23 Chronic Obstructive Pulmonary Disease

Question 1

Chronic obstructive pulmonary disease (COPD):
Global initiative for obstructive lung disease (GOLD) definition

Answer 1

• A common preventable and treatable disease
• Characterized by airflow limitation
  
  • Usually progressive
  • Associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases
• Exacerbations and comorbidities contribute to the overall severity in individual patients

Question 2

Definitions

• Chronic bronchitis
• Emphysema

Answer 2

• Chronic bronchitis
  
  • Defined clinically as the presence of chronic productive cough for 3 months during each of two successive years in a patient in whom other causes of chronic cough have been excluded
  • Airflow limitation is not a required feature for the diagnosis of chronic bronchitis.
• Emphysema
  
  • Defined anatomically as abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls

Question 3

Under-reporting of COPD symptoms by patients

Answer 3

• Many smokers deny their symptoms because they are not motivated to stop smoking
• Lungs have a generous reserve of function
  
  • Shortness of breath does not become prominent until a large proportion of lung function has been lost (about 50%)
• Respiratory function is lost gradually
  
  • Patients adapt to a restricted level of activity and attribute their impairment to normal ageing

Question 4

Mortality of COPD

Answer 4

• 3rd leading cause of death in the US
• Accounts for more than 120,000 deaths annually
• Prevalence and impact have been increasing for several decades following the epidemic of cigarette smoking in the twentieth century
• Mortality may be peaking among men in the United States, but among women, mortality continues to rise
  
  • Deaths from COPD among women now exceed those among men in the US

Question 5

Risk factors for COPD:
Exposure to toxic fumes and gases

• Cigarette smoking
• Environmental air pollution, especially particulates

Answer 5

• Cigarette smoking
  
  • The most important exposure risk factor for COPD
  • Smokers lose lung function in a dose-dependent manner
    
    • Some individuals lose lung function at a much more accelerated rate than others
  • Only 10-15% of smokers develop clinically significant COPD
    
    • Many more may have impaired lung function that is not clinically apparent
• Environmental air pollution, especially particulates
  
  • May contribute to an accelerated decline in lung function
  • Episodes of increased pollution may contribute to acute mortality

Question 6

Risk factors for COPD

• Asthma
• Mucus hypersecretion and exacerbations
• Perinatal and childhood effects

Answer 6

• Asthma
  
  • Accelerated loss of lung function among asthmatics
    
    • May be that all of the risk is in a subset of asthmatics
  • At least in some cases, asthma can progress to fixed airflow obstruction
• Mucus hypersecretion and exacerbations
  
  • Mucus hypersecretion has a modest effect
  • Individuals who experience more frequent acute exacerbations appear to have a more rapid decline in lung function
• Perinatal and childhood effects
  
  • Strong correlation between childhood respiratory infections and the development of COPD

Question 7

Natural history of COPD

• Maximally attained lung function
• Over 50 years of adult life, a normal lung may…
• Smoking during the years of lung growth
• Variation in the rate of lung function decline among individuals

Answer 7

• Maximally attained lung function
  
  • Reached in young adulthood
  • Remains relatively constant for perhaps 10 years
  • Begins to decline in a slowly accelerating manner
• Over 50 years of adult life, a normal lung may…
  
  • Lose 1 liter of FEV1, a decline that averages 20 mL/year
• Smoking during the years of lung growth
  
  • Reduces maximally attained lung function
  • The “plateau phase” is reduced in duration and may be absent
  • The rate at which lung function declines is probably also increased by smoking
• Variation in the rate of lung function decline among individuals
  
  • The 2-year mortality rate for patients admitted to hospital for an acute exacerbation with carbon dioxide retention is about 50%
  • Some patients with severe obstructive airway disease survive for many years
  • Thus, it is not possible to predict the course of an individual with a high degree of certainty

Question 8

Pathogenesis of COPD:
Inflammatory cells

• In response to cigarette smoke,..
• Causes of inflammation

Answer 8

• In response to cigarette smoke,..
  
  • Neutrophils rapidly accumulate in the lung
  • This accumulation results in a significant oxidant burden to the lung due to…
    
    • The oxidants present in smoke
    • Oxidants generated by the recruited inflammatory cells
• Causes of inflammation
  
  • Cigarette smoke (both directly and indirectly)
  • Analysis of end-stage lung tissue obtained from lung volume reduction surgery (later, a decade after smoking cessation

Question 9

Pathogenesis of COPD:
The proteinase : antiproteinase hypothesis

Answer 9

• A deficiency of serum alpha-1 antitrypsin, the endogenous inhibitor of neutrophil elastase, is associated with emphysema
• Experimental animal models using intratracheal elastases result in air-space enlargement
• Other matrix components, such as collagen, must also be lost for an alveolar space to enlarge
• An imbalance of proteinases and antiproteinases can lead to emphysema

Question 10

Pathogenesis of COPD:
Cell death and repair

• Cell death
• Repair

Answer 10

• Cell death
  
  • Because cell viability requires cell-matrix attachment via integrins, loss of matrix disrupts the contact and predisposes to cell death
  • Non-inflammatory cell death can initiate air-space enlargement
• Repair
  
  • In emphysema, alveolar and extracellular matrix (ECM) repair is impaired, resulting in…
    
    • Coalesced and enlarged air spaces with depleted and disordered parenchymal elastic fibers
    • Excessive, abnormally arranged collagen

Question 11

Clinical features of COPD

• Most frequent symptom
• Most patients with COPD manifest…

Answer 11

• Most frequent symptom
  
  • Cough
• Most patients with COPD manifest…
  
  • Cough
  • Expectoration
  • Dyspnea
    
    • Usually causes patients to seek medical attention
    • Many patients avoid dyspnea by avoiding exertion and may become exceedingly sedentary
  • Sputum production is greater in smokers
    
    • Usually mucoid
    • Becomes purulent during infective episodes
    • May take 2 to 3 weeks to clear

Question 12

Clinical features of COPD

• In many patients with COPD, physical examination reveals…
• The most consistent finding in patients with symptomatic COPD
• As COPD becomes severe, other physical signs may become evident
• Patients may be observed…

Answer 12

• In many patients with COPD, physical examination reveals…
  
  • Little abnormality especially during quiet breathing
  • Rhonchi may be present during inspiration and expiration
  • Wheezing is not a consistent finding and does not relate to the severity of the obstruction
• The most consistent finding in patients with symptomatic COPD
  
  • Prolonged expiratory time (longer than 4 seconds)
• As COPD becomes severe, other physical signs may become evident
  
  • Barrel-shaped chest
  • Purse-lipped breathing
  • Emaciation
• Patients may be observed…
  
  • Sitting forward and leaning on their elbows
  • Supporting their upper body with extended arms in a position known as tripodding

Question 13

Clinical features of COPD:
Radiographic findings

• Chest radiography
• Findings suggestive of chronic bronchitis
• Findings suggestive of emphysema

Answer 13

• Chest radiography
  
  • Can help exclude other pathology in patients with COPD
  • COPD is a functional diagnosis and chest radiographs can only suggest this diagnosis
• Findings suggestive of chronic bronchitis
  
  • Increased thickness of bronchial walls viewed on end and an increased prominence of lung markings
  • Neither specific nor sensitive
• Findings suggestive of emphysema
  
  • An arterial deficiency pattern, characterized by the triad of overinflation, oligemia, and bullae

Question 14

Clinical features of COPD:
Radiographic findings

• The best evidence of overinflation
• Computed tomography (CT)

Answer 14

• The best evidence of overinflation
  
  • Flattening of the diaphragms with a concavity of the superior surface of the diaphragm
  • Increase in the width of the retrosternal air space, but this is less sensitive
• Computed tomography (CT)
  
  • Can resolve the pulmonary parenchyma much better than the standard roentgenogram
  • Can establish and quantify the severity of emphysema and its anatomic extent
  • Can also determine the presence of bullae and distribution of emphysema, which is important in selecting patients for surgical intervention

Question 15

Clinical features of COPD:
Pulmonary function testing:
Spirometry

• Procedure
• Diagnostic of obstruction
• Suggestive of asthma excluding COPD
• Helpful for defining therapeutic goals

Answer 15

• Procedure
  
  • Patients take a maximally deep breath then exhale as forcefully as possible
  • The volume exhaled after 1 second, the FEV1, is the most important measure
  • The maximal volume exhaled is the forced vital capacity, or FVC
• Diagnostic of obstruction
  
  • A reduction in the FEV1/FVC ratio (less than 70)
• Suggestive of asthma excluding COPD
  
  • Correction to the normal range with bronchodilator treatment
• Helpful for defining therapeutic goals
  
  • Partial correction, which may vary from day to day in an individual patient

Question 16

Clinical features of COPD:
Pulmonary function testing

• Total lung capacity
• Residual volume
• Functional residual capacity
• Vital capacity
• Single-breath diffusing capacity

Answer 16

• Total lung capacity
  
  • Increased in emphysema because the loss of elastic recoil permits the lungs to stretch to a greater maximal volume
• Residual volume
  
  • May also be increased
• Functional residual capacity
  
  • May also be increased
• Vital capacity
  
  • May be decreased because the residual volume usually increases more than the total lung capacity
• Single-breath diffusing capacity
  
  • Decreased in proportion to the severity of emphysema because of the destruction of the alveoli and loss of the alveolar capillary bed

Question 17

Clinical features of COPD:
Arterial blood gases

Answer 17

• Arterial blood gases show mild or moderate hypoxemia without hypercapnia in the early stages of COPD
• In the later stages of the disease, hypoxemia tends to become more severe and may be accompanied by hypercapnia with increased serum bicarbonate

Question 18

Complications of COPD:
Pneumothorax

Answer 18

• Pneumothorax complicating COPD can precipitate severe dyspnea and acute respiratory failure and may be life-threatening
• Pneumothorax should be suspected in any COPD patient who experiences sudden worsening of dyspnea

Question 19

Complications of COPD:
Cor pulmonale

Answer 19

• Chronic cor pulmonale is defined as enlargement of the right ventricle due to increased right ventricular afterload from diseases of the lungs or pulmonary circulation
• The major cause of increased pulmonary vascular resistance in patients with COPD is vasoconstriction due to alveolar hypoxia
• There is subsequent remodeling of the pulmonary vasculature

Question 20

Complications of COPD:
Systemic manifestations

Answer 20

• Skeletal muscle weakness, bone disease and weight loss may be associated with COPD
• Metabolic alterations are thought to play a role in the pathogenesis of these systemic manifestations
  
  • There is likely a contribution from increased levels of circulating inflammatory cytokines such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)

Question 21

Treatment of COPD

Answer 21

• Smoking cessation
• Medications
• Oxygen therapy
• Pulmonary rehabilitation
• Surgical options
• Long-acting bronchodilators
  
  • Include both anticholinergics (tiotropium) and beta2 agonists (salmeterol and formoterol)
  • Can maintain stability and pre-dose respiratory function, reduce exacerbation frequency, and improve quality of life
• Inhaled steroids
  
  • Have a marginal effect on lung function
  • Reduce exacerbation frequency and improve quality of life
• Continuous oxygen therapy in those that qualify
  
  • Can impact survival
  • Participation in pulmonary rehabilitation can have a major impact on functional capacity and quality of life
• Surgical options
  
  • Lung volume reduction surgery
  • Lung transplantation