Mirjam Stahla,b,c, Cornelia Joachima,b,c, Mark O. Wielpützc,d, and Marcus A. Malla,b,c,e,f


aDivision of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany

bDepartment of Translational Pulmonology, University of Heidelberg, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany

cTranslational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Im Neuenheimer Feld 156, 69120 Heidelberg, Germany

dDepartment of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany

eDepartment of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

fBerlin Institute of Health (BIH), Anna-Louisa-Karsch-Strasse 2, 10178 Berlin, Germany


What was your research question?

We wanted to know if the results of a special lung function test, the multiple breath washout (MBW), to determine the lung clearance index (LCI) are comparable if two different gases, nitrogen (N2) or sulphur hexafluoride (SF6), were used in infants and preschool children.

Why is this important?

CF lung disease has the biggest influence on illness and death in people with CF and starts early after birth. LCI describes the number of lung turnovers necessary to clear a tracer gas from the lungs and high values correspond to poor ventilation homogeneity. The LCI is able to detect CF lung disease from the first months of life. So far, SF6 has been used as the MBW tracer gas in infants and N2 as the MBW tracer gas in older children and adults. As SF6 is a greenhouse gas and not available in all countries, use of N2 in infants and preschoolers would be helpful. Up to now, a direct comparison of these two gases has not been undertaken in infants and young children with CF.

What did you do?

We investigated LCI in 51 infants and preschoolers with CF (n=31) or without lung disease (n=20) aged 0 to 5 years with the MBW using N2 and SF6 successively. Children with CF underwent a chest MRI scan afterwards as part of their annual check-up. The chest MRI also ensured that any abnormal MBW results are true. We compared the main MBW outcome factor LCI, as well as further factors derived from N2– or SF6-MBW. In addition, we compared whether N2– and SF6-LCI were in accordance with MRI findings.

What did you find?

Findings included that both N2– and SF6-LCI discriminate infants and preschoolers with CF from those without lung disease; however, in both groups of children N2-LCI values were much higher than SF6-LCI values. More infants and pre-schoolers with CF had an abnormal N2– than SF6-LCI. The N2-LCI value showed a better agreement with chest MRI findings than the SF6-LCI value. The difference between N2– and SF6-LCI in our study was largely explained by a higher overall expired volume (CEV) in N2-MBW than SF6-MBW.

What does this mean and reasons for caution?

N2– and SF6-LCI are not interchangeable. Our data indicate that N2-LCI might be more sensitive to detect early CF lung disease than SF6-LCI. The higher N2-CEV could be attributed to N2 that is released from the lung tissue, which is enhanced in lung regions that are worse ventilated like in CF lung disease. It will be interesting to see more data over a longer period of time on this comparison to finally decide which tracer gas is more sensitive. However, N2-MBW necessitates inhalation of pure oxygen and there are reports that this could lead to alterations of the breathing pattern, especially in young infants.

What’s next?

It will be interesting to identify the youngest age where N2-MBW is feasible without putting infants at risk.


Original manuscript citation in PubMed



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