Chronic obstructive pulmonary disease

Tobacco smoke

The dominant cause in most countries, including waterpipe and cannabis smoking

Biomass and occupational exposure

Indoor cooking fuel, dust, silica, cadmium, welding fumes — major contributors in low-income settings

Genetic

Alpha-1 antitrypsin deficiency — test all with early-onset or basal-predominant emphysema

Developmental

Prematurity, childhood respiratory infection, low peak lung function attainment

Air pollution

Ambient particulate matter exposure over the life course

Asthma-COPD overlap

Long-standing poorly controlled asthma leading to fixed obstruction

• Affects roughly 390 million people and is among the top three causes of death worldwide.
• Around a quarter to a third of cases globally occur in people who never smoked, particularly women exposed to biomass fuel.
• Substantially under-diagnosed because spirometry is not performed until symptoms are advanced.

• Cumulative tobacco exposure, biomass smoke, occupational dust and fumes, alpha-1 antitrypsin deficiency, childhood infection, prematurity, poorly controlled asthma, HIV, tuberculosis, low socioeconomic status.

1. 1Inhaled particles and gases trigger innate immune activation in the airway epithelium.
2. 2Neutrophils, macrophages and CD8 lymphocytes accumulate and release proteases, oxidants and cytokines.
3. 3Protease-antiprotease imbalance destroys elastin in alveolar walls, producing emphysema.
4. 4Repeated injury and repair cause peribronchiolar fibrosis and small-airway narrowing.
5. 5Mucus hypersecretion and impaired ciliary clearance predispose to bacterial colonisation and exacerbations.

Normal physiology → mechanism → tissue change → clinical picture

1. 1Normal physiology: elastic recoil and airway tethering keep small airways open during expiration.
2. 2Mechanism: chronic inflammation with neutrophils, macrophages and CD8 cells; protease-antiprotease imbalance destroys elastin.
3. 3Tissue change: small airway fibrosis with mucus plugging plus alveolar wall destruction reducing recoil.
4. 4Functional effect: expiratory flow limitation, air trapping, dynamic hyperinflation, increased work of breathing and V/Q mismatch.
5. 5Clinical manifestation: exertional dyspnoea, chronic cough and sputum, barrel chest, hypoxaemia and later hypercapnia and cor pulmonale.

Centriacinar emphysema

Upper lobe predominant, associated with smoking

Panacinar emphysema

Lower lobe predominant, associated with alpha-1 antitrypsin deficiency

Chronic bronchitis

Goblet-cell hyperplasia, mucus gland hypertrophy (Reid index > 0.4), squamous metaplasia

Vascular

Pulmonary arteriolar intimal thickening leading to pulmonary hypertension and cor pulmonale

• Progressive exertional dyspnoea — the cardinal symptom
• Chronic cough with sputum, worse in the morning
• Wheeze and chest tightness
• Frequent winter chest infections
• Fatigue, weight loss and reduced exercise tolerance in advanced disease

• Barrel-shaped chest, reduced cricosternal distance, hyperinflation with reduced expansion
• Hyper-resonant percussion, diminished breath sounds, prolonged expiration, wheeze
• Pursed-lip breathing, accessory muscle use, tripod posture
• Cyanosis, raised JVP, peripheral oedema and loud P2 with cor pulmonale
• Flapping tremor and drowsiness with hypercapnia

Typical

• Smoker over 50 with years of morning cough and progressive exertional dyspnoea, hyperinflated chest, post-bronchodilator FEV1/FVC 0.55 and FEV1 55% predicted.

Atypical

• Never-smoking woman with lifelong biomass cooking exposure
• Young adult with basal emphysema and alpha-1 antitrypsin deficiency
• Presentation only at first hospitalised exacerbation with respiratory failure
• Predominant weight loss and cachexia mistaken for malignancy
• Asthma-COPD overlap with eosinophilia and partial reversibility

1. 1Suspect COPD with dyspnoea, chronic cough or sputum plus a risk exposure.
2. 2Confirm with post-bronchodilator spirometry: FEV1/FVC < 0.70 is required for diagnosis.
3. 3Grade airflow limitation (GOLD 1-4) and assess symptoms with mMRC or CAT plus exacerbation history to assign group A, B or E.
4. 4Check blood eosinophils to guide inhaled corticosteroid use.
5. 5Exclude and manage comorbidity: heart failure, ischaemic heart disease, anxiety and depression, osteoporosis, lung cancer risk.
6. 6Test alpha-1 antitrypsin in early-onset, minimal-smoking or basal emphysema.
7. 7Assess for long-term oxygen therapy and pulmonary rehabilitation eligibility.

Diagnostic requirement

Post-bronchodilator FEV1/FVC < 0.70 in a symptomatic patient with relevant exposure

GOLD 1

FEV1 ≥ 80% predicted

GOLD 2

FEV1 50-79% predicted

GOLD 3

FEV1 30-49% predicted

GOLD 4

FEV1 < 30% predicted

Groups

A: low symptoms, ≤ 1 exacerbation. B: high symptoms (mMRC ≥ 2 or CAT ≥ 10), ≤ 1 exacerbation. E: ≥ 2 moderate or ≥ 1 hospitalised exacerbation

Initial

• Post-bronchodilator spirometry, pulse oximetry, chest radiograph, FBC (eosinophils, polycythaemia), BMI.

Further

• Blood gas if SpO2 < 92% or during exacerbation, alpha-1 antitrypsin level, ECG and echocardiography for cor pulmonale.

Selected

• CT chest for bullae, bronchiectasis, malignancy or lung volume reduction assessment; lung volumes and DLCO.

Monitoring

• Annual spirometry, CAT score, exacerbation count, inhaler technique review, oxygen assessment when stable.

Asthma

Rule in: variability, marked reversibility, atopy, childhood onset. Rule out: fixed obstruction with heavy smoking history.

Heart failure

Rule in: orthopnoea, raised BNP, cardiomegaly, bibasal crackles. Rule out: obstructive spirometry with hyperinflation.

Bronchiectasis

Rule in: high-volume purulent sputum, CT tram-lines and signet-ring sign. Rule out: dry cough with emphysema.

Tuberculosis

Rule in: weight loss, night sweats, cavitation, positive sputum tests. Rule out: negative microbiology with obstructive physiology.

Interstitial lung disease

Rule in: fine inspiratory crackles, restrictive spirometry, reduced DLCO with reticulation. Rule out: obstructive ratio.

Upper airway obstruction

Rule in: stridor, flattened inspiratory flow-volume loop. Rule out: classic expiratory limitation.

Airflow limitation

GOLD 1-4 by FEV1 % predicted (see diagnostic criteria)

Symptom burden

mMRC dyspnoea scale 0-4; CAT score 0-40 with 10 as the threshold for high symptoms

ABE groups

A, B or E based on symptoms plus exacerbation history — drives initial inhaled therapy

Prognostic index

BODE index: BMI, obstruction (FEV1), dyspnoea (mMRC), exercise capacity (6-minute walk)

Exacerbation severity

Mild (bronchodilators only), moderate (steroids/antibiotics), severe (hospitalisation or respiratory failure)

Acute exacerbation

• Controlled oxygen targeting SpO2 88-92% with a Venturi mask — uncontrolled high-flow oxygen risks CO2 retention
• Nebulised salbutamol and ipratropium
• Prednisolone 30-40 mg for 5 days
• Antibiotics when sputum is purulent or consolidation/severe illness is present
• Non-invasive ventilation for respiratory acidosis persisting after 1 hour of medical therapy

Stable pharmacologic therapy

• Group A: a bronchodilator (usually LAMA)
• Group B: LABA + LAMA combination
• Group E: LABA + LAMA; add ICS if blood eosinophils ≥ 300 cells/µL or asthma features
• Escalate only after confirming adherence and inhaler technique

Disease-modifying

• Smoking cessation with pharmacotherapy — the only intervention slowing FEV1 decline.
• Pulmonary rehabilitation for all with mMRC ≥ 2 — improves dyspnoea, exercise capacity and quality of life.
• Long-term oxygen therapy if PaO2 ≤ 7.3 kPa (or ≤ 8.0 with cor pulmonale/polycythaemia) — improves survival.

Advanced

• Roflumilast for chronic bronchitis with FEV1 < 50% and frequent exacerbations; azithromycin prophylaxis in selected non-smokers.
• Lung volume reduction (surgical or endobronchial valves) for upper-lobe emphysema; transplantation in advanced disease.
• Alpha-1 antitrypsin augmentation where indicated and available.

Supportive

• Influenza, pneumococcal, COVID-19, pertussis and RSV vaccination per policy; nutrition support; anxiety and depression treatment; advance care planning; palliative symptom management.

Salbutamol

Short-acting beta-2 agonist for rescue and nebulised exacerbation therapy; watch tremor, tachycardia and hypokalaemia

Ipratropium

Short-acting antimuscarinic; caution in glaucoma and bladder outflow obstruction

Tiotropium (LAMA)

Once-daily maintenance bronchodilator; reduces exacerbations; dry mouth is common

Budesonide-formoterol

ICS/LABA combination; reserve ICS for eosinophils ≥ 300 or asthma features — pneumonia risk

Prednisolone

30-40 mg for 5 days in exacerbation; longer or repeated courses cause osteoporosis and dysglycaemia

Azithromycin

Prophylaxis in selected frequent exacerbators; screen QT, hearing and mycobacteria first

Roflumilast

Chronic bronchitis with FEV1 < 50% and exacerbations; nausea, weight loss and mood change

Respiratory

• Acute exacerbation with respiratory failure, pneumonia, pneumothorax, cor pulmonale, secondary polycythaemia.

Systemic

• Ischaemic heart disease, arrhythmia, pulmonary hypertension, lung cancer (independent of smoking), osteoporosis from steroids and inactivity.

Functional

• Anxiety, depression, cachexia, sarcopenia, social isolation and progressive disability.

• Prognosis relates to FEV1, dyspnoea grade, BMI, exercise capacity (BODE index), exacerbation frequency and comorbidity.
• Hospitalised exacerbations carry substantial in-hospital and one-year mortality, particularly with hypercapnia.
• Smoking cessation at any stage slows decline and improves survival.
• Long-term oxygen therapy improves survival only in genuine chronic hypoxaemia — not for breathlessness alone.

• Tobacco control and cessation support at every contact
• Clean cooking fuel and workplace exposure controls
• Vaccination to reduce exacerbations
• Case finding with spirometry in symptomatic smokers over 40
• Lung cancer screening where nationally available

• Review 4-6 weeks after an exacerbation: symptoms, inhaler technique, oxygenation, rehabilitation referral
• At least annual spirometry and CAT/mMRC assessment
• Reassess long-term oxygen eligibility only when stable for 8 weeks
• Review escalation and ceiling of care and document patient preferences

Pregnancy

Uncommon; continue inhaled therapy, avoid roflumilast, coordinate with obstetrics

Elderly / frail

Device dexterity and cognition determine inhaler choice; consider nebulisers and spacers

Heart failure overlap

Cardioselective beta-blockers are safe and should not be withheld

CKD

Careful with roflumilast and theophylline; adjust antibiotic dosing

Alpha-1 antitrypsin deficiency

Family screening, avoid smoking absolutely, specialist referral

Palliative phase

Opioids and handheld fan for refractory breathlessness; anticipatory care planning

• GOLD 2025 report
• GINA 2025 where asthma features coexist

• Triple inhaled therapy reduces exacerbations and, in some analyses, mortality versus dual bronchodilation in exacerbation-prone disease.
• Blood eosinophil count is an established biomarker for inhaled corticosteroid response.
• Emerging biologics targeting type 2 inflammation show benefit in a subset of eosinophilic COPD.

• GOLD 2025 report (guideline, global).
• DrZep editorial summary, demo dataset v0.1.