Pulmonary

Diagnosis and Management of Stable COPD

SUMMARY:

Chronic obstructive pulmonary disease (COPD), a progressive and heterogenous condition characterized by chronic respiratory symptoms due to airflow obstruction, is the fourth leading cause of death worldwide, and its prevalence is expected to increase 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. The underlying pathophysiology of COPD involves chronic inflammation of the small airways leading to airflow limitation and gas trapping, in conjunction with destruction of the lung parenchyma which impairs gas exchange and promotes CO2 retention. Treatment is primarily aimed at alleviating symptoms, 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~~e.g., Dyspnea | Chronic cough | Sputum production | Recurrent wheeze)
- Recurrent lower respiratory tract infections
- History of exposure to risk factors for the disease (e.g., Tobacco smoke | Household and outdoor air pollution | Occupational exposures | Biomass exposures)
Severe disease may present with symptoms of failure to thrive including
- Fatigue
- Weight loss
- Anorexia (associated with poor prognosis)
Regardless of symptoms, spirometry is mandatory to establish a diagnosis of COPD
Initial assessment of COPD should also include the following to help guide therapy
- Severity of airflow obstruction
- Impact on patient’s health status
- Risk of future events (e.g., Exacerbations | Hospitalizations | Death)
- Concomitant diseases that may contribute to respiratory symptoms or exacerbate COPD

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-Cursor Conditions

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)
These patients are labeled as “Pre-COPD” or “”PRIsm” (Preserved Ratio Impaired Spirometry)
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
Differentiating COPD from asthma
- Asthma usually presents with earlier onset
- Asthma symptoms vary widely day-to-day
- Asthma generally associated with allergic rhinitis/eczema (“atopic triad”)
- Spirometry for asthma should demonstrate variable or reversible airflow limitation

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): Measures degree of dyspnea
- COPD Assessment Test (CAT): 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
≥2 exacerbations or ≥1 exacerbation leading to hospitalization
- Group E

Pharmacologic Therapies

The goal of medical management is to reduce symptoms and future exacerbation risk

Bronchodilators: B₂-agonists or Anti-Muscarinics

B₂-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-muscarinic
- 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)
- Blood eosinophils > 300 cells/µL
Adverse effects are more common in PDE-4 inhibitors and include: Diarrhea | Nausea | Weight loss | Abdominal pain | Sleep disturbance | Headache

PDE 3 and PDE 4 Inhibitors

Ensifentrine is a novel first in class inhaled dual inhibitor of PDE-3 and PDE 4 which anti-inflammatory and bronchodilator effects

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

GOLD group-Based Initial Treatment Recommendations at Time of Diagnosis

GOLD A
- Bronchodilator
GOLD B
- LABA + LAMA
GOLD E
- LAMA + LABA
- Blood eosinophils > 300 cells/µL: Consider ICS in addition to LABA + LAMA

Follow-up Pharmacotherapy

Review Symptoms e.g. Dyspnea and exacerbations
Assess Inhaler technique and adherence and consider pulmonary rehabilitation/self-management techniques
Adjust e.g. de-escalate or escalate
If therapy needs to be escalated, first identify if primary issue is persistent dyspnea or frequent exacerbations | Follow exacerbation pathway if both dyspnea and frequent exacerbations are present

For Persistent Dyspnea

Add second bronchodilator (LABA or LAMA)
If already on LABA + LAMA, consider addition of ICS if meets criteria above or switching inhaler device or addition of ensifentrine
Consider other causes of dyspnea (e.g. Heart failure | Anemia) or comorbid conditions that may worsen COPD (e.g., Exposures | GERD | Asthma)

For Frequent Exacerbations

Add second bronchodilator or ICS
If already on LABA +LAMA
- Blood eosinophils ≥ 100 cells/µL: Escalate to triple therapy (LABA/LAMA/ICS)
- Blood eosinophils < 100 cells/µL: Add roflumilast (for FEV1 < 50% predicted and chronic bronchitis) or azithromycin (preferred for former smokers)
If already on LABA+LAMA+ICS and blood eosinophils ≥ 300 add dupilumab
Consider de-escalation of ICS if
- Pneumonia
- Inappropriate original indication
- Lack of response

Other Pharmacological Treatments

Alpha-1 Antitrypsin Augmentation Therapy for deficiencies may slow down progressive of emphysema
No conclusive evidence that antitussives help
Vasodilators do not improve outcomes and may worsen oxygenation
Long acting low dose opioids and parenteral opioids may be considered for treating severe COPD

Adjunctive Therapies

Smoking cessation (counseling and pharmacotherapy; see ATS guidelines)
Vaccination: Influenza | Pneumococcal | COVID-19 | Tdap | Shingles | RSV
Ensure proper inhaler technique
Pulmonary rehabilitation for GOLD groups B and E
Breathlessness and energy conservation techniques along with stress management techniques
Increase physical activity
Effective ventilation, non-polluting cooking stoves and avoidance of potential irritants

Indications for Chronic Oxygen Therapy

PaO2 ≤55 mmHg or SaO2 ≤88% +/-hypercapnia (measured twice over 3 weeks)
PaO2 55 to 60 mmHg if presence of pulmonary hypertension, congestive heart failure, or polycythemia
Oxygen goal: Titrate to SaO2 ≥90%
CPAP or BIPAP
- Long-term non-invasive ventilation may be indicated for patients with severe daytime hypercapnia
- CPAP recommended for patients with comorbid obstructive sleep apnea

Surgical Intervention

Specific subsets of patients may be eligible for surgical and procedural interventions such as: Bullectomy | Endobronchial valve placement | Lung volume reduction surgery | Lung coils | Vapor Ablation | Lung transplant

Advanced or Treatment-Resistant Symptoms

Palliative and hospice care should be available for patients with advanced or treatment-resistant symptoms
Discuss advance directives, views on resuscitation and place of death preferences
Nutritional supplementation may be offered to malnourished patients to improve respiratory muscle strength and overall health status

COVID-19 and COPD

Only essential spirometry studies should be done in times of high rates of COVID-19 infection
Patients with stable COPD symptoms should continue their inhaled medications, including ICS, if infected with COVID-19
In addition to maintenance COPD therapies, patients should receive guideline directed COVID-19 treatment if they qualify

Differential Diagnosis

Asthma | Congestive Heart Failure | Bronchiectasis | Tuberculosis | Obliterative Bronchiolitis | Diffuse Bronchiolitis | Pneumonia | Pulmonary Embolus | Cystic Fibrosis | Post Nasal Drip Syndrome | Chronic Allergic Rhinitis | GERD | Medications (e.g. Ace-inhibitors) | Upper Airway Cough Syndrome