Chronic Obstructive Diseases of the Lung

Chronic Obstructive Diseases of the Lung

Emphysema
Chronic Bronchitis

Emphysema

Gerald W. Staton, Jr., M.D., F.A.C.P.
Emory University School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

A form of chronic obstructive pulmonary disease (COPD) involving the lung parenchyma, characterized by abnormal, permanent enlargement of air spaces distal to the terminal bronchiole and destruction of the alveolar wall without obvious fibrosis
Dyspnea
Weight loss (patients are usually thin)
Minimal or no cough
Hyperinflated lung fields
No signs of cor pulmonale
Features may overlap significantly with those of chronic bronchitis

Differential Diagnosis

Chronic bronchitis
Congestive heart failure
Asthma
Interstitial lung disease

Best Tests

Physical examination
- Often normal in early stages, but tachypnea and a prolonged expiratory phase are usually present with more advanced disease
- Hyperresonant percussion note and unusually low position of the diaphragm may be associated with an emphysematous hyperinflation of the lungs
- Reduced breath sounds are associated with decreased airflow
- Wheezes are heard in ≥ 40% of patients, especially in the supine position
Directed laboratory investigations
- Hematocrit is normal
- Pulmonary function tests
  - Spirometry shows airflow obstruction that may or may not respond to acute administration of bronchodilator
  - Lung volumes are increased with air trapping
  - Diffusing capacity of lung for carbon monoxide is decreased
- Arterial oxygen tension (P_aO₂) is generally > 65 mm Hg with normal or decreased carbon dioxide tension levels (P_aCO₂)
- During exercise, P_aO₂ and oxygen saturation (SpO₂) levels decrease
Chest imaging
- A chest radiograph will reveal hyperinflation, including a low position of the diaphragm (i.e., at or below the seventh rib anteriorly), with increased depth of the retrosternal air space and a narrow, vertically oriented cardiac silhouette
- The most useful sign of hyperinflation is a flattening of the diaphragmatic contour and loss of the diaphragm's normal domed appearance
- Radiography will reveal decreased vascular markings and, in a small percentage of patients, bullae
- CT of the chest may be useful in differential diagnosis

Best Therapy

Smoking cessation and long-term administration of supplemental oxygen are the only strategies demonstrated to alter the natural history of the disease; patients may respond favorably to a combination of long-acting bronchodilators and inhaled corticosteroids

Maintenance Therapy

Drug Therapy

Inhaled beta-agonists or anticholinergics may improve maximal expiratory airflow by at least 10%
- Inhaled anticholinergics
  - Tiotropium (long-acting)
    - Dose: dry powder inhaler (DPI), lowest effective dose and daily max, 1 capsule daily
    - Cost: N/A
  - Ipratropium bromide (short-acting)
    - Dose: nebulizer, lowest effective dose, 0.5 mg q.i.d.; daily max, 2 mg
    - Cost: N/A
    - Dose: metered-dose inhaler (MDI), lowest effective dose, 2–6 puffs q.i.d.; daily max, 24 puffs
    - Cost/one inhaler: $38
- Inhaled beta₂-agonists
  - Inhaled long-acting beta₂-agonists
    - Salmeterol
      - Dose: MDI, lowest effective dose, 2 puffs b.i.d.; daily max, 4 puffs
      - Cost/60 doses: $114
      - Dose: DPI, lowest effective dose, 1 blister b.i.d.; daily max, 2 blisters
      - Cost/one inhaler: $99
    - Formoterol
      - Dose: DPI, lowest effective dose, 1 capsule b.i.d.; daily max, 2 capsules
      - Cost/30 doses: $98
  - Inhaled short-acting beta₂-agonists
    - Albuterol
      - Dose: nebulizer, lowest effective dose, 1.25 mg q. 4–8 hr p.r.n.; daily max, 5.0 mg q. 4–8 hr p.r.n.
      - Cost/5 days: $16
      - Dose: MDI, 2 puffs q.i.d.; daily max, 16 puffs
      - Cost/one inhaler: $16
      - Dose: DPI, 1 capsule q.i.d.; daily max, 8 capsules
      - Cost/15–30 days: $10
    - Bitolterol
      - Dose: nebulizer, lowest effective dose, 0.5 mg q. 4–8 hr p.r.n.; daily max, 3.5 mg q. 4–8 hr p.r.n
      - Cost: N/A
      - Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max, 16 puffs p.r.n.
      - Cost: N/A
    - Pirbuterol
      - Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max, 16 puffs p.r.n.
      - Cost/one inhaler: $95
- Combined short-acting beta₂-agonists/anticholinergic
  - Albuterol plus ipatropium bromide
    - Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max, 16 puffs
    - Cost: N/A
- Inhaled corticosteroids, whose role is controversial, may have significant benefits because of their effect on airway inflammation
  - Medium to high doses may yield the greatest benefit
  - Fluticasone (highest potency)
    - Dose: lowest effective dose
      - 110 µg/puff, 2 puffs; high dosage, > 6 puffs daily
      - 220 µg/puff, 2 puffs; high dosage, > 3 puffs daily
    - Cost: N/A
  - Budesonide (second-highest potency)
    - Dose: lowest effective dose at 200 µg puff, 1 inhalation; high dosage, > 3 inhalations daily
    - Cost/one inhaler: $148
  - Beclomethasone (third-highest potency)
    - Dose: lowest effective dose
      - 42 µg puff, 4 puffs; high dosage, > 20 puffs daily
      - 84 µg puff, 6 puffs; high dosage, > 10 puffs daily
    - Cost/one inhaler (44 µg): $83

Physical Rehabilitation

Physical training (e.g., treadmill walking) may significantly increase lung/exercise capacity, even in patients with advanced disease

Supplemental Oxygen Support

Recommended for patients with P_aO₂ ≤ 55 mm Hg or ≤ 59 mm Hg with any of the following comorbidities:
- Peripheral edema (signifies cor pulmonale)
- Hematocrit ≥ 55%
- P pulmonale on the ECG

Acute Exacerbations

Drug Therapy

Inhaled short-acting beta₂-agonists
- Albuterol (agent of choice)
  - Dose: nebulizer lowest effective dose, 5.0 mg q. 2 hr, daily max, 60mg
  - Cost/one 20 ml bottle: $16
  - Dose: MDI lowest effective dose, 3 puffs q. 2 hr; daily max, 72 puffs
  - Cost/one inhaler: $14
Inhaled short-acting anticholinergics
- Ipratoprium bromide
  - Dose: MDI, lowest effective dose, 3 puffs q. 3-4 hr; daily max, 64 puffs
  - Cost/one inhaler: $38
Antibiotics should be used if the patient has symptoms and signs suggesting infection; the choice of antibiotics should be based on the severity of the airflow obstruction
- Less severe infections, narrow coverage with agents active against S. pneumoniae and H. influenzae
- More severe infectons, broader coverage with agents active against gram-negative organisms, S. pneumoniae, and H. influenzae.
Corticosteroids such as prednisone (0.6 to 1.0 mg/kg/day) may be beneficial but are associated with side effects of varying severity; best candidates include the following:
- Patients currently taking oral or inhaled steroids
- Patients who have recently completed a regimen of oral steroids
- Patients who have previously responded to oral or inhaled steroids
- Patients who do not respond to initial bronchodilator therapy
- Patients whose oxygen saturation is ≤ 90% with peak expiratory flow rate ≤ 100 L/min
Exacerbations may be associated with hypercapnia and worsening of hypoxemia
- In these cases, oxygen supplementation adjusted to an SpO₂ level of 90% to 92% is recommended
- Ventilatory support should be considered in patients with increasing hypercapnia and blood pH < 7.35 despite initial bronchodilatory therapy

Best References

Currie GP, et al: BMJ 332:1261, 2006 [PMID 16735338]

Currie GP, et al: BMJ 332:1379, 2006 [PMID 16763252]

Currie GP, et al: BMJ 332:1439, 2006 [PMID 16777889]

Currie GP, et al: BMJ 332:1497, 2006 [PMID 16793814]

Currie GP, et al: BMJ 333:87, 2006 [PMID 16825232]

Devereux G: BMJ 332:1142, 2006 [PMID 16690673]

Chronic Bronchitis

Gerald W. Staton, Jr., M.D., F.A.C.P.
Emory University School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy Best References

Definition/Key Clinical Features

A form of chronic obstructive pulmonary disease (COPD) involving the tracheobronchial tree, characterized by hypersecretion of mucus and structural changes in the bronchi, including inflammation, metaplasia of the epithelium, and enlarged mucous glands
Daily cough and sputum production (≥ 2 oz) on most days lasting at least 3 mo of the year for a minimum of 2 yr in succession
May include transient periods of sputum discoloration, often in association with respiratory infections
Frequent chest infection
Severe wheezing attacks mimicking asthma
Recurrent episodes of cor pulmonale
Features may overlap significantly with those of emphysema and asthma

Differential Diagnosis

Emphysema
Asthma
Bronchiectasis
Chronic respiratory infections such as tuberculosis and atypical mycobacterial infection

Best Tests

Physical examination
- Findings will vary with disease severity
  - Often normal in early stages
  - The following are usually present with advanced disease:
    - Prolonged inspiratory and expiratory phases
    - Wheezing
    - Marked, profound hypoxemia with cyanosis
    - Peripheral edema resulting from right heart failure
Directed laboratory investigations
- Hematocrit is often increased
- Pulmonary function tests
  - Spirometry shows airflow obstruction that may or may not respond to acute administration of bronchodilator
- Lung volumes are normal or show minimal air trapping
  - Diffusing capacity of lung for carbon monoxide is typically normal
- Arterial oxygen tension (P_aO₂) levels are markedly reduced, and carbon dioxide tension (P_aCO₂) levels are increased (i.e., > 45 mm Hg) because of limitation of total amount of ventilation to compensate for increased work of breathing
- During exercise, P_aO₂ and oxygen saturation (SpO₂) levels may increase, and there may be a moderate rise in P_aCO₂
Chest imaging
- Rarely recognized on chest radiograph but may occasionally be suspected on basis of a thickening of bronchial walls or accentuated bronchovascular markings at the lung bases
- CT of the chest may be useful in differential diagnosis

Best Therapy

Although smoking cessation and long-term administration of supplemental oxygen are the only management strategies demonstrated to alter the natural history of the disease, patients may respond favorably to a combination of long-acting bronchodilators and inhaled corticosteroids

Maintenance Therapy

Drug Therapy

Inhaled beta₂-agonists or anticholinergics may improve maximal expiratory airflow by at least 10%
- Inhaled anticholinergics
  - Tiotropium (long-acting)
    - Dose: dry-powder inhaler (DPI), lowest effective dose and daily max, 1 capsule daily
    - Cost: N/A
  - Ipratropium bromide (short-acting)
    - Dose: nebulizer, lowest effective dose, 0.5 mg q.i.d.; daily max, 2 mg
    - Cost: N/A
    - Dose: metered-dose inhaler (MDI), lowest effective dose, 2–6 puffs q.i.d.; daily max, 24 puffs
    - Cost/one inhaler: $38
  - Inhaled beta₂-agonists
    - Inhaled long-acting beta₂-agonists
      - Salmeterol
        
        Dose: MDI, lowest effective dose, 2 puffs b.i.d.; daily max, 4 puffs
        Cost/60 doses: $114
        Dose: DPI, lowest effective dose, 1 blister b.i.d.; daily max, 2 blisters
        Cost/one inhaler: $99
      - Formoterol
        
        Dose: DPI, lowest effective dose, 1 capsule b.i.d.; daily max, 2 capsules
        Cost/30 doses: $98
    - Inhaled short-acting beta₂-agonists
      - Albuterol
        
        Dose: nebulizer, lowest effective dose, 1.25 mg q. 4–8 hr p.r.n.; daily max, 5.0 mg q. 4–8 hr p.r.n.
        Cost/5 days: $16
        Dose: MDI, 2 puffs q.i.d.; daily max, 16 puffs
        Cost/one inhaler: $16
        Dose: DPI, 1 capsule q.i.d.; daily max, 8 capsules
        Cost/15–30 days: $10
      - Bitolterol
        
        Dose: nebulizer, lowest effective dose, 0.5 mg q. 4–8 hr p.r.n.; daily max, 3.5 mg q. 4–8 hr p.r.n.
        Cost: N/A
        Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max, 16 puffs p.r.n.
        Cost: N/A
      - Pirbuterol
        
        Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max 16 puffs p.r.n.
        Cost/one inhaler: $95
  - Combined short-acting beta₂-agonists/anticholinergic
    - Albuterol plus ipatropium bromide
      - Dose: MDI, lowest effective dose, 2 puffs q.i.d., p.r.n.; daily max 16 puffs
      - Cost: N/A
  - Inhaled corticosteroids may have significant benefits because of their effect on airway inflammation; their role is controversial
    - Medium to high doses may yield the greatest benefit
    - Fluticasone (highest potency)
      - Dose: lowest effective dose
        
        110 µg/puff, 2 puffs; high dosage, > 6 puffs daily
        220 µg puff, 2 puffs; high dosage, > 3 puffs daily
      - Cost: N/A
    - Budesonide (second-highest potency)
      - Dose: lowest effective dose at 200 µg puff, 1 inhalation; high dosage, > 3 inhalations daily
      - Cost/one inhaler: $148
    - Beclomethasone (third-highest potency)
      - Dose: lowest effective dose
      - 42 µg puff, 4 puffs; high dosage, > 20 puffs dialy
      - 84 µg puff, 6 puffs; high dosage, > 10 puffs daily
      - Cost/one inhaler (44 µg): $83

Physical Rehabilitation

Physical training (e.g., treadmill walking) may significantly increase lung/exercise capacity, even in patients with advanced disease

Supplemental Oxygen Support

Recommended for patients with P_aO₂ ≤ 55 mm Hg or ≤ 59 mm Hg with any of the following comorbidities:
- Peripheral edema (signifies cor pulmonale)
- Hematocrit ≥ 55%
- P pulmonale on ECG

Acute Exacerbations

Drug Therapy

Inhaled short-acting beta₂-agonists
- Albuterol (agent of choice)
  - Dose: nebulizer lowest effective dose, 5.0 mg q. 2 hr; daily max, 60 mg
  - Cost/one 20 ml bottle: $16
  - Dose: MDI lowest effective dose, 3 puffs q. 2 hr; daily max, 72 puffs
  - Cost/one inhaler: $14
Inhaled short-acting anticholinergics
- Ipratoprium bromide
  - Dose: MDI, lowest effective dose, 3 puffs q. 3–4 hr; daily max, 64 puffs
  - Cost/one inhaler: $38
Antibiotics should be used if the patient has symptoms and signs suggesting infection; choice of antibiotics should be based on the severity of the airflow obstruction
- Less severe infection, narrow coverage with agents active against S. pneumoniae and H. influenzae
- More severe infection, broader coverage with agents active against gram-negative organisms, S. pneumoniae, and H. influenzae
Corticosteroids such as prednisone (0.6 to 1.0 mg/kg/day) may be beneficial but are associated with side effects of varying severity; best candidates include the following:
- Patients currently taking oral or inhaled steroids
- Patients who have recently completed a regimen of oral steroids
- Patients who have previously responded to oral or inhaled steroids
- Patients who do not respond to initial bronchodilator therapy
- Patients whose oxygen saturation is ≤ 90% with peak expiratory flow rate ≤ 100 L/min
Exacerbations may be associated with hypercapnia and worsening of hypoxemia
- In these cases, oxygen supplementation adjusted to an SpO₂ level of 90% to 92% is recommended
- Ventilatory support should be considered in patients with increasing hypercapnia and blood pH < 7.30 despite initial bronchodilatory therapy
- Noninvasive positive pressure ventilation should be considered before intubation

Clinical Pearls

The only time that a nebulizer is preferable to an MDI used with a spacer is in patients with extreme dyspnea or altered consciousness
Some medications such as fluoroquinolone antibiotics used to treat exacerbations may precipitate theophylline toxicity in patients already taking theophylline

Best References

Currie GP, et al: BMJ 332:1261, 2006 [PMID 16735338]

Currie GP, et al: BMJ 332:1379, 2006 [PMID 16763252]

Currie GP, et al: BMJ 332:1439, 2006 [PMID 16777889]

Currie GP, et al: BMJ 332:1497, 2006 [PMID 16793814]

Currie GP, et al: BMJ 333:87, 2006 [PMID 16825232]

Devereux G: BMJ 332:1142, 2006 [PMID 16690673]

December 2006