Sooky Lum

The lung clearance index (LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood.Multiple-breath washout data from healthy children and adolescents were collated from three centres using the mass spectrometer system and the inert gas sulfur hexafluoride. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (lambda–mu–sigma) method.Data were available from 497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was dependent on body size, decreasing in a nonlinear pattern as height increased. Changes were particularly marked in the first 5 years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed.LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from 6 years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood.

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population.Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls.Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birthper se.The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

Rationale: Reliable interpretation of pulmonary function tests relies on appropriate reference data, which remain very limited for infants.Objectives: This study aimed to assess the validity of published reference equations for forced expiratory flow‐volume (FEFV) data in infants when using current, commercially available equipment, and how this could impact on interpretation of results from infants with lung disease.Methods: The Jaeger Masterscreen BabyBody (v4.67) equipment was used to perform partial and raised volume FEFV maneuvers in healthy infants and those with cystic fibrosis (CF). Results were initially expressed as Z‐scores using published reference equations. Multilevel modeling was used to calculate differences, if any, from predicted scores in healthy infants.Results: Data were available from 66 healthy full term infants on 89 test occasions; [median (range) postnatal age 49.4 (12–101) weeks. All FEFV outcomes were significantly lower than predicted, with mean (SD) Z‐score differences of −0.4 (1.1) for FVC; −0.6 (1.0) for FEV_0.5; −1.0 (1.0) for FEF_25–75 and −1.4 (1.1) for V'_maxFRC. After adjustments using multilevel modeling, mean Z‐scores were within 0.1 (SD∼1.0) predicted for all outcomes in healthy infants. Among 50 infants with CF, studied on 85 test occasions, results were “abnormal” (<−1.96 Z‐scores) on 35 (41%) and 37 (45%) test occasions for FEV_0.5 and FEF_25–75, respectively, when using published equations. This fell to 24 (28%) and 20 (24%), respectively, after adjustment.Conclusions: Dependence on published equations for interpreting FEFV data in infants may lead to misinterpretation of lung function status, which could impact adversely both in the research setting and on clinical management. Use of a contemporary control group or establishment of equipment‐specific reference data is essential for meaningful interpretation of infant lung function data. Pediatr. Pulmonol. 2010; 45:906–913.

Background: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV_0.5 and FEF_25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV_0.5 Z score; FEF_25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC.

This fourth paper in a review series on the role of lung function testing in infants and young children with acute neonatal disorders and chronic lung disease of infancy (CLDI) addresses measurements of forced expiration using rapid thoraco‐abdominal compression (RTC) techniques and the forced deflation technique. Following orientation of the reader to the subject area, we focus our comments on the areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. All studies on infants and young children with CLDI using forced expiratory or deflation maneuvers demonstrated that forced flows at low lung volume remain persistently low through the first 3 years of life. Measurement of maximal flow at functional residual capacity (V′_maxFRC) is the most commonly used method for assessing airway function in infants, but is highly dependent on lung volume and airway tone. Recent studies suggested that the raised volume RTC technique, which assesses lung function over an extended volume range as in older children, may be a more sensitive means of discriminating changes in airway function in infants with respiratory disease. The forced deflation technique allows investigation of pulmonary function during the early development of CLDI in intubated subjects, but its invasive nature precludes its use in the routine setting. For all techniques, there is an urgent need to establish suitable reference data and evaluate within‐ and between‐occasion repeatability, prior to establishing the clinical usefulness of these techniques in assessing baseline airway function and/or response to interventions in subjects with CLDI. Pediatr Pulmonol.