Key GC Teaching Point: A 70-year-old man with a 40 pack-year smoking history presenting with increased breathlessness, cough, and purulent sputum is the classic COPD presentation. ^[5]

• The conducting zone (trachea → main bronchi → segmental bronchi → terminal bronchioles) conducts air but does not participate in gas exchange. Walls contain cartilage (larger airways) and smooth muscle.
• The respiratory zone (respiratory bronchioles → alveolar ducts → alveolar sacs → alveoli) is where gas exchange occurs. The alveolar walls contain:
  • Type I pneumocytes — thin, flat cells for gas exchange
  • Type II pneumocytes — produce surfactant
  • Elastic fibres — provide elastic recoil to drive expiration passively
  • Capillary network — the vascular side of the gas exchange membrane
• Small airways are defined as airways < 2mm diameter (roughly from the 8th generation onwards, including terminal and respiratory bronchioles). These are the major site of airflow obstruction in COPD. ^[2]

• Normal expiration is passive — driven by elastic recoil of the lung and chest wall.
• During expiration, intrapleural pressure rises. At some point, airway pressure equals intrapleural pressure at the equal pressure point (EPP). Downstream of the EPP, airways are compressed.
• Normally, elastic recoil keeps airways open and drives air out efficiently.
• In COPD:
  • Loss of elastic recoil (emphysema) → reduced driving pressure for expiration
  • Loss of radial traction (elastic fibres normally tether small airways open) → airways collapse during expiration
  • Narrowing of small airways (chronic bronchitis/bronchiolitis) → increased airway resistance
  • Result: air trapping and hyperinflation

This is the fundamental concept in emphysema pathogenesis:

• Neutrophils (recruited to the lungs by inflammatory stimuli such as smoking) release neutrophil elastase (a serine protease) and matrix metalloproteinases (MMPs).
• α₁-Antitrypsin (AAT) is the main anti-protease that neutralises neutrophil elastase in the lung.
• Normally, protease and anti-protease are in balance → no net tissue destruction.
• In COPD, the balance tips towards protease excess:
  • Smoking increases neutrophil recruitment → more elastase
  • Smoking oxidises and inactivates AAT → less anti-protease
  • AAT deficiency (genetic) → constitutionally less anti-protease
• Result: unopposed elastase digests alveolar walls → emphysema

Let's trace the pathophysiology from cigarette smoke inhalation to clinical disease:

Smoking: (1) Induces macrophages to release neutrophil chemotactic factors → elastases → protease-antiprotease imbalance. (2) Causes goblet cell hyperplasia (mucus overproduction). (3) Damages ciliated epithelial cells (mucus retention). ^[2]

Two key mechanisms: ^[4]

1. V/Q Mismatch (the dominant mechanism)

• Airway obstruction causes non-uniform distribution of inspired air (V) — some areas are underventilated relative to their perfusion
• Destruction of alveoli leads to loss of capillary bed (Q) — some areas are overperfused relative to their ventilation
• Both mechanisms create V/Q mismatch → Type I respiratory failure (hypoxaemia with normal/low PaCO₂ initially)

2. Alveolar Hypoventilation (severe cases)

• Alveolar hypoventilation due to respiratory muscle fatigue: ^[4]
  • ↑ Work of breathing due to increased airway resistance and hyperinflation
  • Inadequate supply of fuel to respiratory muscles due to hypoxaemia and poor nutrition
• Hyperinflation flattens the diaphragm → mechanical disadvantage → further fatigue
• Net result: global hypoventilation → CO₂ retention → Type II respiratory failure (hypoxaemia + hypercapnia)

This is the downstream cardiovascular consequence of COPD:

1. Chronic alveolar hypoxia → hypoxic pulmonary vasoconstriction (HPV)
   • HPV is a unique property of the pulmonary vasculature — unlike systemic vessels that dilate in response to hypoxia, pulmonary arterioles constrict to divert blood away from poorly ventilated alveoli to better-ventilated ones
   • In COPD, hypoxia is widespread → widespread HPV → generalised ↑ pulmonary vascular resistance
2. Destruction of capillary bed (emphysema) → reduced cross-sectional area of pulmonary vasculature → further ↑ PVR
3. Polycythaemia (secondary to chronic hypoxia → EPO release → ↑ RBC mass) → ↑ blood viscosity → ↑ PVR
4. Chronic ↑ PVR → pulmonary arterial hypertension → RV pressure overload → RV hypertrophy → eventually RV failure = cor pulmonale

Clinical consequence: RV failure → systemic venous congestion → raised JVP, peripheral oedema, hepatomegaly, ascites.

COPD patients can develop cor pulmonale ^[6] — this is the most important cardiovascular complication and a marker of advanced disease.

In normal physiology:

• The main respiratory drive is via central chemoreceptors in the medulla, which respond to PaCO₂ (via CSF pH changes)
• Peripheral chemoreceptors (carotid and aortic bodies) respond to PaO₂ — this is a secondary, less potent drive

In chronic CO₂ retainers (Type II respiratory failure in COPD):

• Persistently elevated PaCO₂ → central chemoreceptors "reset" and become desensitised to CO₂
• The patient's respiratory drive becomes increasingly dependent on the hypoxic drive from peripheral chemoreceptors
• If you give high-flow O₂ → PaO₂ rises → suppresses hypoxic drive → hypoventilation → CO₂ narcosis → respiratory arrest

However, it's important to note that the "hypoxic drive" theory is somewhat oversimplified. Other mechanisms contributing to O₂-induced hypercapnia include:

• Haldane effect: oxygenated haemoglobin binds CO₂ less well → CO₂ released into blood → ↑ PaCO₂
• Release of HPV: oxygen reverses HPV → increased perfusion of poorly ventilated areas → worsened V/Q mismatch → ↑ dead space → ↑ PaCO₂

This is the classic (somewhat oversimplified but still taught) dichotomy: ^[2]

^[2]

Why "Blue Bloater"?

• "Blue" → cyanosis from severe hypoxaemia (reduced inspiratory drive → poor ventilation → profound V/Q mismatch → ↓PaO₂)
• "Bloater" → oedematous from cor pulmonale (chronic hypoxia → pulmonary HTN → RV failure → fluid retention)
• These patients tolerate hypoxia/hypercapnia — their chemoreceptors have "reset"

Why "Pink Puffer"?

• "Pink" → they maintain near-normal PaO₂ through increased work of breathing (strong inspiratory drive), so no cyanosis
• "Puffer" → they are visibly tachypnoeic with pursed-lip breathing, using enormous energy to ventilate — hence weight loss and cachexia
• These patients fight to maintain oxygenation — the trade-off is the energy cost → muscle wasting

Based on post-bronchodilator FEV₁ (as a percentage of predicted), in a patient with confirmed obstruction (FEV₁/FVC < 0.70):

The GOLD report now uses a combined assessment based on:

• Spirometric grade (1–4 above) — severity of airflow limitation
• Symptom burden — assessed by mMRC dyspnoea scale or CAT score
• Exacerbation risk — number and severity of exacerbations in the past year

("E" stands for Exacerbation — these are the frequent exacerbators who need more aggressive therapy)

Asthma-COPD overlap (ACO): controversial entity but often encountered in clinical practice. ^[3]

• Patients with features of both asthma (reversibility, eosinophilic inflammation, atopy) and COPD (fixed obstruction, smoking history, emphysema on CT)
• Important because these patients respond to inhaled corticosteroids more than "pure" COPD patients
• Suspect ACO when: blood eosinophils ≥ 300 cells/μL, history of asthma before age 40, significant bronchodilator reversibility, or variability in airflow limitation

This is the single most common diagnostic dilemma — "Is it asthma, COPD, or both?"

"Chronic asthma usually affects non-smokers with a history of wheezing since childhood. Chronic asthma exhibits reversibility — FEV₁/FVC increases > 12% after inhaled bronchodilator." ^[4]

Why does this distinction matter?

• Asthma responds dramatically to inhaled corticosteroids (ICS) — these are the cornerstone of asthma therapy
• COPD responds primarily to bronchodilators (LAMA, LABA); ICS is added only in specific circumstances (frequent exacerbations, elevated blood eosinophils, ACO)
• Mislabelling asthma as COPD means the patient may not receive adequate ICS; mislabelling COPD as asthma may lead to over-reliance on ICS with its side effects (pneumonia risk in COPD) without appropriate long-acting bronchodilator therapy

Asthma-COPD Overlap (ACO): ^[3]

• Many patients — especially elderly smokers with childhood asthma — have features of both conditions
• Often co-exists as asthma-COPD overlap syndrome (ACOS/ACO) ^[3]
• Suspect when: blood eosinophils ≥ 300 cells/μL, history of asthma before age 40, significant BD reversibility, AND fixed obstruction on spirometry
• These patients benefit from ICS-containing regimens

"Both bronchiectasis and COPD present with chronic cough and sputum production." ^[4]

Why the confusion? Both cause chronic productive cough and airflow obstruction. The key differentiators are: (1) age of onset, (2) sputum volume/character, (3) clubbing, and (4) HRCT appearances.

Pathophysiology of bronchiectasis: Chronic infection → inflammatory damage to bronchial walls → permanent dilatation → impaired mucociliary clearance → further infection = "vicious cycle" of Cole. This is fundamentally different from COPD where smoke-induced protease-antiprotease imbalance destroys alveolar walls.

This is the most critical non-respiratory differential.

BNP/NT-proBNP can help differentiate cardiac from respiratory causes of shortness of breath: only a cardiac cause of shortness of breath would result in elevated BNP. Respiratory causes would not affect this. ^[14]

Why the overlap? Both cause dyspnoea and can cause crepitations on auscultation. In COPD with cor pulmonale, you can even have peripheral oedema, raised JVP, and hepatomegaly — mimicking congestive HF. The key is recognising the nature of the dyspnoea (orthopnoea/PND = cardiac red flags), using BNP as a biomarker, and confirming with echocardiography.

Particularly important in Hong Kong, which has an intermediate TB burden.

Why include TB? In Hong Kong and endemic areas, TB must always be considered in chronic cough. TB and COPD can coexist — post-TB structural lung damage (bronchiectasis, fibrosis) is itself a risk factor for developing airflow obstruction. ^[4]

COPD is an independent risk factor for lung cancer, and they share the risk factor of smoking. ^[8]

Any COPD patient with new haemoptysis, unexplained weight loss, clubbing, hoarseness, or a new CXR abnormality must be investigated for lung cancer. ^[8]

"Submucosal and peribronchiolar fibrosis leading to narrowing of bronchiolar lumen." ^[4]

This is a rarer diagnosis but appears in exam stems — the clue is a younger patient with fixed obstruction and a history of transplant or severe viral illness.

ILD and COPD are fundamentally different (restrictive vs obstructive), but both cause chronic dyspnoea and reduced DLCO, and both can present with crackles. The nature of the crackles differs: fine, late-inspiratory Velcro crackles in ILD vs coarse crackles in COPD.

Without a plausible exposure history, the diagnosis of COPD should be questioned. The most common is cigarette smoking ( > 20 pack-years significantly raises clinical suspicion, though no minimum threshold is absolute). Other exposures include occupational dusts/fumes, indoor biomass combustion, and air pollution.

The cardinal symptoms — chronic cough (especially productive), progressive dyspnoea, and wheeze — should be present. The GC case describes the classic presentation: "40 pack-years of cigarette smoking, increased breathlessness for 1 week, increased cough and sputum in the past 5 years, exercise tolerance decreased from 2 flights of stairs to level ground." ^[5]

This is mandatory — you cannot diagnose COPD without spirometry.

• Post-bronchodilator FEV₁/FVC < 0.70 (i.e. < 70%) is the GOLD diagnostic threshold ^[2][3]
• "Post-bronchodilator" means the test is performed after administering an inhaled bronchodilator (typically salbutamol 400 μg via MDI + spacer, measured 10–15 minutes later) — this ensures you are measuring fixed obstruction, not reversible bronchospasm
• FEV₁ (and age) are the strongest predictors for survival in COPD — > 50% 5-year mortality if FEV₁ < 30% predicted ^[3]

Once COPD is confirmed, severity of airflow limitation is graded:

What it is: The patient performs a maximal forced expiration from total lung capacity (TLC) into a spirometer. The key measurements are:

• FEV₁ — volume of air exhaled in the first second of a forced expiration
• FVC — total volume of air exhaled during the entire forced expiration
• FEV₁/FVC ratio — the proportion of total air that can be blown out in the first second

How to interpret:

Spirometry: FEV₁, FVC, flow-volume loop → FEV₁/FVC < 70% diagnostic of COPD ^[16]

Post-bronchodilator spirometry:

• Administer salbutamol 400 μg (or equivalent SABA) via MDI + spacer
• Repeat spirometry after 10–15 minutes
• In COPD: FEV₁/FVC remains < 0.70 (fixed obstruction)
• In asthma: FEV₁ improves > 12% AND > 200 mL (variable/reversible obstruction) ^[3]
• Post-bronchodilator spirometry showing variable airflow obstruction is diagnostic of asthma ^[16]

Flow-volume loop in COPD:

• The expiratory limb shows a characteristic "scooped out" concave appearance — the flow rate drops off rapidly after a brief peak, reflecting diffuse intrathoracic airflow obstruction
• This differs from the normal linear decline in the expiratory limb

Measured when: ^[3]

• Concomitant ILD is suspected
• Low FVC < 80% predicted — to determine if this is due to restriction or air trapping

Method: Body plethysmography (the "body box") is the gold standard.

Lung volumes: ↑RV, ↑TLC — only when concomitant ILD suspected or low FVC < 80% predicted ^[3]

What it measures: The efficiency of gas transfer across the alveolar-capillary membrane. The patient inhales a small amount of carbon monoxide (CO) and holds their breath for ~10 seconds; the amount of CO absorbed reflects the gas exchange surface area and capillary blood volume.

DLCO: ↓ in ILD (associated with ↓ lung volume), emphysema (associated with ↑ lung volume), pulmonary vascular disease (associated with normal lung volume) ^[16]

Especially useful if lung transection is contemplated ^[3] — because you need to know if the remaining lung can sustain adequate gas exchange post-surgery.

CXR: mainly to exclude differential diagnoses (e.g. CHF) and look for comorbidities ^[3]

CXR is NOT diagnostic of COPD — spirometry is. However, CXR is essential to exclude other causes and may show supportive features:

Supportive findings in COPD: ^[2][3]

CXR features that should prompt re-evaluation of diagnosis: Mass lesion (lung cancer), consolidation (pneumonia/TB), pleural effusion (CHF, malignancy, infection), upper lobe fibrosis (TB, sarcoidosis), reticulonodular shadowing (ILD).

Not routinely required for COPD diagnosis but indicated in specific situations: ^[3]

HRCT findings in emphysema:

• Low attenuation areas (LAAs) — regions of lung parenchyma with density below a threshold (typically −950 HU), representing destroyed lung tissue
• Centrilobular emphysema: small, round areas of low attenuation in the centre of secondary pulmonary lobules (predominantly upper lobes)
• Panlobular emphysema: uniform low attenuation affecting entire lobules (predominantly lower lobes — think AAT deficiency)
• Air trapping on expiratory images: areas that remain lucent on expiratory-phase imaging, indicating small airway disease

ABG: for PaO₂, PaCO₂ if severe dyspnoea ^[16]

ABG is critical for assessing the severity of respiratory failure and guiding oxygen therapy:

Stepwise ABG interpretation approach: ^[17]

1. Assess oxygenation: Is PaO₂ low? Calculate A-a gradient if needed.
2. Determine acid-base status: Is pH acidotic ( < 7.35), normal, or alkalotic ( > 7.45)?
3. Identify primary disorder: Is PaCO₂ high (respiratory acidosis) or HCO₃⁻ low (metabolic acidosis)?
4. Calculate compensation: Is the compensation appropriate for chronic or acute derangement?

Key ABG patterns in COPD:

Pulse oximetry is a non-invasive bedside tool for continuous monitoring of oxygen saturation. ^[5]

• Target SpO₂ in COPD: 88–92% (NOT 94–98% as in non-COPD patients)
• SpO₂ < 92% at rest should prompt ABG analysis
• SpO₂ < 88% indicates need for long-term oxygen therapy (LTOT) assessment
• Limitation: Pulse oximetry tells you about oxygenation only — it does NOT detect hypercapnia. A patient can have SpO₂ of 92% and still be dangerously hypercapnic. Always do an ABG in suspected CO₂ retainers.

CBC (secondary polycythaemia), ABG (T1RF → T2RF if decompensated), ESR/CRP ^[2]

ECG ± Echo: P pulmonale (tall P waves), RVH ± RV strain, RBBB ^[2]

Echocardiography:

• Assesses RV function, RV size, tricuspid regurgitation (allows estimation of pulmonary artery systolic pressure via TR jet velocity)
• Excludes LV dysfunction as a cause of dyspnoea
• May show RV dilatation, RV hypertrophy, paradoxical septal motion (RV pressure overload pushes the septum leftward during systole)

Echocardiography if clinical findings suggestive of HF (to look for the cause) ^[16]

Sputum C/ST (culture and sensitivity testing) ^[2]

• Sent during acute exacerbations with purulent sputum to guide antibiotic therapy
• Common organisms in COPD exacerbations: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae
• In severe or recurrent exacerbations: consider Pseudomonas aeruginosa (especially if bronchiectasis co-exists)
• Also send sputum for AFB if TB is suspected (chronic cough, haemoptysis, constitutional symptoms, high-risk population)

Skin prick tests are included in the GC interactive tutorial learning objectives ^[5] — these help identify an atopic component, which is relevant for:

• Distinguishing asthma (or ACO) from pure COPD
• Positive skin prick tests to common aeroallergens (house dust mite, cockroach, cat dander) suggest atopy → supports asthma/ACO diagnosis
• Pure COPD patients are typically not atopic

Smoking cessation is the single most effective intervention to reduce the risk of developing COPD and slow its progression. ^[1]

Why? Recall the Fletcher-Peto curve — susceptible smokers have an accelerated decline in FEV₁. Smoking cessation returns the rate of decline to near-normal (though lost lung function is NOT recovered). No pharmacological therapy achieves this.

Approach to smoking cessation (the "5 A's"):

1. Ask — about smoking status at every visit
2. Advise — to quit, in a clear, personalised manner
3. Assess — willingness to make a quit attempt
4. Assist — with a quit plan (pharmacotherapy + behavioural support)
5. Arrange — follow-up

Pharmacotherapy for smoking cessation:

Vaccination against influenza and pneumococcus ^[4]

Pulmonary rehabilitation is one of the most effective non-pharmacological interventions for COPD ^[4][2]

Definition: tailored therapies to improve overall physical and psychological conditions. ^[2]

Components: ^[2]

• Physical training
  • Breathing training (e.g. pursed lip breathing, diaphragmatic breathing) — teaches efficient breathing patterns; pursed lip breathing creates back-pressure to splint airways open during expiration
  • Inspiratory muscle training — strengthens the diaphragm and accessory muscles
  • Energy conservation technique: work ergometry and workflow — teaches patients to pace activities
  • Limbs aerobic and resistive training: increases mitochondrial density → prevents deconditioning, improves ADL — skeletal muscle dysfunction is a major contributor to exercise limitation in COPD (not just the lungs!)
  • Neuromuscular electrical stimulation — for severely deconditioned patients unable to exercise conventionally
• Nutrition: maintain muscle mass — COPD cachexia is driven by systemic inflammation and increased work of breathing
• Behavioural: coping strategies
• Psychological counselling — depression and anxiety are extremely common in COPD
• Education: use of inhalers/LTOT, smoking cessation ^[2]

Evidence: Pulmonary rehabilitation reduces dyspnoea, improves exercise capacity, improves quality of life, and reduces hospital admissions. It is recommended for all COPD patients GOLD B and E (symptomatic patients).

Pulmocare: low carbohydrate but high calorie (↓CO₂ production), for COPD patients ^[19]

Why low carbohydrate? The respiratory quotient (RQ) — the ratio of CO₂ produced to O₂ consumed — is highest for carbohydrate metabolism (RQ = 1.0) compared to fat (RQ = 0.7) and protein (RQ = 0.8). In a CO₂ retainer, reducing dietary carbohydrate reduces CO₂ production, easing the ventilatory burden. High-calorie formulas compensate for the increased energy expenditure of breathing.

The backbone of COPD pharmacotherapy is inhaled bronchodilators ± inhaled corticosteroids:

Why β₂-agonists and antimuscarinics both cause bronchodilation by different pathways:

• β₂-agonists work via the sympathetic (adrenergic) pathway → ↑cAMP → relaxation
• Antimuscarinics work via the parasympathetic (cholinergic) pathway → block bronchoconstriction by blocking vagal tone
• The two pathways are complementary and additive — hence combination therapy (LABA + LAMA) is more effective than either alone

Pharmacological treatment according to patient's group: ^[4]

The GOLD 2024+ system uses the ABE classification (replacing ABCD):

The older GOLD ABCD system (from senior notes): ^[4]

• A: SABA OR SAMA
• B: LABA OR LAMA
• C: ICS + LABA OR LAMA
• D: ICS + LABA AND LAMA

If still exacerbating on dual bronchodilators: ^[20]

1. Investigate alternative causes (is it really COPD exacerbation, or heart failure, PE, etc.?)
2. Dual bronchodilators (LABA + LAMA) if not already ^[20]
3. Consider ICS in those with higher peripheral eosinophil count ^[20]
4. Consider Roflumilast (if FEV₁ < 50% and chronic bronchitis phenotype) and/or Azithromycin (in former smoker) ^[20]

Roflumilast — a selective PDE4 inhibitor ("phosphodiesterase-4"):

• PDE4 breaks down cAMP in inflammatory cells → inhibiting PDE4 → ↑cAMP → reduces inflammation (particularly neutrophilic)
• Specifically indicated for the chronic bronchitis phenotype with FEV₁ < 50% predicted who have frequent exacerbations despite inhaled therapy
• Side effects: nausea, diarrhoea, weight loss, headache, psychiatric effects (insomnia, anxiety)

Azithromycin (long-term, low-dose prophylaxis):

• Macrolide antibiotic with immunomodulatory properties (anti-inflammatory effect independent of antibiotic activity)
• Reduces exacerbation frequency in patients with frequent exacerbations
• In former smokers ^[20] — important because azithromycin in active smokers may promote resistant organisms with less benefit
• Must screen for QTc prolongation before starting, monitor hearing (ototoxicity), and consider the risk of antimicrobial resistance
• Development of resistant organisms should be factored into consideration ^[20]

This is a critical nuanced area:

When to ADD ICS:

• Blood eosinophils ≥ 300 cells/μL → strong predictor of ICS response
• History of asthma or ACO features
• Persistent exacerbations despite LABA + LAMA

When to AVOID or WITHDRAW ICS:

• Blood eosinophils < 100 cells/μL → unlikely to benefit, increases pneumonia risk
• Recurrent pneumonia (ICS increases pneumonia risk in COPD — unlike asthma!)
• Mycobacterial infection

IV methylxanthines (PDE4 inhibitors): Aminophylline (IV) ^[4]

Key pharmacological concerns:

• Narrow therapeutic index (therapeutic range 10–20 μg/mL) → must monitor drug levels
• Toxicity: nausea, vomiting, arrhythmias (SVT, AF), seizures
• Metabolism via CYP1A2 → many drug interactions:
  • Clearance ↑ by: smoking, phenytoin, rifampicin
  • Clearance ↓ by: ciprofloxacin, erythromycin, cimetidine → toxicity risk

LTOT: Improve 3-year survival by 50%, prevent progression of complications ^[2]

This is one of the most commonly examined SAQ topics in HKUMed exams.

Start only when patient is clinically stable with ABG × 2 at least 3–4 weeks apart, and after optimisation of medical therapy. ^[2][20]

Duration: ≥ 15 hours/day ^[2][4]

Target: SaO₂ ≥ 90% / PaO₂ ≥ 8.0 kPa (60 mmHg) ^[4]

Indications (the patient must have stopped smoking +): ^[2][4][20]

There is NO survival benefit in moderate resting desaturation (SaO₂ 89–93%) or moderate exercise-induced desaturation. ^[20]

Non-continuous LTOT: ^[4]

• During exercise: PaO₂ ≤ 7.3 kPa or SaO₂ ≤ 88% with a low level of exertion
• During sleep: PaO₂ ≤ 7.3 kPa or SaO₂ ≤ 88% with associated complications such as cardiac arrhythmia, pulmonary hypertension, or daytime somnolence

Why must the patient have stopped smoking?

• Fire/explosion risk with supplemental O₂ in the home + active smoking
• Continued smoking negates the benefit of LTOT

Target SpO₂ 88–92% ^[2][4]

Start with 24% Venturi mask or 1–2 L/min by nasal cannula ^[2][4]

Avoid high-dose O₂ therapy to prevent removal of hypoxic drive especially in patients without hypercapnic drive ^[4]

Monitor ABG 30–60 minutes after initiation of O₂ therapy and modify flow rate according to PaO₂ and pH ^[2]

Why Venturi mask? A Venturi mask delivers a precise, fixed FiO₂ regardless of the patient's respiratory pattern (unlike nasal cannulae where FiO₂ varies with respiratory rate and tidal volume). The Venturi system uses the Bernoulli principle — oxygen passes through a narrow jet, creating a negative pressure that entrains a precise amount of room air, diluting the O₂ to a known concentration.

Non-invasive ventilation (NIV): ^[4]

Rationale: ^[4]

• Relief of dyspnoea by decreasing work of breathing
• Improve respiratory acidosis and avoid complications

NIV delivers positive pressure ventilation via a face mask or nasal mask (no endotracheal tube). The most common mode is BiPAP (Bilevel Positive Airway Pressure):

• IPAP (Inspiratory Positive Airway Pressure) — assists inspiration → augments tidal volume → improves ventilation → ↓PaCO₂
• EPAP (Expiratory Positive Airway Pressure) — acts like PEEP → splints airways open during expiration → reduces air trapping → improves oxygenation

Indications for NIV in AECOPD: ^[4]

• Respiratory acidosis (pH ≤ 7.35 ± PaCO₂ > 6.0 kPa / 45 mmHg)
• Moderate to severe dyspnoea with signs of respiratory muscle fatigue and increased work of breathing:
  • Use of accessory muscles for breathing
  • Paradoxical abdominal motion (the abdomen moves inward during inspiration instead of outward — indicates diaphragmatic fatigue)
  • Intercostal space retraction
  • RR > 25/min

Check ABG 30–60 minutes after initiation of NIV. Do not delay intubation and mechanical ventilation if no improvement. ^[4]

Patients should be managed in ICU. ^[4]

Indications for invasive ventilation in AECOPD: ^[4]

• Patients unable to tolerate or failed non-invasive ventilation
• Impaired consciousness, massive aspiration, or unable to clear secretions
• Severe haemodynamic instability without response to fluid and vasopressor
• Severe ventricular arrhythmia, cardiac or respiratory arrest

Triggers: ^[2]

• Infection: bacterial (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), viral (rhinovirus) — the most common triggers (~70–80% of exacerbations)
• Environmental pollution — particulate matter, ozone, NO₂

Pathophysiology of an exacerbation:

1. Trigger (usually infection) → amplified airway inflammation → mucosal oedema, mucus hypersecretion, bronchospasm
2. Worsened airway obstruction → increased air trapping → dynamic hyperinflation
3. Increased work of breathing → respiratory muscle fatigue
4. V/Q mismatch worsens → hypoxaemia deepens
5. If severe → alveolar hypoventilation → CO₂ retention → respiratory acidosis → potential respiratory arrest

• Each exacerbation causes a step-wise decline in lung function — FEV₁ drops with each event and may not fully recover
• Frequent exacerbations (≥ 2/year) predict faster disease progression and worse survival
• AECOPD is the most common cause of acute medical admission in HK during winter months
• Hospital mortality for severe AECOPD requiring ICU is ~10–25%

• Definition: PaO₂ < 8 kPa (60 mmHg) with normal or low PaCO₂
• Mechanism in COPD: V/Q mismatch — airway obstruction creates areas of low V/Q (underventilated but still perfused alveoli), causing venous admixture and hypoxaemia. The patient compensates by hyperventilating → PaCO₂ stays normal or falls.
• When: Mild-moderate stable COPD, early exacerbation

• Definition: PaO₂ < 8 kPa (60 mmHg) AND PaCO₂ > 6 kPa (45 mmHg)
• Mechanism in COPD:
  • Increased airway resistance + hyperinflation → enormous work of breathing
  • Respiratory muscle fatigue (diaphragm flattened and mechanically disadvantaged)
  • Eventually the respiratory muscles cannot maintain adequate alveolar ventilation → CO₂ accumulates
  • This is a medical emergency — respiratory acidosis (↓ pH) can lead to coma and death

Chronic respiratory failure is listed as a distinct complication ^[1] because many advanced COPD patients live chronically with Type II respiratory failure (compensated by renal bicarbonate retention) — these are the "blue bloaters."

Acute-on-chronic respiratory failure: A chronic CO₂ retainer (with compensated respiratory acidosis and near-normal pH) develops an exacerbation → acute rise in PaCO₂ overwhelms renal compensation → pH drops → decompensated respiratory acidosis. This is when NIV is indicated.

• Emphysema destroys alveolar walls → formation of bullae (large, thin-walled, air-filled spaces)
• These bullae are structurally weak — they can rupture, especially during exacerbations when intrathoracic pressure fluctuations increase (forceful coughing, increased work of breathing)
• Rupture of a subpleural bulla → air leaks into the pleural space → secondary spontaneous pneumothorax

In a young, healthy person with a primary spontaneous pneumothorax, there is ample respiratory reserve — they may tolerate even a moderate pneumothorax with minimal symptoms. In a COPD patient:

• Respiratory reserve is already severely limited
• Even a small pneumothorax can cause life-threatening respiratory compromise
• Air trapping may cause the pneumothorax to progress to a tension pneumothorax (air enters pleural space during inspiration but cannot escape during expiration → progressive mediastinal shift → cardiac arrest)

During acute exacerbation: exclude and treat pneumothorax ^[1]

Management: Intercostal chest drain (not observation/aspiration as in primary spontaneous pneumothorax in young patients). Consider pleurodesis to prevent recurrence.

Cor pulmonale management: ^[1]

• Diuretics
• Salt and fluid restriction