Normative data for lung function and exhaled nitric oxide in unsedated healthy infants

Abstract

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards.Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, termborn infants at a mean¡SD age of 5.1¡0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (Rint) measurements.Acceptable ) for Rint. In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section.This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

New reference equations to improve interpretation of infant lung function

“…9,11,12 Had we relied on expressing data as weight-corrected values, the current results would be similar to those previously reported for FRC p , 26 and C rs 7,8 but higher than those reported for V T by Fuchs et al 15 when using an ultrasonic flowmeter in a large population of unsedated newborns studied during the first 8 weeks of life. In contrast to previous observations, 7,8,15 after adjustment for body size, significant sex differences were only noted for FRC p , with boys tending to have slightly higher values, a difference that increased with age, and which was therefore adjusted for by including an interaction term in the equation. Differences observed between these studies may be due to the use of different devices and statistical techniques, whether or not sedation was used and the age range covered.…”

“…While the practice of expressing IPF as a ratio of body length 43,44 is fortunately becoming less frequent, infant lung function is still frequently presented as a ratio of weight. This simple approach may be acceptable if limited to a narrow age range of healthy infants during the first months of life, 15 but could lead to considerable bias if used to interpret results from children with chronic respiratory disease in whom somatic growth patterns may be disturbed. While hyperinflation secondary to airways obstruction (as measured by an elevated FRC p ) is a common finding in infants and children with CF, both the prevalence and magnitude of this measure will be exaggerated in children with restricted growth if results are expressed in ml/kg, and under-estimated in those with appropriate somatic growth.…”

“…While some reference values have been published previously, [7][8][9][10][11][12] these were frequently derived using custom-built equipment (which may no longer be appropriate when interpreting results collected using current, commercially available equipment 13,14 ) or only encompass a narrow age range. 15 With increasing use of modern IPF devices, there is an urgent need for appropriate equipment-specific normative data that encompass the entire age range over which such measurements are made (generally 0-2 years).…”

Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children

“…Here, measurements based on quiet tidal breathing usually result in higher proportions of children being able to perform the maneuver satisfactorily than spirometry as a forced expiratory maneuver, as illustrated in a review on lung function tests in preschool children with cystic fibrosis (16). Until now, multiple-breath eNO (eNOmb) measurements have mostly been performed in infants and toddlers (17)(18)(19)(20)(21). Despite requiring less cooperation beyond infancy, criteria for standardization of eNOmb measurements are not yet included in the current ERS/ATS guidelines due to methodological issues (9).…”

“…of the Bern Infant Lung Development (BILD) cohort (20,22) who were enrolled in follow-up at the age of 5-6 y and, to also assess comparability at higher eNO values, in children around 11 y of age with suspected asthma presenting for routine workup in the asthma outpatient clinic of the University Children's Hospital in Bern, Switzerland.…”