Detecting early lung disease in children can be challenging. Spirometry remains an essential test, but it requires forced breathing maneuvers that some young children cannot perform reliably. In cystic fibrosis (CF), spirometry may also remain relatively preserved despite structural lung disease or peripheral airway dysfunction.
Multiple-breath washout (MBW) provides a complementary, effort-independent assessment of global ventilation inhomogeneity during tidal breathing. Its principal outcome, the lung clearance index (LCI), quantifies the number of lung turnovers required to wash out a tracer gas to a predefined concentration. This approach is well established for detecting early lung disease in pediatric cystic fibrosis (CF) and is increasingly studied in primary ciliary dyskinesia (PCD), although evidence for routine clinical monitoring in PCD remains more limited.
By América Torres
What Are MBW and LCI in Pediatric Lung Disease?
During multiple-breath washout (MBW), the child breathes normally while the system measures the washout of an inert tracer gas. The test evaluates how evenly ventilation is distributed and how efficiently the gas is cleared from the lungs.
The principal outcome is the lung clearance index (LCI). It represents the number of lung turnovers required to reduce the tracer gas to a predefined concentration, usually one-fortieth of its starting concentration. A higher LCI indicates greater ventilation inhomogeneity. This matters because disease can affect the small and peripheral airways before it produces clear abnormalities on conventional spirometry. LCI can therefore provide additional information about early lung function changes.
Results depend on the tracer gas, device, software, and testing protocol. Therefore, measurements from different systems are not always interchangeable.
Advantages of Multiple Breath Washout in Pediatric Lung Disease
MBW offers several potential advantages for pediatric lung assessment. In children—particularly those with cystic fibrosis—LCI can provide information beyond spirometry by improving the feasibility of testing in young children, detecting early ventilation abnormalities, identifying treatment-associated changes, and complementing structural lung imaging. Evidence for these applications is promising in primary ciliary dyskinesia but remains less established than in cystic fibrosis. The following four advantages explain where MBW and LCI can add value to pediatric lung function assessment.
1. MBW Is Feasible for Young Children
One major advantage of MBW is that it uses tidal breathing rather than repeated forced expiratory maneuvers. This reduces the coordination and effort required from the child. It may therefore be more feasible than spirometry in preschool children.
The American Thoracic Society (ATS) technical statement provides specific recommendations for MBW testing in children approximately 2–6 years of age. However, successful testing is not guaranteed. It depends on the child’s cooperation, coaching, an adequate mouthpiece or mask seal, a stable breathing pattern, and rigorous quality control. MBW may be particularly useful when spirometry cannot be performed or produces unreliable results. It should not, however, be considered universally superior to spirometry.
2. LCI Can Detect Early Lung Disease
In CF, the lung clearance index (LCI) is often more sensitive than forced expiratory volume in one second (FEV1) for detecting early lung disease. In a longitudinal cohort of preschool children, LCI detected deterioration in lung function over time, whereas spirometric measures did not show the same change. Evidence in primary ciliary dyskinesia (PCD) is also promising. A systematic review3 of 14 studies involving 398 patients found an elevated LCI in every included study, whereas only a minority reported reduced FEV1. LCI also showed stronger associations with computed tomography (CT) and magnetic resonance imaging (MRI) findings than FEV1.
These findings support greater physiological sensitivity, but they do not establish that LCI should replace clinical assessment, spirometry, or imaging.
3. LCI Shows Response to Treatment
LCI is not only useful for detecting disease. It can also capture changes after treatment. The SHIP5 study was a randomized, double-blind, controlled trial involving children aged 3–6 years with CF. Over 48 weeks, participants received either 7% hypertonic saline or 0.9% isotonic saline twice daily.
Hypertonic saline produced a significant improvement in LCI compared with isotonic saline, with a mean treatment difference of −0.63 LCI units. Overall, 89% of MBW tests produced acceptable data. These findings support LCI as an outcome measure in clinical trials. Its role in guiding individual routine treatment should still be interpreted alongside symptoms, pulmonary exacerbations, microbiology, and other functional or structural assessments.
4. MBW Complements Imaging
LCI provides a global measure of ventilation distribution, whereas MRI and CT can show the location and nature of structural abnormalities. In children with cystic fibrosis (CF), LCI correlated with MRI abnormalities, including airway-wall thickening, mucus plugging, and abnormal lung perfusion. Both LCI and MRI detected changes after treatment for pulmonary exacerbations.
MBW therefore does not replace imaging when structural assessment is required. Instead, it can provide a noninvasive functional measure that complements imaging and may help reduce reliance on repeated imaging when appropriate.
Practical Limitations of MBW
MBW requires specialized equipment, trained staff, and rigorous quality control. The test can also take longer than spirometry, and young children may have difficulty maintaining a stable breathing pattern or a proper seal. Results can also vary according to the tracer gas and measurement technology. Nitrogen- and sulfur hexafluoride-based systems are not interchangeable. Standardized procedures are therefore essential for reliable clinical and research results.
Utility of Nitrogen Washout
Nitrogen multiple-breath washout (Nâ‚‚-MBW) uses the nitrogen present in the lungs, which is washed out while the child breathes 100% oxygen. It allows calculation of the lung clearance index (LCI) and functional residual capacity, and may detect ventilation inhomogeneity in children with cystic fibrosis even when spirometry remains relatively preserved. Nâ‚‚-MBW has been used in clinical studies involving preschool children with cystic fibrosis, including the SHIP5 trial. It has also demonstrated abnormal LCI values in patients with primary ciliary dyskinesia.
However, results should be interpreted using reference values specific to the device, software, and protocol used. LCI obtained by Nâ‚‚-MBW and sulfur hexafluoride MBW should not automatically be considered interchangeable. In infants and preschool children with cystic fibrosis, the two methods showed limited agreement, although Nâ‚‚-LCI demonstrated stronger concordance with magnetic resonance imaging findings in that study.
Where Should Pediatric Clinics Consider MBW?
MBW may be particularly useful in specialized CF and PCD programs. Especially for selected longitudinal monitoring, research, and assessment of children who cannot perform reliable spirometry. The ATS guideline on bronchiolitis obliterans syndrome after hematopoietic stem-cell transplantation suggests including MBW at centers with appropriate technical expertise. It may be used alongside spirometry or as an alternative when spirometry is not feasible. This is a conditional recommendation based on low- or very-low-certainty evidence; MBW should not be used as the sole basis for confirming or excluding the diagnosis.
Looking Beyond Spirometry
Spirometry remains essential, but it does not answer every clinical question. MBW and LCI provide a different perspective by assessing ventilation inhomogeneity during tidal breathing and can reveal functional abnormalities that conventional spirometry may miss.
The evidence is strongest in CF and is emerging, but still limited, in PCD and other pediatric lung diseases. LCI can extend pulmonary assessment and serve as a monitoring or research outcome, but it should be interpreted within a multimodal clinical evaluation rather than used as a universal replacement for FEV1 or imaging.
From MBW and LCI to a More Complete View of Lung Function
MBW, with LCI as its principal outcome, can provide complementary information when spirometry does not fully characterize pediatric lung function, particularly in cystic fibrosis. Depending on the clinical question, additional tests such as lung volumes, airway mechanics, or gas-transfer measurements may also be considered. Having these results within an integrated platform can help specialists compare different aspects of lung function and follow changes over time.
SCHILLER-GANSHORN offer a complete of portfolio pulmonary diagnostic systems to help clinicians get comprehensive assessment of patient lung function. Our solutions include:
- PowerCube Body+ body plethysmograph (performs nitrogen washout*)
- SpiroScout ultrasonic spirometer
- tremoflo® airway oscillometry system
- PowerCube Diffusion+ diffusion system
Their advanced testing technology is powered by our dedicated LFX software, which brings results from these pulmonary function tests together on a single platform and makes it easy to compare tests across different visits.
LFX also supports ATS/ERS quality criteria for test validity, provides an easy-to-use interface, allows clinicians to enlarge specific sections of respiratory curves, and generates clear graphical reports. By integrating pulmonary function data on one platform, LFX can help specialists move beyond a single measurement and develop a more complete view of lung function—an approach that is particularly relevant when assessing children with complex or early lung disease.
* DISCLAIMER: The features and functions available on the equipment may vary depending on the configuration selected and product availability in each country. Please contact your SCHILLER representative for further information or assistance with any questions.
See how LFX and SCHILLER-GANSHORN pulmonary function testing solutions can bring a more complete view of lung function to your practice. Request a personalized demo today.
References for the blog
MBW and LCI in Pediatric Lung Disease: Frequently Asked Questions
What is multiple-breath washout (MBW) in pediatric lung disease?
Multiple-breath washout (MBW) is a pulmonary function test that assesses ventilation distribution during tidal breathing. It measures how efficiently an inert tracer gas is cleared from the lungs over successive breaths. Unlike spirometry, MBW does not require repeated forced expiratory maneuvers, which may make it useful for assessing lung function in young children.
What is the lung clearance index (LCI), and what does it measure?
The lung clearance index (LCI) is the principal outcome of multiple-breath washout testing. It indicates how many lung turnovers are required to reduce the concentration of a tracer gas to a predefined level, typically one-fortieth of its starting concentration. A higher LCI indicates greater ventilation inhomogeneity and may be sensitive to early peripheral or small-airway dysfunction, although it is not a specific measure of small-airway disease.
Can LCI detect early lung disease in children with cystic fibrosis?
Yes. LCI can detect early lung function abnormalities in children with cystic fibrosis (CF), including changes that may not be evident on conventional spirometry. Studies have shown that LCI can be more sensitive than FEV1 for identifying early ventilation abnormalities and monitoring changes in lung function over time. However, LCI should complement rather than replace spirometry and other clinical assessments.
Is multiple-breath washout suitable for young children who cannot perform reliable spirometry?
MBW may be particularly useful in young children who have difficulty performing reliable spirometry because it measures lung function during tidal breathing rather than requiring repeated forced maneuvers. The ATS provides technical recommendations for MBW testing in children approximately 2–6 years old. Test quality still depends on factors such as cooperation, breathing stability, an adequate mask or mouthpiece seal, and appropriate quality control.
How does LCI complement spirometry and lung imaging in pediatric lung disease?
LCI provides functional information about ventilation distribution that complements spirometry and lung imaging. Spirometry primarily evaluates airflow, while LCI assesses ventilation inhomogeneity during tidal breathing. CT and MRI can identify structural abnormalities such as airway-wall thickening or mucus plugging. Using these methods together can provide a more comprehensive assessment of pediatric lung disease, particularly in conditions such as cystic fibrosis and primary ciliary dyskinesia.