Basic pulmonary function tests, such as diffusing capacity for carbon monoxide (DLCO), flow-volume loops, lung volumes, and spirometry

Lung volumes

	Definition
TV	Normal breath, ~500 mL
IRV / ERV	Extra volume in / out beyond tidal
RV	Air remaining after maximal expiration - cannot be measured by spirometry
FRC = ERV + RV	Volume at end of a normal expiration; where elastic recoil in = chest wall recoil out
VC = IRV + TV + ERV	Max in to max out
TLC = VC + RV	Everything

RV, FRC and TLC require body plethysmography, helium dilution or nitrogen washout
- Plethysmography measures all intrathoracic gas including trapped gas; dilution/washout measure only communicating gas
- -> Plethysmographic TLC > dilutional TLC in severe obstruction - the difference is trapped gas
RV inc with age and with air trapping in obstructive disease

Reference equations

Reference equations: GLI (Global Lung Initiative) is the current standard - race-neutral equations now recommended, replacing older ethnicity-adjusted values
Report as z-scores; lower limit of normal (LLN) = z -1.64 = 5th percentile
- The fixed FEV1/FVC <0.70 cutoff over-diagnoses obstruction in the elderly and under-diagnoses it in the young - use the LLN
Acceptability: >=3 acceptable manoeuvres, best two FEV1 and FVC within 150 mL

What determines each measurement

FEV1 - airway calibre + elastic recoil + effort (early, effort-dependent portion)
FVC - restriction, air trapping, or poor effort
Mid-flows (FEF 25-75) - small airways; effort-independent but very variable - do not diagnose disease on this alone
TLC - the only true measure of restriction
DLCO - see below

DLCO physiology

Tests the integrity of the alveolar-capillary membrane
Determined by:
- Membrane factor - thickness and available surface area
- Capillary blood volume - i.e. haemoglobin and pulmonary capillary blood
Single-breath technique: inhale 0.3% CO, hold 10 s
*Must be corrected for haemoglobin* (anaemia falsely lowers it), carboxyhaemoglobin, and altitude
KCO (DLCO/VA) - transfer coefficient; corrects for the alveolar volume actually reached
- Distinguishes a small lung with normal alveoli (low DLCO, normal/high KCO - e.g. chest wall/neuromuscular, pneumonectomy) from destroyed alveoli (low DLCO and low KCO - emphysema, ILD)
DLCO does NOT correlate directly with gas exchange efficiency - it is a measure of transfer capacity, not of arterial oxygenation

The three-step read

1. FEV1/FVC ratio -> obstruction?

2. TLC -> restriction?

3. DLCO -> parenchymal or vascular disease?

Pattern	FEV1	FVC	FEV1/FVC	TLC	RV	DLCO
Obstructive	dec dec	dec or normal	*dec (<LLN)*	normal or inc	inc	varies
Restrictive	dec	dec	normal or inc	*dec*	dec	varies
Mixed	dec dec	dec	dec	dec	varies	varies

Obstructive - then split by DLCO

DLCO	Suggests
dec	Emphysema, lymphangioleiomyomatosis
Normal or inc	Asthma (may be inc from increased pulmonary blood volume), chronic bronchitis, bronchiectasis, bronchiolitis

*DLCO is the test that separates asthma from COPD/emphysema on PFTs*

Restrictive - then split by DLCO

DLCO / KCO	Suggests
dec DLCO, dec KCO	Parenchymal (ILD) - IPF, sarcoid, hypersensitivity pneumonitis, drug-induced
dec DLCO, normal/inc KCO	Extrapulmonary - neuromuscular weakness, chest wall (kyphoscoliosis), obesity, pleural disease, pneumonectomy

Isolated low DLCO with normal spirometry and volumes

*Pulmonary vascular disease - pulmonary hypertension, chronic PE* (the key clinical use)
Early ILD, early emphysema, anaemia

Raised DLCO

Alveolar haemorrhage (intra-alveolar blood takes up CO), polycythaemia, asthma, left-to-right shunt, obesity, exercise, supine position, early heart failure

Bronchodilator response

Significant response = inc FEV1 or FVC by >10% of the predicted value (ATS/ERS 2021; the older criterion was >=12% AND >=200 mL from baseline)
Reversibility supports asthma but does NOT exclude COPD, and its absence does not exclude asthma

Bronchial provocation

Methacholine / mannitol / hypertonic saline / exercise
PC20 <8 mg/mL = airway hyperresponsiveness
High negative predictive value - a negative methacholine challenge essentially excludes current asthma

Flow-volume loops - recognise the shape

Shape	Lesion
Scooped/concave expiratory limb, rapid fall from peak	Obstruction (COPD, asthma)
Tall narrow loop, preserved shape, small volumes	Restriction
Flattened expiratory limb only	Variable INTRAthoracic obstruction (tracheomalacia, intrathoracic tumour)
Flattened inspiratory limb only	Variable EXTRAthoracic obstruction (vocal cord dysfunction, laryngeal tumour, unilateral cord palsy)
Both limbs flattened (box-shaped)	Fixed obstruction (tracheal stenosis, post-intubation, goitre, fixed tumour)
Sawtooth pattern	OSA, upper airway instability, neuromuscular

Mnemonic: Extrathoracic affects Expiration? No - extrathoracic affects inspiration. During inspiration, negative intraluminal pressure collapses an extrathoracic airway; during forced expiration, positive pleural pressure collapses an intrathoracic airway

Neuromuscular disease on PFTs

dec VC with a >20% fall from erect to supine = diaphragm weakness
Preserved flows, reduced MIP/MEP/SNIP
See respiratory muscle testing

Quality traps

Submaximal effort - low FEV1 and FVC with a normal ratio mimics restriction. Check flow-volume loop shape and back-extrapolated volume
Obesity - dec ERV and FRC with normal TLC; mimics mild restriction
Poor mouthpiece seal, cough in the first second, early termination
Do not diagnose restriction from spirometry alone - you need TLC

Using PFTs to make decisions

COPD severity (GOLD): FEV1 % predicted - GOLD 1 >=80, 2 50-79, 3 30-49, 4 <30
- But symptoms and exacerbation history, not FEV1, now drive treatment choice
ILD monitoring: FVC decline >=10% or DLCO decline >=15% over 12 months = progression -> antifibrotic therapy, transplant referral
Pre-operative lung resection
- ppoFEV1 and ppoDLCO <60% predicted -> proceed to exercise testing
- <30% -> high risk
- CPET peak VO2 <10 mL/kg/min (or <35% predicted) = very high risk; >20 mL/kg/min = acceptable for pneumonectomy
Transplant referral: CF/bronchiectasis FEV1 <30%, IPF with declining FVC, COPD with BODE index 5-6
Occupational and medico-legal assessment
Drug toxicity surveillance - bleomycin, amiodarone (baseline DLCO), methotrexate, immune checkpoint inhibitors

Confounders

Haemoglobin - always check; correct DLCO for Hb
Smoking - carboxyhaemoglobin falsely lowers DLCO; ask about smoking on the morning of the test
Anaemia, polycythaemia, alveolar haemorrhage, pulmonary vascular disease - DLCO changes
Obesity - dec ERV, dec FRC, preserved TLC
Pregnancy - dec FRC and ERV, unchanged VC and FEV1
Ageing - inc RV, inc FRC, dec DLCO, dec FEV1 (~25-30 mL/yr after 30)
Pleural effusion, pneumonectomy, phrenic nerve palsy - extrapulmonary restriction with preserved KCO

Interpretation pearls

A normal spirometry does not exclude lung disease - always look at volumes and DLCO where the history suggests it
DLCO is the most sensitive single PFT for early ILD and for pulmonary vascular disease
A drop in DLCO on serial testing precedes a fall in FVC in systemic sclerosis-ILD
Serial trends matter more than a single absolute value - always compare with prior studies
"Restriction" reported from spirometry alone is the single most common PFT reporting error
The FEV1/FVC ratio is the diagnostic test for obstruction; the FEV1 % predicted is the severity measure - do not conflate them
An isolated reduced FEF 25-75 is not a disease - do not treat it
Preserved Ratio Impaired Spirometry (PRISm): FEV1 <80% with a normal ratio and normal TLC - associated with inc mortality and progression to COPD; investigate rather than dismiss

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