40 research outputs found
Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis
Introduction Improved nutrition is the major proven
benefit of newborn screening programmes for cystic
fibrosis (CF) and is associated with better clinical
outcomes. It was hypothesised that early pulmonary
inflammation and infection in infants with CF is
associated with worse nutrition.
Methods Weight, height and pulmonary inflammation
and infection in bronchoalveolar lavage (BAL) were
assessed shortly after diagnosis in infants with CF and
again at 1, 2 and 3 years of age. Body mass index (BMI)
was expressed as z-scores. Inflammatory cells and
cytokines (interleukin 1b (IL-1b), IL-6, IL-8 and tumour
necrosis factor a (TNFa)), free neutrophil elastase
activity and myeloperoxidase were measured in BAL.
Mixed effects modelling was used to assess longitudinal
associations between pulmonary inflammation,
pulmonary infection (Staphylococcus aureus and
Pseudomonas aeruginosa) and BMI z-score after
adjusting for potential confounding factors.
Results Forty-two infants were studied (16 (38%) male;
39 (93%) pancreatic insufficient); 36 were diagnosed by
newborn screening (at median age 4 weeks) and six by
early clinical diagnosis (meconium ileus). Thirty-one
(74%) received antistaphylococcal antibiotics. More than
two-thirds were asymptomatic at each assessment.
Mean BMI z-scores wer
Oxidation contributes to low glutathione in the airways of children with cystic fibrosis
Glutathione is an important antioxidant in the lungs but its concentration is low in the
airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress
contributes to lowering glutathione is unknown.
We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous
acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass
spectrometry and immunological techniques.
The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis,
whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised
glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous
acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than
controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of
oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage.
The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age.
Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this
deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset
and progression of lung disease in cystic fibrosis
Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic
Measurement of lung function is an important component of clinical management in cystic fibrosis (CF), but has been difficult in young children. The present study aimed to characterise the utility of the forced oscillation technique for measurement of lung function in preschool-aged children with CF in a routine clinical setting. Lung function was assessed in 56 young children (aged 2–7 yrs) with CF. Respiratory system resistance (Rrs) and reactance (Xrs) at 6, 8 and 10 Hz were measured and expressed as Z-scores. Children were classified as asymptomatic or symptomatic based on an administered respiratory questionnaire and physical examination at the time of testing. Between-test repeatability was assessed in 25 children. Measurement of lung function using the forced oscillation technique was feasible in the CF clinic. The children with CF, as a group, had Z-scores for Rrs at 6 Hz (Rrs,6) Rrs,8, Rrs,10, Xrs at 6 Hz (Xrs,6) and Xrs,8 that were significantly different from zero. Children with current symptoms showed significantly decreased Xrs and increased Rrs,6 compared with asymptomatic children. Measurement of lung function using the forced oscillation technique is feasible in young children with cystic fibrosis in a clinical setting. The technique has the potential to improve knowledge concerning early cystic fibrosis lung disease
Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis
When do infants and young children with cystic fibrosis acquire infection with Pseudomonas aeruginosa? Can this be eradicated when first detected
Early detection of lung function abnormalities in young children with cystic fibrosis
The onset of lung disease in cystic fibrosis (CF) begins early in life with respiratory infection, inflammation, and structural lung damage all reported in infants with CF in the first months of life. As new treatments become available, it is essential that we have outcome measures that can be used to track disease progression and treatment efficacy. In this review, we have examined the role of lung function testing in infants and preschool children with CF. In particular, we have focused on the ability of the various lung function tests to detect the presence of respiratory pathogens and structural lung disease, increased inflammation, and the onset of acute exacerbations