False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms.
BACKGROUND
Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package.


OBJECTIVE
Our aim was to challenge the validity of these software algorithms.


METHODS
We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement.


RESULTS
In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout.


CONCLUSIONS
We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes.
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.|3rd Pediatric Department, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Pinelopi
P
Anagnostopoulou
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.
Sophie
S
Yammine
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.|University Children's Hospital Basel, UKBB, Basel, Switzerland.
Anne
A
Schmidt
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.
Insa
I
Korten
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.|University Children's Hospital Basel, UKBB, Basel, Switzerland.
Elisabeth
E
Kieninger
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.|University Children's Hospital Basel, UKBB, Basel, Switzerland.
Ines
I
Mack
University Children's Hospital Basel, UKBB, Basel, Switzerland.
Daniel
D
Trachsel
Department of Pediatrics, Respiratory Unit, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
Gaudenz
G
Hafen
University Children's Hospital Zürich, Zürich, Switzerland.
Alexander
A
Moeller
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.
Carmen
C
Casaulta
Division of Respiratory Medicine, Department of Pediatrics, Inselspital and University of Bern, Bern, Switzerland.|University Children's Hospital Basel, UKBB, Basel, Switzerland.
Philipp
P
Latzin
D000465:Algorithms; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012016:Reference Values; D012129:Respiratory Function Tests / Q000295:instrumentation* / Q000379:methods*; D012984:Software
cystic fibrosis; infant pulmonary function; multiple breath washout; ultrasonic flowmeter