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Respiratory System

Chronic obstructive pulmonary disease (COPD)

Respiratory disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.

Respiratory disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) definintion of COPD
  • World COPD Day: November 20th

Phenotypes:

COPD has both airway (central and small airways) and airspace abnormalities.
  • Chronic bronchitis: Daily productive cough for at least 3 consecutive months for more than 2 successive years
  • Emphysema: Anatomic alteration of lung characterized by abnormal enlargement of air spaces distal to terminal, non-respiratory bronchiole, accompanied by destructive changes of alveolar walls.
COPD Overview
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Etiology

The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. The interplay of these factors is important in the development of COPD.

  • Smoking hisotry (biggest risk factor, 90% cases): Directly inhibits α-1 antitrypsin
  • Age > 35 years with significant smoking history
  • α1-antitrypsin deficiency (1-2% cases)
  • Exposure to indoor/outdoor air pollution, occupational dusts, or chemicals

Pathophysiology

Airway changes:

Airway obstruction in COPD
Airway obstruction in COPD. | Barnes, P. J., Burney, P. G. J., Silverman, E. K., Celli, B. R., Vestbo, J., Wedzicha, J. A., & Wouters, E. F. M. (2015). Chronic obstructive pulmonary disease. Nature Reviews Disease Primers, 1(1), 15076. https://doi.org/10.1038/nrdp.2015.76

Disease progression:

Disease progression in COPD
Disease progression in COPD. | Barnes, P. J., Burney, P. G. J., Silverman, E. K., Celli, B. R., Vestbo, J., Wedzicha, J. A., & Wouters, E. F. M. (2015). Chronic obstructive pulmonary disease. Nature Reviews Disease Primers, 1(1), 15076. https://doi.org/10.1038/nrdp.2015.76
COPD pathogenesis
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Emphysema “pink puffer”:

Anatomic alteration of the lung characterized by abnormal enlargement of air spaces distal to terminal, non-respiratory bronchiole, accompanied by destructive changes of alveolar walls.
CentriacinarPanacinar
Most frequently associated with cigarette smoking

 

Characterized by enlarged air spaces found (initially) in association with respiratory bronchioles

Most prominent in the upper lobes and superior segments of lower lobes

Observed in patients with α1-AT deficiency

 

Abnormally large air spaces evenly distributed within and across acinar units

Predilection for the lower lobes

Macrophages are activated by cigarette smoke and recruit neutrophils and CD8+ lymphocytes to cause elastolysis and emphysema. Similarly, cigarette smoke activates airway epithelium to trigger airway remodeling. Both of these processes result in airflow obstruction
Macrophages are activated by cigarette smoke and recruit neutrophils and CD8+ lymphocytes to cause elastolysis and emphysema. Similarly, cigarette smoke activates airway epithelium to trigger airway remodeling. Both of these processes result in airflow obstruction. | CXCR3 = chemokine CXC receptor 3; EGF = epidermal growth factor; GROα = chemokine growth-regulated protein alpha; IP-10 = IFN-gamma-inducible 10 kD protein; LTB4 = leukotriene B4; Mig = monokine induced by IFN-gamma; MMPs = matrix metalloproteinases; PDGF = platelet-derived growth factor; TGF-β = transforming growth factor-β. | Sharafkhaneh, A., Hanania, N. A., & Kim, V. (2008). Pathogenesis of emphysema: from the bench to the bedside. Proceedings of the American Thoracic Society, 5(4), 475–477. doi:10.1513/pats.200708-126ET

Chronic bronchitis “blue bloater”:

Daily productive cough for at least 3 consecutive months for more than 2 successive years.
Causes of excessive mucus in COPD
Causes of excessive mucus in COPD | PEF = peak expiratory flow. | Kim, V., & Criner, G. J. (2013). Chronic bronchitis and chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 187(3), 228–237. doi:10.1164/rccm.201210-1843CI

Presentation

In the clinical setting, emphysema and bronchitis/bronchiolitis often coexist with different degree of severity in the same patient making it very difficult to physiologically and clinically identify the contribution of each. Thus, such overlap led to the terminology of COPD.

Type A: Emphysema “pink puffer”

  • Progressive dyspnoea (dominant symptom) and cough & hypersecretion (modest symptom)
  • ↑ Lung volumes
  • ↓ Carbon monoxide (DLCO) diffusing capacity

Type B: Chronic bronchitis “blue bloater”

  • Mucous hypersecretion (dominant symptom), while dyspnea (modest symptom)
  • Hypercapnia and hypoxemia with secondary pulmonary hypertension and cardiovascular comorbidities

General symptoms:

  • Diffuse bilateral wheezing
  • Tripod position
    • Arms serve as extra anchor for accessory respiratory muscles
  • Pursed lips (prolonged expiration)
    • Helps maintain pressure to inflate distal airways
  • Weight loss

Severe COPD:

  • Pulsus paradoxus: Exaggerated negative intrathoracic pressure leads to > 10 mmHg decrease in systolic pressure during inspiration
  • Hoover’s sign: Paradoxical inward movement of the rib cage with inspiration
  • Distant heart sounds
  • Diminished lung/breath sounds
COPD Clinical Findings
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Complications

Acute exacerbation of COPD (AECOPD):

Episodes of increased dyspnea and cough and change in the amount and character of sputum.
Mechanisms and effects of COPD exacerbations
Mechanisms and effects of COPD exacerbations. | Barnes, P., Burney, P., Silverman, E. et al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers 1, 15076 (2015). https://doi.org/10.1038/nrdp.2015.76
  • May/may not be accompanied by other signs of illness, including fever, myalgias, and sore throat.
  • Chronic hypoxemia → Hypoxic vasoconstriction → Pulmonary arterial hypertension 
  • Pulmonary hypertension → Right heart failure (Cor pulmonale)
    • RHF due to lung pathology
COPD Complications
The Calgary Guide | http://calgaryguide.ucalgary.ca/
Major causes of death in COPD
Major causes of death according to chronic obstructive pulmonary disease a) without chronic bronchitis (n=752) or b) with chronic bronchitis (n=172). | Lahousse, L., Seys, L., Joos, G. F., Franco, O. H., Stricker, B. H., & Brusselle, G. G. (2017). Epidemiology and impact of chronic bronchitis in chronic obstructive pulmonary disease. The European respiratory journal, 50(2), 1602470. doi:10.1183/13993003.02470-2016

Diagnosis

COPD Investigations
The Calgary Guide | http://calgaryguide.ucalgary.ca/

GOLD & NIH Severity based classification:

COPD Severity based spirometry results
COPD Severity based spirometry results | Gentry, S., & Gentry, B. (2017). Chronic Obstructive Pulmonary Disease: Diagnosis and Management. American Family Physician, 95(7), 433–441. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28409593

Reid index:

Ratio of the thickness of the mucous gland layer to the thickness of the bronchial wall.
  • > 0.4 suggests mucous gland hyperplasia

Body plethysmography:

Measures the volume of any gas containing space in the thorax, including bullae. It is accurate in both restrictive as well as obstructive lung diseases.
Body plethysmography
Patient sits inside an airtight box, inhales or exhales to a particular volume and then a shutter drops across his breathing tube. The subject makes respiratory efforts against the closed shutter, causing his chest volume to expand and decompressing the air in his lungs. The increase in his chest volume slightly reduces the box volume (the non-person volume of the box) and thus slightly increases the pressure in the box. |

Blood gas analysis:

  • Early emphysema “pink face”:
    • Hyperventilation → Normal arterial oxygen (PaO2)
    • Respiratory alkalosis
  • Late  emphysema “blue face”:
    • ↑ PaCO2 (Hypercarbia)
    • Respiratory acidosis
    • ↓ DLCO → ↓ PaO2 (hypoxemia) → Cyanosis
  • Early chronic bronchitis:
    • ↑ PaCO2 (Hypercarbia)
    • Respiratory acidosis
    • Mucus plugs limit oxygenation → ↓ PaO2 (hypoxemia) → Cyanosis

Chest X-ray:

  • Hyperinflated lung:
    • Flat diaphragm
    • 10+ posterior rib shadows
    • ↑ Parenchymal radiolucency
    • Lengthened cardiac silhouette (vertical heart appearance)
      • Due to loss of parenchyma
Clinical and radiological characteristics of the classic phenotypes of patients with COPD
Clinical and radiological characteristics of the classic phenotypes of patients with COPD. | Barnes, P., Burney, P., Silverman, E. et al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers 1, 15076 (2015). https://doi.org/10.1038/nrdp.2015.76

Management

Algorithm for the diagnosis, staging and management programme for COPD
Algorithm for the diagnosis, staging and management programme for COPD. | Gentry, S., & Gentry, B. (2017). Chronic Obstructive Pulmonary Disease: Diagnosis and Management. American Family Physician, 95(7), 433–441. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28409593

Medical management:

  • Anticholinergic agents: Ipratropium bromide improves symptoms and produces acute improvement in FEV1.
  • Long-acting inhaled β agonists: Salmeterol or formoterol (symptomatic benefit)
  • Theophylline (improvements in expiratory flow rates and vital capacity and a slight improvement in arterial oxygen and carbon dioxide levels in patients with moderate to severe COPD)
  • N-acetyl cysteine (mucolytic and antioxidant)
Effects of bronchodilators in COPD
Effects of bronchodilators in COPD. | Barnes, P., Burney, P., Silverman, E. et al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers 1, 15076 (2015). https://doi.org/10.1038/nrdp.2015.76
Pharmacological managment of COPD based on GOLD Combined Assesment
Pharmacological managment of COPD based on GOLD Combined Assesment | Gentry, S., & Gentry, B. (2017). Chronic Obstructive Pulmonary Disease: Diagnosis and Management. American Family Physician, 95(7), 433–441. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28409593
afp20170401p433-t4
Gentry, S., & Gentry, B. (2017). Chronic Obstructive Pulmonary Disease: Diagnosis and Management. American Family Physician, 95(7), 433–441. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28409593

Summary:

COPD
Barnes, P. J., Burney, P. G. J., Silverman, E. K., Celli, B. R., Vestbo, J., Wedzicha, J. A., & Wouters, E. F. M. (2015). Chronic obstructive pulmonary disease. Nature Reviews Disease Primers, 1(1), 15076. https://doi.org/10.1038/nrdp.2015.76

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