Pathological And Clinical Aspects Of COPD Flashcards
Define COPD
- airflow obstruction
- progressive, not fully reversible and does not change markedly over several months
- commonly caused by smoking
Describe the pathogenesis of COPD
- involves factors such as allergens, smoking, air pollution and pathogens
- dependent on host susceptibility and environmental exposures
- results in neutrophil-predominant inflammation = emphysema and chronic bronchitis
- small airway obliteration, inflammation, mucous plugging, fibrosis
Describe the effect of cigarette smoking on the airway
- cilial motility is reduced (causes mucus pooling = increase in infection susceptibility)
- airway inflammation
- mucus hypertrophy and hypertrophy of goblet cells
- increased protease activity, anti-proteases inhibited (imbalance)
- oxidative stress
- squamous metaplasia and increased permeability to carcinogens (increased risk of lung cancer)
Describe the genetic defect associated with COPD
- alpha 1 anti-trypsin deficiency
- serine proteinase inhibitor
- SS and ZZ homozygotes = clinical disease
- results in inability to counteract destructive enzymes in lung
Define the 2 main clinical components of COPD
Chronic bronchitis (infiltration of neutrophils and CD8 cells + squamous metaplasia) = production of sputum on most days for at least 3 months in at least 2 years
- larger airways >4mm diameter
- scarring and thickening of airways
Emphysema = abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles
- narrowing of bronchioles (2-3mm) due to mucus plugging, inflammation and fibrosis
What are the cell types involved in COPD inflammation?
- macrophages
- CD8 and CD4 T lymphocytes
- neutrophils
List the inflammatory mediators involved in COPD inflammation
- TNF, IL-8 and other chemokines
- neutrophil elastase, proteinase 3, cathespin G (from activated neutrophils)
- elastase and MMPs (from macrophages)
- ROS
Describe the different types of emphysema in COPD
- centri-acinar = damage around the respiratory bronchioles, more in upper lobes
- pan-acinar = uniformly enlarged from the level of the terminal bronchiole distally, can result in large bullae and associated with alpha-1-anti-trypsin
- both result in the loss of surface area for gas exchange
Describe the different mechanisms of airflow obstruction in COPD
- loss of elasticity and alveolar attachments due to emphysema result in airway collapse on expiration
- this causes air-trapping and hyperinflation (needs increased work to breathe)
- goblet cell metaplasia and mucus plugging of lumen causes airway inflammation and thickening of the bronchiolar wall
- smooth muscle hypertrophy and peribronchial fibrosis
Describe when you would consider a diagnosis of COPD
People who are over 35 and smokers, or ex-smokers with any of:
- exertional breathlessness
- chronic cough
- regular sputum production
- frequent winter ‘bronchitis’
- wheeze
Describe the staging of spirometry in COPD
FEV1/FVC ratio
- stage 1 (mild) = 80%
- stage 2 (moderate) = 50-79%
- stage 3 (severe) = 30-49%
- stage 4 (very severe) = <30% or FEV1<50% with resp failure
Describe risk of exacerbations categories in COPD
A = low amount of symptoms and low severity
B = very symptomatic and low severity
C = low symptoms but high severity (airway obstruction)
D = highly symptomatic and highly obstructed airway (severe)
Describe the treatment options for COPD
- inhaled bronchodilators (short = salbutamol, long = salmeterol, tiotropium)
- inhaled corticosteroids (budesonide, fluticasone)
- O2 therapy (for resp failure)
- oral theophyllines
- mucolytics (carbocysteine)
- nebulised therapy
What drives biomarker directed treatment in COPD
Endotypes:
- persistent systemic inflammation
- eosinophilic or Th2 high COPD
- persistent pathogenic bacterial colonisation
- alpha-1 anti-trypsin deficiency
What drives symptom driven treatment in COPD?
Phenotypes:
- frequent exacerbators
- persistent breathlessness
- chronic bronchitis
