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Multiple breath washout is a gentle lung test. You sit and breathe normally through a mouthpiece while the machine follows a harmless tracer gas leaving your lungs — there is no blowing hard and nothing uncomfortable. If air reaches every part of the lungs evenly, the gas clears quickly. If some small airways are narrowed or blocked, it takes longer, and the machine reports that as a higher lung clearance index. Because it needs only normal breathing, it works well in young children and in people too breathless for other tests, and it can pick up changes in the smallest airways well before a standard breathing test would show anything. The main point to know is that it takes longer than you might expect — often half an hour or more, with several repeats.
What the test measures
The multiple breath washout (MBW) test measures how evenly air is distributed through the lungs. The person breathes normally through a mouthpiece while an inert tracer gas is either washed out of the lungs or washed in, and the machine tracks its concentration breath by breath until it has almost gone.
Spirometry asks how much air you can blow out and how fast. MBW asks a different question entirely: does the air reach every part of the lung equally? In a healthy lung the tracer clears quickly and evenly. Where small airways are narrowed, plugged or obstructed, some regions empty far more slowly than others, and the washout takes longer.
Because it is performed during normal tidal breathing, no forced manoeuvre is required — which is why it works in young children, in people too breathless to perform spirometry reliably, and in anyone whose coordination or effort makes forced testing unreliable.
The main number: lung clearance index
The principal output is the lung clearance index (LCI) — the number of lung volumes that must be breathed to clear the tracer gas down to 1/40th of its starting concentration.
| Value | Interpretation |
|---|---|
| LCI around 6–7 | Typical of a healthy lung; the tracer clears in six to seven lung volumes |
| LCI above roughly 7.4 (equipment- and age-dependent) | Ventilation inhomogeneity — commonly used as the upper limit of normal, though the exact threshold depends on the device, gas and reference set |
| Rising LCI over time | Progression of small-airway disease, often while FEV1 remains unchanged |
A higher LCI means a less efficient, less even lung. Additional indices — Scond and Sacin, derived from phase III slope analysis — attempt to localise the inhomogeneity to the conducting or the acinar airways respectively, though these are used mainly in research.
Why it matters: the silent zone
Small airways under about 2 mm in diameter contribute very little to total airway resistance. A substantial proportion can be diseased before FEV1 falls at all — which is why the small airways have long been called the lung's silent zone. MBW is one of the few practical clinical tests that detects disease in that zone.
This is the clinical value: in cystic fibrosis, in bronchiectasis, in early obstructive disease and after lung transplantation, LCI becomes abnormal earlier than spirometry, and continues to discriminate in patients whose spirometry sits within the normal range.
How the test is performed
- The person sits upright with a nose clip, breathing tidally through a mouthpiece with a bacterial filter.
- A washout is run — either nitrogen washout (breathing 100% oxygen to wash out the resident nitrogen) or an inert tracer gas wash-in/washout, most commonly sulphur hexafluoride (SF6) or helium.
- Tidal breathing continues, without sighs or breath-holds, until the tracer falls below 1/40th of its starting concentration.
- The lungs are allowed to return to baseline, and the run is repeated. Usually two or three technically acceptable runs are required, with the reported LCI the mean.
Each run takes a few minutes and the whole test typically 20–40 minutes — considerably longer than spirometry, which is one of the main barriers to routine use. Quality control matters: leaks around the mouthpiece, irregular breathing, sighs and swallowing all invalidate a run.
Where it is used
- Cystic fibrosis — the best-established application. LCI detects early structural lung disease in preschool children, tracks with CT-detected bronchiectasis and air trapping, and has been used as an endpoint in modulator trials.1,2
- Preschool and young children generally — tidal breathing makes assessment feasible from around age 2–3.
- Primary ciliary dyskinesia and non-CF bronchiectasis — a sensitive marker of small-airway involvement.
- Asthma — ventilation inhomogeneity correlates with control and airway hyper-responsiveness, though it has not entered routine care.
- Post lung transplant — earlier detection of chronic lung allograft dysfunction than spirometry.
- Bronchiolitis obliterans after haematopoietic stem cell transplant.
- Clinical trials — increasingly used as a sensitive endpoint where FEV1 is too insensitive to show change.
Strengths and limitations
| Strengths | Limitations |
|---|---|
| Detects small-airway disease long before spirometry changes | Takes 20–40 minutes — a real constraint in a busy clinic |
| Requires only tidal breathing — no forced manoeuvre, no maximal effort | Requires specific equipment and trained staff; not available in most Australian sites outside specialist centres |
| Feasible in preschool children and in the very breathless | Results are not interchangeable between devices, gases or software versions |
| Highly reproducible when performed to standard | Reference values in adults, and in older adults especially, remain limited |
| Sensitive enough to serve as a trial endpoint | Sensitive to leaks, sighs and irregular breathing — quality control is everything |
What it means for the patient
From the person's side this is one of the easier lung tests: sit still, breathe normally, do not talk or sigh, and keep the seal around the mouthpiece. There is no blowing until exhausted and nothing uncomfortable. The main demand is patience — it takes longer than expected and requires several repeats, which is worth explaining in advance, particularly to parents of a young child.
The result is not a pass or fail. A rising LCI over successive visits is information about the small airways, and is most useful when read alongside symptoms, sputum, imaging and spirometry rather than on its own.
Role of the physiotherapist
Physiotherapists rarely perform MBW — it usually sits with respiratory scientists — but they are frequent users of the result and often the clinician who explains it. Three practical uses.
Interpreting a normal spirometry with abnormal LCI. This combination is common and clinically meaningful: it says the small airways are involved even though the flow rates are preserved. It supports continuing airway clearance rather than relaxing it, and it gives an objective counter to the assumption that normal spirometry means nothing to treat.
Tracking response over time. Where a service has access to MBW, LCI is a more sensitive measure of change than FEV1 for airway clearance and for treatment of small-airway disease — useful in CF, PCD and bronchiectasis follow-up.
Timing the test sensibly. Airway clearance immediately beforehand may transiently alter the result; agree local sequencing with the lung function service rather than assuming. And do not treat LCI as a target in itself — the goal is fewer symptoms, fewer exacerbations and better function.
Evidence summary
Framing. Multiple breath washout is the most clinically mature test of ventilation inhomogeneity, and it exists because spirometry is insensitive to precisely the region where obstructive lung disease begins. Its trajectory has been unusual: it moved from physiology laboratory to multicentre trial endpoint largely on the strength of work in cystic fibrosis, and has yet to translate into routine care in most health systems — not because the physiology is contested, but because the test is slow, equipment-specific and poorly reimbursed.
Sensitivity over spirometryAurora and colleagues demonstrated in preschool and school-age children with CF that LCI was abnormal in a substantially higher proportion than FEV1, and that LCI abnormality predicted later spirometric decline.1 Gustafsson's multicentre work confirmed the pattern across centres and equipment, establishing LCI as the more sensitive marker of early disease.3 Against imaging, Owens and colleagues showed LCI correlates with CT-defined structural disease in children with CF, supporting it as a surrogate for structural change rather than merely a physiological curiosity.4 The same sensitivity gradient has been reproduced in primary ciliary dyskinesia, in non-CF bronchiectasis and in the detection of chronic lung allograft dysfunction after transplantation.
As a trial endpointLCI's responsiveness made it attractive where FEV1 is normal or near-normal at baseline. It was used as a primary endpoint in CFTR modulator trials in children with preserved spirometry, detecting treatment effect where FEV1 could not.2 This is the strongest practical argument for the test: it converts a population previously untestable for treatment effect into a population in which effect can be measured. The corresponding weakness is that the minimal clinically important difference in LCI is not firmly established, so a statistically significant change is not automatically a meaningful one.
Standardisation and its limitsThe ERS/ATS consensus statement set out equipment specifications, gas options, quality criteria and reporting standards, and explicitly cautioned that results are not interchangeable between devices and gases.5 Nitrogen washout and SF6 washout yield systematically different LCI values in the same subject; software versions have altered reported values retrospectively. In practice this means longitudinal comparison is only valid on the same platform, and published thresholds must be matched to the equipment in use. Adult reference data, particularly beyond middle age, remain thinner than paediatric data.
Physiotherapy implications- Treat a normal spirometry with a raised LCI as evidence of active small-airway disease — it is a reason to maintain airway clearance, not to step it down.
- Where available, LCI is the more responsive outcome for tracking small-airway disease over time; FEV1 will under-report both deterioration and improvement in this group.
- Do not compare LCI values obtained on different machines or with different tracer gases — check the platform before interpreting a trend.
- Agree with the lung function service where airway clearance sits relative to testing, and keep the sequence consistent between visits so serial results remain comparable.
- Prepare families for the duration. A preschool child who becomes distressed part-way through produces unusable data and an avoidable negative experience.
Ask what decision the result will change. In a child with CF and normal spirometry, a rising LCI is genuinely actionable — it supports intensifying clearance, reviewing adherence and looking harder at imaging. In an adult with established severe disease and an FEV1 of 35% predicted, LCI adds little that the clinical picture does not already show, and the test time is better spent elsewhere. The test earns its 40 minutes in early disease, in young children and in monitoring; it rarely earns them in advanced disease.
Evidence gapsThe minimal clinically important difference for LCI is not established, which limits interpretation of individual change. Adult and older-adult reference values are inadequate, and ethnically diverse reference data barely exist. Whether treatment decisions guided by LCI improve patient-important outcomes — exacerbations, symptoms, survival — has never been tested in a randomised trial; the entire case rests on sensitivity and surrogate validity. Cross-device standardisation remains unsolved. And the role of MBW outside CF — in asthma, COPD and post-COVID small-airway disease — is promising but largely unvalidated for clinical use.
References & evidence base
- Aurora P, Bush A, Gustafsson P, et al. Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis. Am J Respir Crit Care Med 2005;171:249–56.
- Ratjen F, Klingel M, Black P, et al. Changes in lung clearance index in preschool-aged patients with cystic fibrosis treated with ivacaftor. Am J Respir Crit Care Med 2018;198:526–8.
- Gustafsson PM, De Jong PA, Tiddens HAWM, Lindblad A. Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis. Thorax 2008;63:129–34.
- Owens CM, Aurora P, Stanojevic S, et al. Lung clearance index and HRCT are complementary markers of lung abnormalities in young children with CF. Thorax 2011;66:481–8.
- Robinson PD, Latzin P, Verbanck S, et al. Consensus statement for inert gas washout measurement using multiple- and single-breath tests. Eur Respir J 2013;41:507–22.
References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.
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