The Evolution of Airway Function in Early Childhood Following Clinical Diagnosis of Cystic Fibrosis

Abstract

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.

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

“…6 Results from these infants have not been published previously. Healthy controls born at the Homerton University or University College hospitals in London, UK, were recruited as part of ongoing epidemiological studies.…”

“…During the wash-in phase, the infant inspired a dry air mixture containing 4% sulphur hexafluoride (SF 6 ). Wash-in was undertaken using a simple bias flow system and continued until the inspiratory and expiratory SF 6 concentrations were stable and equal to 0.1%, for a minimum of five breaths. The washout phase using room air started when the bias flow was disconnected during expiration.…”

“…However, in a previous cohort of infants with cystic fibrosis, we found that FEV 0.5 was significantly reduced shortly after diagnosis and did not seem to catch up during infancy and early childhood despite treatment. 6 We had no ''gold standard'' of either inflammation or airway structural changes with which to relate our results.…”

“…[1][2][3][4][5][6] Parameters derived from forced expiratory manoeuvres have traditionally been used to monitor lung function in older patients with cystic fibrosis and forced expiratory volume in 1 second (FEV 1 ) is still considered to be a predictor of prognosis in patients with moderate to severe cystic fibrosis lung disease. 7 8 Although infants cannot perform such manoeuvres, forced expiratory flow-volume (FEFV) loops can be obtained by substituting voluntary effort with application of an external pressure to the chest and abdomen to force expiration.…”

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

“…3 Clinically, CF is characterized by elevated sweat chloride concentration, exocrine pancreatic insufficiency, male infertility and progressive obstructive lung disease, the latter being the primary cause of mortality. 4,5 The respiratory disease progression in CF is expressed by various pulmonary dysfunctions, [6][7][8][9][10] such as ventilation inhomogeneities, 8,11 pulmonary hyperinflation, 9,12 bronchial obstruction, trapped gas and gas exchange disturbances, 10 most of them occurring early in life, 7,12,13 and progressing even in the absence of clinical signs and symptoms. 11,14,15 Owing to the great phenotypic variability in lung disease even observed among patients carrying the same CFTR genotype, several association studies have been conducted to find modifying genetic factors and to study their influence on CF disease outcome.…”