COPD

Disease State of COPD

A common, preventable, treatable disease

COPD

Persistent respiratory symptoms and airflow limitation

COPD Cause

* Due to airway and/or alveolar abnormalities
* Usually caused by significant exposure to noxious particles or gases

COPD Modifiable Risk Factors

* Cigarette smoke
* Occupational dust and chemicals
* Environmental tobacco smoke (ETS)
* Indoor and outdoor air pollution
* Infections

COPD Non-Modifiable Risk Factors

* Genes
* __**Socio-economic status**__
* Aging Populations

COPD Pathology

* Chronic inflammation
* Structural changes
* Emphysema

COPD Pathogenesis

* Oxidative stress
* Protease - antiprotease imbalance
* Inflammatory cells
* Inflammatory mediators
* Peribronchiolar and interstitial fibrosis

COPD Pathophysiology

* Airflow limitation and gas trapping
* Gas exchange abnormalities
* Mucus hypersecretion
* Pulmonary hypertension

COPD Symptoms

* Shortness of breath
* Chronic cough
* Sputum
* Saliva + mucus coughed up from respiratory tract

COPD Diagnosis

* Spirometry results:
* ↓ FEV1 (Forced Expiratory Volume in the 1st second)
* ↓ FEV1/FVC (Forced Vital Capacity) ratio
* These results mean:
* Impaired gas exchange
* Not fully reversible

Classification of Airflow Limitation Severity in COPD (Based on Post-Bronchodilator FEV1)

In patients with FEV1/FVC < 0.70

* Gold 1
* Gold 2
* Gold 3
* Gold 4

Classification of Severity of Airflow Limitation: Gold 1

* Mild
* FEV1 ≥ 80% predicted

Classification of Severity of Airflow Limitation: Gold 2

* Moderate
* 50% ≤ FEV1 < 80% predicted

Classification of Severity of Airflow Limitation: Gold 3

* Severe
* 30% ≤ FEV1 < 50% predicted

Classification of Severity of Airflow Limitation: Gold 4

* Very severe
* FEV1 < 30% predicted

COPD: Assessment of Symptoms

* __**COPD Assessment Test (CAT)**__
* An 8-item measure of health status impairment in COPD
* __**Modified Medical Research Council (mMRC) Questionnaire**__
* Relates well to other measures of health status and predicts future mortality risk

GOLD ABE Assessment Tool

* __**Group A and B**__: 0 or 1 moderate exacerbations (not leading to hospitalization)
* __**Groups E**__: ≥ 2 moderate exacerbations or ≥ 1 leading to hospitalization

Treatment of Stable COPD: Group E Treatment

* LABA + LAMA
* Single inhaler therapy may be more convenient and effective than multiple inhaler
* Consider LABA + LAMA + ICS __**if blood eosinophil ≥ 300**__
* In patients that also have asthma, they should be treated appropriately, thus ICS is recommended

Treatment of Stable COPD: Group A Treatment

* Bronchodilator
* Short or long-acting

Treatment of Stable COPD: Group B Treatment

* LABA + LAMA, if no barriers
* Single inhaler therapy may be more convenient and effective than multiple inhaler
* Neither class (LABA or LAMA) is preferred over the other for monotherapy if combination therapy isn’t appropriate
* Long-acting inhaledbronchodilators are superior to short-acting bronchodilators taken as needed
* i.e., pro re nata (prn) and are therefore recommended

Management of Stable COPD: Goals of Therapy

* Reduce symptoms
* Reduce risk

COPD Goals of Therapy: Reduce Symptoms

* Relieve symptoms
* Improve exercise tolerance
* Improve health status

COPD Goals of Therapy: Reduce Risk

* Prevent disease progression
* Prevent and treat exacerbations
* Reduce mortality

Management for Stable COPD

* Smoking Cessation
* Vaccinations

Management for Stable COPD: Smoking Cessation

* __**Greatest capacity to influence natural history of COPD**__
* Slows/halts COPD progression
* Strategies to help:
* 5 A’s
* Ask
* Advice
* Assess
* Assist
* Arrange

Management for Stable COPD: Vaccinations

* Influenza vaccination can reduce serious illness and death in COPD patients
* COVID-19 vaccination recommended for all people with COPD
* Pneumococcal vaccinations, PCV13 andPPSV23, are recommended for all patients >65 years of age
* CDC recommends Tdap vaccination in those who weren’t vaccinated in adolescence and Zoster vaccine to protect against shingles for adults with COPD > 50

COPD Pharmacological Therapies

* Bronchodilators
* Anticholinergics
* Beta-2 agonists
* Theophylline
* Corticosteroids
* Inhaled vs systemic
* Additional therapy
* Antibiotics
* Roflumilast

Anticholinergic Agents

* Ipratropium (Atrovent HFA)
* Tiotropium (Spiriva)

Anticholinergic Agents Indication

Safe & well tolerated considered first line therapy in COPD

Anticholinergic Agents MOA

Airway smooth muscle relaxation

Ipratropium (Atrovent HFA)

* Decreased systemic absorption
* MDI or nebulizer

Ipratropium (Atrovent HFA): Onset and Duration

* Onset 1-2 hours
* Duration 4-6 hours

Ipratropium (Atrovent HFA): Dosing

* MDI: 2 pugs inhaled 4 times daily
* Neb: 0.5mg (2.5mL) inhaled every 6-8 hours

Tiotropium (Spiriva)

* Dry powder & soft mist inhaler
* Newer options:
* Aclidinium bromide (Tudorza Pressair)
* Glycopyrrolate (Seebri Neohaler)
* Umeclidinium (Incruse Ellipta)

Tiotropium (Spiriva) Duration

Duration = 24 hours

Tiotropium (Spiriva) Dosing

Once daily dosing

* DPI: 2 puffs (1 cap) daily
* Soft Mist: 2 pugs (5mcg) daily

Beta 2 Agonists MOA

* Stimulation of beta-2 adrenergic receptors
* Resulting in airway smooth muscle relaxation
* Alternative to anticholinergic agents

Beta 2 Agonists ADE

* Safe and well tolerated
* May use without inhaled corticosteroids (ICS) in COPD

Types of Beta 2 Agonists

* Short-acting
* Long-acting

Short-Acting Beta 2 Agonists Product

* Most common is albuterol
* Levalbuterol also available

Short-Acting Beta 2 Agonists Indication

* “Rescue” inhale for acute symptoms
* Alternative to LABA for maintenance
* Treatment of acute exacerbation

Short-Acting Beta 2 Agonists: Maintenance Dose

2 puffs every 4-5 hours

Long-Acting Beta 2 Agonists Products

* Salmeterol (Serevent Diskus)
* Arformoterol (Brovana)
* Formoterol (Perforomist)
* Indacaterol (Arcapta Neohaler)
* Olodaterol (Striverdi Respimat)

Long-Acting Beta 2 Agonists Dosing

* Salmeterol (Serevent Diskus)
* 1 puff inhaled every 12 hours

Combination Bronchodilators Indication

Better response compared to monotherapy

Types of Combination Bronchodilators

* Short-acting
* Long-acting

Short-Acting Combination Bronchodilator Products

* Ipratropium + albuterol
* Duoneb® (nebulizer)
* Combivent® (inhaler)

Long-Acting Bronchodilators Products

* Umeclidinium + vilanterol (Anoro Elipta®)
* Tiotropium + oladaterol (Stiolto Respimat®)
* Glycopyrrolate + indacaterol (Utibron Neohaler®)
* Glycopyrrolate + formoterol (Bevespi Aerosphere®)

Theophylline Indication

* Place in therapy – controversial
* Less effective than inhaled therapy
* Risks outweigh benefits
* 2nd or 3rd line

Theophylline Dosing

* Use long-acting formulations
* 300-900 mg daily

Theophylline ADE

* Toxicity
* Palpitations (atrial or ventricular)
* Grand mal convulsions (irrespective of prior epileptic history)

Inhaled Corticosteroids

* Decrease symptoms, exacerbations
* Does not alter progression

Inhaled Corticosteroids Indications

Combined with a LABA for patients with exacerbations despite appropriate bronchodilator therapy

Inhaled Corticosteroids ADE

* Pneumonia, increased fracture risk, others
* Increased exacerbation with withdrawal

Inhaled Corticosteroids: Single Agent Product

__**Not approved for COPD**__

* Beclomethasone
* Fluticasone

Inhaled Corticosteroids: Combination Products

* Budesonide + formoterol (Symbicort®)
* Fluticasone + salmeterol (Advair®)
* Fluticasone + vilanterol (Breo Elipta®)

Inhaled Corticosteroids: Newer Therapies

* Trelegy Elpita® (fluticasone + umeclidinium + vilanterol)


* Breztri Aerosphere® (budesonide + glycopyrrolate + formoterol)

Systemic Corticosteroids Indication

* Maintenance therapy
* Avoid if possible
* No evidence of long-term benefits

Systemic Corticosteroids ADE

* Steroid myopathy
* Glucose effects
* Bone effects

Systemic Corticosteroids: Dosing and Administration

* Lowest effective dose
* Dose in the morning, once daily administration

Roflumilast (Daliresp®) MOA

* PDE4 inhibitor
* Reducing inflammation by inhibiting the breakdown of intracellular cyclic AMP

Roflumilast (Daliresp®) Dosing

Once daily oral medication

Roflumilast (Daliresp®) Clinical Effects

Small decrease in the rate of exacerbation

Roflumilast (Daliresp®) ADE

* N/V
* Weight loss
* Abdominal pain
* Sleep disturbance
* Headache
* CNS
* Psychiatric

Other Therapies

* Antibiotics
* Mucolytics–N-acetylcysteine
* Statins
* Leukotriene modifiers
* Vasodilators

COPD: What to Avoid

* Cough suppressants
* Beta-blockers OK if indicated for cardiovascular disease

Antibiotics Indications

Chronic azithromycin reduces exacerbations

Antibiotics ADE

Increases resistance and hearing loss

Treatment of Stable COPD: Reassessment

* Patients should be reassessed for attainment of treatment goals and identification of any barriers for successful treatment
* Following review of the patient response to treatment initiation, adjustments in pharmacological treatment may be needed

What to Check if Patient Isn’t Responsive to Initial Treatment

* Adherence
* Inhaler technique
* Possible interfering comorbidities


* Consider the predominant treatable trait to target
* Dyspnea or exacerbations

COPD Follow-Up Treatment Flow-Chart

Non-Pharmacological Management

* Education and self-management
* Physical activity
* Pulmonary rehabilitation programs
* Exercise training
* Self-management education
* End of life and palliative care
* Nutritional support
* Vaccination
* Oxygen therapy

What to Monitor

* Measurements
* Symptoms
* Exacerbations
* Imaging
* Smoking status

Monitoring and Follow-up: Measurements

Decline in FEV1 can be tracked by spirometry performed at least once a year

Monitoring and Follow-up: Symptoms

* At each visit, information on symptoms since last visit should be collected including:
* Cough and sputum
* Breathlessness
* Fatigue
* Activity limitation
* Sleep disturbances

Monitoring and Follow-up: Exacerbations

The frequency, severity, type and likely causes of all exacerbations should be monitored

Monitoring and Follow-up: Imaging

If there is a clear worsening of symptoms, imaging may be indicated

Monitoring and Follow-up: Smoking Status

At each visit, the current smoking status and smoke exposure should be determined followed by appropriate action

COPD Exacerbations

Defined as an acute worsening of respiratory symptoms that result in additional therapy

COPD Exacerbations Classifications

* Mild
* Moderate
* Severe

Mild COPD Exacerbations

Treated with short-acting bronchodilators (SABD) only

Moderate COPD Exacerbations

Treated with SABD plus antibiotics and/or oral corticosteroids

Severe COPD Exacerbations

* Patient requires hospitalization or visits the emergency room
* May be associated with acute respiratory failure

COPD Exacerbation Causes

* Viral or bacterial infections
* Air pollution
* No identifiable cause
* Rule out other co-morbid conditions
* Pneumonia
* Heart failure exacerbation
* Acute coronary syndrome

Management of Exacerbations

* 3 classes commonly used for COPD exacerbations
* Bronchodilator
* Corticosteroids
* Antibiotics

COPD Exacerbations: Brochodilators

* No high-quality evidence from RCTs
* Recommended that SABAs, with or without short-acting anticholinergics, are the initial bronchodilators for acute treatment of a COPD exacerbation

COPD Exacerbations: Corticosteroids

* Data suggests systemic glucocorticoids in COPD exacerbations shorten recovery time and improve lung function (FEV1)
* They also improve oxygenation, the risk of early relapse, treatment failure, and length of hospitalization

Bronchodilator Therapy

Initiate or continue maintenance inhalers when stable

* Albuterol
* 2.5-10 mg every 20 min x 3 then every 1-4 hours as needed by nebulizer
* Ipratropium
* 0.5 mg every 6 hours by nebulizer

Steroid Therapy in Exacerbation: Benefits

* Moderate benefit
* Improves patient outcomes:
* Recovery time
* Lung function
* Relapse

Steroid Therapy in Exacerbation: Monitoring

* Monitor for adverse effects
* Hyperglycemia
* Worsening heart failure

Steroid Therapy in Exacerbation: Dosing and Administration

**40 mg of prednisone once daily for 5 days**

Antibiotic Therapy Indications

* Still evolving, limited evidence
* 3 cardinal symptoms OR have 2 of the 3 with one being increase of purulence of sputum
* Dyspnea
* Sputum volume
* Sputum purulence

Antibiotic Therapy: Appropriate Agents for Uncomplicated Patient

* Macrolide – azithromycin, clarithromycin
* 2nd or 3rd generation cephalosporin
* Doyxcycline
* May need to consider resistant organisms

Antibiotic Therapy Duration

5-7 days

Other Interventions

* Assess risk for DVT – consider prophylaxis
* Maximize therapy for comorbid conditions
* Knowing patients end of life wishes

Other Interventions: Assess Risk for DVT – Consider Prophylaxis

* Heparin 5000 units SQ every 8 hours
* Enoxaparin 40mg SQ daily
* Fondaparinux 2.5 mg SQ daily

Other Interventions: Maximize Therapy for Comorbid Conditions

* IV fluids
* Diuretics
* Nutrition support

Consequences Of COPD Exacerbations

* Negative impact on quality of life
* Impact on symptoms and lung function
* Increased economic costs
* Increased mortality
* Accelerated lung function decline

COPD: Age of Onset

Usually > 40 yrs