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COPD – Etiology, Pathogenesis, Clinical Features

  • Characterised by persistent, progressive airflow limitation – associated with an enhanced chronic inflammatory response to noxious particles/gases

Epidemiology/etiology

  • MC in developing countries
  • Low socio-economic status
  • Ischaemic heart disease, cancer, DM

Environmental factors

  • Cigarette smoking
  • Occupational exposures – coal dust, silica
  • Low birth weight (<2.5kg)
  • Recurrent infections

Host factors

  • α1-antitrypsin (A1AT) deficiency – leads to ↑neutrophil elastase, which causes destruction of alveolar walls
  • Airway hyper-reactivity

Pathophysiology

Chronic Bronchitis

  • Increased number of mucus secreting goblet cells in bronchial mucosa
  • Infiltration of the bronchial/bronchiolar walls with acute + chronic inflammatory cells
    • Predominantly CD8 – T cells
  • Epithelium can become ulcerated and the columnar cells get replaced with squamous cells
  • The inflam is followed by scarring and thickening of walls – leads to airway narrowing
  • Further progression leads to progressive squamous cell metaplasia and fibrosis – causes airflow limitation

Emphysema – permanent enlargement of airspaces

  • Can be centriacinar , paraseptal, panacinar
  • Emphysema leads to expiratory airflow limitation and air trapping
  • Loss of elastic recoil causes increase in total lung capacity (TCL)

V/Q mismatch is due to 2 main factors

  • damage and mucus plugging of smaller airways due to chronic inflam
  • rapid closure of smaller airways in expiration due to loss of elastic support
  • V/Q mismatch leads to ↓PaO2 and ↑work of respiration

2 types of pts

  • Pink puffers’ – MC in pts with emphysema
    • Pts have low/normal PaCO2 values due to increasing alveolar ventilation in an attempt to correct their hypoxia
  • Blue bloaters’ – MC in chronic bronchitis
    • Pts fail to maintain respiratory efforts – leads to rise in PaCO2
    • In the long term they become Insensitive to CO2 and rely on hypoxemia to drive ventilation
    • Renal hypoxia – leads to fluid retention and ↑erythropoiesis (leads to polycythemia)
    • Pt becomes bloated, plethoric and cyanosed

3 main mechanisms of airflow limitation in small airways

  1. Loss of elasticity due to emphysema – reduces elastic recoil and airways collapse during expiration
  2. Inflam and scarring – causes airway narrowing
  3. Mucus secretion – blocks the airways
  • Leads to narrowing of airways and air trapping → hyperinflation of lungs, V/Q mismatch, ↑work of breathing and breathlessness

Clinical features

Symptoms

  • Productive cough, wheeze, breathlessness
  • Infective exacerbations with purulent sputum
  • Breathlessness
  • Systemic signs – see fig 2

Signs

  • Mild COPD – quiet wheezing
  • Severe
    • tachypnea, prolonged expiration
    • use of accessory muscles, pursed lips during expiration
    • hyperinflated lungs – barrel chest
  • Pink puffers (remain sensitive to CO2) – breathless, pink, NOT cyanosed
  • Blue bloaters (insensitive to CO2) – oedematous, cyanosed, don’t seem breathless

Respiratory failure – in later stages of COPD

  • PaO2 <60mmHg (<7kPa) or PaCO2 >53mmHg (>8kPa)

Pulmonary HTN

  • Cor pulmonale – symptoms of fluid overload secondary to lung disease
    • Characterised by Pulmonary HTN and RVH
  • Fluid retention + peripheral oedema is due to failure of the hypoxic kidney to excrete Na + water (due to RAAS activation)
  • Signs – ↑JVP, ascites, hepatomegaly, ankle pitting oedema

1. DIAGNOSIS

  • History of breathlessness and sputum production in a chronic smoker
  • Family history of α1-antitrypsin deficiency

Investigations

  • LFTs to show evidence of airflow limitation
    • FEV1:FVC 
    • ↓PEFR
  • CXR – hyperinflated lungs, flattened diaphragm,
  • Hb – increased due to secondary polycythemia as a result of persistent hypoxemia, >40 RR,
  • Sputum exam – S.pneumoniae, H.influenza in acute exacerbations of COPD
  • ECG – RVH
  • α1-antitrypsin deficiency

2. COMPLICATIONS

Cor pulmonale – pulmonary HTN and RVH

  • Due to chronic hypoxemia – which causes constriction of pulmonary arterioles

Respiratory failure – PaO2 <60mmHg or PaCO2 >53mmHg

Type 1 respiratory failure

  • Hypoxemia without hypercapnia
  • Due to V/Q mismatch
  • CO2 is normal/low
  • Treatment – O2 to correct hypoxia

Type 2 respiratory failure (mechanical failure)

  • Hypoxemia with hypercapnia – due to alveolar hypoventilation
  • No VQ mismatch
  • Respiratory centre has become desensitised to CO2 levels – so hypoxia is the driving force for ventilation
  • Tx – O2 should be given with precaution
    • Controlled O2 at 24%
    • If PaCO2 continues to rise then give doxapram (respiratory stimulant)

Others

  • Arrhythmias – atrial fibrillation
  • Secondary polycythemia
  • Infection
  • Depression

Treatment

1. Smoking cessation

2. Drug therapy

3. Bronchodilators

Beta agonists

  • Mild COPD – salbutamol 200mcg every 4-6 hrs (SABA)
  • Mod/severe – formoterol 12mcg inhaled bid or salmeterol 50mcg bid

Antimuscarinic

  • More prolonged and greater bronchodilation
  • Tiotropium 18mcg daily

4.PDE-4 inhibitors – Roflumilast used as an adjunct to bronchodilator therapy

5. Corticosteroids

  • Decrease frequency of exacerbation
  • Prednisolone 30mg/day x 2 weeks – measure lung function before and after treatment
  • If FEV1 increased by >15% then discontinue and give inhaled beclomethasone 40mcg bid

6. Antibiotics and vaccines

  • In acute episodes to shorten exacerbation
  • Amoxicillin
  • Cefaclor 500mg x 3/day
  • Cefixime 400mg x1/day
  • H. influenza and pneumococcal vaccines

7. Diuretics – loop/thiazide

8. LTOT – long term oxygen therapy

  • Indications for LTOT – PaO2 <60mmHg or PaCO2 >53mmHg; polycythemia; pulmonary HTN
  • Continuous admin of O2 at 2L/min for ≈15hrs a day – aim to keep saturation >90%
  • CPAP (continuous positive airway pressure), CMV (controlled mechanical ventilation), mask

9. Surgery

  • Bullectomy – for patients in whom large bullae compress surrounding normal lung tissue
    • Improves VQ mismatch
  • Lung transplant – for patients with end stage emphysema

10. Additional measures

  • a1-antitrypsin replacement
  • treatment heart failure
  • venesection for secondary polycythemia

Prognosis of COPD – BODE index

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