Pulmonary

Diagnosis and Management of Stable COPD

SUMMARY:

Chronic obstructive pulmonary disease (COPD) is a progressive and heterogenous respiratory condition characterized by persistent respiratory symptoms and airflow limitation. It is currently among the top three leading cause of death worldwide, and its global prevalence is projected to increase substantially in the coming decades. Though it is strongly associated with smoking, other causes include air pollution, indoor biomass fuel exposure, and occupational exposure to hazardous gases and dusts. There are also genetic and developmental factors that may predispose a person to developing COPD. Treatment is primarily aimed at alleviating symptoms (dyspnea, cough, sputum production and/or exacerbations), as there are currently few therapies that alter the progressive course of the disease. COPD is commonly associated with multiple medical comorbidities, and patients periodically suffer exacerbations during which symptoms acutely worsen, sometimes requiring emergency care or hospitalization. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) provides an evidence-based guide for practitioners to diagnose and treat COPD, which is summarized below.

KEY POINTS:

Diagnosis

Symptoms

A diagnosis of COPD should be considered in patients with:
- Respiratory symptoms (e.g., Dyspnea | Chronic cough +/- sputum production | Wheezing and chest tightness | Activity limitation | Fatigue)
- Recurrent lower respiratory tract infections
- Age ≥ 35 years
- History of exposure to risk factors for the disease (e.g., Tobacco smoke | Household and outdoor air pollution | Occupational exposures | Biomass exposures)
- Genetic factors (most relevant are mutations in the SERPINA1 gene leading to Alpha-1 antitrypsin deficiency) including family history of COPD
- Prematurity and early life disadvantage factors
Spirometry confirms the diagnosis of COPD by demonstrating the presence of non-fully reversible airflow obstructions (FEV₁/FVC <0.7 post-bronchodilation)
Initial assessment of COPD should also include the following to help guide therapy
- Severity of airflow obstruction (FEV₁/FVC ratio)
- Previous history of exacerbations
- Impact of symptoms on patient’s life
- Risk of future events (e.g., Exacerbations | Hospitalizations | Death)
- Concomitant diseases that may contribute to respiratory symptoms or exacerbate COPD
- Obtain blood eosinophil count (associated with airway inflammation)

Spirometry

Spirometry is a low cost, generally accessible test that plays a crucial role in COPD diagnosis and management
FEV₁/FVC < 0.70 (post-bronchodilator) confirms diagnosis of COPD
- Should be repeated at least annually in patients with COPD
- Population-based screening spirometry not recommended
- Screening spirometry may be considered in high-risk patients (e.g., >20 pack year smoking history | Recurrent lower respiratory tract infections)

“Pre-COPD” or “”PRIsm” (Preserved Ratio Impaired Spirometry)

Some patients may lack airflow obstruction on spirometry (i.e., FEV₁/FVC ≥ 0.70) but still have clinical signs or symptoms of COPD including
- Respiratory symptoms
- Structural lung lesions
- Physiological abnormalities (e.g., Low-normal FEV₁ | Gas trapping | Reduced DLCO | Hyperinflation | Rapid FEV₁ decline)
Many of these patients will go on to develop COPD, but prior to developing COPD may need treatment for symptomatic relief

Additional Work-Up

Assess exercise impairment (e.g. 6-minute walk test)
Screen all patients with COPD once for alpha-1-antitrypsin deficiency looking for hereditary sources
CT chest should be obtained to look for alternative diagnoses or to aid in therapy selection in patients with
- Persistent exacerbations
- Symptoms out of proportion to spirometry findings
- Evidence of air trapping/hyperinflation
CT chest may also be obtained in many patients with COPD for lung cancer screening (for individuals aged 50 to 80 with ≥ 20 pack year smoking history)
Differentiating COPD from asthma
- Asthma may be a risk factor for later development of COPD, but it is a separate disease process
- Asthma usually presents at an earlier age (often in children)
- Asthma usually presents with family history of asthma
- Asthma symptoms vary widely day-to-day, but symptoms are usually worse at night/early morning
- Asthma is generally associated with allergic rhinitis/eczema (“atopic triad”)
- In asthma, spirometry should demonstrate variable or reversible airflow linmitation

Disease Severity

GOLD Criteria for Classifying Disease Severity

Spirometry alone is insufficient for making individual treatment decisions
- Patients with severe airflow limitation on spirometry may have minimal symptoms (and vice versa)
GOLD grade vs group
- Grade (1-4): Refers to severity of airflow limitation (based on spirometry)
- Group (A | B | E): Considers patient-reported symptoms and exacerbation risk

Note: Patients with COPD are assigned both a grade and a group

Grade System (1 to 4)

(1-4) for classifying severity of airflow limitation (for patients with FEV₁/FVC <0.70)
- GOLD 1 (mild): FEV₁ ≥80% predicted
- GOLD 2 (moderate): 50% ≤FEV₁<80% predicted
- GOLD 3 (severe): 30% ≤FEV₁<50% predicted
- GOLD 4 (very severe): FEV₁<30% predicted

Group System (A | B | E)

Assess symptom burden using questionnaires
- Modified Medical Research Council (mMRC) Dyspnea Scale: Measures degree of dyspnea
- Chronic Airways Assessment Test h(CAAT): Assesses overall impairment of health in COPD
Record exacerbation risk: Based on number and severity of prior exacerbations

Group System Algorithm for Combined COPD Assessment

0 or 1 exacerbation not leading to hospitalization
- Group A: mMRC 0 to 1 | CAT <10
- Group B: mMRC ≥2 | CAT ≥10
≥1 more or severe exacerbation in the past year
- Group E

Management of Stable COPD

Initial Management

Actively encourage smoking cessation (counseling and pharmacotherapy; see ATS guidelines in references)
Ensure efficiency ventilation at home with non-polluting stoves, etc.
Encourage avoidance of any potential irritants (occupational dusts, fumes, gases, and household and outdoor air pollutants)
Administer all recommended vaccinations (emphasize influenza, pneumonia, RSV)
Encourage active lifestyle and exercise
Initial pharmacotherapy (detailed in next section)
Manage comorbidities
Self-management education
- Manage risk factors
- Review proper inhaler technique
- Create written action plan
- Plan for coping with sensation of breathlessness

Non-pharmacologic Therapies

Pulmonary rehabilitations
Long-term oxygen therapy
Noninvasive positive pressure ventilation
Lung volume reduction surgery

Pharmacologic Therapies

Initiate treatment based on GOLD Category as above
- Group A – initiate a bronchodilator (LABA or LAMA). SABA is almost never the best choice, unless in cases of rare breathlessness
- Group B – initiate LABA + LAMA
- Group E – initiate LABA + LAMA + add ICS if blood eosinophils ≥ 300
Escalate treatments as needed from stages above. If uncontrolled on LABA+ LAMA+ ICS, consider adding Roflumilast, Azithromycin or a Biologic Therapy.

Bronchodilators: Beta₂-agonists or Anti-Muscarinics

Beta₂-agonists
- Classified as short-acting (SABA) or long-acting (LABA)
- SABA are no longer recommended for chronic COPD management outside of exacerbations and as-needed for acute symptoms
- Adverse reactions include: Sinus tachycardia | Arrhythmia | Tremors | Hypokalemia
Anti-muscarinics
- Long-acting formulations (LAMA) used for stable COPD
- Short acting (SAMA) generally reserved for exacerbations
- Poor systemic absorption limits adverse effects, so generally very well tolerated aside from dry mouth

Inhaled Corticosteroids (ICS)

Primary benefit is preventing exacerbations
Prescribed in combination with LABA and LAMA
Greatest benefit: Blood eosinophils > 300 cells/µL | Concomitant asthma | ≥2 exacerbations per year | History of hospitalizations for COPD
Long-term monotherapy not recommended due to risk for pneumonia, oral thrush, and vocal hoarseness
No benefit of long-term oral glucocorticoids for stable COPD

PDE- 4 Inhibitors

PDE-4 inhibitors (e.g., Roflumilast (Daliresp)) recommended for its anti-inflammatory effects
Indicated in patients with persistent exacerbations AND
- FEV₁ < 50% predicted (e.g., GOLD stage 3 or 4)
- Chronic bronchitis
Adverse effects are more common in PDE-4 inhibitors and include: Diarrhea | Nausea | Weight loss | Abdominal pain | Sleep disturbance | Headache

Biologic Agents

Dupilumab recommended to reduce exacerbations and improve lung function and quality of life in patients with moderate-to-severe COPD and chronic bronchitis and higher blood eosinophil counts
Mepolizumab is also an option