Lung function from infancy to the preschool years after clinical diagnosis of cystic fibrosis.

RATIONALE: After recent standardization of forced expiratory maneuvers for both infants and preschool children, longitudinal measurements are now possible from birth. OBJECTIVES: The aim of this study was to investigate the evolution of lung function during the first 6 years of life after a clinical diagnosis of cystic fibrosis (CF) in infancy in children with CF and in healthy control subjects. METHODS: The raised volume technique was used during infancy and incentive spirometry during the preschool years. MEASUREMENTS AND MAIN RESULTS: Forty-eight children with CF and 33 healthy control subjects had up to seven (median, 3) measurements. Over these early years, the diagnosis of CF itself accounted for a significant mean reduction of 7.5% (95% confidence interval, 0.9 - 13.6%) in FEV(0.75) and 15.1% (95% confidence interval, 3.6 - 25.3%) in FEF(25-75). Wheeze on auscultation, recent cough, and Pseudomonas aeruginosa (PsA) infection (even if apparently effectively treated) were all independently associated with further reductions in lung function. Premorbid lung function did not predict infection with PsA. CONCLUSIONS: This is the first study to describe physiologic measurements from infancy through the preschool years in subjects with CF and healthy control subjects, the understanding of which is critical for future intervention trials. Airflow obstruction in uncomplicated CF persists through the preschool years despite treatment, with PsA acquisition being associated with further deterioration in lung function, even when apparently eradicated. This suggests that new therapies are needed to treat the airflow obstruction of uncomplicated CF, and rigorous strategies to prevent PsA acquisition.

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests.

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.

Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis.

Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.

The evolution of airway function in early childhood following clinical diagnosis of cystic fibrosis.

This study aimed to investigate the evolution of airway function in infants newly diagnosed with cystic fibrosis (CF). FEV(0.5) was measured soon after diagnosis (median age of 28 weeks) and 6 months later in subjects with CF and on two occasions 6 months apart (median ages of 7.4 and 33.7 weeks) in healthy infants, using the raised-volume technique. Repeated measurements were successful in 34 CF and 32 healthy subjects. After adjustment for age, length, sex, and exposure to maternal smoking, mean FEV(0.5) was significantly lower in infants with CF both shortly after diagnosis and at the second test, with no significant difference in rate of increase in FEV(0.5) with growth between the two groups. When compared with published reference data, FEV(0.5) was reduced by an average of two z scores on both test occasions in those with CF, with 72% of individuals having an FEV(0.5) of less than 1.64 z-scores (i.e., less than the fifth percentile) on one or both test occasions. On longitudinal analysis, subjects with CF experienced a mean (95% confidence interval) reduction in FEV(0.5) of 20% (11, 28). Airway function is diminished soon after diagnosis in infants with CF and does not catch up during infancy and early childhood. These findings have important implications for early interventions in CF.

Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.