Overview

• COPD is characterized by chronic, progressive, irreversible air flow obstruction
  – Leads to high lung volumes (functional residual capacity, residual volume, and total lung capacity).
• As a result of airway obstruction, the ratio of Forced Expiratory Reserve Volume in 1 second to Forced Vital Capacity is reduced
• COPD includes Chronic bronchitis, small airway disease, and emphysema.
• Asthma-COPD overlap syndrome: Symptoms of airway hyper-reactivity and airway obstruction.
• COPD can lead to V/Q mismatch, hypoxemia, pulmonary hypertension, and right heart failure (cor pulmonale).
• It is estimated that approximately 16 million people in the US have diagnosed COPD, and many are undiagnosed;.
• COPD is a leading cause of death worldwide.
• Previously thought of as a man’s disease, we now see high rates of COPD in both men and women; patients are typically over 65 years of age and are current or former smokers.
• Key risk factors are smoking, air pollution (including indoor pollution, such as the smoke from burning organic fuels for heating), and, genetics.
  – Alpha-1 antitrypsin deficiency is a known genetic cause of emphysema; this defect allows excess elastase in the lungs, which degrades alveoli.
• COPD is not curable
• Treatments are meant to relieve symptoms and slow progression; in addition to quitting smoking and limiting exposure to second hand smoke, patients may be prescribed bronchodilators, steroids, respiratory therapy, or supplemental oxygen. Prevention of respiratory infections via flu and pneumococcal vaccines are also important, as they prevent COPD exacerbations.
• Surgery may be appropriate for some patients.

Signs & Symptoms

COPD is the result of air trapping in the lungs; two key causes of air trapping are:
– Reduced elastic recoil in the lung parenchyma (which occurs in emphysema).
– Increased airway resistance (which occurs in chronic bronchitis and small airway disease, aka, SAD).

• Be aware that most patients have a combination of these disorders, which is why signs and symptoms often overlap – thus, the familiar concept of “pink puffers” vs. “blue bloaters” is an oversimplification.

• Decreased breath sounds, which some describe as “distant” sounds.
• Cough, sputum production, wheezing, and dyspnea.*
• Rhonchi; recall that rhonchi are low-pitched rattling sounds produced by airway secretions.
• Patients who are having difficulty breathing may adopt specific behaviors, such as pursed-lip breathing or tripod position:
  – Pursed-lip breathing slows down the breathing and increases airway pressure; incidentally, learning how to do pursed-lip breathing is also a component of respiratory therapy.
  – In the tripod position, patients brace their upper against their legs or the arms of a chair; this position helps to take some of the work out of breathing.
  – Cyanosis of the lips and nail beds, which are signs of hypoxia.
• Specific morphological changes may also be apparent; these are due to high lung volumes and hyperinflation of the chest.
  – Chronic hyperinflation leads to flattening of the diaphragmand shortening of its muscle fibers, which renders it less mechanically capable.
  – Thus, accessory respiratory muscles must do more work (including the scalenes, sternocleidomastoid, trapezius, abdominal muscles). It may be possible to palpate these hypertrophied muscles.
  – Many patients develop a “barrel-shaped” chest, in which the anterior-posterior diameter of the chest becomes larger.
  – Hoover’s respiratory sign is a pronounced inward movement around the costal margin during inspiration.
• Weight loss and muscle wasting, especially of the lower extremities.
• Peripheral edema
  – Edema is a potential manifestation of the systemic effects of COPD, which can include right heart failure and/or reduced renal flow.
• Be aware that COPD is associated with various cardiac, renal, and metabolic co-morbidities.
• Markers of systemic inflammation are often elevated.

• Exacerbations are defined as acute bouts of worse symptoms that require changes in treatment.
  – Exacerbations are often due to bacterial or viral infections, or exposure to air pollution.

Pathologic Changes

• Smoking leads to pulmonary dysfunction via multiple mechanisms:
  – Increased mucus production, impaired ciliary clearance, oxidative stress, and inflammatory cell recruitment.
• We draw the lower respiratory system, so that we can show how different portions are affected by these mechanisms, and we label the bronchi and bronchioles of the conducting zone, and the respiratory bronchioles and alveoli of the respiratory zone.

Chronic Bronchitis affects the bronchi, which are the larger airways of the lungs.
– Clinically defined as a chronic cough with sputum production that lasts for three or more months in two consecutive years.

• We show the histopathology of chronic bronchitis, from outermost to innermost:
  – For context, show some hyaline cartilage
  – Mucosa is characterized by hypertrophy and hyperplasia of mucous glands
  – Smooth muscle is also hypertrophied
  – Submucosa is infiltrated by inflammatory cells (specifically, CD8+ T-cells, neutrophils, and macrophages)
  – Respiratory epithelium has excessive goblet cells and possible squamous cell metaplasia
  – Respiratory cilia are impaired
  – The mucus, which is normally thin and runny, becomes abundant and viscous, thanks to mucus gland hyperplasia.
• Cumulatively, these changes produce a thicker bronchial wall, with limited ability to clear debris; thus, airway obstruction can occur.

Small Airway Disease affects the bronchioles.

• Small changes in bronchiole airflow have influence over total airflow, so this is where the most significant airway obstruction occurs.
• Small airway disease is characterized by mucus plugging, inflammation, and airway remodeling, which comprises fibrosis and thickening; together, these factors narrow the bronchiole lumen.
• Variation in V/Q can result from airway obstruction that leaves some alveoli under-ventilated and other alveoli holding trapped air.

Emphysema affects the respiratory bronchioles and alveoli.

• Inflammatory cells, which are recruited in response to cigarette smoke and other irritants, secrete elastase, which is an enzyme that breaks down alveolar walls.
  – Alpha-1 antitrypsin is a protective protein that inhibits elastase, which is why individuals with alpha-1 antitrypsin deficiency are more susceptible to emphysema.
• Oxidative stress from smoking damages pulmonary collagen and elastin.
• Elastase and oxidative damage break down the walls of the respiratory bronchioles and alveoli.
• Thus, there is less elastic recoil; thus, there is a reduction in the driving force to expel air during expiration.
• There is also loss of structural support, so the alveoli and alveolar ducts are prone to collapse and trap air.
• With the loss of respiratory zone structures, there is less surface area for gas exchange.*
• Because of variation in the disease process, emphysema is associated with variation in V/Q.