Background Information

Definitions

COPD

• Common lung condition characterised by persistent respiratory symptoms and airflow obstruction that is typically progressive and not fully reversible.
• COPD is the umbrella term that includes chronic bronchitis and emphysema, which often coexist:
  • Chronic bronchitis
    • Clinical diagnosis defined by cough and sputum production for at least 3 months per year, for 2 consecutive years
  • Emphysema
    • Pathological diagnosis referring to irreversible enlargement and destruction of airspaces distal to terminal bronchioles

COPD exacerbation / AECOPD 

• Episodes of acute worsening of COPD symptoms (e.g., increased breathlessness, cough), beyond normal day-to-day variations.

Epidemiology

Age of onset: typically 40-50 y/o ^[Ref]

Prevalence: ~6-7% of adults >40 y/o ^[Ref]

Aetiology

COPD Risk Factors

Exogenous (Environmental) 

• Smoking (Major risk factor)
  • Cigarette smoking → ~ 90% of cases
  • Risk also ↑ with pipes, cigars, marijuana & passive smoking
•  Occupational exposures (~20% of COPD cases overall)
  • Dusts: coal, grains, silica
  • Fumes/chemicals: welding fumes, isocyanates, PAHs
• Air pollution (i.e., biomass fuels)
• Early-life exposures 
  • In utero → maternal smoking
  • Childhood → severe respiratory infections, passive smoke

Endogenous (Host/Intrinsic) 

• Genetic factors 
  • Alpha-1 antitrypsin deficiency (rare but important cause)
    • Presents in <45 yrs
    • Affects both smokers & non-smokers
• Prematurity → Impaired lung development
  • Prematurity
• Asthma
  • Independent risk factor for COPD

COPD Exacerbation

1. Infections (most common trigger) ^[Ref]
   • Respiratory viruses (up to 60%)
     • Rhinovirus (most common)
     • Other: Influenza, RSV, parainfluenza, coronavirus, adenovirus
   • Bacterial (40-60%)
     • Most frequently, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa
2. Environmental triggers
   • Air pollution (e.g., particulates, NO₂, ozone)
   • Cold weather / winter seasonality
3. Host factors
   • Defective mucociliary clearance (smoking damage)
   • Immune dysfunction → poor pathogen clearance

Clinical features

COPD

Symptoms

• Chronic cough (often productive, worse in the morning)
• Dyspnoea
  • Early → exertional breathlessness
  • Advanced → breathlessness at rest
• Wheezing
• Nonspecific
  • Fatigue / Reduced exercise tolerance
  • Weight loss / Anorexia (advanced, linked to cachexia)

Signs

Early / General

• Tachypnoea / Tachycardia (due to hypoxaemia)
• Pursed-lip breathing
• Prolonged expiratory phase (due to airflow obstruction)
• Cyanosis (esp. in advanced disease)

Advanced

• Barrel chest (↑ anteroposterior diameter of chest in emphysema)
• Cor pulmonale (raised JVP, peripheral oedema, hepatomegaly)
• Cachexia & muscle wasting

Examination Findings

Examination may be normal. Potential findings may include:

• Palpation → hyperinflated chest & reduced chest expansion
• Percussion → hyperresonance 
• Auscultation
  • ↓ breath sounds
  • prolonged expiration
  • Wheeze and/or crackles
  • Signs of cor pulmonale (loud P2, RV heave)

COPD Exacerbation

Symptoms

• Common
  • ↑ breathlessness, cough and/or sputum production
  • change in sputum colour
• Other
  • ↑ wheeze & chest tightness
  • URTI symptoms
  • Reduced exercise tolerance / increased fatigue

Prognosis

COPD has a variable but generally progressive course, with gradual lung function decline and worsening symptoms over time.

Poor prognostic factors

• Severe airflow limitation (low FEV1)
• High symptom burden (e.g., high MRC dyspnoea scale / CAT scores, poor 6-min walk test)
• Chronic hypoxia / cor pulmonale
• Low BMI, muscle wasting, cachexia
• Frequent / Severe exacerbations
• Current smoking
• Multimorbidity and frailty

Complications

Systemic

• Muscle wasting & cachexia
• Psychological: depression & anxiety (very common)

Respiratory

• ↑ Risk of respiratory infections (esp. pneumonia)
• Pneumothorax → due to rupture of bullae (present in emphysema)
• Respiratory failure

Cardiovascular / Haematological

• Cor pulmonale
• Secondary polycythaemia → compensatory ↑ RBCs due to chronic hypoxia

Oncological

• ↑Lung cancer risk

Severity Classification

COPD severity is classified based on post-bronchodilator FEV₁:

Guidelines

Investigation and Diagnosis

NICE recommends suspecting COPD in:

• >35 y/o with a risk factor for COPD (e.g. significant smoking history), and
• Present with ≥1 of the following:
  • Exertional dyspnoea
  • Chronic cough
  • Regular sputum production
  • Frequent winter ‘bronchitis’
  • Wheeze

Confirmatory test: post-bronchodilator spirometry demonstrating FEV₁/FVC <0.7

Standard work-up for all suspected COPD cases:

• Chest X-ray (to exclude other pathologies)
• FBC (to identify anaemia or polycythaemia)
• Measure BMI

Consider serum alpha-1 antitrypsin, sputum cultures, DLCO, and CT thorax on a case-by-case basis

COPD vs Asthma

NICE provided this table to help differentiate between COPD and asthma based on clinical features:

When there is diagnostic uncertainty, or both COPD and asthma are present, NICE recommend using the following findings to help identify asthma:

• Large response (FEV1 improvement >400 mL) to bronchodilators
• Large response (FEV improvement >400 mL) to oral prednisolone for 2 weeks
• ≥20% diurnal or day-to-day variability in serial peak flow measurements

COPD Exacerbation Management

Hospital admission is indicated in:

• Severe breathlessness
• Cyanosis
• Arterial pH <7 kPa / Arterial PaO2 <7 kPa / SaO2 <90%
• Worsening peripheral oedema
• ↓ Level of consciousness
• Already receiving LTOT
• Significant comorbidity (esp. cardiac disease and insulin-dependent diabetes)

Patients who do not need to be admitted can be treated as outpatients.

Primary Care (Outpatient) Management

Offer all the following:

• ↑ Frequency or dose of the reliever inhaler (short-acting bronchodilator)
• Oral prednisolone 30mg for 5 days

Secondary Care (Hospital) Management

Initial Therapy

Offer ALL 3 of the following:

Further Therapy (By Specialist)

• Theophylline
• Non-invasive ventilation is indicated if respiratory acidosis (pH 7.25-7.35) occurs despite optimal medical therapy
• Doxapram – only indicated if non-invasive ventilation is not suitable

Self Management

Patients with a recent exacerbation (≥1 in the last year) who remain at risk are prescribed a ‘rescue pack’ to enable self-management of future exacerbations at home.

Rescue pack includes:

• Oral corticosteroid 
• Oral antibiotic (as per local guidance)

COPD Long-Term Management

Conservative / General Management

• Smoking cessation – most effective intervention for improving COPD prognosis
• Pulmonary rehabilitation – offered to those who are functionally disabled by COPD
• Vaccination
  • One-off pneumococcal vaccination
  • Annual influenza vaccination

Inhaler Therapy

• Step 1: reliever inhaler with SABA or SAMA
• Step 2: assess for steroid responsiveness to determine step-up therapy
  • +ve → add LABA + ICS in addition to reliever inhaler in step 1
  • -ve → add LABA + LAMA in addition to reliever inhaler in step 1
• Step 3: add triple therapy (LABA + LAMA + ICS) in addition to reliever inhaler
  • Most common: beclometasone + formoterol + glycopyrronium (Trimbow®)
  • Fluticasone + umeclidinium + vilanterol (Trellegy Ellipta®)

Examples of some inhaler drugs:

Oral Medications

All of the following are initiated by specialists.
Oral theophylline is used if:

• Unable to use inhalers, or
• Inhaler therapy was unsuccessful

Oral roflumilast is used if:

• Severe disease (FEV₁ <50%), and
• ≥2 exacerbations in the past 12 months despite triple inhaler therapy

Regular oral azithromycin to prevent infective exacerbations can be offered if:

• Patient stopped smoking, AND
• Referred for pulmonary rehabilitation + optimised non-pharmacological and inhaler therapies, AND
• Has had ≥4 exacerbations with sputum production OR exacerbations resulting in hospitalisation OR prolonged exacerbations with sputum production

Long-Term Oxygen Therapy (LTOT)

Consider LTOT if:

• Patient stopped smoking (or does not smoke), and
• ABG on 2 occasions at least 3 weeks apart shows:
  • PaO₂ <7.3 kPa, OR
  • PaO₂ 7.3-8.0 PLUS 1 of the 3Ps (secondary polycythaemia, peripheral oedema, pulmonary hypertension)

Duration: If offered, LTOT should be used for at least 15 hours per day

Interventional Therapy

References