Respiratory : Investigations (Complete)

• Basics: Respiratory Symptoms and Signs
• Lung function: Spirometry | Flow–Volume Loops | Lung Volumes and Gas Transfer | Peak Flow Monitoring | FeNO and Bronchial Challenge Tests | Respiratory Muscle Tests
• Gases and oxygen: Arterial Blood Gases | Pulse Oximetry
• Imaging: Chest X-ray | CT and PET-CT | Thoracic Ultrasound
• Procedures: Bronchoscopy and EBUS | Pleural Procedures
• Other tests: Exercise and Fitness-to-Fly Tests | Sleep Studies | Sputum and Blood Tests
• Revision: Patterns at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🫁 Respiratory investigations turn a history of breathlessness or cough into a diagnosis. The key tools are lung function tests (is the problem obstruction, restriction or gas exchange?), imaging (where and what is the abnormality?), and sampling (bronchoscopy, pleural fluid, sputum). This chapter explains how each test works and how to read it.
Your four questions for every patient: Is the airflow obstructed or the lung restricted? Is gas transfer normal? What does the imaging show, and where? Which test will give a tissue or microbiological diagnosis most safely?

Respiratory Symptoms and Signs

Key symptoms:

• Breathlessness: Grade it with the MRC dyspnoea scale:
  • 1 - only on strenuous exercise.
  • 2 - when hurrying or walking up a slight hill.
  • 3 - walks slower than people of the same age, or stops for breath on the flat.
  • 4 - stops after about 100 m.
  • 5 - too breathless to leave the house.
  Ask about speed of onset, orthopnoea, wheeze and triggers.
• Cough: Acute (under 3 weeks) is usually infection. Chronic (over 8 weeks) causes:
  • Asthma.
  • Reflux.
  • Upper airway (rhinosinusitis).
  • ACE inhibitors.
  • COPD; bronchiectasis.
  • Lung cancer; ILD.
• Sputum: Large daily volumes suggest bronchiectasis.
• Haemoptysis: Always needs a chest X-ray. Smokers over 40 need urgent cancer assessment.
• Chest pain: Pleuritic (sharp, worse on breathing) suggests pleurisy, PE or pneumothorax.
• Systemic and other: Weight loss, night sweats (TB, cancer, lymphoma), snoring and daytime sleepiness (sleep apnoea).
• Exposures: Smoking (pack-years = packs a day × years), occupation (asbestos, dusts, birds, moulds), travel, pets, drugs.

Key signs:

• Clubbing:
  • Lung cancer, ILD (especially IPF), bronchiectasis and CF, empyema and lung abscess, mesothelioma.
  • Also cyanotic heart disease, endocarditis, IBD, cirrhosis.
  • Not caused by COPD or asthma - clubbing in COPD should prompt a search for cancer.
• Crackles:
  • Fine, late inspiratory ("Velcro") crackles - pulmonary fibrosis.
  • Coarse crackles - bronchiectasis, pulmonary oedema, pneumonia.
• Wheeze: Widespread (asthma, COPD) or fixed monophonic (a single narrowed airway - tumour, foreign body).
• Stridor: Upper airway narrowing.
• Dullness to percussion:
  • "Stony" dullness with absent breath sounds - effusion.
  • Dull with bronchial breathing - consolidation.
• Hyper-resonance with reduced breath sounds - pneumothorax, emphysema.
• Tracheal deviation:
  • Away from a large effusion or tension pneumothorax.
  • Towards collapse or fibrosis.
• Signs of right heart failure (cor pulmonale) - raised JVP, oedema, loud P2.

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Spirometry

What it measures: The patient breathes in fully, then blows out as hard and as long as possible.

• FEV1: Volume blown out in the first second.
• FVC: Total volume blown out (forced vital capacity).
• FEV1/FVC ratio: The key to telling obstruction from restriction.

Reading the result:

• Obstructive pattern - air cannot get out quickly:
  • FEV1/FVC ratio low - below the lower limit of normal (LLN), or below 0.7 in traditional COPD criteria.
  • FEV1 reduced; FVC normal or mildly reduced.
  • Causes: Asthma, COPD, bronchiectasis, CF, obliterative bronchiolitis.
• Restrictive pattern - the lungs cannot fill:
  • FEV1 and FVC both reduced, with a normal or high ratio.
  • Confirm restriction with lung volumes (low TLC) - a low FVC alone can be caused by air trapping or poor effort.
  • Causes:
    • Lung: ILD and fibrosis.
    • Outside the lung: obesity, chest wall deformity (kyphoscoliosis), neuromuscular weakness, pleural thickening, large effusion.
• Mixed: Both a low ratio and low lung volumes.

Severity of obstruction (by FEV1 % predicted, as used for COPD):

• Mild: 80% or more.
• Moderate: 50–79%.
• Severe: 30–49%.
• Very severe: below 30%.

Bronchodilator reversibility: Repeat spirometry 15–20 minutes after salbutamol. An FEV1 rise of 12% or more and 200 mL or more supports asthma. Large reversibility is unusual in COPD.

Reference values: UK guidance (ARTP/BTS) now recommends Global Lung Function Initiative equations and using the lower limit of normal and z-scores, rather than fixed cut-offs, to reduce over-diagnosis in older people.

💡 Clinical Pearl: Spirometry needs good technique - a hard, fast start and at least 6 seconds of blowing. Poor effort lowers both FEV1 and FVC and can look "restrictive". Always look at the trace, not just the numbers.

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Flow–Volume Loops

A flow–volume loop plots airflow (vertical axis) against lung volume (horizontal axis) through a full forced breath out and in. Its shape gives extra diagnostic clues:

• Normal: A sharp expiratory peak followed by a straight-ish decline, and a rounded inspiratory curve below.
• Obstructive (asthma, COPD): The expiratory limb is "scooped out" (concave) as small airways collapse. In emphysema there is a sharp fall after the peak.
• Restrictive: A normal shape but narrow (small volume), sometimes a tall "witch's hat" shape.
• Upper airway obstruction:
  • Fixed (tracheal stenosis, goitre, tumour): Both limbs flattened - a "box" shape.
  • Variable extrathoracic (vocal cord palsy, laryngeal problems): The inspiratory limb is flattened.
  • Variable intrathoracic (tracheomalacia, tumour in the lower trachea): The expiratory limb is flattened.

💡 Clinical Pearl: A "box-shaped" loop or an unexpectedly low peak flow compared with FEV1 suggests upper airway narrowing. Think tracheal stenosis after intubation, or a retrosternal goitre, in "asthma" that doesn't respond to treatment.

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Lung Volumes and Gas Transfer

Lung volumes (body plethysmography or gas dilution):

• Total lung capacity (TLC):
  • Low - true restriction (ILD, chest wall or neuromuscular disease).
  • High - hyperinflation (emphysema, severe asthma).
• Residual volume (RV): High in air trapping (COPD, asthma).

Gas transfer (TLCO, also called DLCO): The patient breathes in a tiny amount of carbon monoxide and holds the breath. TLCO measures how well gas crosses from the alveoli into the blood. KCO is the transfer per unit of lung volume.

💡 Clinical Pearl: Breathless with normal spirometry? Check the TLCO. A low TLCO with normal lung volumes and clear lungs suggests pulmonary vascular disease (PE, pulmonary hypertension) or early emphysema or ILD.

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Peak Flow Monitoring

• Peak expiratory flow (PEF): The fastest flow of air in a short, sharp blow. Simple and cheap - patients can measure it at home.
• Uses:
  • Assessing acute asthma severity (PEF as % of best or predicted).
  • Diagnosing asthma: Record PEF twice daily for 2 weeks. Variability (amplitude % mean) of 20% or more supports the diagnosis.
  • Occupational asthma: Serial PEF at least 4 times a day, at work and away from work - analysed with OASYS.
  • Asthma self-management plans.
• Limitations: Effort-dependent; less sensitive than spirometry; not useful in COPD diagnosis.

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FeNO and Bronchial Challenge Tests

• Fractional exhaled nitric oxide (FeNO):
  • What it shows: Nitric oxide in breath, which rises with eosinophilic (type 2) airway inflammation.
  • Diagnosis: In adults, a FeNO of 50 ppb or more confirms asthma when the history is typical (BTS/NICE/SIGN 2024).
  • Monitoring: A high FeNO in treated asthma suggests poor adherence to inhaled steroid, or ongoing inflammation. It helps choose patients for biologics.
  • Lowered by smoking and inhaled steroids. Raised by atopy and rhinitis.
• Bronchial challenge testing (specialist):
  • Inhaled methacholine, histamine or mannitol in increasing doses.
  • A fall in FEV1 at low doses shows bronchial hyperresponsiveness.
  • Useful when the diagnosis of asthma is still uncertain after other tests. A negative test makes current asthma unlikely.
• Blood eosinophils: A count above the laboratory range supports asthma (BTS/NICE/SIGN). In COPD, eosinophils of 300 cells/µL or more predict benefit from inhaled steroids.

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Respiratory Muscle Tests

• Who needs them: Neuromuscular disease (MND, myasthenia, GBS, muscular dystrophy), unexplained breathlessness on lying flat, or a raised hemidiaphragm.
• Lying and standing FVC: A fall of more than 20% on lying down suggests diaphragm weakness. In bilateral diaphragm paralysis there is marked orthopnoea and paradoxical abdominal movement.
• Sniff nasal inspiratory pressure (SNIP) and maximal inspiratory and expiratory pressures (MIP, MEP): Measure breathing muscle strength directly. Used to monitor MND and to decide when to start NIV.
• Peak cough flow: Below about 270 L/min means a weak cough, and a risk of chest infections and secretion retention.
• Overnight oximetry or CO2 monitoring: Detects nocturnal hypoventilation, which comes before daytime respiratory failure.

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Arterial Blood Gases

Normal values:

• pH 7.35–7.45.
• PaO2 above 10 kPa on air.
• PaCO2 4.7–6.0 kPa.
• Bicarbonate 22–26 mmol/L.
• Base excess −2 to +2.

Step-by-step:

• 1. Oxygenation: Is PaO2 low for the inspired oxygen? A quick rule: PaO2 (kPa) should be about 10 less than the inspired oxygen %.
• 2. pH: Acidaemia or alkalaemia?
• 3. Primary disturbance:
  • Respiratory: PaCO2 moves in the opposite direction to pH.
  • Metabolic: Bicarbonate moves in the same direction as pH.
• 4. Compensation: The kidneys compensate for respiratory problems (slowly, over days); the lungs compensate for metabolic problems (quickly).

Common patterns:

• Type 1 respiratory failure: Low PaO2, normal or low PaCO2 - pneumonia, PE, pulmonary oedema, ILD.
• Type 2 respiratory failure: Low PaO2 and high PaCO2.
  • Acute: Low pH.
  • Chronic: Normal pH, high bicarbonate.
  • Acute-on-chronic: Low pH despite a high bicarbonate.
• Respiratory alkalosis: Low PaCO2, high pH - hyperventilation (anxiety, early asthma, PE, pain, salicylates early).

Alveolar–arterial (A–a) gradient: Shows whether low oxygen is due to lung disease or just under-breathing.

• Calculation: Alveolar PO2 (PAO2) ≈ (FiO2 × 94.8) − (PaCO2 ÷ 0.8) in kPa. A–a gradient = PAO2 − PaO2.
• Normal: Below about 2–4 kPa in young adults on air (rises with age).
• Raised: Lung disease (V/Q mismatch, shunt, diffusion problem).
• Normal gradient with low oxygen: Pure hypoventilation (opioids, neuromuscular disease) or high altitude.

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Pulse Oximetry

• What it measures: The percentage of haemoglobin carrying oxygen (SpO2), by shining light through the finger.
• Limitations:
  • Overestimates saturation in people with darker skin - "occult hypoxaemia" (MHRA and NHS Race and Health Observatory warnings).
  • Falsely normal in carbon monoxide poisoning and methaemoglobinaemia (which reads about 85%).
  • Inaccurate with poor circulation, cold hands, nail varnish, movement, or severe anaemia.
  • Says nothing about CO2 - a patient can have a normal SpO2 on oxygen with a dangerously high CO2.
• Oxygen–haemoglobin curve: Saturations hold up well until PaO2 falls to about 8 kPa (about 90%), then drop steeply. Small falls below 90% mean large falls in oxygen content.
• Overnight oximetry: A screening test for sleep apnoea (repeated dips - oxygen desaturation index) and nocturnal hypoventilation.

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Chest X-ray

A systematic approach:

• Check patient details, projection (PA or AP), rotation and inspiration.
• Airway (trachea central).
• Breathing (lungs, pleura).
• Cardiac (size, borders).
• Diaphragm (free air underneath).
• Everything else (bones, soft tissues, lines and tubes).
• Review areas: Apices, behind the heart, hila, below the diaphragm.

Common patterns:

• Consolidation: White area with air bronchograms. A lost heart or diaphragm border localises it (silhouette sign):
  • Right heart border - right middle lobe.
  • Left heart border - lingula.
  • Diaphragm - lower lobe.
• Collapse: Volume loss - the trachea, fissures and hila are pulled towards it. Left lower lobe collapse gives a "sail sign" behind the heart. In an adult smoker, think obstructing tumour.
• Pleural effusion: Blunted costophrenic angle with a meniscus. A large effusion pushes the mediastinum away.
• Pneumothorax: A visible lung edge with no lung markings beyond it.
• Nodule or mass: Compare with old films; CT if new.
• Cavitation:
  • Squamous cell carcinoma.
  • TB.
  • Staphylococcus aureus or Klebsiella pneumonia; lung abscess.
  • GPA (vasculitis).
  • Septic emboli.
• Bilateral hilar lymphadenopathy: Sarcoidosis, lymphoma, TB, metastases.
• Reticular (interstitial) shadowing:
  • Lower zone: IPF, asbestosis, connective tissue disease, drugs.
  • Upper zone: Sarcoidosis, hypersensitivity pneumonitis, silicosis, TB, ankylosing spondylitis.
• Pulmonary oedema: Upper lobe diversion, bat's wing shadowing, Kerley B lines, effusions.

⚠️ Safety Pearl: A normal chest X-ray does not exclude lung cancer - about 1 in 5 lung cancers is missed on plain film. Persisting unexplained symptoms (haemoptysis, weight loss) in a smoker need a CT.

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CT and PET-CT

• Contrast-enhanced CT chest (and abdomen): Lung cancer diagnosis and staging, masses, mediastinum, pleura.
• CT pulmonary angiography (CTPA): Pulmonary embolism.
• High-resolution CT (HRCT): Thin slices without contrast for ILD and bronchiectasis.
  • Usual interstitial pneumonia (UIP) pattern - subpleural, basal reticulation with honeycombing and traction bronchiectasis - typical of IPF.
  • Ground-glass opacity - hazy grey lung (inflammation, infection, oedema, haemorrhage).
  • Mosaic attenuation with air trapping on expiratory images - small airways disease, hypersensitivity pneumonitis.
  • Tree-in-bud - small airway infection (TB, non-tuberculous mycobacteria, aspiration).
  • Bronchiectasis - an airway wider than the accompanying artery ("signet ring").
  • Crazy paving - ground glass with septal thickening (pulmonary alveolar proteinosis, PCP, oedema).
• Low-dose CT: Used in the NHS Lung Cancer Screening Programme and nodule follow-up.
• PET-CT (FDG - a radiolabelled glucose taken up by active cells):
  • Assesses nodules and staging (nodes, metastases) in lung cancer.
  • False positives: infection, inflammation, sarcoidosis.
  • False negatives: small (under 8 mm) nodules, slow-growing tumours (adenocarcinoma in situ, carcinoid).

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Thoracic Ultrasound

• Bedside, no radiation, increasingly done by respiratory doctors.
• Uses:
  • Detects and characterises pleural effusions - septations suggest infection; pleural nodules suggest malignancy.
  • Guides pleural aspiration and drains - standard of care (BTS), reducing complications.
  • Detects pneumothorax (absent lung sliding).
  • B-lines (pulmonary oedema or ILD).
  • Consolidation.
  • Diaphragm movement.

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Bronchoscopy and EBUS

• Flexible bronchoscopy: A camera passed through the nose or mouth into the airways, under sedation and local anaesthetic.
  • Diagnostic uses:
    • Central tumours - biopsy and brushings.
    • Bronchoalveolar lavage (BAL) for infection (TB, PCP, fungi) and ILD (cell counts - e.g. lymphocytes in sarcoidosis and hypersensitivity pneumonitis).
    • Haemoptysis; persistent collapse.
  • Therapeutic uses: Removing secretions or foreign bodies; stents; valves for emphysema.
• Endobronchial ultrasound (EBUS): An ultrasound probe on the bronchoscope lets the operator see and needle-sample lymph nodes next to the airways (EBUS-TBNA).
  • Used to diagnose and stage lung cancer (mediastinal nodes).
  • Also diagnoses sarcoidosis, lymphoma and TB.
• Other sampling:
  • CT-guided percutaneous lung biopsy for peripheral lesions - risk of pneumothorax (about 1 in 5) and bleeding.
  • Navigational or robotic bronchoscopy for small peripheral nodules.
  • Cryobiopsy or surgical (VATS) lung biopsy for ILD when the diagnosis is uncertain.
• Before procedures: Check FBC and clotting; stop anticoagulants and some antiplatelets per protocol; check fitness for sedation.

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Pleural Procedures

• Diagnostic pleural aspiration (ultrasound-guided) - send for:
  • Appearance.
  • Protein and LDH (with serum values, for Light's criteria).
  • pH; glucose.
  • Cytology.
  • Microbiology (Gram stain, culture, AFB).
  • Amylase, triglycerides or haematocrit if relevant.
• Light's criteria - the fluid is an exudate if any of:
  • Pleural protein ÷ serum protein above 0.5.
  • Pleural LDH ÷ serum LDH above 0.6.
  • Pleural LDH above two-thirds of the upper limit of normal serum LDH.
  Use Light's criteria when pleural protein is borderline (25–35 g/L). Above 35 g/L is likely exudate; below 25 g/L likely transudate.
• Therapeutic aspiration: Relieves breathlessness. Usually remove no more than about 1.5 L at a time.
• Chest drain: For pneumothorax, pleural infection or large effusions - inserted in the "triangle of safety" with ultrasound guidance.
• Local anaesthetic thoracoscopy: A camera into the pleural space to biopsy the pleura (cancer, mesothelioma, TB) and perform talc pleurodesis.
• Indwelling pleural catheter (IPC): A tunnelled drain for recurrent malignant effusions, drained at home.

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Exercise and Fitness-to-Fly Tests

• Six-minute walk test: Distance walked and oxygen saturations. Tracks ILD, COPD and pulmonary hypertension, and checks for exertional desaturation (ambulatory oxygen assessment).
• Incremental shuttle walk test: Walking between cones at increasing speed - used in pulmonary rehabilitation and before surgery.
• Cardiopulmonary exercise testing (CPET):
  • Measures oxygen use and CO2 output during cycling.
  • Separates cardiac, respiratory and deconditioning causes of breathlessness.
  • Assesses fitness for major surgery (including lung resection).
• Hypoxic challenge test ("fitness to fly"):
  • Breathing 15% oxygen mimics an aircraft cabin.
  • If PaO2 falls below about 6.6 kPa (or SpO2 below about 85%), in-flight oxygen is recommended (BTS air travel guidance).

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Sleep Studies

• Screening questionnaires: Epworth Sleepiness Scale (daytime sleepiness, out of 24 - above 10 is excessive); STOP-Bang (OSA risk).
• Overnight oximetry: Counts oxygen dips (oxygen desaturation index). Simple, but misses non-desaturating events.
• Respiratory polygraphy (home study - the usual first test in NICE NG202): Airflow, breathing effort, oximetry and position. It gives the apnoea–hypopnoea index (AHI), events per hour:
  • Mild: 5–14.
  • Moderate: 15–29.
  • Severe: 30 or more.
• Polysomnography (in a sleep lab): Adds EEG, eye movements and muscle activity - for complex cases and non-respiratory sleep disorders (narcolepsy, parasomnias).
• Transcutaneous CO2 monitoring: For suspected nocturnal hypoventilation (obesity hypoventilation, neuromuscular disease).

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Sputum and Blood Tests

• Sputum:
  • Culture (bacteria including Pseudomonas in bronchiectasis).
  • AFB smear, TB culture and PCR - three samples.
  • Fungi; cytology (rarely used now).
• Bloods:
  • FBC - eosinophils (asthma, ABPA, EGPA, eosinophilic pneumonia).
  • CRP.
  • Total IgE, aspergillus-specific IgE and IgG (ABPA, chronic pulmonary aspergillosis).
  • Alpha-1 antitrypsin level - young or non-smoking emphysema, basal emphysema, family history.
  • Immunoglobulins (bronchiectasis).
  • Autoimmune screen - ANA, rheumatoid factor, anti-CCP, myositis antibodies, ANCA (ILD, vasculitis).
  • Serum precipitins (specific IgG) to birds and moulds - hypersensitivity pneumonitis.
  • Serum ACE and calcium (sarcoidosis - supportive only).
  • Interferon-gamma release assay (latent TB); HIV test.
  • NT-proBNP (heart failure); D-dimer.
• Sweat test and CFTR genetics: Cystic fibrosis.
• Nasal cilia studies (nasal nitric oxide, ciliary beat analysis): Primary ciliary dyskinesia.

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Patterns at a Glance

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Spot the Diagnosis

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Exam-style Scenarios

1. A 58-year-old ex-smoker has progressive breathlessness. FEV1 1.4 L (52%), FVC 3.2 L (95%), ratio 0.44; post-bronchodilator FEV1 rises by 90 mL. TLCO is 45%.
Answer: Obstructive pattern without significant reversibility, with low gas transfer - COPD with emphysema (moderate airflow obstruction).

• Check alpha-1 antitrypsin if young or with basal emphysema.
• CT chest if cancer is suspected, or for emphysema assessment.

2. A 65-year-old woman with rheumatoid arthritis has a dry cough. FEV1 2.0 L (80%), FVC 2.2 L (70%), ratio 0.91; TLC 68%, TLCO 50%.
Answer: Restrictive pattern with low gas transfer - interstitial lung disease (possibly RA-ILD, or drug-induced, e.g. methotrexate).

• HRCT and specialist ILD review.

3. A 30-year-old man with "asthma" has worsening noisy breathing despite inhalers, 6 months after an ICU admission with intubation.
Answer: Suspect post-intubation tracheal stenosis.

• Flow–volume loop (box shape), CT of the neck and chest, and bronchoscopy.

4. A patient with COPD has ABG on air: pH 7.38, PaO2 7.1 kPa, PaCO2 7.4 kPa, bicarbonate 33 mmol/L.
Answer: Chronic (compensated) type 2 respiratory failure.

• Assess for long-term oxygen therapy - repeat when stable.
• Consider home NIV if hypercapnia persists after an admission.

5. A 42-year-old woman has breathlessness on exertion. Spirometry and lung volumes are normal; TLCO is 55%; chest X-ray is normal.
Answer: Isolated low gas transfer.

• Look for pulmonary vascular disease: echo for pulmonary hypertension, CTPA or V/Q for chronic thromboembolic disease.
• Also consider anaemia, and early ILD or emphysema on HRCT.

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Key Points

• A low FEV1/FVC ratio means obstruction. Low FEV1 and FVC with a normal ratio suggests restriction - confirm it with lung volumes.
• Bronchodilator reversibility of 12% or more and 200 mL or more supports asthma.
• FeNO of 50 ppb or more, or raised blood eosinophils, confirms asthma when the history is typical (BTS/NICE/SIGN 2024).
• TLCO is low in emphysema, ILD and pulmonary vascular disease; KCO is preserved in extrapulmonary restriction; TLCO is high in alveolar haemorrhage.
• An FVC fall of more than 20% on lying suggests diaphragm weakness.
• A box-shaped flow–volume loop means fixed upper airway obstruction.
• Oximetry misses hypercapnia and overestimates saturation in darker skin.
• A normal chest X-ray does not exclude lung cancer.
• HRCT patterns guide ILD diagnosis - UIP (honeycombing) suggests IPF.
• EBUS samples mediastinal nodes for cancer staging and sarcoidosis.
• Light's criteria separate exudates from transudates.

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Guidelines and Further Reading

• ARTP/BTS: Spirometry and lung function interpretation statements (Global Lung Function Initiative reference equations)
• BTS/NICE/SIGN Asthma guideline (2024): diagnostic algorithm
• BTS Guideline for pleural disease (2023)
• BTS Guideline for diagnostic flexible bronchoscopy in adults
• BTS Clinical statement on air travel
• NICE NG202: Obstructive sleep apnoea/hypopnoea syndrome and obesity hypoventilation syndrome in over 16s
• BTS Guideline for oxygen use in healthcare and emergency settings

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