Other

• Alpha-1-antitrypsin

  A protease inhibitor that is synthesized in the liver and protects elastin from breakdown by neutrophil elastase
• AATD patients

  • Typically < 45 years with panlobular basal emphysema (destruction or airways due to relative excess in protease (elastase) activity that is released by PMNs, or relative deficiency of antiprotease (AATD) activity in the lung)

  
• Types of A1AD

  • Functional A1AD: occurs due to tobacco smoking
  • Congenital A1AD: Autosomal co-dominant disorder due to a mutation in SERPINA1 gene, patients usually present with hepatitis and liver cirrhosis
• WHO recommends that all patients with a diagnosis of COPD should be screened once especially in areas with high AATD prevalence
• Delay in diagnosis in older AATD patients presents as more typical distribution of emphysema (centrilobular apical)
• A low concentration (< 20% normal) of alpha-1-antitrypsin is highly suggestive of homozygous deficiency. Advise the family to check since it is genetic
• If you see a 10 YO child who is breathless, it is more likely to be asthma or another disease rather than COPD
• Because of incidence of smoking that is higher among men, however this might have changed, as the prevalence of smoking is increasing among women
• Using E-cigarettes to quit tobacco smoking is not effective. Studies have shown that those who try to use E-cigarettes to stop tobacco smoking usually end up smoking both (Tobacco and E-cigarettes)
• 1. cigarettes (vaping) cause significant disease where they have inflammation in their airways (alveoli). Patients become very sick and unwell so they die or end up with lung transplant. So although vaping does not contain the noxious gases that cause COPD, it does cause acute lung injury
• Smoking is the most common cause of COPD. Tobacco smoking increases number of activated PMNs and macrophages and digests human lungs, this is inhibited by a1-antitrypsin

  
• Climate and air pollution are lesser causes of COPD, but mortality from COPD increases dramatically during periods of heavy atmospheric pollution
• Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable but not fully reversible disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases
• COPD is a combination of emphysema and bronchitis which by prolonged exhalation

  
• COPD is higher in smokers and ex-smokers compared to non-smokers, cigarette smoking accounts for 90% of cases in developed countries. However, only 10-20% of smokers develop COPD, indicating individual susceptibility (host factors)

  
• COPD is higher ≥ 40 year group compared to those < 40, and higher in men than women
• Estimated 384 million COPD cases in 2010
• The prevalence of smoking is increasing all over the world
• Three million deaths annually by COPD, predicted to increase to 4.5 million by 2030
• Risk factors for COPD

  • Tobacco Smoking
  • α1-Antitrypsin deficiency
  • Environmental factors (biomass fuel exposure, air pollution)
  • Chronic Asthma
  • Asthma-COPD overlap syndrome
  • Low birth weight
  • Infections
  • Low socioeconomic status

  
• α1-Antitrypsin deficiency (AATD) is the most likely cause for young and non-smoker COPD
• COPD is characterized by: structural changes (emphysema) and chronic inflammation (chronic bronchitis) leading to airflow limitation and gas trapping, gas exchange abnormalities, mucus hypersecretion, and pulmonary hypertension

  
• Cor Pulmonale

  Symptoms and signs of fluid overload secondary to lung disease. The fluid retention and peripheral oedema is due to failure of excretion of sodium and water by the hypoxic kidney rather than heart failure

  
• Characteristics of Cor Pulmonale

  • Pulmonary hypertension
  • Right ventricular hypertrophy
• Signs and Symptoms of Cor Pulmonale

  • Initially there may be a prominent parasternal heave (due to right ventricular hypertrophy) and a loud pulmonary second sound
  • Central cyanosis (owing to the lung disease) → patient later becomes more breathless
  • Ankle oedema

  
• In case of very severe pulmonary hypertension, the pulmonary valve becomes incompetent
• In case of severe fluid overload, tricuspid incompetence may develop → elevated jugular venous pressure (JVP), ascites and upper abdominal discomfort due to liver swelling

  
• COPD isn't just limited to the lungs, you could have inflammation elsewhere in the body. The most common causes of death in COPD patients are lung cancer, Cardiovascular diseases and respiratory failure

  
• Pathogenesis of COPD

  • Oxidative stress
  • Protease-Antiprotease imbalance
  • Inflammatory cells
  • Inflammatory mediators
  • Peribronchiolar fibrosis
  • Interstitial fibrosis
• Emphysema


  Permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls, without obvious fibrosis. (Associated with loss of recoil and support of small airways —> tendency to collapse with obstruction)

  
• Types of emphysema

  • Centriacinar (centrilobular)
  • Panacinar (panlobular)
  • Distal acinar (paraseptal)
  • Irregular
• Centriacinar emphysema


  • Most common, associated with smoking, common in upper lobes
• Panacinar emphysema


  • Associated with alpha-1 antitrypsin deficiency, common in lower lobes, leads to V/Q mismatch
• Distal acinar emphysema

  • Associated with scarring, asymptomatic, more severe in the upper half of the lungs

  
• Emphysema leads to expiratory airflow limitation and air trapping. The loss of lung elastic recoil results in an increase in TLC. Premature closure of airways limits expiratory flow while the loss of alveoli decreases capacity for gas transfer
• V/Q mismatch in COPD is due to damage and mucus plugging of smaller airways from chronic inflammation, and partly due to rapid closure of smaller airways in expiration owing to loss of elastic support. The mismatch leads to a fall in PaO2 and increased work of respiration

  
• Pathogenesis of emphysema

  1. Attraction of inflammatory cells (e.g. neutrophils, macrophages, CD4, CD8)

  2. Inflammatory reaction with increased chemotactic factors (e.g. LTB4, IL-8, TNF)

  3. Release of reactive oxygen species

  4. Protease-antiprotease imbalance (increase protease & decrease anti-protease)

  5. Alveolar wall destruction

  
• Chronic bronchitis

  A chronic obstructive airway disease characterized by the presence of chronic productive cough that persists for at least 3 consecutive months in at least 2 consecutive years

  
• Pathogenesis of chronic bronchitis

  1. Cigarette smoking and/or air pollutants

  2. Inflammation

  3. Release of histamine, bradykinin and prostaglandin

  4. Edema of mucus membrane

  5. Cellular exudation

  6. Increased capillary permeability

  7. Hypersecretion of mucus

  8. Persistent cough

  
• Etiology of chronic bronchitis

  • Cigarette smoking
  • Atmospheric pollution