COPD: Chronic Bronchitis and Emphysema

• COPD stands for Chronic Obstructive Pulmonary Disease, the airflow limitation is not fully reversible, which contrasts with asthma, where airflow limitation is reversible
• COPD is a common lung disease and is both chronic and progressive
• COPD is associated with an abnormal inflammatory response of the lungs to noxious particles or gases
• Chronic bronchitis and emphysema are the two principal conditions and phenotypes of COPD
• Guidelines for COPD management are provided by Global Initiative for Chronic Obstructive Lung Disease (GOLD)

Chronic Bronchitis

• It is a presence of chronic or recurrent excessive mucus secretion into the bronchial tree
• It includes cough that is present on most days for at least 3 months of the year for at least two consecutive years
• Diagnosis requires exclusion of other causes of chronic cough

Emphysema

• abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis

Epidemiology of COPD

• Affects 16-28 million Americans

Etiology of COPD

• Cigarette smoking is the most common risk factor and accounts for 85-90% of cases in the US
• 50% of all smokers develop COPD
• Environmental factors like tobacco smoke, occupational dust, and chemicals are modifiable and their avoidance may reduce disease risk
• Specific genes: matrix metalloproteinase 12 (MMP12), α₁-antitrypsin, and other genetic markers being implicated
• α₁-antitrypsin (AAT) has been definitively shown to correlate with the development of emphysema and pulmonary dysfunction
• AAT, a plasma protein synthesized in hepatocytes, primary role is to protect cells, from neutrophil elastase destruction, accounts for < 1% of all COPD cases

Pathophysiology

• Characterized by chronic inflammatory changes that lead to destructive tissue changes and development of chronic airflow limitation
• Inflammation seen is referred to as neutrophilic in nature, although macrophages and CD8+ lymphocytes also play role
• Increased oxidative stress and imbalance between destructive and protective defense systems in the lungs (proteases and antiproteases) are also implicated
• Mucus secretion is increased, and ciliary motility is impaired
• Thickening of smooth muscle and connective tissue occur in the airways
• Chronic inflammation results in repeated injury and repair, leading to scarring and fibrosis
• Reversible factors include mucus and inflammatory cells, smooth muscle contraction, and dynamic hyperinflation
• Irreversible factors include fibrosis, reduced elastic recoil, and alveolar destruction
• Abnormalities in gas exchange lead to hypoxemia and/or hypercapnia as the disease progresses
• Hypoxemia occurs due to hypoventilation of lung tissue relative to perfusion
• Low V/Q ratio progresses, resulting in a consistent decline in the partial pressure of arterial oxygen (PaO₂)
• ↓ PaO₂ = 45-60 mm Hg (6.0-8.0 kPa) and ↑ PaCO₂ = 50-60 mm Hg (6.7-8.0 kPa)
• pH balance is maintained by the kidneys, but patients are at risk for respiratory acidosis
• Pulmonary hypertension, thoracic hyperinflation, and dyspnea are implicated in COPD
• Systemic effects include cardiovascular events associated with ischemia, cachexia, osteoporosis, and anemia

Clinical Presentations of COPD include:

• Chronic cough (may be intermittent or unproductive)
• Chronic sputum production
• Dyspnea (worse with exercise, progressive over time)
• Decreased exercise tolerance or decline in physical activity
• Chest tightness or wheezing
• Risk Factors - tobacco smoke exposure, indoor air pollution, occupational hazards, or a₁-antitrypsin deficiency
• Examination - shallow breathing, increased respiratory rate, barrel chest, pursed lips, use of accessory muscles, or cyanosis
• Diagnostic Tests - Spirometry with postbronchodilator testing, radiograph of chest, or lab testing for blood gases

Clinical diagnosis

• Should be considered for any patient, age 40 years or older, with persistent or progressive dyspnea, with chronic cough productive of sputum, and who exhibits an unusual or abnormal decline in activity, especially in the presence of exposure to environmental tobacco smoke
• With physical examination improves the diagnostic accuracy of COPD
• Reduction in FEV1/FVC ratio to less than 70% (0.70)

COPD measurements

• FVC (forced vital capacity) is the total volume of air exhaled after maximal inhalation and FEV₁ (forced expiratory volume in one second) is the total volume of air exhaled in one second
• Measured at baseline and then during routine visits using CAT or mMRC
• Patients over 2 exacerbations in 12 months or one requiring hospitalization are considered high risk for future exacerbations (category E)
• Prognostic indices increasing mortality - Lower FEV₁, greater age, lower body mass index, higher dyspnea score (mMRC), shorter 6-minute walk distance, continued smoking, frequent exacerbations, presence of selected comorbidities
• Goals are to prevent progression, relieve symptoms, improve exercise tolerance and overall health status, prevent exacerbations, complications, morbidity, assessed using CAT and mMRC

Treatment Regimens for COPD:

• Goals are to prevent progression, relieve symptoms, improve exercise tolerance and overall health status, prevent exacerbations and complications, and reduce morbidity and mortality
• Four major components of management: assess and monitor the condition; avoid or reduce exposure to risk factors; manage stable disease; and treat exacerbations
• Smoking cessation is the only intervention proven to affect long-term decline in FEV₁ and progression of COPD
• Tobacco cessation (sustained or intermittent) is beneficial at any point; pharmacotherapies double effectiveness
• Available pharmacotherapies will double the effectiveness of a cessation effort
• Pulmonary rehab (3-7x/week) produces long-term improvement in activities of daily living, quality of life, exercise, dyspnea (moderate to severe)
• Oxygen therapy instituted with PaO₂ < 55 mm Hg or SaO₂ < 88% with or without hypercapnia, or PaO₂ between 55-60 mm Hg or SaO₂ < 88% with evidence of heart failure, polycythemia, or pulmonary hypertension and raised to 60mmHG

Medications:

• Short-acting beta agonists (SABA) - Albuterol and Levalbuterol, can cause skeletal muscle tremors, palpitations, and arrhythmias

• Anticholinegics - MOA – acetylcholine antagonism

• Monotherapy is not associated with increased mortality and the 2023 guidelines recommend combination therapy (LAMA + LABA)

• LABAs are not for acute relief

• Corticosteriod use may be indicated in some circumstances, but may pose a risk of fracturing

Additional notes on drug therapies

• Methylxanthines improve lung function and gas exchange, can reduce dyspnea and increase exercise tolerance.
• PDE4 Inhibitors relax of airway smooth muscle cells and decreases activity of inflammatory cells and mediators such as TNF-α and IL-8, but include risks of headaches and diarrhea
• Macrolides and Azithromycin are antibiotics that reduce lower rates of exacerbations and improved quality-of-life scores, but hold a risk of hearing loss

Exacerbation Treatment

• Defined as a change in the patient's baseline symptoms (dyspnea, cough, or sputum production) beyond day-to-day variability sufficient enough to warrant change in management
• Diagnsosis of acute respiratory failure - Drop in PaO₂ of 10 to 15 mm Hg (1.3 to 2.0 kPa) or any acute increase in PaCO₂ that decreases the serum pH to 7.3 or less
• Oxygen therapy to be greater than 60 mmHg
• A systemic corticosteroid like Prednisone 40mg is administered daily for 5 days

This lesson covers Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive lung disease characterized by airflow limitation. It distinguishes COPD from asthma and discusses chronic bronchitis and emphysema as principal conditions. Guidelines for COPD management by GOLD are also mentioned.