capacity - amount of gas released in a full breath

FEV1

Forced expiratory volume in 1 second - around of gas released in 1 second of a breath

Use of FEV1/FVC

Measure to show how hard it is for a patient to push air out of the lungs

Diagnosis of COPD is made based on...

Symptoms
Risk Factors
Spirometry

Initial Tx option for GOLD Category A

Bronchodilator ONLY

Initial Tx option for GOLD Category B

LABA + LAMA

Initial Tx option for GOLD Category E

LABA + LAMA
*consider + ICS is eos \> 300*

Metered Dose Inhaler Use

Dry Powder Inhaler Use

Vaccines needed for COPD patients

Influenza Vaccine
COVID-19 Vaccine w/booster
Pneumococcal Pneumonia Vaccines
Tdap
Zoster (if over 50)

Exacerbations

Characterized by increased dyspnea and/or cough and sputum production that worsens in less than 14 days

Exacerbations are usually caused by...

Increased local and systemic inflammation form:
Infection
Pollution
Insults to airways

When diagnosing an exacerbation it is important to rule out...

Decompensated HF
Pneumonia
Pulmonary Embolism

Pneumonia can be ruled out via...

Chest radiography

Pulmonary embolism can be ruled out via...

Clinical probability assessments
D-dimers
CT scans

Heart failure can be rules out via...

Chest radiography
NT Pro-BNP
ECHO

Goal of exacerbation treatment is....

To minimize negative impacts of current exacerbation and prevent subsequent ones

VAS (Visual Analogue Scale)

Subjective scoring of the apparent degree of difficulty the patient is having with breathing

Pneumococcal Vaccine Options

PCV20
OR
PCV15 followed by PPSV23 more than 1 year after

Characteristics of mild exacerbations

Dyspnea VAS of less than 5
RR of less than 24 breaths per minute
HR of less than 95 beats per minute
Resting SaO2 is greater than or equal to 92% at normal O2 requirement AND has changed at least 3%
CRP of less than 10 mg/L

Characteristics of moderate exacerbations

Dyspnea VAS of greater than 5
RR of greater than 24 breaths per min
HR greater than 95 bpm
Resting SaO2 of less than 92% at normal o2 requirement AND a change of at least 3%
CRP of greater than 10 mg/L
ABG should show hypoxemia (PaO2 less than 60) and/or hypercapnia (PaCO2 greater than 45) but no acidosis

Characteristics of severe exacerbations

Same as moderate, however ABG shows new or worsening onset of hypercapnia (PaCO2 \> 45) and acidosis (pH

Tx for mild exacerbations

Short acting bronchodilators (SABA's) +/- short acting anticholinergics (SAMA's)

Tx for moderate exacerbations

Short acting bronchodilators (SABA +/- SAMA)
Oral corticosteroids +/- ABX

Is there a difference between the use of MDI or nebulizer Tx for exacerbations?

NO, however nebulization is likely to be much easier for the patient

How frequently should bronchodilators be used during mild exacerbations?

Every 2-4 hours PRN based on the patients response as monitored by O2 and Sx

Long-acting therapy should be changed at what time when a patient has an exacerbation?

AFTER the patients exacerbation has ended/patient is stable

Outcomes from oral corticosteroid use during moderate exacerbations

Shorten recovery time
Improve FEV1 and O2
Decrease risk of early relapse, treatment failure, and duration of hospitalization

What dose of oral corticosteroids should be used during a moderate exacerbation?

Equivalent of 40 mg of prednisone daily for 5 days
*Important note - 60 mg may be beneficial for high risk patients*

Steroid Conversions

Hydrocortisone 20 mg \=
Prednisone 5 mg \=
Prednisolone 5 mg \=
Methylprednisolone 4 mg \=
Dexamethasone 0.75 mg

Prednisolone is the preferred steroid for exacerbation management in what patient population?

Patients with liver failure

Why should long courses of oral corticosteroids NOT be used for an exacerbation?

Associated with increased in side effects, as well as with increased overall mortality

ABX treatment in exacerbations has the most data for...

Patients with increased sputum production

Clinical outcomes from ABX use in COPD exacerbations

Shortens recovery time
Reduces risk of early relapse, treatment failure, and duration of hospitalization

ABX treatment is warranted if...

Patient is experiencing increased dyspnea
Patient is experiencing increased sputum volume
Patient is experiencing increased sputum purulence

ABX treatment options should be picked based on....

Risk factors for poor outcomes
AND
Risk factors of pseudomonas infection

Risk factors for poor outcomes in exacerbations include....

Comorbid conditions (HF, IHD, etc.)
Severe underlying COPD (FEV1 < 50%)
Frequent exacerbation Hx (2 or more per year)
Hospitalization for an exacerbation within the past 3 months
Receipt of Cont. O2
Age of 65 or greater

Risk factors for pseudomonas infection include...

Chronic colonization/previous isolation of Pseudomonas
Very severe COPD (FEV1 < 30%)
Bronchiectasis on chest imaging
Broad-spectrum ABX use within past 3 months
Chronic use of systemic corticosteroids

Duration of ABX use in COPD exacerbations should be...

Between 5 and 7 days

ABX options for pt w/ no risk factors for poor outcomes OR pseudomonas infection

Macrolides
2nd or 3rd Gen Cephalosporins

Macrolide ABX options

Azithromycin 500 mg QD F3D
ZPAK

Azithromycin should not be used in which patients?

Patients with baseline QTc prolongation \> 500

2nd/3rd Gen Cephalosporin Tx options

Cefuroxime 500 mg BID F5-7D
Cefpodoxime 300 mg BID F5-7D
Cefdinir 300 mg BID F5-7D
Cefdinir 600 mg QD F5-7D

ABX Tx options for pt w/ risk factors for poor outcomes BUT no risk for pseudomonas infection

Augmentin
Respiratory Fluoroquinolones

Augmentin Tx Options

Augmentin 500 mg TID F5-7D
Augmentin 875 mg BID F5-7D

Respiratory Fluoroquinolone Tx Options

Levofloxacin 500 mg QD F5-7D
Moxifloxacin 400 mg QD F5-7D

ABD Tx for pt w/ risk factors for poor outcomes AND risk for pseudomonas infection

Cipro +/- Amoxicillin for strep pneumo coverage

Cipro dosing

750 mg BID x5-7 days

Why is Cipro the preferred fluoroquinolone for pt w/ risk factors for poor outcomes AND risk for pseudomonas infection

Cipro has better coverage against pseudomonas than other FQ's

Amoxicillin dosing

1 g TID x5-7 days

What ABX should no longer be used in COPD exacerbations?

Doxycycline

Beta-2 Receptor Agonist MOA

Relaxes smooth muscle tissue within the bronchiole by stimulating the beta-2 adrenergic receptor which increases the [cAMP]

Clinical effect of beta-2 receptor agonists

Reduction in hyperinflation
Improvement in exercise performance
Relaxation of smooth muscle tissue

SABA duration of action

Wears off in ~4 to 6 hours

LABA duration of action

Wears off in more than 12 hours

ADE's related to use of beta-2 receptor agonists

Resting sinus bradycardia
Hypokalemia

Antimuscarinic agent MOA

Blocks bronchoconstrictive effects of ACh on the M3 receptor of the airway smooth muscle tissue

Specific MOA for SAMA agents

SAMA's also block the M2 receptor which reduces vaguely induced bronchoconstriction in the short term

Specific MOA for LAMA agents

LAMA's have prolonged binding to the M3 receptors and faster dissociation from the M2 receptor leading to prolonged duration

ADE's related to use of antimuscarinic agents

Dry Mouth
Bitter/Metallic taste

SABA examples

LABA examples

SAMA examples

LAMA examples

Inhaled corticosteroid (ICS) MOA

Suppresses inflammation in the airway by decreasing overall inflammatory responses

ICS examples

Why should ICS NOT be used as mono therapy?

Associated with an increased risk of pneumonia

ICS is most useful in what patient population?

Patients with high (\> 300) eos counts

What does eos count predict about ICS use?

Eos counts predict magnitude of effect of an ICS on preventing an exacerbation

Outcomes related to use of combination bronchodilators

Improves degree of bronchodilation and lung function
Increases QOL
Reduces exacerbations

LABA+LAMA examples

Formoterol + Aclidinium (Duaklir Pressair)
Formoterol + Glycopyrronium (Bevespi Aerosphere)
Vilanterol + Umeclidinium (Anoro Ellipta)
Olodaterol + Tiotropium (Stiolto Respima)

Effects of LABA/LAMA + ICS

Improves lung function, health status, and reduces exacerbations

Effects of LABA+LAMA+ICS

Improves lung functions, symptoms, health status, and reduces exacerbations

LABA/LAMA + ICS examples

Fluticasone + Salmeterol (Advair HFA/Diskus)
Fluticasone + Vilanterol (Breo Ellipta)
Mometasone + Formoterol (Dulera)

LABA + LAMA + ICS examples

Fluticasone + Umeclidinium + Vilanterol (Trilogy Ellipta)
Budesonide + Formoterol + Glycopyrrolate (Breztri Aerosphere)

When should a patient NOT be taken off of a ICS?

When eos counts are above 300

PDE4 Inhibitor MOA

Reduces the breakdown of intracellular cAMP, leading to reduction in airway inflammation

PDE4 Inhibitor example

Roflumilast

Roflumilast dosing

500 mcg daily

Clinical effects of Roflumilast

Reduces moderate and severe exacerbations in patients who:
- Have been treated with systemic corticosteroids w/chronic bronchitis
- Have severe or very severe COPD
- Have a Hx of exacerbations

Methylxanthines MOA

Work as non-selective PDE inhibitors and maybeeeeee have non-bronchodilatory actions as well

Methylxanthine example

Theophylline

Theophylline dosing

300 mg daily (in divided doses IF done as IR)

Beta blocker use in COPD

Only beta-1 selective agents should be used

Beta-1 selective beta blockers

Atenolol
Metoprolol
Nebivolol
Bisoprolol

Beta blocker clinical benefit in COPD patients

Reduced mortality in patients with HF or post MI **ONLY BENEFICIAL IN THESE PATIENTS**

WISDOM Trial - Overview

Designed to look at differences in outcomes for patients using LAMA + LABA vs. patients using LAMA + LABA + ICS

WISDOM Trial - Inclusion criteria

History of COPD exacerbations
Greater than 40 yo
Current or former smokers
Severe/very severe COPD
1 or more exacerbations in the past 12 months

WISDOM Trial - Treatment

All patients got triple Tx of Fluticasone + Salmeterol + Tiotropium for 6 weeks
Control group: Continued triple therapy x52 weeks
Treatment group: Withdrew fluticasone x52 weeks

WISDOM Trial - Outcomes

Time to first moderate to severe exacerbation

WISDOM Trial - Findings

There is NO significant difference between LAMA + LABA Tx and LAMA + LABA + ICS Tx in terms of rate of exacerbations occurring

JM is a 60 yo M presenting to the outpatient clinic following a hospitalization due to a COPD exacerbation. In looking through his chart, you note this is his first exacerbation. JM was diagnosed with COPD last year, and endorses a 40 pack year smoking history. JM describes that he often has to catch his breath after walking short distances. JM is here today for pharmacotherapy optimization (none of his home medications have changed since his exacerbation). PMH: COPD, T2DM.

Current medications: Advair (fluticasone 250 mcg/salmeterol 50 mcg) one inhalation daily, metformin 1000 mg PO BID, liraglutide 1.2 mg SC daily

Vitals: BP 120/82 mmHg, HR 88 bpm, RR 19, SpO2 97% (on room air), T 99.7 F, Wt 101 kg, ht 68 in

BMP: SCr 0.9mg/dL, BG 110mg/dL, BUN 10 mg/dL, Na 140 mEq/L, Cl 100 mEq/L, CO2 24 mEq/L, Ca 9.5 mg/dL

CBC: WBC 9.0 cells/L, RBC 5.2 cells/L, Hg 15.2 g/dL, Ht 48.2%, Plt 305,000 cells/uL, Eosinophil count 470 cells/uL

FEV1/FVC: 0.4, FEV1: 35%; mMRC 1, CAT 9

How would you classify JM's COPD as he presents today?

JM is a 60 yo M presenting to the outpatient clinic following a hospitalization due to a COPD exacerbation. In looking through his chart, you note this is his first exacerbation. JM was diagnosed with COPD last year, and endorses a 40 pack year smoking history. JM describes that he often has to catch his breath after walking short distances. JM is here today for pharmacotherapy optimization (none of his home medications have changed since his exacerbation). PMH: COPD, T2DM.

Current medications: Advair (fluticasone 250 mcg/salmeterol 50 mcg) one inhalation daily, metformin 1000 mg PO BID, liraglutide 1.2 mg SC daily

Vitals: BP 120/82 mmHg, HR 88 bpm, RR 19, SpO2 97% (on room air), T 99.7 F, Wt 101 kg, ht 68 in

BMP: SCr 0.9mg/dL, BG 110mg/dL, BUN 10 mg/dL, Na 140 mEq/L, Cl 100 mEq/L, CO2 24 mEq/L, Ca 9.5 mg/dL

CBC: WBC 9.0 cells/L, RBC 5.2 cells/L, Hg 15.2 g/dL, Ht 48.2%, Plt 305,000 cells/uL, Eosinophil count 470 cells/uL

FEV1/FVC: 0.4, FEV1: 35%; mMRC 1, CAT 9

Based on JM's known history, what is one non-pharmacologic recommendation you can make?