COPD

• COPD risk factors:

  • Environmental - smoking (most dominant), air pollution (PM 2.5)
  • Family history
  • Gene polymorphisms/mutations - Alpha-1 antitrypsin, Growth factor beta 1, Serpine 2, CFTR, Glutathione S-transferases, Superoxide dismutase
  • Metalloproteinase dysregulation - particularly MMP-12
  • Atopy
  • Asthma
  • Development abnormalities - bronchopulmonary dysplasia
  • Infections - RSV, HIV
• COPD risk reductive factors:

  • Smoking cessation
  • Air pollutant avoidance
  • Physical activity
  • Anti-inflammatory and antioxidant therapy
• COPD epidemiology:

  • Peak incidence - 60 - 70 years
  • Slightly more common in males
• Chronic Obstructive Pulmonary Disease (COPD) is characterised by airflow obstruction that is not fully reversible, and is an umbrella term that encompasses both emphysema and chronic bronchitis.
• Emphysema pathophysiology:

  • destruction in terminal bronchioles and distal airways
  • is a result of the breakdown of elastin - a key component in alveolar walls
  • loss of alveolar wall integrity and destruction of surrounding small airways, causing formation of distal bullae - useless air pockets
  • lack of elastic tissue causes airways to collapse on expiration, causing obstruction. They also hyperinflate as there is no recoil.
• Chronic bronchitis pathophysiology:

  • Repeated exposure to noxious substances causes inflammation in large airways
  • there is hypersecretion of mucus and ciliary dysfunction, causing mucus to build up.
  • predisposition to respiratory infections
  • remodeling and narrowing of airways causes obstruction
• Airway changes in COPD:

  • Mucus-secreting gland hypertrophy
  • Replacement of ciliated cells with goblet cells, and dysfunction of ciliated cells
  • Elastin breakdown, leading to formation of large air spaces and loss of elastic recoil
  • Persistent hypoxia, leading to subsequent pulmonary vasoconstriction, leading to vascular smooth muscle thickening and then pulmonary hypertension.
  • Smooth muscle hypertrophy leading to airway wall thickening
• COPD clinical features:

  • Productive cough
  • Dyspnoea
  • Wheeze
  • Tachypnoea
  • Inspection - barrel-chest deformity and accessory muscle usage
  • Hyper-resonance on percussion
  • Flapping tremor - caused by hypercapnia
  • Central cyanosis - due to hypoxia
  • Right-sided heart failure - distended neck veins, ankle oedema
• COPD investigations:

  • Spirometry - FEV:FVC <0.7
  • Chest X-ray
  • Blood tests - polycythemia or renal impairment
  • HRCT - to detect emphysema and bronchiectasis
  • Echocardiogram - assess right sided heart failure
  • Sputum culture - assess infective exacerbations
  • Alpha-1 antitrypsin deficiency screening
  • Pulmonary rehabilitation assessment
  • Oxygen assessment
• NICE recommendation for considering diagnosis of COPD:

  • >35 years of age
  • Smokers or ex-smokers
  • Symptoms - exertional breathlessness, chronic cough, regular sputum production
• In COPD, the post-bronchodilator FEV1:FVC ratio should always be under 0.7
• COPD severity index:

  • Stage 1 (mild) - FEV1 > 80%
  • Stage 2 (moderate) - FEV1 50 - 79%
  • Stage 3 (Severe) - FEV1 30 - 49%
  • Stage 4 (Very severe) - FEV1 < 30%
• General (non-pharmacological) management of COPD:

  • Smoking cessation (most important) - offer nicotine replacement therapy e.g. varenicline or bupropion
  • Annual influenza vaccination
  • One-off pneumococcal vaccination
  • pulmonary rehabilitation to all people who view themselves as functionally disabled by COPD (usually Medical Research Council [MRC] grade 3 and above)
• Pharmacological management of COPD:

  1. SABA or SAMA
  2. Assess asthmatic features/steroid responsiveness
  3. If absent - Add LABA + LAMA and if already taking SAMA, discontinue and switch to SABA
  4. If present - Add LABA + ICS
  5. Triple therapy - LABA + LAMA + ICS
• NICE criteria to assess asthmatic features/steroid responsiveness:

  • Any previous secure diagnosis of asthma or atopy
  • Higher blood eosinophil count
  • Substantial variation in FEV1 over time (400 ml)
  • Substantial diurnal variation in peak expiratory flow rate (20%)
• • If short or long acting bronchodilators do not work in patients, or inhaled therapy is contraindicated, then patients may trial oral theophylline
  • The dose may be reduced if they are co-prescribed macrolide or fluoroquinolone antibiotics.
• Prerequisites for oral azithromycin prophylaxis in COPD:

  • No smoking
  • Optimized standard treatments
  • Continued exacerbations
  • CT thorax to exclude bronchiectasis and sputum culture to exclude atypical infections and tuberculosis
  • LFTs and ECG to exclude QT prolongation
• Standby medication: NICE recommend offering a short course of oral corticosteroids and oral antibiotics to keep at home if: 

  • have had an exacerbation within the last year
  • understand how to take the medication, and are aware of associated risks and benefits
  • know to when to seek help and when to ask for replacements once medication has been used
• Mucolytics can be considered for COPD patients if they have a chronic productive cough and symptoms improve with usage.
• • Oral PDE-4 inhibitors such as roflumilast reduce the risk of COPD exacerbations in patients with severe COPD and a history of frequent COPD exacerbations
  • NICE recommend if:
  • the disease is severe, defined as a forced expiratory volume in 1 second (FEV1) after a bronchodilator of less than 50% of predicted normal, and
  • the person has had 2 or more exacerbations in the previous 12 months despite triple inhaled therapy with a long-acting muscarinic antagonist, a long-acting beta-2 agonist and an inhaled corticosteroid
• COPD complications:

  • Respiratory - Pneumonia, acute exacerbations, hypoxia and hypercapnia
  • CV complications - pulmonary hypertension, Cor pulmonale, Ischemic heart disease , arrhythmias
  • Musculoskeletal and metabolic - Osteoporosis (due to long-term steroid usage), weight loss
  • Mental - anxiety and depression