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AIRWAY DISEASES

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I. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

QUESTIONS TO CONSIDER AS LEARNING OBJECTIVES:

Asthma is defined functionally by this term.
This most common type of asthma is mediated by IgE.
Mast cells release this substance which triggers mucosal edema and smooth muscle contraction.
These predominantly inhaled substances are almost always proteins and trigger bronchospasm in patients with atopic (allergic) asthma.
Unremitting attacks of bronchospasm in asthmatic individuals are known by this term and may prove fatal.
This highly addictive habit is the single most common cause of clinically significant chronic bronchitis in the world today.
Individuals who live in these environments are predisposed to chronic bronchitis.
Patients with pure chronic bronchitis have been referred to by this term that refers to their color and general habitus.
This portion of the respiratory tree is most susceptible to the mucous hypersecretion present in chronic bronchitis.
Chronic bronchitis and this disorder are linked etiologically and cause high morbidity when both are severe in the same patient.
The emphysematous patient's ability to maintain oxygenation by extraordinary effort is embodied by this term used to describe patients with this disease.
A patient attempting to equalize pressures across her terminal airways, to prevent collapse and air trapping, may be breathing in this manner.
These two structural abnormalities combine to produce tachypnea in the patient with emphysema.
Envisioned by some as a ball valve, these airways, weakened by emphysema, open on inspiration but flop shut on expiration.
This theory proposes the neutrophil as the originator of unchecked digestion of lung tissue.
Emphysema can be broadly categorized relative to its distribution in the acinar unit. This acinar pattern of emphysema is commonly seen in smokers.
These cells are believed to be the key players in producing emphysema
A. What are neutrophils (polys)?
These two changes characterize the microscopic appearance of emphysema.
This inherited disease became a "lesson of nature" for emphysema, leading to our current understanding of emphysema's pathogenesis.
Originally described in patients homozygous for the PiZ allele, this form of emphysema may be patchy in the lungs (contrary to the implication of its name) and is more pronounced in the lower lung zones.
This pathologic change are definitional for bronchiectasis.
These two principal causes of bronchiectasis may occur separately but are often etiologically related.
Recurrent bacterial pneumonias plague patients with bronchiectasis because of these two resultant problems.
These inherited disease commonly results in bronchiectasis.

I. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Refers to the diseases of:

asthma
chronic bronchitis
emphysema
bronchiectasis

All of these diseases affect the terminal airways of the lung. They are all characterized clinically by a chronic or recurrent obstructive pattern on pulmonary function testing-- hence the term obstructive lung disease. Other airway diseases are classified as restrictive.

Asthma, also known as reactive airway disease, is a condition characterized by increased responsiveness to a variety of stimuli that lead to episodic, reversible bronchospasm.
- The most common form of asthma is mediated by allergy.
  - Environmental antigens are the triggers for this form of asthma (pollens, animal dander, foods, dusts).
  - The disease is mediated by IgE directed against the particular antigen in question. The IgE becomes bound to mast cells present on the surface of the lung epithelium. Once this immunoglobulin encounters its antigen, degranulation of the attached mast cell occurs with release of histamine and other mediators. These agents cause constriction of the bronchiolar smooth muscle and thus bronchoconstriction.
  - Epithelial injury also occurs during attacks as a result of the participation of eosinophils in the late phase of the response.
- Nonallergic (nonatopic) asthma occurs in response to respiratory tract infection.
  - Viruses such as rhinovirus are the principal culprits.
  - The exact mechanism for bronchoconstriction is unknown but hyperreactivity of the airways is a favored hypothesis.
- Three other forms of asthma occur: drug induced, occupational and allergic bronchopulmonary aspergillosis.
- Asthmatic attacks are characterized by several hours of bronchoconstriction followed by prolonged coughing. Subcutaneous injection of epinephrine provides acute relief, but inhaled or systemic corticosteroid therapy and bronchodilator therapy is necessary in many patients to control the disease.
- Rarely, asthmatic individuals may experience unremitting bronchoconstriction known as status asthmaticus, a sometimes fatal complication of this disease.
- The most common pathologic findings in patients with asthma who die is thickening of the airway basement membranes, increased numbers of submucous bronchial glands and mucous plugs in airways. The lungs may be overinflated if the patient dies in status asthmaticus.
- The sputum of patients with asthma commonly shows thick mucous with Curschmann's spirals (whorls of shed epithelial cells) and Charcot-Leyden crystals (crystalloids made up of eosinophil cell membranes).
- For most patients with asthma, the disease is discouraging and somewhat limiting, but does not preclude a normal lifespan.
Chronic bronchitis is a disease of smokers and those living in dusty and smog-laden environments.
- Chronic bronchitis is defined as "persistent cough with sputum production for at least 3 months in at least two consecutive years".
- Chronic bronchitis may occur with and without physiologic evidence of airway obstructive changes. In its most florid obstructive form, patients are overweight, cyanotic, and produce copious sputum (so-called "blue bloater").
- The most important cause of chronic bronchitis is recurrent irritation of the bronchial mucosa by inhaled substances, as occurs in cigarette smokers.
- The pathologic hallmarks of chronic bronchitis are congestion of the bronchial mucosa and a prominent increase in the number and size of the bronchial mucous glands. Copious mucous may be seen within airway lumens. The terminal airways are most susceptible to obstruction by mucous.

Emphysema is defined as the permanent, destructive enlargement of the airspaces distal to the terminal bronchiole. Emphysema is different from overinflation.
- There is overlap between chronic bronchitis and emphysema, though relatively pure forms of each can be appreciated. The main reason for this overlap has to do with the prevalence in the population of cigarette smoking-- an addictive habit that causes both conditions.
- Patients with pure emphysema are thin, agitated, and breathe rapidly through pursed lips (so-called "pink puffers").
- The proposed cause of emphysema is based on the protease-antiprotease theory proposed first for patients with the inherited disorder known as alpha-1-antitrypsin deficiency.
  - Antiproteases keep the local destructive effects of neutrophil lysozymal enzymes in check after they are released into tissues. In patients without tissue antiproteases, inflammatory effects involving neutrophils are amplified and tissue digestion results. Cigarette smoke stimulates neutrophilic infiltration in the lung and also inhibits the activity of naturally occurring antiproteases.
  - The combination results in slowly progressive digestion of the delicate alveolar walls beginning at the center of the acinus, producing centriacinar emphysema. Since patients with inherited deficiency of antiproteases have little or no natural antiproteases, digestion is more wholesale in the lung, involving the entire acinus, producing what is called panacinar emphysema.
- The reason some smokers develop emphysema after as few as ten years of smoking, while other smokers may not develop clinically evident emphysema (despite "chain" smoking even longer), has to do with genetic factors. Some individuals may be at greater risk for cigarette induced emphysema because their antiprotease levels are suboptimal or deficient.
- Patients with emphysema breath through pursed lips in order to maintain intraluminal pressure across their weakened and digested terminal airways. They breathe fast (tachypnea) because the have increased "dead space" in their lungs and decreased surface area from alveolar loss.
- The clinical signs of emphysema are barrel chest, hypertrophy of the accessory muscles of breathing and clubbing of the digits.
- The radiographic hallmarks of emphysema are "empty" lung fields (hyperlucent), and flattened diaphragms.
- The microscopic findings in emphysema are dilated alveoli with "clubbed" septa.

Bronchiectasis is defined as a chronic necrotizing infection within airways that leads to permanent dilatation and scarring of airway walls.
- Bronchiectasis is caused by obstruction and infection within the airways.
  - An excellent example that illustrates the pathogenesis of bronchiectasis is the inherited disorder known as cystic fibrosis. Recurrent or persistent mucous plugging in this disorder of mucous production results in obstruction followed by air resorption beyond the level of blockage. The distal lung collapses and cannot be properly cleaned by the normal lung mechanisms. Infection develops in the blocked segments with resultant necrosis and permanent damage to the airway walls. Over time the airways dilate as their walls become weakened.
  - Other hereditary conditions are associated with bronchiectasis.
- Localized bronchiectasis may occur after severe infection. The damaged area often becomes a focus for recurrent lung infection and may have to be surgically removed.
- Patients with bronchiectasis have low grade fever, cough, shortness of breath and foul smelling (sometimes bloody) sputum. They frequently "flare" into full blown pneumonia.

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